Dipterocarpus tuberculatus as a promising anti-obesity treatment in Lep knockout mice.

Introduction: The therapeutic effects and mechanisms of Dipterocarpus tuberculatus (D. tuberculatus) extracts have been examined concerning inflammation, photoaging, and gastritis; however, their effect on obesity is still being investigated. Methods: We administered a methanol extract of D. tuberculatus (MED) orally to Lep knockout (KO) mice for 4 weeks to investigate the therapeutic effects on obesity, weight gain, fat accumulation, lipid metabolism, inflammatory response, and ß-oxidation. Results: In Lep KO mice, MED significantly reduced weight gains, food intake, and total cholesterol and glyceride levels. Similar reductions in fat weights and adipocyte sizes were also observed. Furthermore, MED treatment reduced liver weight, lipid droplet numbers, the expressions of adipogenesis and lipogenesis-related genes, and the expressions of lipolysis regulators in liver tissues. Moreover, the iNOS-mediated COX-2 induction pathway, the inflammasome pathway, and inflammatory cytokine levels were reduced, but ß-oxidation was increased, in the livers of MED-treated Lep KO mice. Conclusion: The results of this study suggest that MED ameliorates obesity and has considerable potential as an anti-obesity treatment.

Information flow dynamics between geopolitical risk and major asset returns.

We quantify information flows between geopolitical risk (GPR) and global financial assets such as equity, bonds, and commodities, with a focus on the Russian-Ukrainian conflict. We combine transfer entropy and the I-CEEMDAN framework to measure information flows at multi-term scales. Our empirical results indicate that (i) in the short term, crude oil and Russian equity show opposite responses to GPR; (ii) in the medium and long term, GPR information increases the risk in the financial market; and (iii) the efficiency of the financial asset markets can be confirmed on a long-term scale. These findings have important implications for market participants, such as investors, portfolio managers, and policymakers.

Radical Scavenging-Linked Anti-Obesity Effect of Standardized Ecklonia stolonifera Extract on 3T3-L1 Preadipocytes and High-Fat Diet-Fed ICR Mice.

Ecklonia stolonifera, belonging to the Laminariaceae family, is an edible widely distributed perennial brown marine alga that is rich in polyphenols. Dieckol, a bioactive component of the E. stolonifera extract (ESE), is a major phlorotannin compound found only in brown algae. This study aimed to evaluate the ability of ESE to inhibit lipid accumulation caused by oxidative stress in 3T3-L1 adipocytes and high-fat diet-fed obese ICR mice. We report that ESE-treated obese ICR mice, which were fed a high-fat diet, showed reduced whole-body and adipose tissue weights with improved plasma lipid profiles. In vitro and in vivo studies have indicated that ESE inhibited the expression of adipogenesis-related genes associated with fat accumulation through AMP-activated protein kinase activity and increased the expression of lipolysis-related genes. In addition, ESE reduced the expression of enzymes involved in reactive oxygen species (ROS) production and increased the expression of antioxidant enzymes, thereby reducing ROS levels. These findings suggest that ESE possesses strong antioxidant properties and inhibits oxidative stress-induced lipid accumulation by reducing ROS production during adipocyte generation.

Anti-adipogenic Effects of Sulforaphane-rich Ingredient with Broccoli Sprout and Mustard Seed in 3T3-L1 Preadipocytes.

Glucoraphanin (GRA) is a precursor of sulforaphane (SFN), which can be synthesized by the enzyme myrosinase. In this study, we developed and validated HPLC analytical methods for the determination of GRA and SFN in mustard seed powder (MSP), broccoli sprout powder (BSP), and the MSP-BSP mixture powder (MBP), and evaluated their anti-adipogenic effects in 3T3-L1 adipocytes. We found that the analysis methods were suitable for the determination of GRA and SFN in MSP, BSP, and MBP. The content of GRA in BSP was 131.11 ± 1.84 µmol/g, and the content of SFN in MBP was 162.29 ± 1.24 µmol/g. In addition, BSP and MBP effectively decreased lipid accumulation content without any cytotoxicity. Both BSP and MBP significantly inhibited the expression of adipogenic proteins and increased the expression of proteins related to lipolysis and lipid metabolism. BSP and MBP inhibited the expression of adipocyte protein 2 (aP2), CCAAT/enhancer-binding protein-α (C/EBP-α), and peroxisome proliferator-activated receptor-γ (PPAR-γ) in 3T3-L1 adipocytes, and inhibited the expression of fatty acid synthase (FAS) through AMP-activated protein kinase (AMPK). Meanwhile, BSP and MBP also increased the expression of the lipolysis-related proteins, uncoupling protein-1 (UCP-1) and carnitine palmitoyltransferase-1 (CPT-1). Moreover, MBP exerted anti-adipogenic to a greater extent than BSP in 3T3-L1 preadipocytes.

