Kaempferol, a flavonoid, found in traditional medicine, fruits, and vegetables, and an HDAC inhibitor, is a powerful anti-cancer reagent against various cancer cell lines. However, detailed mechanisms involved in the treatment of gastric cancer (GC) using kaempferol are not fully understood. In our study, we investigated the biological activity and molecular mechanism involved in kaempferol-mediated treatment of GC. Kaempferol promoted autophagy and cell death, and increased LC3-I to LC3-II conversion and the downregulation of p62 in GC. Furthermore, our results showed that kaempferol induces autophagic cell death via the activation of the IRE1-JNK-CHOP signaling, indicating ER stress response. Indeed, the inhibition of ER stress suppressed kaempferol-induced autophagy and conferred prolonged cell survival, indicating autophagic cell death. We further showed that kaempferol mediates epigenetic change via the inhibition of G9a (HDAC/G9a axis) and also activates autophagic cell death. Taken together, our findings indicate that kaempferol activates the IRE1-JNK-CHOP signaling from cytosol to nucleus, and G9a inhibition activates autophagic cell death in GC cells.

Pancreatic cancer, the seventh most lethal cancer around the world, is considered complicated cancer due to poor prognosis and difficulty in treatment. Despite all the conventional treatments, including surgical therapy and chemotherapy, the mortality rate is still high. Therefore, the possibility of using natural products for pancreatic cancer is increasing. In this study, 68 natural products that have anti-pancreatic cancer effects reported within five years were reviewed. The mechanisms of anti-cancer effects were divided into four types: apoptosis, anti-metastasis, anti-angiogenesis, and anti-resistance. Most of the studies were conducted for natural products that induce apoptosis in pancreatic cancer. Among them, plant extracts such as Eucalyptus microcorys account for the major portion. Some natural products, including Moringa, Coix seed, etc., showed multi-functional properties. Natural products could be beneficial candidates for treating pancreatic cancer.

Introduction: Ménière’s disease (MD) is a disease of the inner ear. In Asian countries, there is one previous epidemiologic study that used a retrospective survey of a specific district. Previous studies have demonstrated that weather variables are strongly associated with symptom aggravation in MD. However, no study has reported on seasonal variation of MD. Methods: We conducted a retrospective population-based study using the Korean national health insurance claims database (NHICD). In the present study, the prevalence and incidence of MD from 2013 to 2017 were calculated. Prevalence and incidence of MD according to sex, age group, and monthly incidence are presented. Seasonal incidence was calculated for four seasons. The seasonal average humidity and atmospheric pressure were also calculated. Results: The incidence rate of MD showed a rapid yearly increase from 2013 to 2017 in Korea. The prevalence and incidence rate by age group continued to increase up to the 70 year olds. The female-to-male ratio was 2.17. The seasonal incidence of MD was relatively high in summer and autumn and relatively low in winter and spring; however, there were no significant differences. Discussion/Conclusions: The rapid progression to an aging society, increase in medical accessibility, and lifestyle changes could be the reasons for the elevation of the incidence rate in the Korean population. Consistent with a previous study, the incidence of MD was higher in seasons with high humidity and low atmospheric pressure; however, there were no significant differences. Further studies about the relationship between diet and MD, seasonality of MD with long-term analysis, and investigating the underlying mechanisms connecting weather and MD are needed.

The root of Platycodon grandiflorum (PG) has long been used as a traditional herbal medicine in Asian country. Platycondin D (PD), triterpenoid saponin that is a main constituent of PG, exhibits various biological activities such as anti-inflammatory, anti-oxidant, anti-diabetic, and anti-cancer effects. A previous study showed that PD had cholesterol-lowering effects in mice that develop hypercholesterolemia, but the underlying molecular mechanisms have not been elucidated during the last decade. Here, we demonstrated that both PG and PD markedly increased levels of cell surface low-density lipoprotein receptor (LDLR) by down-regulation of the E3 ubiquitin ligase named inducible degrader of the LDLR (IDOL) mRNA, leading to the enhanced uptake of LDL-derived cholesterol (LDL-C) in hepatic cells. Furthermore, cycloheximide chase analysis and in vivo ubiquitination assay revealed that PD increased the half-life of LDLR protein by reducing IDOL-mediated LDLR ubiquitination. Finally, we demonstrated that treatment of HepG2 cells with simvastatin in combination with PG and PD had synergistic effects on the improvement of LDLR expression and LDL-C uptake. Together, these results provide the first molecular evidence for anti-hypercholesterolemic activity of PD and suggest that PD alone or together with statin could be a potential therapeutic option in the treatment of atherosclerotic cardiovascular disease.

Traditional, complementary, and alternative medicine (TC&AM) play an exceptional role in health care around the world as many patients has sought a holistic approach. In this study, a multinational survey was developed and administered to obtain experience, attitude, and promotion information with regard to the international use of TC&AM among nine countries: Germany, United States, Japan, China, Malaysia, Vietnam, Russia, Kazakhstan, and United Arab Emirates (UAE). The survey was administered via online to members of SurveyMonkey Audience, a proprietary panel of respondents who were recruited from a diverse population worldwide. A total of 1071 participants has completed the survey. The participants were in favor of the treatments and therapies as well as expressed positive attitudes and also have used herbal medicine treatment more than acupuncture therapy and also used the modalities to promote metabolism rather than treating musculoskeletal diseases. Moreover, participants mentioned that TC&AM should be applied for treating and managing infectious diseases, such as COVID-19. Additionally, participants recommended using Facebook channel to promote its treatments and therapies. Based on the results, this study provides initial insights on TC&AM that may influence the non-users globally and perhaps inspire a need for further research including more countries in different continents.

Jawoongo is an herbal mixture used in traditional medicine to treat skin diseases. This study aimed to investigate whether Jawoongo ameliorates Atopic dermatitis (AD)-like pathology in mice and to understand its underlying cellular mechanisms. AD was induced by 2, 4-Dinitrocholrlbenzene (DNCB) in BALB/c mice. Treatment with Jawoongo was assessed to study the effect of Jawoongo on AD in mice. Histological Analysis, blood analysis, RT-PCR, western blot analysis, ELISA assay and cell viability assay were performed to verify the inhibitory effect of Jawoongo on AD in mice. We found that application of Jawoongo in an ointment form on AD-like skin lesions on DNCB-exposed BALB/c mice reduced skin thickness and ameliorated skin infiltration with inflammatory cells, mast cells and CD4+ cells. The ointment also reduced the mRNA levels of IL-2, IL-4, IL-13 and TNF-α in the sensitized skin. Leukocyte counts and the levels of IgE, IL-6, IL-10 and IL-12 were decreased in the blood of the DNCB-treated mice. Furthermore, studies on cultured cells demonstrated that Jawoongo exhibits anti-inflammatory activities, including the suppression of proinflammatory cytokine expression, nitric oxide (NO) production, and inflammation-associated molecule levels in numerous types of agonist-stimulated innate immune cell, including human mast cells (HMC-1), murine macrophage RAW264.7 cells, and splenocytes isolated from mice. These findings indicate that Jawoongo alleviates DNCB-induced AD-like symptoms via the modulation of several inflammatory responses, indicating that Jawoongo might be a useful drug for the treatment of AD.