Risk factors for critical COVID-19 illness during Delta- and Omicron-predominant period in Korea; using K-COV-N cohort in the National health insurance service.

BACKGROUND: This study evaluated the clinical characteristics of patients with COVID-19 in Korea, and examined the relationship between severe COVID-19 cases and underlying health conditions during the Delta (September 20, 2021 to December 4, 2021) and the Omicron (February 20, 2022 to March 31, 2022) predominant period. METHODS: This study assessed the association between critical COVID-19 illness and various risk factors, including a variety of underlying health conditions, using multiple logistic regression models based on the K-COV-N cohort, a nationwide data of confirmed COVID-19 cases linked with COVID-19 vaccination status and the National Health Insurance claim information. RESULTS: We analyzed 137,532 and 8,294,249 cases of COVID-19 infection during the Delta and the Omicron variant dominant periods, respectively. During the Delta as well as the Omicron period, old age (≥80 years) showed the largest effect size among risk factors for critical COVID-19 illness (aOR = 18.08; 95% confidence interval [CI] = 14.71-22.23 for the Delta; aOR = 24.07; 95% CI = 19.03-30.44 for the Omicron period). We found that patients with solid organ transplant (SOT) recipients, unvaccinated, and interstitial lung disease had more than a two-fold increased risk of critical COVID-19 outcomes between the Delta and Omicron periods. However, risk factors such as urban residence, underweight, and underlying medical conditions, including chronic cardiac diseases, immunodeficiency, and mental disorders, had different effects on the development of critical COVID-19 illness between the Delta and Omicron periods. CONCLUSION: We found that the severity of COVID-19 infection was much higher for the Delta variant than for the Omicron. Although the Delta and the Omicron variant shared many risk factors for critical illness, several risk factors were found to have different effects on the development of critical COVID-19 illness between those two variants. Close monitoring of a wide range of risk factors for critical illness is warranted as new variants continue to emerge during the pandemic.

Intranasal delivery of herbal medicine for disease treatment: A systematic review.

BACKGROUND: Intranasal administration has been adopted in traditional medicine to facilitate access to the bloodstream and central nervous system (CNS). In modern medicine, nasal drug delivery systems are valuable for disease treatment because of their noninvasiveness, good absorption, and fast-acting effects. OBJECTIVE: This study aimed to systematically organize preclinical and clinical studies on intranasal herbal medicines to highlight their potential in drug development. METHODS: A comprehensive search for literature until February 2023 was conducted on PubMed and the Web of Science. From the selected publications, we extracted key information, including the types of herbal materials, target diseases, intranasal conditions, methods of toxicity evaluation, main outcomes, and mechanisms of action, and performed quality assessments for each study. RESULTS: Of the 45 studies, 13 were clinical and 32 were preclinical; 28 studies used herbal extracts, 9 used prescriptions, and 8 used natural compounds. The target diseases were rhinosinusitis, influenza, fever, stroke, migraine, insomnia, depression, memory disorders, and lung cancer. The common intranasal volumes were 8-50 µl in mice, 20-100 µl in rats, and 100-500 µl in rabbits. Peppermint oil, Ribes nigrum folium, Melia azedarach L., Elaeocarpus sylvestris, Radix Bupleuri, Da Chuan Xiong Fang, Xingnaojing microemulsion, and Ginsenoside Rb1 emerged as potential candidates for rapid intranasal therapy. The in vivo toxicity assessments were based on mortality, body weight, behavioral changes, mucociliary activity, histopathology, and blood tests. Most intranasal treatments were safe, except for Cyclamen europaeum, Jasminum sambac, Punica granatum L., and violet oil, which caused mild adverse effects. At lower doses, intranasal herbal treatments often show greater effects than oral administration. The actions of intranasal herbal medicine mainly involve regulating inflammation and neurotransmission, with the olfactory bulb and anterior cingulate cortex to be relevant brain regions. CONCLUSION: Intranasal delivery of herbal materials holds promise for enhancing drug delivery efficacy and reducing treatment duration, offering a potential future perspective for developing intranasal therapies for various diseases.

The efficacy and safety of non-resistance manual therapy in inpatients with acute neck pain caused by traffic accidents: A randomized controlled trial.

