FoxO6-Mediated TXNIP Induces Lipid Accumulation in the Liver through NLRP3 Inflammasome Activation.

BACKGRUOUND: Hepatic steatosis, which involves the excessive accumulation of lipid droplets in hepatocytes, presents a significant global health concern due to its association with obesity and metabolic disorders. Inflammation plays a crucial role in the progression of hepatic steatosis; however, the precise molecular mechanisms responsible for this process remain unknown. METHODS: This study investigated the involvement of the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome and the forkhead box O6 (FoxO6) transcription factor in the pathogenesis of hepatic steatosis. We monitored the NLRP3 inflammasome and lipogenesis in mice overexpressing the constitutively active (CA)-FoxO6 allele and FoxO6-null mice. In an in vitro study, we administered palmitate to liver cells overexpressing CA-FoxO6 and measured changes in lipid metabolism. RESULTS: We administered palmitate treatment to clarify the mechanisms through which FoxO6 activates cytokine interleukin (IL)-1ß through the NLRP3 inflammasome. The initial experiments revealed that dephosphorylation led to palmitate-induced FoxO6 transcriptional activity. Further palmitate experiments showed increased expression of IL-1ß and the hepatic NLRP3 inflammasome complex, including adaptor protein apoptotic speck protein containing a caspase recruitment domain (ASC) and pro-caspase-1. Furthermore, thioredoxin-interacting protein (TXNIP), a key regulator of cellular redox conditions upstream of the NLRP3 inflammasome, was induced by FoxO6 in the liver and HepG2 cells. CONCLUSION: The findings of this study shed light on the molecular mechanisms underpinning the FoxO6-NLRP3 inflammasome axis in promoting inflammation and lipid accumulation in the liver.

Molecular Foundations of Inflammatory Diseases: Insights into Inflammation and Inflammasomes.

Inflammatory diseases are a global health problem affecting millions of people with a wide range of conditions. These diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), osteoarthritis (OA), gout, and diabetes, impose a significant burden on patients and healthcare systems. A complicated interaction between genetic variables, environmental stimuli, and dysregulated immune responses shows the complex biological foundation of various diseases. This review focuses on the molecular mechanisms underlying inflammatory diseases, including the function of inflammasomes and inflammation. We investigate the impact of environmental and genetic factors on the progression of inflammatory diseases, explore the connection between inflammation and inflammasome activation, and examine the incidence of various inflammatory diseases in relation to inflammasomes.

The Potential of Korean Bioactive Substances and Functional Foods for Immune Enhancement.

In this review, we explore the immunomodulatory properties of Korean foods, focusing on ginseng and fermented foods. One notable example is Korean red ginseng, known for its immune system-regulating effects attributed to the active ingredient, ginsenoside. Ginsenoside stimulates immune cells, enhancing immune function and suppressing inflammatory responses. With a long history, Korean red ginseng has demonstrated therapeutic effects against various diseases. Additionally, Korean fermented foods like kimchi, doenjang, chongkukjang, gochujang, vinegar, and jangajji provide diverse nutrients and bioactive substances, contributing to immune system enhancement. Moreover, traditional Korean natural herbs such as Cirsium setidens Nakai, Gomchwi, Beak-Jak-Yak, etc. possess immune-boosting properties and are used in various Korean foods. By incorporating these foods into one's diet, one can strengthen their immune system, positively impacting their overall health and well-being.

Immune Diseases Associated with Aging: Molecular Mechanisms and Treatment Strategies.

