Estrogen Receptor ß Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis.

Alterations in estrogen-mediated cellular signaling play an essential role in the pathogenesis of endometriosis. In addition to higher estrogen receptor (ER) ß levels, enhanced ERß activity was detected in endometriotic tissues, and the inhibition of enhanced ERß activity by an ERß-selective antagonist suppressed mouse ectopic lesion growth. Notably, gain of ERß function stimulated the progression of endometriosis. As a mechanism to evade endogenous immune surveillance for cell survival, ERß interacts with cellular apoptotic machinery in the cytoplasm to inhibit TNF-α-induced apoptosis. ERß also interacts with components of the cytoplasmic inflammasome to increase interleukin-1ß and thus enhance its cellular adhesion and proliferation properties. Furthermore, this gain of ERß function enhances epithelial-mesenchymal transition signaling, thereby increasing the invasion activity of endometriotic tissues for establishment of ectopic lesions. Collectively, we reveal how endometrial tissue generated by retrograde menstruation can escape immune surveillance and develop into sustained ectopic lesions via gain of ERß function.

Steroid receptor coactivator 3 is a key modulator of regulatory T cell-mediated tumor evasion.

Steroid receptor coactivator 3 (SRC-3) is most strongly expressed in regulatory T cells (Tregs) and B cells, suggesting that it plays an important role in the regulation of Treg function. Using an aggressive E0771 mouse breast cell line syngeneic immune-intact murine model, we observed that breast tumors were "permanently eradicated" in a genetically engineered tamoxifen-inducible Treg-cell-specific SRC-3 knockout (KO) female mouse that does not possess a systemic autoimmune pathological phenotype. A similar eradication of tumor was noted in a syngeneic model of prostate cancer. A subsequent injection of additional E0771 cancer cells into these mice showed continued resistance to tumor development without the need for tamoxifen induction to produce additional SRC-3 KO Tregs. SRC-3 KO Tregs were highly proliferative and preferentially infiltrated into breast tumors by activating the chemokine (C-C motif) ligand (Ccl) 19/Ccl21/chemokine (C-C motif) receptor (Ccr)7 signaling axis, generating antitumor immunity by enhancing the interferon-γ/C-X-C motif chemokine ligand (Cxcl) 9 signaling axis to facilitate the entrance and function of effector T cells and natural killer cells. SRC-3 KO Tregs also show a dominant effect by blocking the immune suppressive function of WT Tregs. Importantly, a single adoptive transfer of SRC-3 KO Tregs into wild-type E0771 tumor-bearing mice can completely abolish preestablished breast tumors by generating potent antitumor immunity with a durable effect that prevents tumor reoccurrence. Therefore, treatment with SRC-3-deleted Tregs represents an approach to completely block tumor growth and recurrence without the autoimmune side effects that typically accompany immune checkpoint modulators.

High body weight variability is associated with increased risk of depression: a nationwide cohort study in South Korea.

BACKGROUND: Body weight variability (BWV) negatively affects the incidence and outcomes of various diseases, but the nature of the association between BWV and depression remains unclear. In this study, we aimed to test the hypothesis that BWV is associated with the risk of new-onset depression. METHODS: Data from a nationwide population-based cohort in the Korean National Health Insurance Service database were analyzed for 6 598 570 adults with no history of depression and reports of at least three health examinations. BWV was estimated using variability independent of the mean indices and divided into quartiles (Q1 lowest, Q4 highest BWV). Cox proportional hazard models were applied to assess the risk of depression according to the quartile of BWV. RESULTS: The incident rate for depression from Q1 to Q4 of BWV was 20.7, 20.3, 20.8, and 22.2 per 1000 person-years, respectively. BWV, especially high BWV, was associated with an increased risk of depression after adjusting for age, sex, smoking, alcohol consumption, physical activity, income, diabetes mellitus, hypertension, and dyslipidemia. The hazard ratio (HR) of new-onset depression was highest in Q4 relative to Q1 in the total population (HR 1.12, p < 0.0001) and was higher in women than in men (HR 1.72 v. 1.16, p < 0.0001). In stratified analyses, regardless of obesity or weight change status at baseline, the risk of depression was increased when bodyweight fluctuated highly during follow-up. CONCLUSIONS: High BWV was associated with an increased risk of depression. Further studies need to evaluate the role of high BWV with respect to the onset of depression.