BACKGROUND: Neck pain and functional impairment are common complications of traffic accidents (TAs); however, the effects of manual therapy on these symptoms have rarely been studied in the literature. Thus, this randomized controlled trial aims to assess the effectiveness and safety of non-resistance manual therapy (NRT)-a treatment combining mobilization and pressure release techniques-on acute neck pain caused by TA. METHOD: This study will use a two-armed, parallel, assessor-blinded randomized controlled trial design and will be conducted in the Daejeon Jaseng Hospital of Korean Medicine in South Korea. One hundred twenty patients will be recruited and randomized into an integrative Korean medicine treatment (IMKT) + NRT group and IMKT group in a 1:1 ratio. The primary outcome is a change in the numeric rating scale for neck pain immediately after treatment on hospital day 5 compared to those at baseline. The secondary outcomes are numeric rating scale for radiating arm pain, visual analogue scale for neck pain and radiating arm pain, cervical active range of motion, neck disability index, Patient Global Impression of Change, Short Form-12 Health Survey, and Posttraumatic Stress Disorder Checklist for DSM-5. DISCUSSION: The findings of this study on the effectiveness and safety of NRT will be helpful for patients with TA-induced neck pain in clinical practice and will provide evidence for developing relevant healthcare-related policies. TRIAL REGISTRATION: This protocol has been registered at Clinicaltrials.gov (NCT04660175).

Effect of Cirsium japonicum Flower Extract on Skin Aging Induced by Glycation.

Advanced glycation end products (AGEs) have recently been increasingly discussed as one factor of skin aging. In this study, we investigated the effects of Cirsium japonicum flower (CFE) extract on glycation in relation to skin aging and skin elasticity. Moreover, we learned the main active constituent of CFE that has effects against glycation. To demonstrate the effects of CFE on glycation, we carried out an in vitro glycation study, 3-dimensional culture, and clinical study. As a result, CFE inhibited formation of AGEs in both bovine serum albumin (BSA)/glucose glycation system and aldehyde-derived glycation system. Moreover, CFE reduced Nε-(carboxymethyl), lysine (CML), and carbonylated proteins that increased by glycation. Furthermore, CFE broke crosslinks of collagen-AGEs and inhibited the increase of matrix metalloproteinase-1 (MMP-1) gene expression by AGEs. In the 3D culture condition, CFE restored the reduction of collagen gel contraction by glycation. Moreover, apigenin was detected as the main active constituent in CFE that has anti-glycation effects. In the clinical study, we confirmed that CFE has effects on skin wrinkles and skin elasticity. Our findings suggest that CFE can be used as a cosmetic or cosmeceutical ingredient for improving skin elasticity and wrinkles. Regulation of AGEs can be an interesting target for anti-aging.

Melanogenesis-promoting effect of Cirsium japonicum flower extract in vitro and ex vivo.

OBJECTIVE: In this study, we examined the effect of C. japonicum flower extract (CFE) on melanogenesis and its mechanism in vitro and ex vivo. METHODS: The effect of CFE on melanogenesis was investigated with lightly (HEMn-LP) and moderately (HEMn-MP) pigmented normal human melanocytes, reconstituted three-dimensional skin (3D skin) model and ex vivo human hair follicles. The melanogenesis-inducing effect of CFE was evaluated using melanin content and intracellular tyrosinase activity assay. The amount and type of eumelanin and pheomelanin were analysed by using HPLC method. The mechanism involved in the effect of CFE on hyperpigmentation was explored by cyclic adenosine monophosphate (cAMP) immunoassay and western blot analysis for tyrosinase, microphthalmia-associated transcription factor (MITF) and phosphorylated CRE-binding protein (pCREB) expression. The degree of pigmentation in 3D skin and L-values were measured using a CR-300 chroma meter. The amount of dissolved melanin was measured using a spectrophotometer. The content of melanin in the hair follicles was evaluated by Fontana Masson staining. RESULTS: C. japonicum flower extract significantly increased the melanin content and cellular tyrosinase activity in both HEMn-LP and HEMn-MP cells. The markers of pheomelanin and eumelanin in HEMn-LP and HEMn-MP were also increased by CFE. We observed that CFE treatment on melanocytes increased intracellular cAMP with inducing pCREB and up-regulating the protein levels of TYR and MITF. Furthermore, CFE considerably increased the melanin content in a 3D skin model and ex vivo human hair follicles. CONCLUSIONS: These results suggest that CFE exerts hyperpigmentation activity through cAMP signalling in human melanocytes that it can improve follicular depigmentation and vitiligo by stimulating the melanin synthesis.