Aging is associated with a decline in immune function, thereby causing an increased susceptibility to various diseases. Herein, we review immune diseases associated with aging, focusing on tumors, atherosclerosis, and immunodeficiency disorders. The molecular mechanisms underlying these conditions are discussed, highlighting telomere shortening, tissue inflammation, and altered signaling pathways, e.g., the mammalian target of the rapamycin (mTOR) pathway, as key contributors to immune dysfunction. The role of the senescence-associated secretory phenotype in driving chronic tissue inflammation and disruption has been examined. Our review underscores the significance of targeting tissue inflammation and immunomodulation for treating immune disorders. In addition, anti-inflammatory medications, including corticosteroids and nonsteroidal anti-inflammatory drugs, and novel approaches, e.g., probiotics and polyphenols, are discussed. Immunotherapy, particularly immune checkpoint inhibitor therapy and adoptive T-cell therapy, has been explored for its potential to enhance immune responses in older populations. A comprehensive analysis of immune disorders associated with aging and underlying molecular mechanisms provides insights into potential treatment strategies to alleviate the burden of these conditions in the aging population. The interplay among immune dysfunction, chronic tissue inflammation, and innovative therapeutic approaches highlights the importance of elucidating these complex processes to develop effective interventions to improve the quality of life in older adults.

Evaluating the Reliability and Validity of the Korean Version of the Pandemic-Related Pregnancy Stress Scale.

Purpose: This study aimed to translate the Pandemic-Related Pregnancy Stress Scale into Korean and validate the translated instrument. Patients and Methods: After translating the instrument, seven items of two factors (preparedness and perinatal infection stress) were selected for content validity testing. Validity and reliability were evaluated using SPSS 25.0 and AMOS 26.0. An online survey, via Google Forms, was conducted from January 20 to January 26, 2022. Participants were 283 pregnant women in Korea who consented to participate in the study. Results: Exploratory factor analysis revealed factor loadings on two factors of 0.64-0.87 with a total variance explained of 69.77%. Confirmatory factor analysis indicated good model fit (RMR = 0.03, RMSEA = 0.06, GFI = 0.98, SRMR = 0.03), and convergent and discriminant validity were established. Concurrent validity was established based on the correlation with the Revised Prenatal Distress Questionnaire (r = 0.45), and the reliability of the final instrument was indicated by Cronbach's α = 0.87. Conclusion: The Pandemic-Related Pregnancy Stress Scale was validated for use in the Korean population. The Korean version of the Pandemic-Related Pregnancy Stress Scale can be utilized to measure pandemic-related stress in pregnant women.

Can online learning be a reliable alternative to nursing students' learning during a pandemic? - A systematic review and meta-analysis.

OBJECTIVES: To compare online learning with traditional face-to-face and blended learning, based on randomized controlled trials, to determine the impact of online learning on nursing students' learning outcomes. DESIGN: A systematic review and meta-analysis. DATA SOURCES: A systematic search was conducted via English (PubMed, ERIC, Embase, CENTRAL, and CINAHL) and Korean databases (RISS, DBpia, and KISS). REVIEW METHODS: Studies published up to the first week of April 2022 were reviewed with a focus on the participants, intervention, comparison, outcome, and study design format. Following a primary screening of titles and abstracts, and secondary screening of full texts, 10 randomized controlled trial studies were selected, of which eight were included in the meta-analysis. Two researchers independently reviewed the literature, and the final selection was made in consensus. RESULTS: Online learning had a statistically significant positive effect on nursing students' knowledge, compared with no educational intervention (standardized mean difference (SMD) = 1.63; 95 % confidence interval (CI): 1.31 to 1.95). However, there was no significant difference in the impact of online learning on knowledge compared with blended learning (SMD = -0.14; 95 % CI: -0.70 to 0.41) and face-to-face learning (SMD = 0.37; 95 % CI: -0.32 to 1.06). Furthermore, compared with blended learning (SMD = -0.18; 95 % CI: -0.43 to 0.06) and face-to-face learning (SMD = 0.05; 95 % CI: -0.31 to 0.41), there was no significant difference in the impact of online learning on attitudes toward learning. CONCLUSIONS: Online learning in nursing education is not significantly different from blended or face-to-face learning in terms of its impact on knowledge acquisition and attitudes toward learning. The results of this review and meta-analysis highlight the need for selective application of learning methods, taking into account learning environments as well as curricular subjects and topics.

Prevalence and associated factors of prenatal depression in pregnant Korean women during the COVID-19 pandemic: a cross-sectional study.