Analysis of Newborn Hearing Screening Results in South Korea after National Health Insurance Coverage: A Nationwide Population-Based Study.

Newborn hearing screening (NHS) has been covered by national health insurance since October 2018 in Korea. However, the results of the NHS are not reported due to the absence of a follow-up tracking system. This study analyzed the status and the predicted referral rates of NHS after the Korean national health insurance coverage by analyzing the National Health Insurance Service database in 2019 and 2020. The NHS coverage was 91.7% of total birth in 2019 and 92.1% in 2020. The predicted referral rate of NHS calculated by the duplicated NHS cases was 1.05% in 2019 and 0.99% in 2020. However, another predicted referral rate calculated by the number of diagnostic auditory brainstem responses (ABRs) performed was 1.44% in 2019 and 1.43% in 2020. The first NHS was performed within one day of birth for 96.5% of the babies and within three days of birth for 97%. However, diagnostic ABR was adequately performed within three months of birth for only 4.3%, while 82.3% performed the test after six months which delays appropriate intervention for hearing loss. National support such as national coordinators, follow-up tracking, and data management systems are needed for early hearing detection and intervention of newborns and infants in Korea.

Herbal Medicines for Post-Acute Sequelae (Fatigue or Cognitive Dysfunction) of SARS-CoV-2 Infection: A Phase 2 Pilot Clinical Study Protocol.

Long-term sequelae refer to persistent symptoms or signs for >6 months after SARS-CoV-2 infection. The most common symptoms of sequelae are fatigue and neuropsychiatric symptoms (concentration difficulty, amnesia, cognitive dysfunction, anxiety, and depression). However, approved treatments have not been fully established. Herbal medicines are administered for 12 weeks to patients who continuously complain of fatigue or cognitive dysfunction for >4 weeks that only occurred after COVID-19 diagnoses. Based on the Korean Medicine syndrome differentiation diagnosis, patients with fatigue will be administered Bojungikgi-tang or Kyungok-go, whereas those with cognitive dysfunction will be administered Cheonwangbosim-dan. Results could support evidence that herbal medicines may mitigate fatigue and cognitive dysfunction caused by COVID-19. Furthermore, by investigating the effects of herbal medicines on changes in metabolite and immune response due to COVID-19, which may be responsible for sequelae, the potential of herbal medicines as one of the therapeutic interventions for post-acute sequelae of SARS-CoV-2 infection can be evaluated. Therefore, the effects of herbal medicine on fatigue and cognitive dysfunction sequelae due to COVID-19 will be elucidated in this study to provide an insight into the preparation of medical management for the post-acute sequelae of SARS-CoV-2 infection.

Saam Acupuncture for Treating Functional Dyspepsia: A Feasibility Randomized Controlled Trial.