OBJECTIF: Dans cette étude, nous avons examiné l'effet de l'extrait de fleur de C. japonicum (EFC) sur la mélanogenèse et son mécanisme in vitro et ex vivo. MÉTHODES: L'effet du EFC sur la mélanogenèse a été étudié avec des mélanocytes humains normaux légèrement (HEMn-LP) et modérément (HEMn-MP) pigmentés, un modèle de peau reconstituée en 3 dimensions (peau 3D) et des follicules pileux ex vivo. L'effet inducteur de la mélanogénèse de la EFC a été évalué en utilisant la teneur en mélanine et le dosage de l'activité de la tyrosinase intracellulaire. La quantité et le type d'eumélanine et de phéomélanine ont été analysés en utilisant la méthode HPLC. Le mécanisme impliqué dans l'effet de la EFC sur l'hyperpigmentation a été exploré par immunoessai à l'adénosine monophosphate cyclique (AMPc) et Western blot pour l'expression de la tyrosinase, du facteur de transcription associé à la microphtalmie (MITF) et l'expression de la protéine CREB phosphorylée. Le degré de pigmentation de la peau 3D, les valeurs L ont été mesurées à l'aide d'un chromamètre CR-300. La quantité de mélanine dissoute a été mesurée à l'aide d'un spectrophotomètre. La teneur en mélanine des follicules pileux a été évaluée par coloration Fontana Masson. RÉSULTATS: EFC a augmenté de manière significative la teneur en mélanine et l'activité de la tyrosinase cellulaire dans les cellules HEMn-LP et HEMn-MP. Les marqueurs de phéomélanine et d'eumélanine dans HEMn-LP et HEMn-MP ont également été augmentés par EFC. Nous avons observé que le traitement EFC sur les mélanocytes augmentait l'AMPc intracellulaire en induisant pCREB et en régulant à la hausse les niveaux de protéines de TYR et MITF. De plus, le EFC a considérablement augmenté la teneur en mélanine dans un modèle de peau 3D et dans les follicules pileux humains ex vivo. CONCLUSIONS: Ces résultats suggèrent que la EFC exerce une activité d'hyperpigmentation via la signalisation de l'AMPc dans les mélanocytes humains qu'elle peut améliorer la dépigmentation folliculaire et le vitiligo en stimulant la synthèse de mélanine.

Effect of Phlorofucofuroeckol A and Dieckol Extracted from Ecklonia cava on Noise-induced Hearing Loss in a Mouse Model.

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

Acupuncture combined with multidisciplinary care for recovery after traumatic multiple rib fractures: a prospective feasibility cohort study.

INTRODUCTION: Acute pain significantly delays early physiological recovery and results in chronic functional disability in patients with traumatic multiple rib fractures (MRFs). This prospective cohort study aimed to investigate the feasibility of acupuncture combined with multidisciplinary care during recovery in patients with traumatic MRFs. METHODS: Twenty patients with traumatic MRFs who were admitted to a regional trauma centre in South Korea were enrolled. A combination of acupuncture and multidisciplinary inpatient ward management was provided at the trauma ward. Patients were permitted to continue acupuncture treatments at outpatient clinics for 3 months after the traumatic events. Clinical outcomes, including pain, acute physiological recovery, quality of life, patient satisfaction with the care provided, respiratory function and use of opioids, were evaluated up to 6 months after trauma. RESULTS: Seventeen (85%) participants completed the 6-month follow-up. One patient withdrew consent during admission due to discomfort after three sessions of acupuncture. The proportion of patients with above-moderate level of pain decreased from 95% at baseline to 41% at 6 months. Quality of life appeared to deteriorate consistently throughout the study period. Around 80% of respondents expressed satisfaction with the acupuncture treatments and stated that they found acupuncture to be acceptable. Over 94% of respondents reported slight or considerable improvement. CONCLUSION: The provision of acupuncture combined with multidisciplinary care for recovery in patients with traumatic MRFs was feasible in a regional trauma centre in South Korea. Randomised trials are needed to investigate the role of acupuncture combined with multidisciplinary care in the future. TRIAL REGISTRATION NUMBER: KCT0002911 (Clinical Research Information Service).

Antiaging Activity of Peptide Identified from Fermented Trapa Japonica Fruit Extract in Human Dermal Fibroblasts.