PURPOSE: This study investigated the effects of prenatal education characteristics, pandemic-related pregnancy stress, and health behaviors during pregnancy on prenatal depression in pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: The participants were 180 pregnant Korean women, recruited from internet communities for pregnancy preparation, childbirth, and childcare, from July 5 to 15, 2022. The collected data were analyzed using the t-test, analysis of variance, the Mann-Whitney U-test, the Kruskal-Wallis test, and multiple regression analysis. RESULTS: The scores for pandemic-related pregnancy stress (24.50±6.37) and health behaviors during pregnancy (67.07±9.20) were high. Nearly half of the participants (n=89, 49.4%) presented with prenatal depression, with scores of 10 or greater. Prenatal depression had a positive correlation with gestational age (r=.18, p=.019) and pandemic-related pregnancy stress (r=.27, p<.001), and a negative correlation with health behaviors during pregnancy (r=-.42, p<.001). The factors associated with prenatal depression were pandemic-related pregnancy stress (t=4.70, p<.001), marital satisfaction (dissatisfied) (t=3.66, p<.001), pregnancy healthcare practice behaviors (t=-3.31, p=.001), family type (weekend couple) (t=2.84, p=.005), and gestational age (t=2.32, p=.022). The explanatory power of these variables was 38.2%. CONCLUSION: Since participants had a high level of prenatal depression during the pandemic, and infectious diseases such as COVID-19 may recur, strategies should be developed to improve pregnant women's mental health with consideration of the unique variables that are relevant in a pandemic. It is also necessary to develop efficient online prenatal education programs that can be implemented even in special circumstances such as social distancing, and to evaluate their effectiveness.

Sargassum horneri (Turner) C. Agardh Extract Regulates Neuroinflammation In Vitro and In Vivo.

Previously, we reported that Sargassum horneri (Turner) C. Agardh (S. horneri) is a brown algae species that exerts anti-inflammatory activity toward murine macrophages. However, the anti-neuroinflammatory effects and the mechanism of S. horneri on microglia cells are still unknown. We investigated the anti-neuroinflammatory effects of S. horneri extract on microglia in vitro and in vivo. In the present study, we found that S. horneri was not cytotoxic to BV-2 microglia cells and it significantly decreased lipopolysaccharide (LPS)-induced NO production. Moreover, S. horneri also diminished the protein expression of iNOS, COX-2, and cytokine production, including IL-1ß, TNF-α, and IL-6, on LPS-stimulated microglia activation. S. horneri elicited anti-neuroinflammatory effects by inhibiting phosphorylation of p38 MAPK and NF-κB. In addition, S. horneri inhibited astrocytes and microglia activation in LPS-challenged mice brain. Therefore, these results suggested that S. horneri exerted anti-neuroinflammatory effects on LPS-stimulated microglia cell activation by inhibiting neuroinflammatory factors and NF-κB signaling.

Transcription Factors as Targets of Natural Compounds in Age-Related Diseases and Cancer: Potential Therapeutic Applications.

Inflammation exacerbates systemic pathophysiological conditions and chronic inflammation is a sustained and systemic phenomenon that aggravates aging that can lead to chronic age-related diseases. These inflammatory phenomena have recently been redefined and delineated at the molecular, cellular, and systemic levels. Many transcription factors that are activated in response to tumor metabolic state have been reported to be regulated by a class of histone deacetylase called sirtuins (SIRTs). Sirtuins play a pivotal role in the regulation of tumor cell metabolism, proliferation, and angiogenesis, including oxidative stress and inflammation. The SIRT1-mediated signaling pathway in diabetes and cancer is the SIRT1/forkhead-box class O (FoxO)/nuclear factor-kappa B (NF-κB) pathway. In this review, we describe the accumulation of SIRT1-, NF-κB-, and FoxO-mediated inflammatory processes and cellular proinflammatory signaling pathways. We also describe the proinflammatory mechanisms underlying metabolic molecular pathways in various diseases such as liver cancer and diabetes. Finally, the regulation of cancer and diabetes through the anti-inflammatory effects of natural compounds is highlighted. Evidence from inflammation studies strongly suggests that cells may be a major source of cytokines secreted during various diseases. A better understanding of the mechanisms that underpin the inflammatory response and palliative role of natural compounds will provide insights into the molecular mechanisms of inflammation and various diseases for potential intervention.