Objective: Functional dyspepsia (FD) is a common gastrointestinal disorder that significantly affects sufferers' quality of life and increases the economic burden on society. Saam acupuncture, a form of traditional Korean acupuncture, is frequently used to treat FD in Korean medicine clinical settings. This study aimed to evaluate the feasibility and preliminary effectiveness and safety of Saam acupuncture for treating FD. Methods: We conducted a pilot, pragmatic, assessor-blinded randomized controlled trial. Patients with FD according to the ROME III criteria were randomly allocated to an acupuncture plus usual care group or a usual care group. Saam acupuncture based on individualized FD and systemic symptoms was conducted in the acupuncture group three times per week for 4 weeks. Study feasibility outcomes, including recruitment, completion, and acupuncture adherence rates, were calculated. In addition, preliminary evaluation of participant responses to the intervention was tested using the gastrointestinal symptom (GIS), FD-related quality of life (FD-QoL), visual analog scale (VAS), patient global assessment (PGA), and EuroQol-5 Dimensions (EQ-5D) scores. Results: Twenty-four participants who met the eligibility criteria were included. The recruitment and completion rates of the clinical trials were 60% and 79.2%, and the acupuncture adherence rate was 83.3%. Although there was no significant difference between the two groups in the dyspepsia symptoms as measured by GIS, VAS, and PGA at Week 4, significant differences were found between the two groups at the follow-up assessments (Weeks 8 and 12). In particular, the early satiety subscore of GIS was significantly improved in the Saam acupuncture group compared with the usual care group at Week 4. The quality of life measured by FD-QoL and EQ-5D improved only in the Saam acupuncture group, although there were no significant differences between the two groups. No adverse events related to Saam acupuncture were reported. Conclusions: Saam acupuncture can be a feasible, preliminarily effective, and safe treatment for FD. Further confirmatory trials with a larger sample size are needed to confirm its effectiveness and safety. The trail is registered with CRIS-KCT0000164, URL: https://cris.nih.go.kr/cris/search/detailSearch.do/2098.

[Effect of Auriculotherapy on Musculoskeletal Pain: A Systematic Review and Meta-Analysis].

PURPOSE: The aim of this study was to evaluate the effect of auriculotherapy on musculoskeletal pain in adults. METHODS: A total of 885 studies were retrieved from nine databases (PubMed, Scopus, CINAHL, Web of Science, Ovid Medline, Cochrane Library, RISS, KMbase, and KISS). Sixteen studies were selected for meta-analysis, which satisfied the inclusion criteria and the evaluation of risk of bias. Demographic data, auriculotherapy types, intervention characteristics, auricular points, and outcomes related to pain (subjective pain scale, and amount of analgesic) were extracted from all included studies. The effect size of auriculotherapy was analyzed through comprehensive meta analysis 3.0, and the presence of publication bias was analyzed through a funnel plot and Egger's regression. RESULTS: The results of the meta-analysis (n = 16) revealed that the auriculotherapy was significantly superior to the control group on present pain in adults (Hedges' g = -0.35, 95% Confidence Interval [CI] = -0.55~-0.15). According to the results of subgroup analysis, the effect size of auricular acupuncture therapy (Hedges' g = 0.45, 95% CI = -0.75~-0.15) was higher than the auricular acupuncture (Hedges' g = 0.27, 95% CI = -0.53~0.00): the longer the intervention period, the greater the effect size. CONCLUSION: In this study, auriculotherapy demonstrates a significant reduction in musculoskeletal pain in adults. Therefore, it is necessary to refine the curriculum to include auriculotherapy as a nursing intervention to relieve musculoskeletal pain in adults and encourage its use in clinical settings.

Treatment with Light-Emitting Diodes of Wavelength 863 nm Delays DMBA/TPA-Induced Skin Tumor Formation and Decreases Proinflammatory Cytokine Levels in ICR Mice.

The popularity of light/energy devices for cosmetic purposes (e.g., skin care) is increasing. However, the effects and underlying mechanisms remain poorly understood. Commencing in the 1960s, various studies have evaluated the beneficial effects of a light source on cells and tissues. The techniques evaluated include low-level light (laser) therapy and photobiomodulation (PBM). Most studies on PBM used red light sources, but, recently, many studies have employed near-infrared light sources including those of wavelength 800 nm. Here, we used a light-emitting diode (LED) array with a wavelength of 863 nm to treat DMBA/TPA-induced mouse skin tumors; treatment with the array delayed tumor development and reduced the levels of systemic inflammatory cytokines. These results suggest that light therapy could be beneficial. However, the effects were small. Further studies on different skin tumors using an optimized LED setup are required. Combination therapies (conventional methods and an LED array) may be useful.

Regulation of Cytokines and Dihydrotestosterone Production in Human Hair Follicle Papilla Cells by Supercritical Extraction-Residues Extract of Ulmus davidiana.

