Essential oils extracted from nine different plants exhibit differential effects on skin antioxidation and elasticity.

Essential oils derived from plants are major ingredients in the medical and cosmetic industry. Here, we evaluated nine types of plant essential oils to identify potential candidates with antioxidant and elasticity-enhancing properties. Seven essential oils showed at least 10% radical scavenging activity at the highest concentration. Essential oils extracted from Aster glehnii, Cinnamomum cassia, Citrus unshiu, Juniperus chinensis L., and Juniperus chinensis var. sargentii significantly enhanced fibroblast viability, and oils from Cit. unshiu, J. chinensis L., and J. chinensis var. sargentii significantly increased cell proliferation and migration. Expression of extracellular matrix proteins, including collagen 1, collagen 3, and elastin, were upregulated by J. chinensis L. and J. chinensis var. sargentii oil, which also significantly enhanced the contractile activity of skin cells in a three-dimensional gel contraction assay. The results suggest that J. chinensis L. and J. chinensis var. sargentii essential oils may be potential anti-wrinkling and anti-oxidative agents for future consideration of use in the medical and cosmetic industry.

Development of Pinaceae and Cupressaceae Essential Oils from Forest Waste in South Korea.

The growing awareness of environmental issues has garnered increasing interest in the use of waste material in a wide variety of applications. From this viewpoint, developing essential oils from forest waste can bring new cost opportunities for the effective and sustainable management of unused forestry biomass. However, better knowledge of the production, chemical constituents, and application of essential oils is necessary. Among the species considered to be of interest from the point of view of their essential oils and forest biomass, Pinaceae and Cupressaceae were selected in this study as potential candidates for commercial essential oils based on previous studies. This current study focuses on investigating Pinaceae (Larix kaempferi, Pinus densiflora, and Pinus koraiensis) and Cupressaceae (Chamaecyparis obtusa and Chamaecyparis pisifera) essential oils extracted from various parts from the perspective of their bioactive compounds and potential applications. This is followed by an overview of the essential oils industry in South Korea, with particular attention being paid to utilising unused forest biomass. Therefore, this is a comprehensive review suggesting that Pinaceae and Cupressaceae essential oils extracted from various parts of forest waste could be utilised in various industries, adding value to the aspect of sustainable industry. Furthermore, our study contributes towards capturing the value of forest resources through the utilisation of native essential oils in South Korea.

Anti-Inflammatory Effects of Essential Oils from the Peels of Citrus Cultivars.

Citrus cultivars have remarkable health benefits, but only the anti-inflammatory activities of the major varieties have been studied. This study investigated the anti-inflammatory effects of various citrus cultivars and their active anti-inflammatory components. The essential oils of 21 citrus peels were extracted via hydrodistillation using a Clevenger-type apparatus, and the chemical compositions of the essential oils were analyzed. D-Limonene was the most abundant constituent. To evaluate the anti-inflammatory effects of the citrus cultivars, the gene expression levels of an inflammatory mediator and proinflammatory cytokines were investigated. Among the 21 essential oils, those extracted from C. japonica and C. maxima exhibited superior anti-inflammatory activities, being able to inhibit the expression of the inflammatory mediators and proinflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 cells. The essential oils of C. japonica and C. maxima were distinguished into seven distinct constituents, α-pinene, myrcene, D-limonene, ß-ocimene, linalool, linalool oxide, and α-terpineol, compared with other essential oils. The anti-inflammatory activities of the seven single compounds significantly inhibited the levels of inflammation-related factors. In particular, α-terpineol exhibited a superior anti-inflammatory effect. This study showed that the essential oils from C. japonica and C. maxima exhibit high anti-inflammatory activity. In addition, α-terpineol is an active anti-inflammatory compound that contributes to inflammatory responses.

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.

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 pre-established breast tumors by generating potent antitumor immunity with a durable effect that prevents tumor reoccurrence. Therefore, treatment with SRC-3 deleted Tregs represents a novel approach to completely block tumor growth and recurrence without the autoimmune side-effects that typically accompany immune checkpoint modulators. Significance statement: Tregs are essential in restraining immune responses for immune homeostasis. SRC-3 is a pleiotropic coactivator, the second-most highly expressed transcriptional coactivator in Tregs, and a suspect in Treg function. The disruption of SRC-3 expression in Tregs leads to a 'complete lifetime eradication' of tumors in aggressive syngeneic breast cancer mouse models because deletion of SRC-3 alters the expression of a wide range of key genes involved in efferent and afferent Treg signaling. SRC-3KO Tregs confer this long-lasting protection against cancer recurrence in mice without an apparent systemic autoimmune pathological phenotype. Therefore, treatment with SRC-3 deleted Tregs could represent a novel and efficient future target for eliminating tumor growth and recurrence without the autoimmune side-effects that typically accompany immune checkpoint modulators.

