Discovery of a New Compound, Erinacerin W, from the Mycelia of Hericium erinaceus, with Immunomodulatory and Neuroprotective Effects.

One new compound with an isoindolinone skeleton, along with erinacines A, C, and S, was isolated from the mycelia of Hericium erinaceus, an edible fungus with a long history of use in traditional Chinese medicine. Based on analysis of MS and NMR spectral data, the structure of the compound was identified as (2E,6E)-8-(2-(1-carboxy-3-methylbutyl)-4,6-dihydroxy-1-oxoisoindolin-5-yl)-2,6-dimethylocta-2,6-dienoic acid. In light of this discovery, we have given this compound the name erinacerin W. Using a co-culture in vitro LPS-activated BV2 microglia-induced SH-SY5Y neuroinflammation model, the results showed that erinacerin W demonstrated protection against the LPS-activated BV-2 cell-induced overexpression of IL-6, IL-1ß, and TNF-α on SH-SY5Y cells. This finding may provide potential therapeutic approaches for central nervous disorders.

Licochalcone A regulates viral IRES activity to inhibit enterovirus replication.

Enterovirus D68 (EV-D68), belonging to the genus Enterovirus of the Picornavirus family, is an emerging pathogen that can cause neurological and respiratory diseases in children. However, there is little understanding of the pathogenesis of EV-D68, and no effective vaccine or drug for the prevention or treatment of the diseases caused by this virus is available. Autophagy is a cellular process that targets cytoplasmic proteins or organelles to the lysosomes for degradation. Enteroviruses strategically harness the host autophagy pathway to facilitate the completion of their life cycle. Therefore, we selected an autophagy compound library to screen for autophagy-related compounds that may affect viral growth. By using the neutralization screening assay, we identified a compound, 'licochalcone A' that significantly inhibited EV-D68 replication. To investigate the mechanism by which licochalcone A inhibits EV-D68 replication and to identify the viral life cycle stage it inhibits, the time-of-addition, viral attachment, viral entry, and dual-luciferase reporter assays were performed. The results of the time-of-addition assay showed that licochalcone A, a characteristic chalcone found in liquorice roots and widely used in traditional Chinese medicine, inhibits EV-D68 replication during the early stages of the viral life cycle, while those of the dual-luciferase reporter assay showed that licochalcone A does not regulate viral attachment and entry, but inhibits EV-D68 IRES-dependent translation. Licochalcone A also inhibited enterovirus A71 and coxsackievirus B3 but did not significantly inhibit dengue virus 2 or human coronavirus 229E replication. Licochalcone A regulates IRES translation to inhibit EV-D68 viral replication.

A novel curriculum for the Same-Sex Marriage Act and Patient Right to Autonomy Act (SMPRA) module based on two new laws in Taiwan: a mixed-methods study.

BACKGROUND: The establishment of laws has had a tremendous impact on holistic medical care. The Patient Right to Autonomy (PRA) Act and the Same-Sex Marriage Act have been passed in Taiwan, and both have sparked intense societal debate. The Same-Sex Marriage Act and PRA Act (SMPRA) teaching module was created for the Gender, Medicine, and Law (GML) course of the medical curriculum. This video trigger-assisted problem-based learning (VTA-PBL) software has integrated content on the aforementioned legislative proclamations. It upends conventional beliefs and fosters reflective practices on sexual rights and the right to representation among medical students. This study examined how the SMPRA module affected the knowledge and attitudes of medical students taking up the GML course. METHODS: A simple pre-/post-test design evaluated the outcomes of the PBL module to examine the changes in knowledge and attitudes of medical students toward same-sex marriage rights. In 2019 and 2020, 126 and 49 5th-year medical students took up the GML course, respectively. The GML components included a video scenario representing advanced decision-making and a healthcare agency with a same-sex couple, a PBL discussion, and student feedback presentations. The mechanisms of feedback collection and measuring student knowledge and attitudes toward sexual rights differed between one cohort in 2019 and the other in 2020. Pre- and post-lecture tests were used in the first school year, whereas a post-lecture open-ended questionnaire survey was used in the second school year. RESULTS: In total, 90 and 39 eligible questionnaires were received in the first and second school years, respectively, which corresponded to response rates of 71% and 80%. Students showed a better understanding of and positive enhancement of proficiency in legal and ethical content and relevant clinical practice. Qualitative analysis revealed that students viewed healthcare providers as checkpoints for conflicts of interest; medical ethics as the cornerstone of clinical practice; cultural background as a significant influence on decision-making; and empathetic communication as the cornerstone of relationships between patients, family members, and doctors. CONCLUSION: The GML course of the SMPRA module fosters reflective practices on ethical and legal sexual rights issues.

Idebenone relieves the damage of heat stress on the maturation and developmental competence of porcine oocytes.

