Procyanidin C1 (PC1), a trimer of (-)-epicatechin units found in cocoa, grapes, and apples, exhibits various health benefits. Nevertheless, its absorption rate is low, and the molecular mechanisms underlying biological regulation remain unknown. Here, we demonstrate how PC1 influences neural function and reveal a key regulator mediating these effects. Our results showed that PC1 improves spatial working memory and cognitive ability mediated by circulating microRNA(miR)-181a-5p. PC1 upregulates miR-181a-5p via the 67-kDa laminin receptor (67LR), which modulates brain-derived neurotrophic factor (BDNF) and its downstream signaling pathway. Furthermore, cognitive improvement, increased cyclic AMP-responsive element-binding protein (CREB) levels, extracellular signal-regulated kinase (ERK) phosphorylation, and upregulated BDNF in the hippocampus after oral PC1 gavage were entirely negated by miR-181a-5p inhibitor. This study provides mechanistic insights into how poorly absorbed dietary polyphenols modulate brain function, suggesting a previously unrecognized route by which gut-PC1-miRNA via 67LR signaling influences cognitive regulation.

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder affecting both children and adults, characterized by intense itching, erythema, and xerosis. The pathogenesis of AD is multifactorial, involving genetic predisposition, immune dysregulation, skin barrier dysfunction, and environmental factors. A growing body of evidence suggests that oxidative stress plays a critical role in AD, contributing to chronic inflammation, immune cell activation, and skin barrier disruption. Oxidative stress arises from an imbalance between Reactive Oxygen Species (ROS) production and antioxidant defenses, leading to cellular damage and the exacerbation of AD symptoms. Recent research has highlighted the potential of plant-derived bioactive compounds, particularly those with antioxidant properties, to mitigate oxidative stress and provide therapeutic benefits in AD. These compounds, including quercetin, resveratrol, curcumin, silymarin, baicalin, luteolin, and epigallocatechin gallate, not only neutralize ROS but also exhibit anti-inflammatory, immunomodulatory, and skin barrier-restoring effects. Natural antioxidants from plants offer a safer alternative to conventional treatments, which may have long-term side effects. This review provides a comprehensive overview of the mechanisms by which oxidative stress contributes to AD and examines the potential of plant-derived antioxidants in alleviating AD symptoms. The growing interest in these compounds underscores the need for further research to harness their full therapeutic potential in AD management.

Abstract Background There are limited and conflicting data regarding the incidence and prognostic impact of in-hospital heart failure (HF) complicating acute myocardial infarction (MI). The aim of this study was to examine temporal trends in the incidence and outcomes of systolic HF after acute MI in a large national cohort in South Korea. Methods The nationwide Korea Acute Myocardial Infarction Registry records baseline characteristics, treatments, and outcome of consecutive patients with acute MI admitted to hospitals capable of primary percutaneous coronary intervention (PCI) in South Korea. Systolic HF was defined as an ejection fraction ≤40% by echocardiography at admission. This study included 68,123 patients admitted for index acute MI between 2005 and 2020 (phase 1: 2005-2007, n=14,735; phase 2: 2008-2011, n=24,656; phase 3: 2012-2015, n=13,104; phase 4: 2016-2020, n=15,628). Results In all patients, the incidence of HF declined from 19.4% in phase 1 to 14.1% in phase 4 (p<0.001). This decrease was more pronounced in patients with ST-segment elevation MI (STEMI, from 20.9% to 15.8%) compared to those with non-ST-segment elevation MI (NSTEMI, from 17.9% to 12.3%). The use of PCI and of statins at discharge increased from 86% to 91.2% and from 75.1% to 92.2%, respectively (p<0.001 for all). Previous history of MI increased from 8.4% to 10.4% (p<0.001) whereas previous history of HF and stroke decreased from 6.3% to 1.3% and from 17.4% to 6.4%, respectively (p<0.001). The median symptom-to-door time decreased from 3.5 hours to 2.1 hours for STEMI and from 6.3 hours to 5.5 hours for NSTEMI (p<0.001). The median door-to-balloon time decreased from 107 min to 64 min for STEMI and from 26 hours to 14 hours for NSTEMI (p<0.001). The in-hospital and 12-month mortality rates for all patients decreased over the years from 5.0% to 3.3% and from 7.6% to 6.1%, respectively (p<0.001). However, in those who developed HF during the index MI, no significant declining trends were observed in in-hospital mortality (phase 1: 8.8%, phase 2: 7.95%, phase 3: 8.3%, phase 4: 7.3%, p=0.123) and 12-month mortality (phase 1: 15.4%, phase 2: 12.6%, phase 3: 19.4%, phase 4: 15.2%, p=0.270). Independent predictors of developing in-hospital HF were age >75 years, body mass index <18.5 kg/m2, symptom-to-door and door-to-balloon times, systolic blood pressure <100 mmHg at presentation, heart rate >90 min at presentation, presence of atrial fibrillation or diabetes, and previous history of MI, HF or stroke. Conclusions A marked reduction was found in the incidence of HF after acute MI between 2005 and 2020 in South Korea. However, in-hospital and 12-month mortality rates in HF patients remain unchanged, warranting intensive post-MI management with more aggressive efforts for secondary prevention.