This study was conducted to examine the anti-hair loss mechanism of the supercritical fluid extraction-residues extract of Ulmus davidiana by the regulation of cytokine production and hormone function in human dermal follicle papilla cells (HDFPCs). To investigate the modulatory effects on H2O2-induced cytokines, we measured transforming growth factor-beta and insulin-like growth factor 1 secreted from HDFPCs. To investigate the regulatory effects of supercritical extraction-residues extract of Ulmus davidiana on dihydrotestosterone hormone production, cells were co-incubated with high concentrations of testosterone. The supercritical extraction-residues extract of Ulmus davidiana significantly inhibited the secretion of transforming growth factor-beta but rescued insulin-like growth factor 1 in a dose-dependent manner. The supercritical extraction-residues extract of Ulmus davidiana markedly reduced dihydrotestosterone production. These results suggest that the supercritical fluid extract residues of Ulmus davidiana and their functional molecules are candidates for preventing human hair loss.

Sophorolipid protects against early-weaning syndrome by improving the gut microenvironment in early-weaned piglets.

BACKGROUND: In animals, weaning stress is the first and most critical stress. Weaning can negatively affect the growth performance of animals physically, psychologically, and pathologically. Our previous studies on the HT-29 cell line and early-weaned rats demonstrated that adequate sophorolipid (SPL) supplementation in feed could enhance the mucin-producing and wound healing capacities of the gut defense system by modulating gut microbiota. METHODS: We conducted an experiment with one hundred forty 21-day-old early weaned piglets (L x Y x D). They were allocated into 4 treatment and 7 replications (4 pigs per pen) according to their initial body weight. Body weight and feed intake were measured biweekly during experimental period. After 6 weeks, 28 pigs were randomly selected and sacrificed to collect plasma, jejunum, and cecal content samples. RESULTS: Dietary SPL supplementation at 5 and 10 mg/kg quadratically increased the average daily gain during the experimental period in the treatment groups when compared with the control group. The albumin levels of piglets fed with the SPL supplemented diet were downregulated to the normal range. Moreover, in feed, SPL supplementation at 5 and 10 mg/kg improved jejunal histological indices and gene expression levels related to mucin secretion and local inflammation markers. Consistent with these results, adequate SPL supplementation (5 and 10 mg/kg) increased the population of Prevotella, a beneficial bacterium, and its short-chain fatty acid production in the ceca of piglets. CONCLUSIONS: The occurrence of diarrhea after weaning in piglets could be reduced by feeding a 10 ppm of SPL supplemented diet which improves the gut defense system by improving the microbial population and enhancing mucin layer integrity.

Effect of the Gintonin-Enriched Fraction on Glucagon-Like-Protein-1 Release.

Ginseng-derived gintonin reportedly contains functional lysophosphatidic acids (LPAs) as LPA receptor ligands. The effect of the gintonin-enriched fraction (GEF) on in vitro and in vivo glucagon-like protein-1 (GLP-1) secretion, which is known to stimulate insulin secretion, via LPA receptor(s) remains unclear. Accordingly, we examined the effects of GEF on GLP-1 secretion using human enteroendocrine NCI-H716 cells. The expression of several of LPA receptor subtypes in NCI-H716 cells using qPCR and Western blotting was examined. LPA receptor subtype expression was in the following order: LPA6 > LPA2 > LPA4 > LPA5 > LPA1 (qPCR), and LPA6 > LPA4 > LPA2 > LPA1 > LPA3 > LPA5 (Western blotting). GEF-stimulated GLP-1 secretion occurred in a dose- and time-dependent manner, which was suppressed by cAMP-Rp, a cAMP antagonist, but not by U73122, a phospholipase C inhibitor. Furthermore, silencing the human LPA6 receptor attenuated GEF-mediated GLP-1 secretion. In mice, low-dose GEF (50 mg/kg, peroral) increased serum GLP-1 levels; this effect was not blocked by Ki16425 co-treatment. Our findings indicate that GEF-induced GLP-1 secretion could be achieved via LPA6 receptor activation through the cAMP pathway. Hence, GEF-induced GLP secretion via LPA6 receptor regulation might be responsible for its beneficial effects on human endocrine physiology.

Wound Healing Effect of Gintonin Involves Lysophosphatidic Acid Receptor/Vascular Endothelial Growth Factor Signaling Pathway in Keratinocytes.