Inhibition of Melanogenesis by Essential Oils from the Citrus Cultivars Peels.

Citrus is one of the most popular and widely grown fruit crops in the world. However, the bioactivity of only certain species of citrus cultivars is studied. In this study, the effects of essential oils from 21 citrus cultivars on melanogenesis were investigated in an effort to identify active anti-melanogenesis constituents. The essential oils from the peels of 21 citrus cultivars obtained by hydro-distillation were analyzed using gas chromatography-mass spectrometry. Mouse melanoma B16BL6 cells were used in all assays conducted in this study. The tyrosinase activity and melanin content were determined using the lysate of α-Melanocyte-stimulated B16BL6 cells. In addition, the melanogenic gene expression was determined by quantitative reverse transcription-polymerase chain reaction. Overall, the essential oils of (Citrus unshiu X Citrus sinensis) X Citrus reticulata, Citrus reticulata, and ((Citrus unshiu X Citrus sinensis) X Citrus reticulata) X Citrus reticulata provided the best bioactivity and comprised five distinct constituents compared to other essential oils such as limonene, farnesene, ß-elemene, terpinen-4-ol, and sabinene. The anti-melanogenesis activities of the five individual compounds were evaluated. Among the five essential oils, ß-elemene, farnesene, and limonene showed dominating properties. The experimental results indicated that (Citrus unshiu X Citrus sinensis) X Citrus reticulata, Citrus reticulata, and ((Citrus unshiu X Citrus sinensis) X Citrus reticulata) X Citrus reticulara are potential candidates with anti-melanogenesis activity for use as cosmetics and pharmaceutical agents against skin hyperpigmentation.

Oleuropein suppresses endometriosis progression and improves the fertility of mice with endometriosis.

BACKGROUND: Endometriosis is an estrogen-dependent inflammatory reproductive disease. Therefore, systematic estrogen depletion and anti-inflammatory drugs are the current treatment for endometriosis. However, current endometriosis treatments have low efficacy and cause adverse effects in endometriosis patients. Consequently, alternative endometriosis treatments targeting endometriosis-specific factors are in demand. In this context, ERß was selected as a druggable target for endometriosis due to its critical role in progression. Therefore, selective targeting of ERß without inhibiting ERα activity would be a new paradigm for endometriosis treatment to overcome the low efficacy and adverse effects of hormonal endometriosis therapy. METHODS: Cell-based ERß and ERα activity assay systems were employed to define a selective ERß-inhibiting chemical product from a library of natural products. A surgically induced endometriosis mouse model was used to determine whether an ERß inhibitory drug suppressed endometriosis progression. Mice with endometriosis were randomly separated and then orally treated with vehicle or 25 mg/kg oleuropein (once a day for 21 days), an ERß inhibitory drug. The volume of endometriotic lesions or luciferase activity of endometriotic lesions was examined to define the growth of ectopic lesions in mice with endometriosis. The metabolite and levels of metabolic enzymes of the liver and kidney were determined in the serum of female mice treated with vehicle and oleuropein (25 mg/kg, once a day for 21 days) to define the toxicity of oleuropein. The in vitro decidualization assay was conducted with normal human endometrial stromal cells and endometriotic stromal cells to determine whether oleuropein overcomes decidualization in endometriosis patients. The pregnancy rate and pup numbers of C57BL/6 J female mice with endometriosis treated with vehicle or oleuropein (n = 10/group) were determined after mating with male mice. The cytokine profile in endometriotic lesions treated with vehicle and oleuropein (25 mg/kg) was determined with a Mouse Cytokine Array Kit. RESULTS: Among natural products, oleuropein selectively inhibited ERß but not ERα activity in vitro. Oleuropein treatment inhibited the nuclear localization of ERß in human endometrial cells upon estradiol treatment. Oleuropein (25 mg/kg) treatment suppressed the growth of mouse (6.6-fold) and human (sixfold) ectopic lesions in mice with endometriosis compared to the vehicle by inhibiting proliferation and activating apoptosis in endometriotic lesions. Oleuropein treatment did not cause reproductive toxicity in female mice. Additionally, mice with endometriosis subjected to oleuropein treatment had a higher pregnancy rate (100%) than vehicle-treated mice (70%). Furthermore, oleuropein treatment partially recovered the decidualization impact of human endometriotic stromal cells from endometriotic lesions compared to the vehicle. Oleuropein-treated mice with endometriosis exhibited significantly lower levels of cytokines directly regulated by ERß in ectopic lesions than vehicle-treated mice, illustrating the improvement in the hyperinflammatory state of mice with endometriosis. CONCLUSIONS: Oleuropein is a promising and novel nutraceutical product for nonhormonal therapy of endometriosis because it selectively inhibits ERß, but not ERα, to suppress endometriosis progression and improve the fertility of mice with endometriosis.