Diallyl disulfide (DADS) is a well-known principal functional component derived from garlic (Allium sativum) that has various health benefits. Previously, we identified a 67-kDa laminin receptor, a receptor for oolong tea polyphenol oolonghomobisflavan B (OHBFB). However, its molecular mechanisms still remain to be elucidated. Here, we show that DADS synergistically enhanced the effect of the oolong tea polyphenol oolonghomobisflavan B (OHBFB), which induces apoptosis in acute myeloid leukemia (AML) cancer cells without affecting normal human peripheral blood mononuclear cells (PBMCs). The underlying mechanism of OHBFB-induced anti-AML effects involves the upregulation of the 67-kDa laminin receptor/endothelial nitric oxide synthase/cyclic guanosine monophosphate (cGMP)/protein kinase c delta (PKCδ)/acid sphingomyelinase (ASM)/cleaved caspase-3 signaling pathway. In conclusion, we show that the combination of OHBFB and DADS synergistically induced apoptotic cell death in AML cells through activation of 67LR/cGMP/PKCδ/ASM signaling pathway. Moreover, in this mechanism, we demonstrate DADS may reduce the enzyme activity of phosphodiesterase, which is a negative regulator of cGMP that potentiates OHBFB-induced AML apoptotic cell death without affecting normal PBMCs.

Rotavirus is the main causative agent of viral gastroenteritis among young animals worldwide. Currently, no clinically approved or effective antiviral drugs are available to combat rotavirus infections. Herein, we evaluated the anti-rotaviral activities of extracts and bavachin isolated from Psoralea corylifolia L. (Fabaceae) (P. corylifolia) against the bovine rotavirus G8P[7] and porcine rotavirus G5P[7] in vitro. Two assay strategies were performed: (1) a virucidal assay to reduce viral infectivity by virus neutralization and (2) a post-treatment assay to assess viral replication suppression. The results from the virucidal assay showed that the extracts and bavachin did not exert anti-rotaviral activities. In the follow-up analysis after treatment, bavachin exhibited robust antiviral efficacy, with 50% effective concentration (EC50) values of 10.6 μM (selectivity index [SI] = 2.38) against bovine rotavirus G8P[7] and 13.0 μM (SI = 1.94) against porcine rotavirus G5P[7]. Bavachin strongly suppressed viral RNA synthesis in the early (6 h) and late stages (18 h) after rotaviral infection. These findings strongly suggest that bavachin may have hindered the virions by effectively inhibiting the early stages of the virus replication cycle after rotaviral infection. Furthermore, confocal imaging showed that bavachin suppressed viral protein synthesis, notably that of the rotaviral protein (VP6). These results suggest that bavachin has strong antiviral activity against rotaviruses, inhibits viral replication, and is a candidate natural therapeutic drug targeting rotaviral infection. The utilization of bavachin isolated from P. corylifolia may contribute to decreased mortality rates, lower medication expenses, and enhanced economic viability in domestic farms.

Ethics is the basis and conditions necessary for humans to live together, so all education is based on an ethical consciousness. However, educators should reflect on the fact that these functions of education are not working well in real life. In particular, the reason why medicine should not let go of the value of living together in a community is that the human dignity stipulated by the constitution of each country should not be violated by anything. Therefore, the medical college curriculum needs speculative theories and discourses that were discussed in traditional medical education to understand the purpose of their existence in the medical-philosophy relationship, strengthen their sense of ethics as a doctor, and embody roles and responsibilities for the community. In this way, 10 educational experts in medicine, philosophy, (medical) education, psychology, and social welfare at the university and the medical school in Daegu discussed and developed medical humanities subjects and conducted lectures. The education method was conducted through lectures, discussions, and presentations, and was evaluated by attendance and attitude, peer evaluation, and portfolio. In addition to theoretical knowledge about community spirit, the importance of discussion and communication and cooperation were induced in the process. Faculty members participated together to reflect on the nature of education based on the results of a semester-long study of medical humanities subjects and consider the direction that medical education should pursue in the future.