Gintonin, a novel compound of ginseng, is a ligand of the lysophosphatidic acid (LPA) receptor. The in vitro and in vivo skin wound healing effects of gintonin remain unknown. Therefore, the objective of this study was to investigate the effects of gintonin on wound healing-linked responses, especially migration and proliferation, in skin keratinocytes HaCaT. In this study, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay, Boyden chamber migration assay, scratch wound healing assay, and Western blot assay were performed. A tail wound mouse model was used for the in vivo test. Gintonin increased proliferation, migration, and scratch closure in HaCaT cells. It also increased the release of vascular endothelial growth factor (VEGF) in HaCaT cells. However, these increases, induced by gintonin, were markedly blocked by treatment with Ki16425, an LPA inhibitor, PD98059, an ERK inhibitor, 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester), a calcium chelator, and U73122, a PLC inhibitor. The VEGF receptor inhibitor axitinib also attenuated gintonin-enhanced HaCaT cell proliferation. Gintonin increased the phosphorylation of AKT and ERK1/2 in HaCaT cells. In addition, gintonin improved tail wound healing in mice. These results indicate that gintonin may promote wound healing through LPA receptor activation and/or VEGF release-mediated downstream signaling pathways. Thus, gintonin could be a beneficial substance to facilitate skin wound healing.

Protective Effects of Gintonin on Reactive Oxygen Species-Induced HT22 Cell Damages: Involvement of LPA1 Receptor-BDNF-AKT Signaling Pathway.

Gintonin is a kind of ginseng-derived glycolipoprotein that acts as an exogenous LPA receptor ligand. Gintonin has in vitro and in vivo neuroprotective effects; however, little is known about the cellular mechanisms underlying the neuroprotection. In the present study, we aimed to clarify how gintonin attenuates iodoacetic acid (IAA)-induced oxidative stress. The mouse hippocampal cell line HT22 was used. Gintonin treatment significantly attenuated IAA-induced reactive oxygen species (ROS) overproduction, ATP depletion, and cell death. However, treatment with Ki16425, an LPA1/3 receptor antagonist, suppressed the neuroprotective effects of gintonin. Gintonin elicited [Ca2⁺]i transients in HT22 cells. Gintonin-mediated [Ca2⁺]i transients through the LPA1 receptor-PLC-IP3 signaling pathway were coupled to increase both the expression and release of BDNF. The released BDNF activated the TrkB receptor. Induction of TrkB phosphorylation was further linked to Akt activation. Phosphorylated Akt reduced IAA-induced oxidative stress and increased cell survival. Our results indicate that gintonin attenuated IAA-induced oxidative stress in neuronal cells by activating the LPA1 receptor-BDNF-TrkB-Akt signaling pathway. One of the gintonin-mediated neuroprotective effects may be achieved via anti-oxidative stress in nervous systems.

Vernicia fordii (Hemsl.) Airy Shaw extract stimulates insulin secretion in pancreatic ß-cells and improves insulin sensitivity in diabetic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Vernicia fordii (Hemsl.) Airy Shaw (V. fordii) is also known as the tung tree and its leaves and fruit are used as an oriental treatment for dyspepsia, edema, and skin diseases, which are known as diabetic complications. AIM OF THE STUDY: In this study, we aimed to investigate the methanolic extract (VF5) of the leaves of V. fordii as an insulin secretagogue and its probable mechanism and verify the effect in HFD-fed mice. MATERIALS AND METHODS: The insulin secretagogue activity of different doses of VF5 (0.1, 0.3 and 1.0 µg/ml) was assessed using in vitro insulin secretion assay and confirmed the anti-diabetic effect in mice fed HFD for 4 weeks with different doses of VF5 (10, 20 and 50 mg/kg oral) for another 6 weeks. Glbenclamide (30 mg/kg, oral) was used as positive control drug. The possible mechanisms were evaluated by using Gö6983 (10 µM), U73122 (10 µM) and nifedipine (10 µM). The major constituents of VF5 were analyzed by UPLC-QToF-MS and 1H and 13C NMR spectroscopy. RESULTS: UPLC-QToF-MS and NMR spectroscopy analysis indicated that one of the main active components of VF5 was tigliane-diterpene esters. VF5 functioned as an insulin secretagogue and enhanced mitochondria respiration and insulin homeostasis. We confirmed that VF5 preserved the ß-cell and reduced the ß-cell expansion which caused by metabolic stress under HFD. The antidiabetic role of VF5 in HFD fed mice was assessed by glucose tolerance test (GTT) and insulin tolerance test (ITT), fasting plasma insulin level, fasting blood glucose level, AKT signal in peripheral tissue in the absence of toxic effects. Mechanistically, insulinotropic effect of VF5 was mediated by activation of PKCα via intracellular Ca2+ influx and enhanced mitochondria function. CONCLUSION: VF5 exhibits potent insulin secretagogue function and improves insulin sensitivity and protection of pancreatic ß-cells from metabolic stress without toxicity. Taken together, our study suggests that VF5 could be potentially used for treating diabetes and metabolic diseases through improving ß-cell function.