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.

Integrative metabolomics of plasma and PBMCs identifies distinctive metabolic signatures in Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a systemic inflammatory disease that involves various organs. The clinical manifestation-based diagnosis of BD is a time-consuming process, which makes it difficult to distinguish from patients with similar symptoms. Moreover, an authentic biomarker has not been developed for accurate diagnosis yet. Our current study investigated the unique metabolic signatures of BD and explored biomarkers for precise diagnosis based on an untargeted metabolomic approach. METHODS: Integrative metabolomic and lipidomic profiling was performed on plasma samples of BD patients (n = 40), healthy controls (HCs, n = 18), and disease controls (DCs, n = 17) using GC-TOF MS and LC-Orbitrap MS. Additionally, the lipid profiles of 66 peripheral blood mononuclear cells (PBMCs) were analyzed from 29 BD patients, 18 HCs, and 19 DCs. RESULTS: Plasma metabolic dysfunction in BD was determined in carbohydrate, hydroxy fatty acid, and polyunsaturated fatty acid metabolisms. A plasma biomarker panel with 13 compounds was constructed, which simultaneously distinguished BD from HC and DC (AUCs ranged from 0.810 to 0.966). Dysregulated PBMC metabolome was signatured by a significant elevation in lysophosphatidylcholines (LPCs) and ether-linked lysophosphatidylethanolamines (EtherLPEs). Ten PBMC-derived lipid composites showed good discrimination power (AUCs ranged from 0.900 to 0.973). Correlation analysis revealed a potential association between disease activity and the metabolites of plasma and PBMC, including sphingosine-1 phosphate and EtherLPE 18:2. CONCLUSIONS: We identified metabolic biomarkers from plasma PBMC, which selectively discriminated BD from healthy control and patients with similar symptoms (recurrent mouth ulcers with/without genital ulcers). The strong correlation was determined between the BD activity and the lipid molecules. These findings may lead to the development for diagnostic and prognostic biomarkers based on a better understanding of the BD pathomechanism.

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.

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.

Early psychiatric referral after attempted suicide helps prevent suicide reattempts: A longitudinal national cohort study in South Korea.

Introduction: Although people who attempted suicide tend to repeat suicide attempts, there is a lack of evidence on the association between psychiatric service factors and suicide reattempt among them. Methods: We used a nationwide, population-based medical record database of South Korea to investigate the use of psychiatric services before and after the index suicide attempt and the association between psychiatric service factors after the index suicide attempt with the risk of suicide reattempt. Results: Among 5,874 people who had attempted suicide, the all-cause mortality within 3 months after the suicide attempt was 11.6%. Among all subjects who attempted suicide, 30.6% of them had used psychiatric services within 6 months before the suicide attempt; 43.7% of them had used psychiatric services within 3 months after the suicide attempt. Among individuals who had visited clinics following attempted suicide, the cumulative incidence of suicide reattempt over a mean follow-up period of 5.1 years was 3.4%. About half of suicide reattempts occurred within 1 year after the index suicide attempt. Referral to psychiatric services within 7 days was associated with a decreased risk of suicide reattempt (adjusted hazard ratio, 0.51; 95% confidence intervals, 0.29-0.89). Conclusion: An early psychiatric referral within 1 week after a suicide attempt was associated with a decreased risk of suicide reattempt.

Association between pre-pregnancy tobacco smoking and postpartum depression: A nationwide cohort study.

BACKGROUND: Prior literature examining the association between cigarette smoking and postpartum depression (PPD) has focused primarily on smoking behaviors during pregnancy or postpartum. However, there is a dearth of studies assessing pre-pregnancy smoking in relation to PPD. METHOD: A retrospective national cohort data from the National Health Insurance of South Korea were analyzed. A total of 392,394 women who gave birth between 2011 and 2015 and received health checkups within a year before pregnancy without a history of diagnosed depression were included. During the health checkup, participants self-reported their smoking status, amount, and duration in a health questionnaire. The diagnosis of PPD was defined by ICD-10 codes F32 and F33 during hospital visits within two years postpartum. RESULT: Overall, 24,441 (6.2 %) women were newly diagnosed with depression within two years postpartum. Those who reported that they had quit smoking or were currently smoking before pregnancy were more likely to be diagnosed with PPD compared to nonsmokers. A greater number of cigarettes smoked was associated with a higher risk of PPD for both current and former smokers. Results of cumulative lifetime smoking exposure demonstrated that even those with 2 pack-years of smoking had an increased risk of developing PPD within two years postpartum (HR: 1.44, 95 % CI: 1.29-1.60). Those who smoked >10 pack-years had the highest risk of developing PPD (HR: 1.86, 95 % CI: 1.14-3.04) compared to nonsmokers. CONCLUSION: Greater amount and duration of cigarette smoking in pre-pregnancy can increase the risk of PPD.