Obsessive Thought, Compulsive Behavior, and Their Associations With Suicide Ideation and Attempts and Major Depressive Disorder: A Nationwide Community Sample of Korean Adults.

ABSTRACT: In this study, we defined obsessive thoughts (OT) as bothersome, unpleasant thoughts about oneself that keep entering the mind against one's will, and compulsive behavior (CB) as behavior that a person repeats against his or her wishes. The study included 12,532 adults selected randomly through a one-person-per-household method. Each subject selected underwent a face-to-face interview using the Korean version of the Composite International Diagnostic Interview with a questionnaire that examines lifetime suicide attempts (LSAs). Among the participants, 341 (2.74%) had OT and 639 (5.14%) had CB. The highest LSA rate was in subjects with both OT and CB, followed by those with either OT or CB; subjects with neither OT nor CB had the lowest LSA rate. In a multivariate logistic regression analysis of OT and CB, OT, ordering, and rituals of repeating words were significantly associated with LSAs. In subjects with OT and CB, those with MDD had a significantly higher risk of LSAs compared with those without, and MDD with both OT and CB showed odds of approximately 27-fold (adjusted odds ratio, 27.24; 13.29-55.82; p < 0.0001) compared with those without MDD, OT, or CB. OT and CB were associated with increased risk of LSAs, and comorbid MDD further increased LSAs.

Multilevel Effect of Neighborhood Social Cohesion and Characteristics on Suicidal Ideation Among Korean Older Adults.

This study examined the effect of neighborhood factors on suicidal ideation of community-dwelling older adults in Korea. To understand the effect of neighborhood factors (neighborhood social cohesion, satisfaction with neighborhood safety, living environment, suicide rate, proportion of social welfare agencies, proportion of social welfare expenses) and individual factors (health, social relationships) on suicidal ideation of older adults, we conducted a multilevel logistic regression analysis. The 2017 Community Health Survey of Korea included data on 67,820 people aged 65 years or older and in 255 neighborhoods. At the individual level, the presence of suicidal ideation was associated with less education attainment, lower family income, not living with a spouse, fewer social networks, fewer social activities, more depressive symptoms, and lower health-related quality of life. At the neighborhood level, lack of social cohesion, a higher suicide rate, and a smaller social welfare budget were significantly effect related to the probability of suicidal ideation.

Differential expression of novel genes and signalling pathways of senescent CD8+ T cell subsets in Behçet's disease.

OBJECTIVES: Behçet's disease (BD) is a rare disease characterised by recurrent mucocutaneous ulceration and chronic multi-systemic inflammation; however, its pathogenic mechanisms and biomarkers have not been fully discovered. Previously, we found that peripheral blood CD8+CD27-CD28- T cell frequency was higher in patients with BD than in healthy controls (HCs). In this study, we used global gene expression analysis to identify candidate genes that might be related to pathogenesis or developed as biomarkers in two CD8+ T cell subsets from BD patients and HCs. METHODS: We performed RNA sequencing analysis in CD8+CD27-CD28- and CD8+CD27+CD28+ T cell subsets isolated from 18 patients with BD and healthy controls. Real time qPCR was used to validate the differential expression of genes in five patients with BD and healthy controls. RESULTS: We found that 1,103 genes and 652 genes were differentially expressed in the CD8+CD27-CD28- and CD8+CD27+CD28+ T cell subsets of patients with BD, respectively. We validated the differential expression of COL5A1 in CD8+CD27-CD28- T cells and TRPV3 and ARHGEF10 in CD8+CD27+CD28+ T cells. Furthermore, Ingenuity Pathway Analysis indicated that eleven pathways were more active in BD CD8+CD27-CD28- T cells and more suppressed in BD CD8+ CD27+CD28+ T cells than in the HCs. CONCLUSIONS: Our study is the first transcriptome analysis of CD8+ T cell subsets in patients with BD and our results provide novel genes that might be related to BD pathogenesis.