We have previously shown that Trapa japonica fruit extract (TJE) as well as its fermented extract (FTJ) can be potentially used to treat alopecia. In the current study, a newly synthesized peptide (PEP) was detected in an active compound isolated from FTJ. Several biological assays were conducted to verify the antiaging effects of TJE, FTJ, and PEP on the skin. We examined the effects of TJE, FTJ, and PEP on cell viability, collagen synthesis, and inhibition of mRNA expression of matrix metalloproteinases (MMPs), induced by tumor necrosis factor alpha (TNF-α), in human dermal fibroblasts (HDFs). In addition, a wound-healing assay of the human keratinocyte cell line (HaCaT) and a clinical study of antiaging activity were conducted. The findings confirmed that PEP exerted an effect on cell proliferation in a dose-dependent manner. Treatment with TJE, FTJ, and PEP increased collagen synthesis but inhibited TNF-α-induced mRNA expression of MMPs. Compared with TJE and FTJ, PEP promoted a significant level of wound recovery in HaCaT cells and also exhibited antiaging effect, as demonstrated by a clinical study. These results suggest that PEP shows potential as a skin antiaging cosmetic product.

Amentoflavone, a novel cyanobacterial killing agent from Selaginella tamariscina.

Harmful cyanobacterial bloom (HCB) by Microcystis aeruginosa is increasingly becoming a serious concern to the environment and human health alike. Currently, many physical, chemical, and biological controls are underway to eliminate HCB, but natural chemicals are rarely used. To find a control agent with low environmental toxicity and high potential for practical use, 60 plant extracts were screened. Only Selaginella tamariscina extract killed all four Microcystis aeruginosa strains, but not the other tested bacteria. Chloroform fraction of S. tamariscina extract (CSE) showed the highest killing activity. The effects of CSE on M. aeruginosa were monitored using differential interference contrast microscopy and flow-cytometry analysis, scanning electron microscopy, and transmission electron microscopy. The images showed that CSE-treated cells were abnormally altered, with damaged cell membranes, peptidoglycan layers, and cytoplasm. Quadrupole time-of-flight liquid chromatography-mass spectrometry was used to identify amentoflavone as a major active compound. Pure amentoflavone, even at low concentrations showed a powerful killing effect on M. aeruginosa, but not on other non-cyanobacteria. Overall, in this study, we have highlighted the potentials of S. tamariscina extracts and amentoflavone as selective HCB control agents.

The effects of nattokinase supplementation on collagen-epinephrine closure time, prothrombin time and activated partial thromboplastin time in nondiabetic and hypercholesterolemic subjects.

The aim of this study was to investigate whether supplementation with nattokinase, which is considered one of the most active functional ingredients found in natto, alters hemostatic factors. Subjects presenting with hypercholesterolemia (serum cholesterol: 200-280 mg dL-1) were randomly divided into nattokinase and placebo groups (n = 50, respectively). No significant between-group differences were found at baseline in collagen-epinephrine closure time (C-EPI CT), prothrombin time (PT), or activated partial thromboplastin time (aPTT). After 8 weeks of treatment, the nattokinase group exhibited significant increases in C-EPI CT, PT, and aPTT. The nattokinase group showed significantly greater increases in C-EPI CT (P = 0.001) and aPTT (P = 0.016) than the placebo group. Moreover, at 8 weeks, the nattokinase group showed a significantly higher C-EPI CT than the placebo group (P = 0.001). Additionally, a significant correlation between PT and aPTT was observed (r = 0.491, P < 0.001). In conclusion, nattokinase supplementation was associated with prolonged C-EPI CT and aPTT in nondiabetic and borderline-to-moderate hypercholesterolemic subjects.

Protective effects of Camellia japonica flower extract against urban air pollutants.