Female reproductive factors are associated with the risk of newly diagnosed bipolar disorder in postmenopausal women.

Changes in the levels of female sex hormones are associated with mood disorders in middle-aged women. This study investigated the association between female reproductive factors and the development of newly diagnosed bipolar disorder (BD). We used a South Korean nationwide medical records database. Postmenopausal women aged 40 or older who underwent health examinations were identified and followed for the occurrence of BD. We identified female reproductive factors including the age at menarche and menopause, parity, history of breastfeeding, oral contraceptive (OC) use, and hormone therapy (HT), and investigated their association with the occurrence of newly diagnosed BD. During an average of 8.32 years (SD 0.83) of follow-up, the incidence of BD was 0.50 per 1000 person-years in postmenopausal women. Compared to women with menopause at an age of 40 years or younger, those with menopause at an age of 45 years or older showed decreased risks of BD. Compared to women who had never breastfed, those who had breastfed for more than 12 months showed a decreased risk of BD. Compared to women who never received HT, those who received HT showed an increased risk of BD in a time-dependent manner. Among postmenopausal women, later menopause and breastfeeding for more than one year were associated with a decreased risk of BD occurrence, and receiving HT was associated with an increased risk.

Impaired Oxygenation of the Prefrontal Cortex During Verbal Fluency Task in Young Adults With Major Depressive Disorder and Suicidality: A Functional Near-Infrared Spectroscopy Study.

Background: Few previous studies have focused on prefrontal activation in young adults diagnosed with major depressive disorder (MDD) and suicidality via functional near-infrared spectroscopy (fNIRS). Materials and Methods: A total of 59 healthy controls (HCs), 35 patients with MDD but without suicidality, and 25 patients with MDD and suicidality, between the ages of 18-34 years, were enrolled. Changes in oxygenated hemoglobin (oxy-Hb) levels of the prefrontal cortex at baseline, 4 weeks, and 8 weeks, were evaluated using a protocol consisting of three consecutively repeated trials of rest, speech, and verbal fluency test (VFT) via fNIRS. MDD was diagnosed and suicidality was evaluated based on Mini International Neuropsychiatric Interview (MINI). Results: Oxy-Hb levels were impaired in patients with MDD compared with HCs (p = 0.018 for left prefrontal cortex; p = 0.021 for right ventromedial prefrontal cortex; p = 0.002 for left frontopolar cortex). Among the three groups including HCs, MDD without suicidality, and MDD with suicidality, prefrontal oxygenation was most decreased in MDD patients with suicidality. A significantly impaired prefrontal oxygenation in the right ventrolateral prefrontal cortex (VLPFC) was detected after adjusting for covariates in MDD patients with suicidality, compared to those without suicidality. Conclusion: Impaired prefrontal oxygenation during cognitive execution may serve as a diagnostic biomarker for suicidality in young adult patients with MDD.

Comparison of Peripheral Biomarkers and Reduction of Stress Response in Patients With Major Depressive Disorders vs. Panic Disorder.

Alteration in stress response seems to affect the development of psychiatric disorders. In this study, we aimed to investigate whether baseline peripheral biomarkers could predict the reduction of stress response among patients with major depressive disorder (MDD) and panic disorder (PD). Patients with MDD (n = 41) and PD (n = 52) and healthy controls (HC, n = 59) were selected and regularly followed up with five visits for 12 weeks. The severity of stress at every visit was assessed using the Stress Response Inventory (SRI), and peripheral biomarkers were measured by blood tests at baseline and 2, 4, 8, and 12 weeks. Interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, C-reactive protein (CRP), adiponectin, and leptin levels were analyzed using enzyme-linked immunosorbent assays. Reduction of stress response was defined as the difference in SRI score between baseline and 12 weeks divided by the baseline score. SRI scores were significantly (p < 0.0001) higher in patients with MDD and PD than in HC at every visit after adjusting for variables. In multivariable linear regression, adiponectin levels at baseline were significantly associated with reduction of stress response in patients with PD. When adiponectin increased 1 mg/l, stress response decreased 0.781 points (ß = -0.781, S.E. = 0.220, p = 0.001). Among the subscales of SRI, somatization had a moderate negative correlation with adiponectin levels (r = -0.469). There was no significant association between baseline peripheral biomarkers and reduction of stress response in patients with MDD. Our study showed an inverse association between baseline adiponectin levels and stress response changes in patients with PD, but not in patients with MDD. Thus, differentiated approaches for assessing and treating stress responses of patients with PD and MDD might be helpful. Larger and longitudinal studies are necessary to establish the role and mechanism of action of adiponectin in regulating stress responses in PD.