An Easy-to-Use Machine Learning Model to Predict the Prognosis of Patients With COVID-19: Retrospective Cohort Study.

BACKGROUND: Prioritizing patients in need of intensive care is necessary to reduce the mortality rate during the COVID-19 pandemic. Although several scoring methods have been introduced, many require laboratory or radiographic findings that are not always easily available. OBJECTIVE: The purpose of this study was to develop a machine learning model that predicts the need for intensive care for patients with COVID-19 using easily obtainable characteristics-baseline demographics, comorbidities, and symptoms. METHODS: A retrospective study was performed using a nationwide cohort in South Korea. Patients admitted to 100 hospitals from January 25, 2020, to June 3, 2020, were included. Patient information was collected retrospectively by the attending physicians in each hospital and uploaded to an online case report form. Variables that could be easily provided were extracted. The variables were age, sex, smoking history, body temperature, comorbidities, activities of daily living, and symptoms. The primary outcome was the need for intensive care, defined as admission to the intensive care unit, use of extracorporeal life support, mechanical ventilation, vasopressors, or death within 30 days of hospitalization. Patients admitted until March 20, 2020, were included in the derivation group to develop prediction models using an automated machine learning technique. The models were externally validated in patients admitted after March 21, 2020. The machine learning model with the best discrimination performance was selected and compared against the CURB-65 (confusion, urea, respiratory rate, blood pressure, and 65 years of age or older) score using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 4787 patients were included in the analysis, of which 3294 were assigned to the derivation group and 1493 to the validation group. Among the 4787 patients, 460 (9.6%) patients needed intensive care. Of the 55 machine learning models developed, the XGBoost model revealed the highest discrimination performance. The AUC of the XGBoost model was 0.897 (95% CI 0.877-0.917) for the derivation group and 0.885 (95% CI 0.855-0.915) for the validation group. Both the AUCs were superior to those of CURB-65, which were 0.836 (95% CI 0.825-0.847) and 0.843 (95% CI 0.829-0.857), respectively. CONCLUSIONS: We developed a machine learning model comprising simple patient-provided characteristics, which can efficiently predict the need for intensive care among patients with COVID-19.

Integrated Analysis of Tissue-Specific Promoter Methylation and Gene Expression Profile in Complex Diseases.

This study investigated whether the promoter region of DNA methylation positively or negatively regulates tissue-specific genes (TSGs) and if it correlates with disease pathophysiology. We assessed tissue specificity metrics in five human tissues, using sequencing-based approaches, including 52 whole genome bisulfite sequencing (WGBS), 52 RNA-seq, and 144 chromatin immunoprecipitation sequencing (ChIP-seq) data. A correlation analysis was performed between the gene expression and DNA methylation levels of the TSG promoter region. The TSG enrichment analyses were conducted in the gene-disease association network (DisGeNET). The epigenomic association analyses of CpGs in enriched TSG promoters were performed using 1986 Infinium MethylationEPIC array data. A correlation analysis showed significant associations between the promoter methylation and 449 TSGs' expression. A disease enrichment analysis showed that diabetes- and obesity-related diseases were high-ranked. In an epigenomic association analysis based on obesity, 62 CpGs showed statistical significance. Among them, three obesity-related CpGs were newly identified and replicated with statistical significance in independent data. In particular, a CpG (cg17075888 of PDK4), considered as potential therapeutic targets, were associated with complex diseases, including obesity and type 2 diabetes. The methylation changes in a substantial number of the TSG promoters showed a significant association with metabolic diseases. Collectively, our findings provided strong evidence of the relationship between tissue-specific patterns of epigenetic changes and metabolic diseases.

Isolation of Isocoumarins and Flavonoids as α-Glucosidase Inhibitors from Agrimonia pilosa L.