The reproductive function of animals is often affected by climatic conditions. High-temperature conditions can cause damage to oocyte maturation and embryonic development in a variety of ways. The purpose of this study was to prove that supplementation idebenone (IDB) to the maturation medium can improve the maturation and development of porcine oocytes after heat stress (HS). Porcine cumulus-oocyte complexes (COCs) were cultured in the maturation medium with different concentrations of IDB (0, 0.1, 1 and 10 µM) for 44 hr at either 38.5°C or under the HS conditions. The cumulus oophorus expansion, nuclear maturation and blastocyst rate after parthenogenetic activation (PA) were measured. We found that HS (in vitro maturation 20-24 hr, 42°C) exposure significantly reduced cumulus expansion index and maturation rate of oocytes and the blastocyst rate of PA embryos, while IDB supplementation significantly improved oocyte maturation and development to the blastocysts stage after PA. Moreover, the addition of IDB decreased the intracellular level of ROS and increased GSH content, hence enhancing the antioxidant capacity of oocytes under HS. Meanwhile, IDB treatment also obviously improved the mitochondrial membrane potential and ATP synthesis of oocytes under HS conditions. Furthermore, IDB treatment increased the expression of GDF9 and BMP15 in IVM oocytes which attribute to improve the quality and outcome of IVM oocytes and the development competence of PA embryos in pigs. In summary, we demonstrated that IDB supplementation into the maturation medium exerted protective effects and improved the ability of maturation and developmental competence of porcine oocytes exposed to HS.

Effects of astaxanthin on plasma membrane function and fertility of boar sperm during cryopreservation.

Mammalian sperm is highly susceptible to reactive oxygen species (ROS) during the cryopreservation process. Astaxanthin (AST), a red pigment of the carotenoid family, is recognized as having a variety of beneficial biological activities and effects, including antioxidant, anticancer, anti-diabetic, and anti-inflammatory. The present study aimed to investigate whether the presence of AST protected boar sperm from ROS stress during cryopreservation. Boar sperm was diluted with a freezing medium supplemented with different concentrations of AST (0, 0.5, 1, 2, or 5 µM). The addition of AST, especially at a concentration of 2 µM, exerted positive effects on post-thaw sperm motility parameters. Meanwhile, sperm plasma membrane integrity and acrosome integrity of post-thaw sperm were significantly increased, while lipid peroxidation was inhibited in response to 2 µM AST treatment. Interestingly, compared to the control, supplementation with 2 µM AST increased unsaturated fatty acids (UFAs) levels and decreased saturated fatty acids (SFAs) content in post-thaw sperm, leading to a decreased ratio of SFAs/UFAs in the AST group. In conclusion, the addition of AST to freezing extenders inhibited lipid peroxidation and regulated fatty acid composition of the sperm membrane, improved post-thaw sperm quality, and had no adverse effect on boar sperm in vitro fertilization (IVF) capacity and potential for embryonic development. Our data provide a novel insight into understanding the mechanisms of AST concerning protecting boar sperm quality against ROS damage during cryopreservation.

Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians.

OBJECTIVE: To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai). METHODS: We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate of HLA-B*15:02 and HLA-A*31:01 of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)-induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database. RESULTS: We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6 drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all ≦5%) and no mortality. There was a significant association between HLA-B*15:02 and OXC-SJS (p = 1.87 × 10-10; odds ratio 27.90; 95% confidence interval [CI] 7.84-99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values of HLA-B*15:02 for OXC-SJS/TEN were 0.73% and 99.97%, respectively. HLA-A*31:01 was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p = 0.003; relative risk 0.212; 95% CI 0.077-0.584). CONCLUSIONS: Our findings suggest that HLA-B*15:02 is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptive HLA-B*15:02 screening should be evaluated further.

Topical isoflavones provide effective photoprotection to skin.

BACKGROUND/PURPOSE: Isoflavones, one main group of phytoestrogens, have antioxidative and photoprotective effects in cellular and mouse studies. The aim of this study is to obtain a more comprehensive understanding of the isoflavone-mediated photoprotection with the pig skin model, a more human-resembling model. METHODS: The pig skin was treated with five well-known isoflavone compounds (genistein, equol, daidzein, biochanin A, and formononetin) and one antioxidant combination solution of 15% vitamin C and 1% vitamin E and 0.5% ferulic acid (CEF) daily for 4 days. Skin was irradiated with solar-simulated UV irradiation, 1 to 5 minimal erythema dose (MED) at 1-MED intervals. Evaluation was carried out 24 h later by colorimeter-measured erythema and sunburn cell numbers. RESULTS: Topical application of 0.5% solutions of three individual phytoestrogens - genistein, daidzein, biochanin A - are better than similar solutions of equol or formononetin in protecting pig skin from solar-simulated ultraviolet (SSUV)-induced photodamage, as measured by sunburn cell formation and/or erythema. However, the protection was less than that provided by a topical combination antioxidant standard containing 15% L-ascorbic acid, 1%alpha-tocopherol, and 0.5% ferulic acid. CONCLUSION: Isoflavones provide effective photoprotection and are good candidate ingredients for protection against ultraviolet (UV) photodamage.