Bullying, Psychological, and Physical Trauma During Early Life Increase Risk of Major Depressive Disorder in Adulthood: A Nationwide Community Sample of Korean Adults.

Background: There is an association between early life traumas and the development of depression in adults. Few studies have used nationwide population-based samples to investigate whether the type of early life trauma differentially influences the risk of developing depression. Methods: Major depressive disorder and early life trauma were assessed using the Korean version of the Composite International Diagnostic Interview (K-CIDI) for DSM-IV psychiatric disorder and a questionnaire for early life trauma in the Korean Epidemiological Catchment Area Study in 2016. A total of 4,652 participants were included in the final analysis. This study evaluated the effect of the type and frequency of reported early life trauma on the risk of developing MDD and the association between reported early life trauma and differential symptoms of MDD. Results: Individuals with reported early life trauma had a 3.7-fold increased risk of MDD. The risk of MDD was associated with bullying trauma (odds ratio (OR) = 1.847, p = 0.005) after adjusting for age, gender, marriage, job, and education years. The risk of MDD was increased as the types of reported early life traumas increased. Conclusion: Bullying trauma during early life represents a risk factor for MDD, especially in individuals exposed to multiple traumas in early life.

Inhibitory effects and underlying mechanisms of Artemisia capillaris essential oil on melanogenesis in the B16F10 cell line.

The present study investigated the anti­melanogenic activity of 10 essential oils using the B16F10 cell model. Initially, a wide range of concentrations of these essential oils were screened in order to determine their toxicity levels. The assigned non­toxic concentrations of the tested essential oils were then used to evaluate their effects on melanogenesis. The effects of the essential oils with potent anti­melanogenic activity on cell proliferation, protection against H2O2­induced cell death and the expression of certain melanogenesis­related genes, including MITF, tyrosinase, tyrosinase related protein (TRP)­1 and TRP­2 were also evaluated. The results revealed that the essential oils extracted from Citrus unshiu, Juniperus chinensis L., Zanthoxylum piperitum and Artemisia capillaris (A. capillaris) inhibited melanogenesis. However, among these four extracts, only A. capillaris extract enhanced cell proliferation, exhibited anti­H2O2 activities and decreased the expression level of TRP­1. It was demonstrated that A. capillaris extract inhibited melanin synthesis via the downregulation of the TRP­1 translational level. These essential oil extracts, particularly that of A. capillaris, may thus be used as natural anti­melanogenic agents for therapeutic purposes and in the cosmetic industry for skin whitening effects with beneficial proliferative properties. However, further studies using in vivo models are required to validate these findings and to examine the effects of these extracts on various molecular pathways.

Cold-pressed oil from Citrus aurantifolia inhibits the proliferation of vascular smooth muscle cells via regulation of PI3K/MAPK signaling pathways.

Vascular occlusive disease is a chronic disease with significant morbidity and mortality. Although a variety of therapies and medications have been developed, the likelihood of disease re-emergence is high and this can be life-threatening. Based on a previous screening experiment related to vascular obstructive diseases using 34 types of essential oils, cold-pressed oil (CpO) from Citrus aurantifolia (lime) has been demonstrated to have the best effect for the inhibition of vascular smooth muscle cells (VSMCs) proliferation. The aim of the present study was to evaluate the effect of lime CpO on the pathological changes of VSMCs. To determine this, the effect of lime CpO on VSMC proliferation, a major cause of vascular disease, was investigated. To determine the safe concentration interval for toxicity of CpO during VSMC culture, a dilution of 1x10-5 was determined using Cell Counting Kit-8 assay, which was confirmed to be non-toxic using a lactate dehydrogenase assay. To examine the effect of lime CpO in cellular signaling pathways, changes in phosphorylation of both the PI3K/AKT/mTOR and extracellular signal-regulated MEK/ERK signaling pathways with serum were investigated. Furthermore, lime CpO with FBS also significantly decreased the expression levels of the cell cycle regulators cyclin D1 and proliferating cell nuclear antigen. Additionally, lime CpO with FBS significantly inhibited the sprouting of VSMCs in an ex vivo culture system. These results suggested that lime CpO inhibited the abnormal proliferation of VSMCs and can be developed as a nature-based therapeutic agent for obstructive vascular disease.

