Improvement in Yield of Extracellular Vesicles Derived from Edelweiss Callus Treated with LED Light and Enhancement of Skin Anti-Aging Indicators.

The process of skin aging is currently recognized as a disease, and extracellular vesicles (EVs) are being used to care for it. While various EVs are present in the market, there is a growing need for research on improving skin conditions through microbial and plant-derived EVs. Edelweiss is a medicinal plant and is currently an endangered species. Callus culture is a method used to protect rare medicinal plants, and recently, research on EVs using callus culture has been underway. In this study, the researchers used LED light to increase the productivity of Edelweiss EVs and confirmed that productivity was enhanced by LED exposure. Additionally, improvements in skin anti-aging indicators were observed. Notably, M-LED significantly elevated callus fresh and dry weight, with a DW/FW ratio of 4.11%, indicating enhanced proliferation. Furthermore, M-LED boosted secondary metabolite production, including a 20% increase in total flavonoids and phenolics. The study explores the influence of M-LED on EV production, revealing a 2.6-fold increase in concentration compared to darkness. This effect is consistent across different plant species (Centella asiatica, Panax ginseng), demonstrating the universality of the phenomenon. M-LED-treated EVs exhibit a concentration-dependent inhibition of reactive oxygen species (ROS) production, surpassing dark-cultured EVs. Extracellular melanin content analysis reveals M-LED-cultured EVs' efficacy in reducing melanin production. Additionally, the expression of key skin proteins (FLG, AQP3, COL1) is significantly higher in fibroblasts treated with M-LED-cultured EVs. These results are expected to provide valuable insights into research on improving the productivity of plant-derived EVs and enhancing skin treatment using plant-derived EVs.

The Effectiveness and Safety of Nurse-Led Auricular Acupressure on Chemotherapy-Induced Peripheral Neuropathy Among Patients With Breast Cancer: A Randomized, Double-Blind, Sham-Controlled Trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a major symptom of distress among chemotherapy-treated cancer survivors. Although various interventions have been attempted, there is no criterion-standard treatment. OBJECTIVE: The aim of this study was to examine the efficacy and safety of auricular acupressure (AA) in improving peripheral neuropathy symptoms in breast cancer patients undergoing taxane-based treatment. METHODS: A total of 51 eligible participants were enrolled and randomly allocated (1:1) to AA or sham control groups. The intervention was performed weekly for 3 weeks using different ear points, depending on the group. The Total Neuropathy Score was used to measure CIPN objectively. The Numerical Rating Scale and the European Organization for Research and Treatment of Cancer Quality of Life Chemotherapy-Induced Peripheral Neuropathy-20 were used to measure the subjective symptoms of CIPN. Outcomes were compared between groups by time interaction using generalized estimating equations based on the intention-to-treat principle. RESULTS: Only 1 participant dropped out because of nausea and mild fever. The results of generalized estimating equations showed significant improvement in Numerical Rating Scale scores on the hands and feet and total Chemotherapy-Induced Peripheral Neuropathy-20 in the experimental group compared with the sham control group (all Ps < .05). Although the experimental group showed a greater reduction in Total Neuropathy Score scores than the sham control group, no significant differences were found. CONCLUSION: Auricular acupressure is an effective and safe nurse-led intervention for managing CIPN symptoms in breast cancer patients. IMPLICATIONS FOR PRACTICE: The findings help nurses to integrate AA easily and usefully into nursing care, contributing to managing symptoms of CIPN in cancer patients and survivors.

Wound Healing-Promoting and Melanogenesis-Inhibiting Activities of Angelica polymorpha Maxim. Flower Absolute In Vitro and Its Chemical Composition.

Angelica polymorpha Maxim. (APM) is used in traditional medicine to treat chronic gastritis, rheumatic pain, and duodenal bulbar ulcers. However, it is not known whether APM has epidermis-associated biological activities. Here, we investigated the effects of APM flower absolute (APMFAb) on responses associated with skin wound healing and whitening using epidermal cells. APMFAb was obtained by solvent extraction and its composition was analyzed by GC/MS. Water-soluble tetrazolium salt, 5-bromo-2'-deoxyuridine incorporation, Boyden chamber, sprouting, and enzyme-linked immunosorbent assays and immunoblotting were used to examine the effects of APMFAb on HaCaT keratinocytes and B16BL6 melanoma cells. APMFAb contained five compounds and induced keratinocyte migration, proliferation, and type IV collagen synthesis. APMFAb also induced the phosphorylations of ERK1/2, JNK, p38 mitogen-activated protein kinase, and AKT in keratinocytes. In addition, APMFAb decreased serum-induced B16BL6 cell proliferation and inhibited tyrosinase expression, melanin contents, and microphthalmia-associated transcription factor expression in α-melanocyte-stimulating hormone-stimulated B16BL6 cells. These findings demonstrate that APMFAb has beneficial effects on skin wound healing by promoting the proliferation, migration, and collagen synthesis of keratinocytes and on skin whitening by inhibiting melanin synthesis in melanoma cells. Therefore, we suggest that APMFAb has potential use as a wound healing and skin whitening agent.

A Clinical Trial to Evaluate the Efficacy of α-Viniferin in Staphylococcus aureus - Specific Decolonization without Depleting the Normal Microbiota of Nares.