BACKGROUND: Exposure of skin to urban air pollutants is closely related to skin aging and inflammatory responses such as wrinkles formation, pigmentation spot, atopic dermatitis, and acne. Thus, a great deal of interest has been focused on the development of natural resources that can provide a protective effect to skin from pollutants. METHODS: The antioxidative activity of Camellia japonica flower extract (CJFE) was evaluated by 1,2-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assay, and the inhibitory effect of CJFE by urban air pollutants-induced reactive oxygen species (ROS) production was determined in cultured normal human dermal fibroblasts (NHDFs). We additionally investigated the protective effects of CJFE against urban air pollutant using in vitro and ex vivo model. RESULTS: CJFE with high phenolic concentration showed antioxidative activity on scavenging capacity of 1,2-diphenyl-2-picrylhydrazyl (DPPH) radicals and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical cation in a concentration dependent manner. CJFE inhibited urban air pollutants-induced ROS generation, matrixmetalloproteinase-1 (MMP-1) production and a xenobiotic response element (XRE)-luciferase activity indicating the aryl hydrocarbon receptor (AhR) transactivation. In addition, CJFE showed an excellent protective activity against pollutants-induced deteriorating effect in ex vivo model. CJFE reduced the level of pollutants-induced malondialdehyde (MDA), lipid peroxidation marker, inhibited MMP-1 expression and increased collagen synthesis. It also reduced the cell numbers with pyknotic nuclei (mainly occurring in apoptosis) and detachment of dermo-epidermal junction (DEJ) induced by pollutants. CONCLUSIONS: Apparently, it is proposed that CJFE can be used as a protective material against pollutant-induced skin damages.

Anti-Thermal Skin Aging Activity of Aqueous Extracts Derived from Apple Mint (Mentha suaveolens Ehrh.) in Human Dermal Fibroblasts.

Thermal skin aging refers to skin aging induced by heat shock treatment. Apple mint (Mentha suaveolens Ehrh.) has been used as a folk medicine to treat various diseases. However, the activity of apple mint in thermal skin aging has yet to be investigated. In this study, we conducted various biological assays to demonstrate the anti-thermal skin aging activity of extracts of apple mint leaves (ALE). As a result, ALE showed significant antioxidant activities and inhibited the production of reactive oxygen species (ROS), matrix metalloproteinases (MMPs), and interleukin-8 (IL-8) as well as suppressed mitogen-activated proteins kinases (MAPKs) such as extracellular signal regulated kinases (ERK), c-Jun N terminal kinases (JNK), and p38 MAPK triggered by heat shock treatment in human dermal fibroblasts (HDFs). Consequently, ALE could be used as attractive cosmetic materials with anti-thermal skin aging activity.

Ketamine Inhibits Ultrasound Stimulation-Induced Neuromodulation by Blocking Cortical Neuron Activity.

Ultrasound (US) can be used to noninvasively stimulate brain activity. However, reproducible motor responses evoked by US are only elicited when the animal is in a light state of anesthesia. The present study investigated the effects of ketamine on US-induced motor responses and cortical neuronal activity. US was applied to the motor cortex of mice, and motor responses were evaluated based on robustness scores. Cortical neuronal activity was observed by fluorescence calcium imaging. US-induced motor responses were inhibited more than 20 min after ketamine injection, and US-triggered Ca2+ transients in cortical neurons were effectively blocked by ketamine. Our results indicate that ketamine suppresses US-triggered Ca2+ transients in cortical neurons and, therefore, inhibits US-induced motor responses in a deep anesthetic state.

Anticancer Effect of Nemopilema nomurai Jellyfish Venom on HepG2 Cells and a Tumor Xenograft Animal Model.

Various kinds of animal venoms and their components have been widely studied for potential therapeutic applications. This study evaluated whether Nemopilema nomurai jellyfish venom (NnV) has anticancer activity. NnV strongly induced cytotoxicity of HepG2 cells through apoptotic cell death, as demonstrated by alterations of chromatic morphology, activation of procaspase-3, and an increase in the Bax/Bcl-2 ratio. Furthermore, NnV inhibited the phosphorylation of PI3K, PDK1, Akt, mTOR, p70S6K, and 4EBP1, whereas it enhanced the expression of p-PTEN. Interestingly, NnV also inactivated the negative feedback loops associated with Akt activation, as demonstrated by downregulation of Akt at Ser473 and mTOR at Ser2481. The anticancer effect of NnV was significant in a HepG2 xenograft mouse model, with no obvious toxicity. HepG2 cell death by NnV was inhibited by tetracycline, metalloprotease inhibitor, suggesting that metalloprotease component in NnV is closely related to the anticancer effects. This study demonstrates, for the first time, that NnV exerts highly selective cytotoxicity in HepG2 cells via dual inhibition of the Akt and mTOR signaling pathways, but not in normal cells.

Effects of weight loss using supplementation with Lactobacillus strains on body fat and medium-chain acylcarnitines in overweight individuals.