FoxO Transcription Factors: Applicability as a Novel Immune Cell Regulators and Therapeutic Targets in Oxidative Stress-Related Diseases.

Forkhead box O transcription factors (FoxOs) play an important role in maintaining normal cell physiology by regulating survival, apoptosis, autophagy, oxidative stress, the development and maturation of T and B lymphocytes, and the secretion of inflammatory cytokines. Cell types whose functions are regulated by FoxOs include keratinocytes, mucosal dermis, neutrophils, macrophages, dendritic cells, tumor-infiltrating activated regulatory T (Tregs) cells, B cells, and natural killer (NK) cells. FoxOs plays a crucial role in physiological and pathological immune responses. FoxOs control the development and function of Foxp3+ Tregs. Treg cells and Th17 cells are subsets of CD4+ T cells, which play an essential role in immune homeostasis and infection. Dysregulation of the Th17/Treg cell balance has been implicated in the development and progression of several disorders, such as autoimmune diseases, inflammatory diseases, and cancer. In addition, FoxOs are stimulated by the mitogen-activated protein (MAP) kinase pathway and inhibited by the PI3 kinase/AKT pathway. Downstream target genes of FoxOs include pro-inflammatory signaling molecules (toll-like receptor (TLR) 2, TLR4, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α), chemokine receptors (CCR7 and CXCR2), B-cell regulators (APRIL and BLYS), T-regulatory modulators (Foxp3 and CTLA-4), and DNA repair enzymes (GADD45α). Here, we review the recent progress in our understanding of FoxOs as the key molecules involved in immune cell differentiation and its role in the initiation of autoimmune diseases caused by dysregulation of immune cell balance. Additionally, in various diseases, FoxOs act as a cancer repressor, and reviving the activity of FoxOs forces Tregs to egress from various tissues. However, FoxOs regulate the cytotoxicity of both CD8+ T and NK cells against tumor cells, aiding in the restoration of redox and inflammatory homeostasis, repair of the damaged tissue, and activation of immune cells. A better understanding of FoxOs regulation may help develop novel potential therapeutics for treating immune/oxidative stress-related diseases.

Quantitative proteomic analysis comparing grades ICRS1 and ICRS3 in patients with osteoarthritis.

Osteoarthritis (OA), which is caused by joint damage, is the most common form of arthritis, affecting millions of people worldwide. This damage can accumulate over time, which is why aging is one of the main contributors to joint damage associated with OA. The OA-related proteins that have been reported to date have been identified by the comparative analysis of OA patients with normal controls, following surgical or pharmacological treatment. For the first time, the present study analyzed OA-related proteins in patients with OA according to the International Cartilage Repair Society (ICRS) scale. Changes in protein expression can be observed during the OA process. The present study demonstrated differential protein expression patterns in articular cartilage from ICRS1- and ICRS3-graded OA patients. ICRS grade-matched OA knee samples from 12 OA patients, 6 ICRS grade 1 patients and 6 ICRS3 patients were subjected to proteomic analysis using the LTQ-Orbitrap mass spectrometry system. A total of 231 unique proteins were identified as expressed across the ICRS1 and ICRS3 OA patient groups. Relative differences in protein expression associated with the following classifications were observed: Biological adhesion, cell killing, cellular process, development process and molecular function. Although some of these proteins have been previously reported to be associated with rheumatoid arthritis, including cartilage oligomeric matrix protein, collagen types, angiogenin, complement C5 and CD59 glycoprotein, numerous additional proteins were newly identified, which may further help our understanding of disease pathogenesis. These findings suggested that these proteins may be used to develop novel therapeutic targets for OA.

Bone-Forming Peptide-4 Induces Osteogenic Differentiation and VEGF Expression on Multipotent Bone Marrow Stromal Cells.