Agrimonia pilosa L. (AP) showed potent α-glucosidase inhibitory (AGI) activity, but it is uncertain what phytochemicals play a key factor. The phytochemical study of AP based on AGI activity led to the isolation of four isocoumarins; agrimonolide (1), agrimonolide-6-O-ß-d-glucopyranoside (2), desmethylagrimonolide (3), desmethylagrimonolide-6-O-ß-d-glucopyranoside (4), and four flavonoids; luteolin (5), quercetin (6), vitexin (7), and isovitexin (8). The four isocoumarins were isolated as α-glucosidase inhibitors for the first time. Isocoumarins, compound 1 (agrimonolide) and 3 (desmethylagrimonolide) showed strong α-glucosidase inhibitory activities with IC50 values of 24.2 and 37.4 µM, respectively. Meanwhile, isocoumarin and flavonoid glycosides showed weak AGI activity. In the kinetic analysis, isocoumarins, compounds 1 and 3 showed non-competitive inhibition, whereas flavonoid, compound 6 showed competitive inhibition.

Multiple types of somatic pain increase suicide attempts and depression: A nationwide community sample of Korean adults.

OBJECTIVE: Somatic pain is an important risk factor for suicide and suicidal behaviors. However, the association between the number of somatic pain conditions and lifetime suicide attempts (LSA) has not been well established yet. Therefore, the objective of this study was to examine associations between LSA and multiple somatic pain (MSP), singe pain, and no pain in a nationwide survey. METHODS: A total of 12,532 adults were randomly selected from the population using the one-person-per-household method. Each participant completed a face-to-face interview using the Korean Composite International Diagnostic Interview (K-CIDI) with Suicide Module, and the Barratt Impulsiveness Scale 11 (BIS-11). The MSP was defined as pain in two or more parts of one's body, including abdominal pain, back pain, arthralgia, arm or leg pain, chest pain, headache, menstrual pain, dysuria, genital pain, and other pain. RESULTS: Among 12,532 subjects, 858 (6.85%) had MSP. Among the three groups (MSP, single pain, and no pain) of subjects, the MSP group had higher percentages of females, those with lower education, and divorced/widowed/separated individuals. However, there were no significant differences in monthly income or residence among the three groups. The MSP group showed four times higher suicide attempts and six times higher multiple attempts than did the no pain group. The BIS total score of the MSP group was the highest among the three groups. Genital pain showed the highest odds ratio for LSA. The higher the number of somatic pain, the higher the odds ratios were for LSA, major depressive disorder (MDD), and anxiety disorders. Subjects having both MSP and MDD showed a significant association with LSA (AOR = 14.78, 95% CI 10.08-21.67, p < 0.001) compared to those having neither somatic pain nor MDD. CONCLUSIONS: MSP was significantly associated with LSA. It had greater prevalence among individuals reporting a higher number of somatic pain conditions and comorbid MDD.

The relationship between autophagy, increased neutrophil extracellular traps formation and endothelial dysfunction in chronic kidney disease.

In chronic kidney disease (CKD), the number of circulating neutrophils are increased, and this is usually accompanied by an increased basal activation state. However, the possible association between neutrophil extracellular traps (NETs) with vascular complications has not been evaluated. We assessed the relationship between NETs, autophagy and endothelial dysfunction in maintenance hemodialysis (MHD) patients. NET formation, neutrophil elastase (NE) activities, and serum nucleosome levels were measured in MHD (n = 60) and controls (n = 20). Basal NET formation were markedly increased in MHD patient compared to controls. After PMA stimulation, MHD neutrophils showed significantly increased NETs formation response than controls. The degree of NETs was strongly associated with lower flow-mediated dilatation(%) of brachial artery even after adjustment for cardiovascular risk factors and uremic toxins. Moreover, MHD neutrophils showed increased basal autophagy activity. Interestingly, the levels of NETs were markedly augmented after autophagy inhibition, suggesting a protective role of autophagy in excessive NET formation.

A latent class analysis of social activities and health among community-dwelling older adults in Korea.