Our previous study showed that supplementation with a combination of Lactobacillus curvatus (L. curvatus) HY7601 and Lactobacillus plantarum (L. plantarum) KY1032 reduced the body weight, body fat percentage, body fat mass and L1 subcutaneous fat area in overweight subjects. We aimed to evaluate whether the changes in adiposity after supplementation with Lactobacillus strains were associated with metabolic intermediates. A randomized, double-blind, placebo-controlled study was conducted on 66 non-diabetic and overweight individuals. Over a 12-week period, the probiotic group consumed 2 g of probiotic powder, whereas the placebo group consumed the same product without the probiotics. To investigate metabolic alterations, we performed plasma metabolomics using ultra-performance liquid chromatography and mass spectrometry (UPLC-LTQ/Orbitrap MS). Probiotic supplementation significantly increased the levels of octenoylcarnitine (C8:1), tetradecenoylcarnitine (C14:1), decanoylcarnitine (C10) and dodecenoylcarnitine (C12:1) compared with the levels from placebo supplementation. In the probiotic group, the changes in the body weight, body fat percentage, body fat mass and L1 subcutaneous fat area were negatively associated with changes in the levels of C8:1, C14:1, C10 and C12:1 acylcarnitines. In overweight individuals, probiotic-induced weight loss and adiposity reduction from the probiotic supplementation were associated with an increase in medium-chain acylcarnitines.

Consumption of dairy yogurt with the polysaccharide rhamnogalacturonan from the peel of the Korean citrus hallabong enhances immune function and attenuates the inflammatory response.

The aim of this study was to investigate the impact of consuming dairy yogurt supplemented with rhamnogalacturonan (RG), a polysaccharide from the peel of the Korean citrus hallabong, on natural killer (NK) cell activity and circulating cytokine levels. A randomized, double-blind, placebo-controlled study was conducted on 120 nondiabetic and nonobese subjects. Over an eight-week period, the test group consumed one pack (150 mL) of dairy yogurt containing 50 mg of probiotics and 100 mg of hallabong peel polysaccharide (60% RG) each day, whereas the placebo group consumed the same product without the hallabong peel supplement. NK cell activity (%) was measured based on the ratios of the effector cells (E; peripheral blood mononuclear cells, PBMCs) from each participant relative to the target cells (T; K562 cells) at E : T ratios of 10 : 1, 5 : 1, 2.5 : 1, or 1.25 : 1. NK cell activities under all assay conditions and interleukin (IL)-12 and interferon (IFN)-γ levels were significantly increased in the test group at eight weeks compared to the baseline values, whereas the placebo group showed a significant increase only in NK cell activity at E : T = 1.25 : 1. The test group had significantly greater increases in the changes in serum NK cell activity at the E : T ratios of 10 : 1, 5 : 1, and 2.5 : 1 and in the increases in IL-12 and IFN-γ levels than were observed in the placebo group, after adjusting for baseline values. After eight weeks of treatment, significant reductions were found in IL-6 and IL-1ß levels in both the placebo and test groups. The daily consumption of dairy yogurt supplemented with RG, a polysaccharide from the peel of the Korean citrus hallabong, enhanced NK cell function and attenuated pro-inflammatory cytokine levels (ClinicalTrials.gov: NCT02535663).

Blood pressure-lowering effect of Korean red ginseng associated with decreased circulating Lp-PLA2 activity and lysophosphatidylcholines and increased dihydrobiopterin level in prehypertensive subjects.

We evaluated the effects of red ginseng consumption on blood pressure (BP) and the fasting plasma metabolome. This randomized, double-blind, placebo-controlled study included nonobese, nondiabetic, prehypertensive subjects consuming 10 capsules daily containing 5 g red ginseng (n=31) or placebo (n=31). Fasting plasma metabolome profiles were obtained using ultra performance liquid chromatography-linear trap quadrupole Orbitrap MS. After 12 weeks, participants consuming red ginseng showed reductions of 6.5 and 5.0 mm Hg in systolic and diastolic BP, respectively. Compared with controls, those consuming red ginseng showed greater reductions in changed values of systolic BP, diastolic BP and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, after adjusting for baseline values. In addition, the red ginseng group showed a greater increase in dihydrobiopterin levels and greater decrease in palmitic amide and lysophosphatidylcholines (lysoPCs). The change in diastolic BP positively correlated with changes in lysoPCs and Lp-PLA2 activity. The BP-lowering effect of red ginseng is associated with decreased Lp-PLA2 and lysoPCs and increased dihydrobiopterin levels in prehypertensive subjects (ClinicalTrials.gov: NCT02326766).