Although vaccines have been developed for rotavirus infections, there is currently no effective therapeutic treatment. Therefore, this study aimed to evaluate the efficacy of 18-hydroxyferruginol ( 1 ) and 18-oxoferruginol ( 2 ) isolated from Torreya nucifera (T. nucifera) against bovine G8P[7] and porcine G5P[7] rotaviruses using two different assay strategies: 1) reduction of viral infectivity by neutralizing the virus (virucidal assay) and 2) inhibition of viral replication after infection (post-treatment assay). In the post-treatment assay, compounds 1 and 2 exhibited strong anti-rotavirus activity, with 50% effective concentration values of 24.7 μM (selectivity index; SI= 2.52) and 23.2 μM (SI= 1.75) against bovine G8P[7], 21.1 μM (SI= 2.95) and 22.6 μM (SI= 1.80) against porcine G5P[7], respectively. During viral replication, the two compounds demonstrated stronger inhibition of viral RNA synthesis in the late stages (18 h) than in the early stages (6 h). Compounds 1 and 2 also inhibited the synthesis of viral proteins such as VP6, as determined by immunofluorescence assay. Thus, it appears that compounds 1 and 2 isolated from T. nucifera possess strong antiviral activity against rotaviruses, inhibit viral replication, and may be developed into potential plant-derived therapeutic candidates against rotavirus infection.

(−)‐Epigallocatechin‐3‐O‐gallate (EGCG) is one of the major components of green tea polyphenol. Previous studies have shown that EGCG induces cancer‐specific cell death in vitro and in vivo without causing severe side effects. However, the anti‐cancer effect of EGCG alone is limited. 5,7‐dimethoxyflavone (5,7‐DMF), one of the principal functional components of black ginger (Kaempferia parviflora), also exerts anti‐cancer effects. Here, we show that 5,7‐DMF synergistically enhances the anti‐cancer effect of EGCG in multiple myeloma cells by potentiating EGCG‐induced intracellular cyclic guanosine monophosphate (cGMP) production. Moreover, the combination of EGCG and 5,7‐DMF induces apoptotic cell death in multiple myeloma cells, and this is accompanied by activation of the cGMP/acid sphingomyelinase (ASM)/cleaved caspase‐3 pathway. In conclusion, we have shown that 5,7‐DMF enhances the anti‐cancer effect of EGCG by upregulating cGMP in multiple myeloma cells.

Although vaccines and antiviral drugs are available, influenza viruses continue to pose a significant threat to vulnerable populations globally. With the emergence of drug-resistant strains, there is a growing need for novel antiviral therapeutic approaches. We found that 18-hydroxyferruginol (1) and 18-oxoferruginol (2) isolated from Torreya nucifera exhibited strong anti-influenza activity, with 50% inhibitory concentration values of 13.6 and 18.3 μM against H1N1, 12.8 and 10.8 μM against H9N2, and 29.2 μM (only compound 2) against H3N2 in the post-treatment assay, respectively. During the viral replication stages, the two compounds demonstrated stronger inhibition of viral RNA and protein in the late stages (12–18 h) than in the early stages (3–6 h). Moreover, both compounds inhibited PI3K-Akt signaling, which participates in viral replication during the later stages of infection. The ERK signaling pathway is also related to viral replication and was substantially inhibited by the two compounds. In particular, the inhibition of PI3K-Akt signaling by these compounds inhibited viral replication by sabotaging influenza ribonucleoprotein nucleus-to-cytoplasm export. These data indicate that compounds 1 and 2 could potentially reduce viral RNA and viral protein levels by inhibiting the PI3K-Akt signaling pathway. Our results suggest that abietane diterpenoids isolated from T. nucifera may be potent antiviral candidates for new influenza therapies.