Increased metabolic variability is associated with newly diagnosed depression: A nationwide cohort study.

BACKGROUND: The effect of dynamic changes in metabolic parameters over time on the development of depression has yet to be examined. In this study, we aimed to determine the association between the variability of metabolic parameters and the development of depression using nationally representative data. METHODS: We used health examination data provided by the South Korean National Health Insurance System (NHIS) and included those who underwent the examination ≥ 3 times within five years of enrollment, without a previous history of depression (n = 9,058,424). The variability of each metabolic parameter including weight circumference, blood pressure, fasting blood glucose, high-density lipoprotein cholesterol, and triglyceride levels was estimated using variability independent of mean (VIM) indices. High variability was defined as the highest quartile (Q4) of variability. RESULTS: Each metabolic parameter with high variability was associated with a higher risk of newly diagnosed depression compared to those with low variability, after adjusting for age, sex, smoking, alcohol drinking, regular exercise, income status, baseline diabetes, hypertension, and dyslipidemia. As the number of highly variable metabolic parameters increased, the risk for newly diagnosed depression increased even after adjusting for the aforementioned covariates (hazard ratio (HR) = 1.4, 95% confidence interval (CI): 1.3 - 1.4 in those with five highly variable parameters compared to those with no highly variable parameter). LIMITATIONS: relatively short observation period; no systematic measure of depression severity. CONCLUSIONS: Our results suggest that the variability of metabolic parameters is an independent risk factor for depression.

Association of smartphone overuse with depression, anxiety, and other addictive behaviors: A nationwide community sample of Korean adults.

Smartphone is one of the essential items. However, it may negatively affect a user's mental health when it is overused. The study aimed to investigate associations of smartphone overuse with depression, anxiety, and the relationship with other addictive behaviors and disorders. A total of 2,509 subjects were randomly selected through a one-person-per-household method. Smartphone Overuse Screening Questionnaire (SOS-Q) and the Korean version of the Composite International Diagnostic Interview (K-CIDI) were used. Linear regression and Pearson correlation analyses were performed to evaluate associations of smartphone overuse with depression, anxiety, and relationship with other addictive psychiatric disorders respectively. Among 2509 participants, 138 (14.76%) demonstrated smartphone overuse. Participants who used their smartphones for more than three hours a week were more likely to be single and females compared to those who used their smartphones for less than three hours a week. Smartphone overuse showed significant associations with depression, anxiety disorder, and a significant relationship with internet and game overuse, alcohol dependence, and nicotine dependence disorder. Internet-related behavior showed the strongest relationship with smartphone overuse. Although the sample size was adequate, a large number of subjects did not complete the questionnaire. People with psychiatric disorders should be advised to use smartphones in moderation.

Alteration of the Fecal but Not Salivary Microbiome in Patients with Behçet's Disease According to Disease Activity Shift.

The human microbiome plays an important role in various diseases, including Behçet's disease (BD). However, the effects of disease activity and covariates influencing the microbial composition have not yet been investigated. Therefore, we investigated the fecal and salivary microbiomes of BD patients compared to those of recurrent aphthous ulcer (RAU) patients, as well as dietary habit-matched healthy controls (HCs) selected from immediate family members using 16S rRNA gene sequencing. The fecal microbiome alpha diversity of BD patients was not different from that of their matched HCs, although it was higher than that of unrelated HCs and decreased in BD patients with disease activity. A tendency toward clustering in the beta diversity of the fecal microbiome was observed between the active BD patients and their matched HCs. Active BD patients had a significantly higher abundance of fecal Bacteroides uniformis than their matched HCs and patients with the disease in an inactive state (p = 0.038). The abundance of salivary Rothia mucilaginosa group was higher in BD patients than in RAUs patients. BD patients with uveitis had different abundances of various taxa, compared to those without uveitis. Our results showed an association of fecal microbiome composition with BD disease activity and symptoms, suggesting the possible role of the gut microbiome in BD pathogenesis.