OBJECTIVES: This study presents an empirical typology of social activity and its association with the depressive symptoms and self-rated health of community-dwelling older adults (n = 464) in South Korea. METHOD: Latent class analysis (LCA) was used to classify the types of social activities. Data analyses were conducted using Mplus 7.2 program for LCA and SPSS 22.0 for multiple regression analyses. RESULTS: LCA identified people who fell into one of the four activity groups: Diverse, Community Center/Disengaged, Religion Plus, and Friendship/Leisure. Membership in these four groups predicted differences in depressive symptoms and self-rated health. CONCLUSIONS: Results indicate that typologies of social activity could enhance practitioners' understanding of activity patterns and their associations with health and well-being.

Efficient micro-cavity top emission OLED with optimized Mg:Ag ratio cathode.

Micro-cavity top-emitting organic light emitting diodes (TEOLEDs) are now receiving prominence as a technology for the active matrix display applications. The semi-transparent metal cathode plays the crucial role in realizing TEOLEDs structure. Here, we report the optimization results on Mg:Ag ratio as the semitransparent cathode deposited by vacuum thermal evaporation. The optimized Mg:Ag cathode with 1:10 ratio (wt %) shows a sheet resistance value as low as 5.2 Ω/□, an average transmittance of 49.7%, reflectance of 41.4%, and absorbance of 8.9% over the visible spectral region (400~700 nm). The fabricated red TEOLEDs device implemented using LiF (1nm)/Mg:Ag (1:10) cathode shows the voltage value of 4.17 V at a current density of 10.00 mA/cm2, and current efficiencies variation from 55.3 to 50.1 cd/A over the brightness range 2,000 - 12,000 cd/m2. The electroluminescence (EL) spectrum displays the light emission at 608 nm wavelength with a half width of 29.5 nm. The narrow half-width of red light emission is attributed to the micro-cavity effects due to the semitransparent cathode.

Impact of social capital on depression trajectories of older women in Korea.

OBJECTIVES: This study examines the impact of social capital on depressive symptoms trajectories among Korean women aged 65 years or older. It also examines the difference in depressive symptoms and social capital by economic status (poverty group, non-poverty group) among community-dwelling older women in Korea. METHOD: This study used 2435 older women of the Korean Welfare Panel Study from 2006 (wave 1) to 2013 (wave 8) data using latent growth modeling. Social capital variables were cognitive (interpersonal trust, reciprocity) and structural (the size of family, the number of friends or neighbors, participation in leisure and volunteer activities). RESULTS: The results showed both intra- and inter-individual variability in depressive symptoms over time. Interpersonal trust and reciprocity as cognitive social capital had an effect on the change of depressive symptoms in intercept and slope. The size of family, participation in leisure activities among structural social capital were associated with lower levels of depressive symptoms in intercept and slope. CONCLUSION: The results of this study suggest some practical implications for depression intervention and prevention and further research on late-life depression.

Leptin, pre-existing vascular disease, and increased arteriovenous fistula maturation failure in dialysis patients.

BACKGROUND: The adipocytokine leptin is an independent cardiovascular risk factor and exerts proatherogenic effect. Pre-existing vascular disease is an important cause of arteriovenous fistula (AVF) maturation failure. We explored the association between serum leptin, pre-existing vascular disease, and AVF maturation failure in incident hemodialysis patients. METHODS: Vein samples from 62 patients were collected at the time of AVF creation. Pre-existing vascular disease was evaluated with histologic changes and immunohistochemical characteristics of cellular phenotypes in intima. AVF maturation failure was defined as an AVF that could not be used successfully by the third month after its creation. RESULTS: The prevalence of body mass index ≥30 kg/m2 was 17%, and AVF maturation failure occurred in 28 (45%) patients. Patients within the highest leptin tertile showed significantly higher maturation failure rate, independent of age, gender, diabetes, and body mass index. On histologic examination, significant differences in intimal hyperplasia (13.3 ± 4.5 vs 18.2 ± 5.2 vs 30.3 ± 14.3 µm) and medial thickening (76.8 ± 23.7 vs 103.9 ± 33.6 vs 109.3 ± 36.5 µm) were observed across leptin tertiles. Similarly, medial fibrosis was most severe in the highest tertile. According to the immunohistochemical staining, most intimal cells were α-smooth muscle actin-positive, vimentin-positive, desmin-negative myofibroblasts. However, in the lowest tertile, desmin-positive contractile smooth muscle cells were also frequently observed, suggesting relatively slow phenotypic changes in this group. Furthermore, as leptin tertiles increased, the expression of leptin receptor in the luminal border of intima was significantly decreased. CONCLUSIONS: Obesity-related higher fistula maturation failure rate may be partly mediated by higher leptin level-associated pre-existing vascular diseases in end-stage renal disease patients. Decreased expression of leptin receptor may be related to this association.