Effects of Acupuncture on Lowering Blood Pressure in Postmenopausal Women with Prehypertension or Stage 1 Hypertension: A Propensity Score-Matched Analysis.

Postmenopausal women have a higher prevalence of hypertension compared to premenopausal women. Hypertension is a risk factor for cardiovascular diseases, the prevalence of which is ever increasing. This study investigated the effects of long-term acupuncture on lowering the blood pressure of postmenopausal women with prehypertension and stage 1 hypertension. Participants were 122 postmenopausal women aged less than 65 years, diagnosed with prehypertension or stage 1 hypertension (systolic blood pressure 120-159 mmHg or diastolic blood pressure 80-99 mmHg). We used a propensity score-matched design. The experimental group (n = 61) received acupuncture for four weeks every six months over a period of two years. The control group (n = 61) received no intervention. An Analysis of covariance (ANCOVA) was performed for the primary efficacy analysis. Relative risk ratios were used to compare group differences in treatment effects. Acupuncture significantly reduced the participants' diastolic blood pressure (-9.92 mmHg; p < 0.001) and systolic blood pressure (-10.34 mmHg; p < 0.001) from baseline to follow-up. The results indicate that acupuncture alleviates hypertension in postmenopausal women, reducing their risk of developing cardiovascular diseases and improving their health and quality of life.

Gintonin facilitates brain delivery of donepezil, a therapeutic drug for Alzheimer disease, through lysophosphatidic acid 1/3 and vascular endothelial growth factor receptors.

BACKGROUND: Gintonin is a ginseng-derived exogenous G-protein-coupled lysophosphatidic acid (LPA) receptor ligand, which exhibits in vitro and in vivo functions against Alzheimer disease (AD) through lysophosphatidic acid 1/3 receptors. A recent study demonstrated that systemic treatment with gintonin enhances paracellular permeability of the blood-brain barrier (BBB) through the LPA1/3 receptor. However, little is known about whether gintonin can enhance brain delivery of donepezil (DPZ) (Aricept), which is a representative cognition-improving drug used in AD clinics. In the present study, we examined whether systemic administration of gintonin can stimulate brain delivery of DPZ. METHODS: We administered gintonin and DPZ alone or coadministered gintonin with DPZ intravenously or orally to rats. Then we collected the cerebral spinal fluid (CSF) and serum and determined the DPZ concentration through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. RESULTS: Intravenous, but not oral, coadministration of gintonin with DPZ increased the CSF concentration of DPZ in a concentration- and time-dependent manner. Gintonin-mediated enhancement of brain delivery of DPZ was blocked by Ki16425, a LPA1/3 receptor antagonist. Coadministration of vascular endothelial growth factor (VEGF) + gintonin with DPZ similarly increased CSF DPZ concentration. However, gintonin-mediated enhancement of brain delivery of DPZ was blocked by axitinip, a VEGF receptor antagonist. Mannitol, a BBB disrupting agent that increases the BBB permeability, enhanced gintonin-mediated enhancement of brain delivery of DPZ. CONCLUSIONS: We found that intravenous, but not oral, coadministration of gintonin facilitates brain delivery of DPZ from plasma via LPA1/3 and VEGF receptors. Gintonin is a potential candidate as a ginseng-derived novel agent for the brain delivery of DPZ for treatment of patients with AD.