Background: Oolonghomobisflavans are unique polyphenols found in oolong teas. Oolonghomobisflavan B (OHBFB), a dimer of (-)-epigallocatechin-3-O-gallate (EGCG), is an active compound found in green tea.Purpose: OHBFB has been reported to exert an inhibitory effect on lipase enzyme activity. However, little is known regarding its intercellular signaling induction effect. Further, there are no reports describing the anticancer effects of OHBFB. Methods: The effect of OFBFB on B16 melanoma cells was evaluated by cell counting, and its mechanisms were determined by western blot analysis with or without protein phosphatase 2A (PP2A) inhibitor treatment. Intracellular cyclic adenosine monophosphate (cAMP) levels were evaluated by time-resolved fluorescence resonance energy transfer analysis. Quartz crystal microbalance (QCM) analysis was performed to assess the binding of OHBFB to 67LR. Results: Cell growth assay and western blot analyses showed that OHBFB inhibited melanoma cell growth, followed by myosin phosphatase target subunit 1 (MYPT1) and myosin regulatory light chain (MRLC) dephosphorylation via protein phosphatase 2A (PP2A)-dependent mechanisms. These effects are mediated by intracellular cAMP- and protein kinase A (PKA) A-dependent mechanisms. QCM analysis identified the 67-kDa laminin receptor (67LR) as an OHBFB receptor with a Kd of 3.7 mu M. We also demonstrated for the first time that OHBFB intake suppresses tumor growth in vivo. Conclusions: Taken together, these results indicate that the cAMP/PKA/PP2A/MYPT1/MRLC pathway is a key mediator of melanoma cell growth inhibition following OHBFB binding to 67LR and that OHBFB suppresses tumor growth in vivo.

The discovery of limocitrin in Sedum sarmentosum Bunge, a compound known for its potent antitumor activity, has sparked interest in understanding its molecular mechanisms and bioactive effects. Breast cancer, particularly triple-negative breast cancer (TNBC), presents a challenging prognosis with a higher likelihood of recurrence, metastasis, and lower survival rates compared to most other cancer types. This study aimed to explore the anticancer potential of limocitrin on two different human breast cancer cell lines. The results of the study revealed that limocitrin effectively reduced the viability of breast cancer cells, with IC50 values of 29.33 +/- 0.010 and 28.70 +/- 0.030 mu M for MDA-MB-231 and MCF-7 cells, respectively. Further investigations demonstrated that limocitrin induced apoptotic cell death, characterized by an increase in the population of apoptotic cells and the formation of apoptotic bodies. Limocitrin induced the upregulation of apoptosis-related protein expressions such as apoptosis-inducing factor, Bax, endonuclease G, and cleaved-poly ADP-ribose polymerase, while downregulating the expression of proteins associated with cell survival, including Akt, Bcl-2, Bid, mTOR, PI3K, procaspases, and p70 S6 kinase. Notably, the response to limocitrin treatment varied between the two types of breast cancer cells, indicating a differential effect of limocitrin on the intracellular signaling pathways related to cell survival in breast cancer. These findings open up avenues for further research and exploration of limocitrin as a potential therapeutic agent for breast cancer treatment, especially for challenging subtypes like TNBC.

Many patients with allergies have anxiety about taking anti-allergic medicines due to their side effects and increased medical expenses. Thus, developing functional foods/agricultural products for allergy prevention is strongly desired. In this study, we revealed that a Citrus flavanone, hesperetin, amplified IgE/antigen-mediated degranulation-inhibitory potency of anti-allergic catechin, (–)-epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3ʹʹMe), in the rat basophilic/mast cell line RBL-2H3. Hesperetin also significantly elevated the activation of acid sphingomyelinase (ASM), essential for eliciting anti-allergic effect of EGCG3ʹʹMe through the cell surficial protein, 67-kDa laminin receptor (67LR). Furthermore, oral administration of the highly absorbent hesperidin, α-glucosyl hesperidin, also enhanced the inhibitory potency of EGCG3ʹʹMe-rich ‘Benifuuki’ green tea (Camellia sinensis L.) on passive cutaneous anaphylaxis (PCA) reaction evoked by IgE/antigen in BALB/c mice. These observations indicate that hesperetin amplifies the ability of EGCG3ʹʹMe to inhibit the IgE/antigen-mediated degranulation through activating ASM signaling.