Bone morphogenetic proteins (BMPs) have been widely used as treatment for bone repair. However, clinical trials on fracture repair have challenged the effectiveness of BMPs and suggested that delivery of multipotent bone marrow stromal cells (BMSCs) might be beneficial. During bone remodeling and bone fracture repair, multipotent BMSCs differentiate into osteoblasts or chondrocytes to stimulate bone formation and regeneration. Stem cell-based therapies provide a promising approach for bone formation. Extensive research has attempted to develop adjuvants as specific stimulators of bone formation for therapeutic use in patients with bone resorption. We previously reported for the first time bone-forming peptides (BFPs) that induce osteogenesis and bone formation. BFPs are also a promising osteogenic factor for prompting bone regeneration and formation. Thus, the aim of the present study was to investigate the underlying mechanism of a new BFP-4 (FFKATEVHFRSIRST) in osteogenic differentiation and bone formation. This study reports that BFP-4 induces stronger osteogenic differentiation of BMSCs than BMP-7. BFP-4 also induces ALP activity, calcium concentration, and osteogenic factors (Runx2 and osteocalcin) in a dose dependent manner in BMSCs. Therefore, these results indicate that BFP-4 can induce osteogenic differentiation and bone formation. Thus, treatment of multipotent BMSCs with BFP-4 enhanced osteoblastic differentiation and displayed greater bone-forming ability than BMP-7 treatment. These results suggest that BFP-4-stimulated cell therapy may be an efficient and cost-effective complement to BMP-7-based clinical therapy for bone regeneration and formation.

The impact of a team-based learning group readiness assurance test on nursing students' problem solving, learning satisfaction, and team efficacy: A crossover study.

BACKGROUND: Team-based learning in nursing education has shown higher rates of students that meet the learning outcomes in problem-solving. But students claim team-based learning has its drawbacks, and that the readiness assurance test takes too much time. Therefore, it is necessary to examine how the group readiness assurance test in team-based learning effects student's educational outcomes. OBJECTIVES: This study was conducted to investigate the effects of the group readiness assurance tests on nursing students' problem solving, learning satisfaction, and team efficacy. DESIGN & METHOD: This study used a crossover study design. The researchers conducted their study in team-based learning classes at a Korean university. The classes were conducted for eight weeks with nursing majors. In total, 194 students in their third year participated. Students received two different treatments: with and without a team test. The washout period was four weeks. RESULTS: There was no statistically significant difference in nursing students' problem solving (t = 0.41, p = .679), learning satisfaction (t = 0.80, p = .420), or team efficacy (t = 1.20, p = .228) depending on the presence or absence of a team test. CONCLUSIONS: When using team-based learning with nursing students, instructors should consider whether to conduct group readiness assurance tests are an efficient educational intervention and if they achieve the expected educational goals.

Hizikia fusiforme extract enhances dendritic cell maturation in vitro and in vivo.

Dendritic cells (DCs) are play critical roles in the priming and regulation of immune responses. DCs rapidly process and convey these antigens to prime antigen-specific T cells. Therefore, regulation of DCs functions is important for immunity and immunotherapies. Immune adjuvants for DCs activation are needed to improve the efficacy of vaccines against tumors and many infectious diseases. Therefore, we demonstrate that H. fusiformis extract can regulate DCs maturation and activation. H. fusiformis extract induced costimulatory molecules (CD 80 and CD86), antigen-presenting molecules (major histocompatibility complex (MHC) I and II), CCR7 expression, and interleukin (IL)-12 production in DCs. These effects are associated with upregulation of mitogen-activated protein kinase (MAPK) signaling pathway. In addition, H. fusiformis extract induces costimulatory molecules on splenic DCs and activated CD8+ T cells in vivo. Taken together, these findings suggest that H. fusiformis extract may be a potential efficient immune therapeutic compound in DCs-mediated immunotherapies. ABBREVIATIONS: CTL: cytotoxic T lymphocytes; DCs: dendritic cells; ERK: extracellular signal-regulated kinases; IL: interleukini; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinase; MHC: major histocompatibility complex.

Hesperetin inhibits neuroinflammation on microglia by suppressing inflammatory cytokines and MAPK pathways.