CD11c is upregulated in CD8+ T cells of patients with Behçet's disease.

OBJECTIVES: Single nucleotide polymorphisms of CD11a and CD11c have been suggested as susceptibility loci in Korean patients with Behçet's disease (BD). As immunoregulatory roles of CD11c+CD8+T cells were previously observed in multiple autoimmune and autoinflammatory diseases, we aimed to investigate CD11a and CD11c in CD4+ and CD8+ subpopulation of BD patients. METHODS: Peripheral-blood mononuclear cells were isolated from 21 patients with active BD, 26 patients with inactive BD, 20 patients with recurrent aphthous ulcers (RAU), and 23 healthy controls (HCs). The surface expression of CD11a and CD11c in CD4+ and CD8+ cell populations was analyzed by flow cytometry, and CD11a and CD11c mRNA and protein levels from puri ed CD8(+) T cells were analyzed using real-time polymerase chain reaction and western blot. RESULTS: The frequencies of CD11a+ and CD11c+ cells were significantly increased in the CD4+ and CD8+ cell populations of active-BD patients, respectively, than that in the HCs. Additionally, both CD11a and CD11c mRNA and protein levels were significantly elevated in the CD8+ T cells of active-BD patients than that in the HCs. CONCLUSIONS: The CD8+ T cells of BD patients exhibited increased CD11c expression levels. Upregulation of CD11c in CD8+ cells may contribute to BD pathogenesis.

MicroRNA-155 regulates the Th17 immune response by targeting Ets-1 in Behçet's disease.

OBJECTIVES: The goal of this study was to investigate whether microRNA-155 might be a potential therapeutic target for Behçet's disease (BD). METHODS: Expression levels of miR-155 were quantified using TaqMan microRNA assays in peripheral blood mononuclear cells and in isolated CD4+ T cells from BD patients and healthy controls. To identify targets of miR-155, luciferase reporter assays and western blotting were performed. The effect of miR-155 on Th17 polarisation was analysed in patients with active BD by using flow cytometry and enzyme-linked immunosorbent assay. RESULTS: The expression of miR-155 and IL-17 was significantly increased in CD4+ T cells of patients with active BD. A luciferase reporter assay and western blot showed that Ets-1 expression was reduced by miR-155 mimics. Furthermore, the expression of Ets-1 was significantly decreased in patients with active BD compared to healthy controls. More importantly, repression of miR-155 in CD4+ T cells from active BD patients increased Ets-1 expression and reduced the number of IL- 17-expressing T cells and overall IL-17 production. CONCLUSIONS: MiR-155 regulates the Th17 immune response by targeting Ets-1. Suppression of miR-155 reduced the amount of pathogenic IL-17-expressing T cells and may be a potential therapeutic strategy for BD.

Mangosenone F, A Furanoxanthone from Garciana mangostana, Induces Reactive Oxygen Species-Mediated Apoptosis in Lung Cancer Cells and Decreases Xenograft Tumor Growth.

Mangosenone F (MSF), a natural xanthone, was isolated form Carcinia mangotana, and a few studies have reported its glycosidase inhibitor effect. In this study we investigated the anti lung cancer effect of MSF both in vitro and in vivo. MSF inhibited cancer cell cytotoxicity and induced and induced apoptosis via reactive oxygen species (ROS) generation in NCI-H460. MSF treatment also showed in pronounced release of apoptogenic cytochrome c from the mitochondria to the cytosol, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bax, suggesting that caspase-mediated pathways were involved in MSF-induced apoptosis. ROS activation of the mitogen-activated protein kinase signaling pathway was shown to play a predominant role in the apoptosis mechanism of MSF. Compared with cisplatin treatment, MSF treatment showed significantly increased inhibition of the growth of NCI-H460 cells xenografted in nude mice. Together, these results indicate the potential of MSF as a candidate natural anticancer drug by promoting ROS production.