The purpose of this study was to analyze the results of a study on the psychological state, lifestyle, self-management ability, and academic adaptation of medical students, and to present examples of improvement of a student support center based on the results. A medical school in Daegu has been surveying the living conditions of students every year for 6 years since 2016. More than 60% of medical students experienced depression and more than 70% experienced stress, but these rates have significantly improved over the past 5 years. There were many cases of drinking or smoking to relieve stress, but the frequency of drinking recently decreased substantially. Some students had difficulties in emotional regulation (11.5%) and time management (16.6%), and challenges in planning and self-management increased significantly during the coronavirus disease 2019 (COVID-19) pandemic. The satisfaction and adaptability of medical students are high, but the number of students who are not satisfied with but negative response rate is 2%-3% in every year. However, satisfaction has significantly increased in tandem with curriculum changes and COVID-19. Based on these data, the counseling system was reorganized to support psychological stability, the medical humanities curriculum was improved, and changes in actual quality of life were induced by developing and operating non-curricular programs. Furthermore, standardized questionnaires will be developed and data from many medical schools will be shared, which is expected to support medical students more effectively.

Epigallocatechin 3-O-gallate (EGCG) is a predominant component in green tea with various health benefits. The 67 kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that is overexpressed in various types of cancer; 67LR was identified a cell surface EGCG target that plays a pivotal role in tumor growth, metastasis, and resistance to chemotherapy. However, the plasma concentration of EGCG is limited, and its molecular mechanisms remain unelucidated in colon cancer. In this study, we found that the phosphodiesterase 5 (PDE5) inhibitor, vardenafil (VDN), potentiates EGCG-induced apoptotic cell death in colon cancer cells. The combination of EGCG and VDN induced apoptosis via activation of the endothelial nitric oxide synthase/cyclic guanosine monophosphate/protein kinase Cδ signaling pathway. In conclusion, the PDE5 inhibitor, VDN, may reduce the intracellular PDE5 enzyme activity that potentiates EGCG-induced apoptotic cell death in Caco-2 cells. These results suggest that PDE5 inhibitors can be used to elevate cGMP levels to induce 67LR-mediated, cancer-specific cell death. Therefore, EGCG may be employed as a therapeutic candidate for colon cancer.

The purpose of this study is to verify the pedagogical necessity of the medical humanities and to analyze the educational contents of medical humanities in medical schools of Korea. Medical humanities education should reflect the students' real life situations and attitudes because the educational goal of medical school students is to live as happy persons and good doctors. Understanding the medical humanities education that can achieve this goal will enable students to overcome various difficulties they will face in the future, and these contents should be included in graduation outcomes. The curriculum of medical humanities in Keimyung University School of Medicine was also analyzed, and based on this, we suggest the direction of education to be pursued. According to the analyzed data, medical humanities should be avoided from knowledge-oriented memorization education, and the curriculum should be supplemented by finding ways to integrate with basic and clinical medicine subjects. In addition, education that can increase resilience and form the identity of a doctor who can love and care for oneself is required even in difficult situations. Many attention and research will be needed in the future to achieve the original purpose of medical humanities education to understand others and society and to recognize the value of empathy and consideration. Keywords: Humanism education, Medical education, Medical humanities, Professionalism

Symplocos sumuntia Buch.-Ham. ex D. Don (S. sumuntia) is a traditional medicinal herb used in Asia to treat various pathologies, including cough, stomachache, tonsillitis, hypertension, and hyperlipidemia. Although the anti-inflammatory activity of S. sumuntia has been reported, little is known about its anti-inflammatory activity and molecular mechanisms in microglial cells. Therefore, we investigated the inhibitory effects of S. sumuntia methanol extract (SSME) on the inflammatory responses in lipopolysaccharide (LPS)-treated BV2 cells. The SSME significantly inhibited the LPS-stimulated inducible nitric oxide synthase and cyclooxygenase-2 expression, as well as the production of nitric oxide (NO), a proinflammatory mediator. The production of proinflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor-α, and IL-1β, was suppressed by the SSME in the LPS-induced BV2 cells. The mechanism underlying the anti-inflammatory effects of SSME involves the suppression of the LPS-stimulated phosphorylation of mitogen-activated protein kinases (MAPKs) such as JNK. Moreover, we showed that the LPS-stimulated nuclear translocation of the nuclear factor-κB (NF-κB)/p65 protein, followed by IκB degradation, was decreased by the SSME treatment. Collectively, these results showed that the SSME induced anti-inflammatory effects via the suppression of the MAPK signaling pathways, accompanied by changes in the NF-κB translocation into the nucleus. Therefore, SSME may be employed as a potential therapeutic candidate for various inflammatory diseases.