Neuroinflammation is a specific or nonspecific immunological reaction in the central nervous system that is induced by microglia activation. Appropriate regulation of activated microglial cells is therefore important for inhibiting neuroinflammation. Hesperetin is a natural flavanone and an aglycone of hesperidin that is found in citrus fruits. Hesperetin reportedly possesses anti-inflammatory, anti-cancer, and antioxidant effects. However, the anti-neuroinflammatory effects of hesperetin on microglia are still unknown. Here, we investigated the anti-neuroinflammatory effects of hesperetin on lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We found that hesperetin strongly inhibited nitric oxide production and expression of inducible nitric oxide synthase in LPS-stimulated BV-2 microglial cells. Hesperetin also significantly reduced secretion of inflammatory cytokines including interleukin (IL)-1ß and IL-6. Furthermore, hesperetin down-regulated the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase, exerting anti-inflammatory effects. Hesperetin suppressed astrocyte and microglia activation in the LPS-challenged mouse brain. Collectively, our findings indicate that hesperetin inhibits microglia-mediated neuroinflammation and could be a prophylactic treatment for neurodegenerative diseases.

FoxO6-mediated IL-1ß induces hepatic insulin resistance and age-related inflammation via the TF/PAR2 pathway in aging and diabetic mice.

FoxO has been proposed to play a role in the promotion of insulin resistance, and inflammation. FoxO is a pro-inflammatory transcription factor that is a key mediator of generation of inflammatory cytokines such as IL-1ß in the liver. However, the detailed association of FoxO6 with insulin resistance and age-related inflammation has not been fully documented. Here, we showed that FoxO6 was elevated in the livers of aging rats and obese mice that exhibited insulin resistance. In addition, virus-mediated FoxO6 activation led to insulin resistance in mice with a notable increase in PAR2 and inflammatory signaling in the liver. On the other hand, FoxO6-KO mice showed reduced PAR2 signaling with a decrease in inflammatory cytokine expression and elevated insulin signaling. Because FoxO6 is closely associated with abnormal production of IL-1ß in the liver, we focused on the FoxO6/IL-1ß/PAR2 axis to further examine mechanisms underlying FoxO6-mediated insulin resistance and inflammation in the liver. In vitro experiments showed that FoxO6 directly binds to and elevates IL-1ß expression. In turn, IL-1ß treatment elevated the protein levels of PAR2 with a significant decrease in hepatic insulin signaling, whereas PAR2-siRNA treatment abolished these effects. However, PAR2-siRNA treatment had no effect on IL-1ß expression induced by FoxO6, indicating that IL-1ß may not be downstream of PAR2. Taken together, we assume that FoxO6-mediated IL-1ß is involved in hepatic inflammation and insulin resistance via TF/PAR2 pathway in the liver.

[Effects of Aromatherapy on Sleep Quality: A Systematic Review and Meta-Analysis].

PURPOSE: The purpose of this study was to investigate the effects of aromatherapy on sleep quality. METHODS: This is a systematic review of randomized controlled trial studies (PROSPERO registration number CRD42017064519). In this study, the PICO were adults and the elderly, aromatherapy intervention, a comparative intervention with the control and placebo oil groups, and sleep. The selected articles were in English, Korean, and Chinese. RESULTS: The results of the meta-analysis showed that the effect sizes of the experimental group were 1.03 (n=763, SMD=1.03, 95% CI 0.66 to 1.39) (Z=5.47, p<.001). In the aromatherapy intervention group, the effect size of sleep was statistically significant (QB=9.39, df=2, p=.009), with a difference of 0.77 for inhalation, 1.12 for oral intake and 2.05 for massage. A post-analysis showed that the effect of massage on sleep was significantly greater than the inhalation method. The regression coefficient of the intervention period, B=0.01 (Z=1.43, p=.154), also showed that the longer the intervention period, the larger the effect size; however, it was not statistically significant. CONCLUSION: A total of 23 literature analyses showed that aromatherapy is effective in improving quality of sleep, and the massage method is more effective in improving quality of sleep than the inhalation method. A meta-ANOVA showed that the aromatherapy intervention affected the high heterogeneity of the effect size. Thus, future research with stricter control in methods and experimental procedures is necessary.