470 nm LED Irradiation Inhibits the Invasiveness of CD133-positive Human Colorectal Cancer Stem Cells by Suppressing the Cyclooxygenase-2/prostaglandin E2 Pathway.

BACKGROUND/AIM: Recurrence and metastasis of cancer caused by cancer stem cells (CSCs) is a challenge to overcome. Low level laser therapy is a new treatment strategy to suppress their invasiveness. We have assessed the inhibitory effects of 470 nm blue LED on the invasiveness of them to determine the molecular mechanisms of anti-invasiveness. MATERIALS AND METHODS: The effects of blue LEDs on their viability, proliferation and invasion were analyzed using MTT and transwell methods. In addition, the anti-invasiveness effect of blue LED on them was evaluated by zymography, semi-quantitative RT-PCR and western blot analysis. RESULTS: Irradiation with blue LED at 3 J/cm2 resulted in inhibition of their viability, proliferation and invasiveness. Their matrix metalloproteinase 2 (MMP-2) and MMP-9 activities were reduced by blue LED irradiation. Semi-quantitative RT-PCR also showed similar results. In addition, western blotting analyses showed that cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) synthesis were significantly inhibited by LED irradiation in CD133+ colorectal CSCs. CONCLUSION: Down-regulation of the COX-2/PGE2 signaling pathway by blue LED irradiation led to reduce expression of MMP-2 and MMP-9, inhibiting the invasiveness of CD133+ colorectal CSC.

A 60% Edible Ethanolic Extract of Ulmus davidiana Inhibits Vascular Endothelial Growth Factor-Induced Angiogenesis.

As abnormal angiogenesis is associated with exacerbation of various diseases, precise control over angiogenesis is imperative. Vascular endothelial growth factor (VEGF), the most well-known angiogenic factor, binds to VEGF receptor (VEGFR), activates various signaling pathways, and mediates angiogenesis. Therefore, blocking the VEGF-induced angiogenic response-related signaling pathways may alleviate various disease symptoms through inhibition of angiogenesis. Ulmus davidiana is a safe natural product that has been traditionally consumed, but its effects on endothelial cells (ECs) and the underlying mechanism of action are unclear. In the present study, we focused on the effect of a 60% edible ethanolic extract of U. davidiana (U60E) on angiogenesis. U60E inhibited the VEGF-mediated proliferation, tube formation, and migration ability of ECs. Mechanistically, U60E inhibited endothelial nitric oxide synthase activation and nitric oxide production by blocking the protein kinase B signaling pathway activated by VEGF and consequently inhibiting proliferation, tube formation, and migration of ECs. These results suggest that U60E could be a potential and safe therapeutic agent capable of suppressing proangiogenic diseases by inhibiting VEGF-induced angiogenesis.

Effects of Cirsium setidens (Dunn) Nakai on the osteogenic differentiation of stem cells.

Cirsium setidens (Dunn) Nakai, commonly known as gondre, is a perennial herb that grows predominantly in South Korea. It contains several bioactive phytochemicals with antioxidant, anti­cancer, anti­tumor and anti­inflammatory properties. The present study aimed to investigate the effects of methanolic extracts of gondre on osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). As characterized by nuclear magnetic resonance spectroscopy and matrix­assisted laser deposition/ionization (time­of­flight) mass spectrometry, the methanol extract of gondre was found to be enriched with pectolinarin. After 48 h, enhanced viability of hPDLSCs was observed in the presence of gondre compared with under control conditions, suggesting the biocompatibility of gondre. Notably, biocompatibility was markedly affected by gondre concentration in cultured media. Relatively high cell viability was observed in medium containing 0.05% gondre. Furthermore, mineralization was significantly higher in hPDLSCs in the presence of gondre compared with that in control cells, indicating their mineralization potential. Increased expression of various transcription markers, such as collagen 1, runt­related transcription factor 2, bone sialoprotein and alkaline phosphatase, was also detected when hPDLSCs were stimulated with gondre compared with in the control groups, further confirming the superior osteogenic potential of gondre extract for tissue engineering applications, particularly in bone tissues.