Developmental guidance of the retroflex tract at its bending point involves Robo1-Slit2-mediated floor plate repulsion.

The retroflex tract contains medial habenula efferents that target the hindbrain interpeduncular complex and surrounding areas. This tract displays a singular course. Initially, habenular axons extend ventralwards in front of the pretectum until they reach the basal plate. Next, they avoid crossing the local floor plate, sharply changing course caudalwards (the retroflexion alluded by the tract name) and navigate strictly antero-posteriorly across basal pretectum, midbrain and isthmus. Once they reach rhombomere 1, the habenular axons criss-cross the floor plate several times within the interpeduncular nuclear complex as they innervate it. Here we described the timing and details of growth phenomena as these axons navigate to their target. The first dorsoventral course apparently obeys Ntn1 attraction. We checked the role of local floor plate signaling in the decision to avoid the thalamic floor plate and bend caudalwards. Analyzing the altered floor and basal plates of Gli2 knockout mice, we found a contralateral projection of most habenular axons, plus ulterior bizarre navigation rostralwards. This crossing phenotype was due to a reduced expression of Slit repulsive cues, suggesting involvement of the floor-derived Robo-Slit system in the normal guidance of this tract. Using Slit and Robo mutant mice, open neural tube and co-culture assays, we determined that Robo1-Slit2 interaction is specifically required for impeding that medial habenular axons cross the thalamic floor plate. This pathfinding mechanism is essential to establish the functionally important habenulo-interpeduncular connection.

Inhibition of melanogenesis by Gaillardia aristata flower extract.

BACKGROUND: The purpose of the study was to determine the anti-melanogenic and anti-oxidant properties of Gaillardia aristata flower extract (GAE). METHODS: Melanogenesis inhibition by GAE was investigated in cultivated cells and in a human skin model. In cultivated cells, the melanogenesis regulatory effect of GAE was evaluated using melanin content, intracellular tyrosinase activity and anti-oxidant characteristics. In addition, the expression of melanogenesis-related proteins was determined by western blot assay and real-time PCR. RESULTS: GAE reduced the amount of melanin in B16F10 and normal human epidermal melanocyte cells and suppressed intracellular tyrosinase activity in a dose-dependent pattern. Also, GAE significantly decreased the expression of melanogenesis-related proteins (microphthalmia associated transcription factor, tyrosinase, tyrosinase-related protein-1, and dopachrome tautomerase). Real-time PCR results revealed a down-regulation of the mRNAs of these proteins. GAE possessed anti-oxidant characteristics as free radical-scavenging capacity and reducing power. In the three-dimensional human skin model, GAE applied to hyperpigmented skin significantly increased the degree of skin lightening within 2 weeks of treatment. The safety of GAE on human skin was confirmed. CONCLUSIONS: These results indicate the potential of GAE for use in suppressing skin pigmentation. We proposed GAE as a new candidate of anti-melanogenic and antioxidant agents that could be used for cosmetic skin care products.

Ameliorating Effect of Akebia quinata Fruit Extracts on Skin Aging Induced by Advanced Glycation End Products.

The accumulation of free radicals and advanced glycation end products (AGEs) in the skin plays a very important role in skin aging. Both are known to interact with each other. Therefore, natural compounds or extracts that possess both antioxidant and antiglycation activities might have great antiageing potential. Akebia quinata fruit extract (AQFE) has been used to treat urinary tract inflammatory disease in traditional Korean and Chinese medicines. In the present study, AQFE was demonstrated to possess antioxidant and antiglycation activity. AQFE protects human dermal fibroblasts (HDFs) from oxidative stress and inhibits cellular senescence induced by oxidative stress. We also found that AQFE inhibits glycation reaction between BSA and glucose. The antiglycation activity of AQFE was dose-dependent. In addition, the antiglycation activity of AQFE was confirmed in a human skin explant model. AQFE reduced CML expression and stimulated fibrillin-1 expression in comparison to the methyglyoxal treatment. In addition, the possibility of the extract as an anti-skin aging agent has also been clinically validated. Our analysis of the crow's feet wrinkle showed that there was a decrease in the depth of deep furrows in RI treated with AQFE cream over an eight-week period. The overall results suggest that AQFE may work as an anti-skin aging agent by preventing oxidative stress and other complications associated with AGEs formation.