Anti-Neuroinflammatory Effects of Vanillin Through the Regulation of Inflammatory Factors and NF-κB Signaling in LPS-Stimulated Microglia.

Microglia, resident macrophages of the central nervous system (CNS), is responsible for immune responses and homeostasis of the CNS. Microglia plays a complex role in neuroinflammation, which has been implicated in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Therefore, therapeutic agents that suppress the microglia-mediated inflammatory response could potentially be used in the prevention or treatment of neurodegenerative diseases. Vanillin, a primary component of vanilla bean extract, has anti-inflammatory, anticancer, and antitumor properties. However, the effects of vanillin on the anti-neuroinflammatory responses of microglial cells are still poorly understood. In this study, we investigated the mechanism by which vanillin induces anti-neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We found that vanillin significantly decreased the production of nitric oxide and pro-inflammatory cytokines, including interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Vanillin also reduced the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the mRNA expression levels of IL-1ß, TNF-α, and IL-6. Moreover, vanillin inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB. Collectively, these results suggest that vanillin has anti-neuroinflammatory properties and may act as a natural therapeutic agent for neuroinflammatory diseases.

Mussel adhesive Protein-conjugated Vitronectin (fp-151-VT) Induces Anti-inflammatory Activity on LPS-stimulated Macrophages and UVB-irradiated Keratinocytes.

BACKGROUND: Skin inflammation and dermal injuries are a major clinical problem because current therapies are limited to treating established scars, and there is a poor understanding of healing mechanisms. Mussel adhesive proteins (MAPs) have great potential in many tissue engineering and biomedical applications. It has been successfully demonstrated that the redesigned hybrid type MAP (fp-151) can be utilized as a promising adhesive biomaterial. The aim of this study was to develop a novel recombinant protein using fp-151 and vitronectin (VT) and to elucidate the anti-inflammatory effects of this recombinant protein on macrophages and keratinocytes. METHODS: Lipopolysaccharide (LPS) was used to stimulate macrophages and UVB was used to stimulate keratinocytes. Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were analyzed by Western Blot. Inflammatory cytokines and NO and ROS production were analyzed. RESULT: In macrophages stimulated by LPS, expression of the inflammatory factors iNOS, COX-2, and NO production increased, while the r-fp-151-VT-treated groups had suppressed expression of iNOS, COX-2, and NO production in a dose-dependent manner. In addition, keratinocytes stimulated by UVB and treated with r-fp-151-VT had reduced expression of iNOS and COX-2. Interestingly, in UVB-irradiated keratinocytes, inflammatory cytokines, such as interleukin (IL)-1b, IL-6, and tumor necrosis factor (TNF)-a, were significantly reduced by r-fp-151-VT treatment. CONCLUSIONS: These results suggest that the anti-inflammatory activity of r-fp-151-VT was more effective in keratinocytes, suggesting that it can be used as a therapeutic agent to treat skin inflammation.

Identification and localization of epithelial progenitor cells in the vagina.

The purpose of this study was to identify and localize mucosal epithelial progenitor cells (EPCs) in the rat vagina. Rat vagina was obtained from f77emale Sprague-Dawley rats (12 weeks old, n = 20). To identify EPCs in vagina, we followed a single-cell isolation protocol and analyzed the number of cells staining positive for EPC markers by flow cytometry. The expression of EPC-specific markers (CD44, ERα, PR) was evaluated by immunofluorescence. As shown by confocal immunofluorescence, CD44/ERα double-labeled cells were mainly expressed in the basal cell and suprabasal cell layers. Immunofluorescent staining of CD44 was expressed in the plasma membrane of the vaginal epithelium, and ERα was expressed in the cytoplasm of the vaginal epithelium. The CD44/ERα double-positive cells were noted in the rat vagina by flow cytometric analysis. PR-labeled cells were localized in the intermediate layer of the epithelial space of the vagina. The results revealed the existence of EPCs in the vagina. These findings imply that resident EPCs may have a role in the regeneration of vaginal mucosa.