Staphylococcus aureus is currently a significant multidrug-resistant bacterium, causing severe healthcare-associated and community-acquired infections worldwide. The current antibiotic regimen against this pathogen is becoming ineffective due to resistance, in addition, they disrupt the normal microbiota. It highlights the urgent need for a pathogen-specific drug with high antibacterial efficacy against S. aureus. α-Viniferin, a bioactive phytochemical compound, has been reported to have excellent anti-Staphylococcus efficacy as a topical agent. However, so far, there were no clinical trials that have been conducted to elucidate its efficacy. The present study aimed to investigate the antibacterial efficacy of α-viniferin against S. aureus in a ten-day clinical trial. Based on the results, α-viniferin showed 50% minimum inhibitory concentrations (MIC50 values) of 7.8 µg/ml in culture broth medium. α-Viniferin was administered in the nares three times a day for ten days using a sterile cotton swab stick. Nasal swab specimens were collected before (0 days) and after finishing the trial (10th day), and then analyzed. In the culture and RT-PCR-based analysis, S. ureus was reduced significantly: 0.01. In addition, 16S ribosomal RNA-based amplicon sequencing analysis showed that S. aureus reduced from 51.03% to 23.99% at the genus level. RNA-seq analysis was also done to gain insights into molecular mechanisms of α-viniferin against S. aureus, which revealed that some gene groups were reduced in 5-fold FC cutoff at two times MIC conditions. The study results demonstrate α-viniferin as a potential S. aureus-specific drug candidate.

Efficacy and safety of auricular acupressure for chemotherapy-induced peripheral neuropathy among patients with breast cancer: a study protocol for a randomized controlled trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequently-reported distress symptom in breast carcinoma patients under chemotherapy. Although previous studies emphasized lack of ideal neuroprotective or therapeutic agents for CIPN, there are no strongly recommended treatments. Nevertheless, auricular acupressure (AA) is a novel remedy for controlling symptoms in many healthcare settings. However, therapeutic effects of AA among patients with CIPN have not yet been elucidated fully. Therefore, we designed a trial to examine the effectiveness and safety of AA in breast cancer patients. METHODS: This randomized, double-blind, sham-controlled trial will assess 120 breast cancer survivors. After enrollment, the participants will be stratified depending on administration of medications prescribed for CIPN treatment, and then assigned randomly to the experimental or control groups in an allocation ratio of 1:1. For experimental groups, AA will be applied on four points, namely, shemen, liver, spleen, and finger/toe, while for the control groups, sham AA will be exerted on other four points that are remote from the treatment points and unrelated to neuropathic symptoms. All participants will undergo the same acupressure procedure, for two minutes each time, thrice daily for 3 weeks, and CIPN symptoms and health-related quality of life will be assessed by a blinded research assistant and a physician before, during, immediately after, and 4 weeks after AA. Occurrence, type, and severity of safety issues will be routinely monitored to confirm the non-toxic nature of AA. Repeated measures analysis of variance will be used to examine the changing pattern of CIPN symptoms and based on sensitivity analysis. DISCUSSION: It is expected that the rationale and design of this protocol will offer knowledge regarding a standardized process to guide current and future studies and accumulates clinical experiences in applying non-pharmacological intervention. The present trial is the first to examine the therapeutic effects of AA in breast cancer patients with CIPN. The findings of the study may provide convincing evidence regarding the effectiveness of CIPN symptoms. TRIAL REGISTRAION: Clinical Research Information Service, Republic of Korea, ID: KCT0004930. Registered retrospectively on April 14, 2020.

Behaviors and Attitudes toward the Use of Complementary and Alternative Medicine among Korean Cancer Patients.

PURPOSE: A cross-sectional survey was conducted to explore the current awareness and use of complementary and alternative medicine (CAM), as well as attitudes toward CAM, in patients with cancer and their family members in South Korea. MATERIALS AND METHODS: Between September 21 and October 31, 2017, a 25-item questionnaire regarding CAM experiences among cancer patients and their family members was conducted in 10 oncology clinics in South Korea after institutional review board approval at each institution. RESULTS: In total, 283/310 patients were analyzed. The median age was 60 years, and 60% were male. Most of the patients were actively receiving anticancer treatment at the time of the survey. A total of 106 patients (37%) had experienced a median of two types (interquartile range, 1 to 3) of CAM. Belief in CAM (odds ratio [OR], 3.015; 95% confidence interval [CI], 1.611 to 5.640) and duration of disease (OR, 1.012; 95% CI, 1.004 to 1.020) were independent factors for using CAM in multivariable analysis. Belief in CAM was significantly associated with current use of CAM (OR, 3.633; 95% CI, 1.567 to 8.424). Lay referral was the most common reason for deciding to use CAM, and only 25% of patients (72/283) discussed CAM with their physicians. CONCLUSION: Patient attitudes toward and confidence in CAM modalities were strongly associated with their CAM experiences, and only a small number of patients had an open discussion about CAM with their physicians. A patient education program for CAM is needed.

C/N/O/S stable isotopic and chemometric analyses for determining the geographical origin of Panax ginseng cultivated in Korea.

BACKGROUND: The geographical origin of Panax ginseng Meyer, a valuable medicinal plant, is important to both ginseng producers and consumers in the context of economic profit and human health benefits. We, therefore, aimed to discriminate between the cultivation regions of ginseng using the stable isotope ratios of C, N, O, and S, which are abundant bioelements in living organisms. METHODS: Six Korean ginseng cultivars (3-yr-old roots) were collected from five different regions in Korea. The C, N, O, and S stable isotope ratios in ginseng roots were measured by isotope ratio mass spectrometry, and then these isotope ratio profiles were statistically analyzed using chemometrics. RESULTS: The various isotope ratios found in P. ginseng roots were significantly influenced by region, cultivar, and the interactions between these two factors (p ≤ 0.001). The variation in δ15N and δ13C in ginseng roots was significant for discriminating between different ginseng cultivation regions, and δ18O and δ34S were also affected by both altitude and proximity to coastal areas. Chemometric model results tested in this study provided discrimination between the majority of different cultivation regions. Based on the external validation, this chemometric model also showed good model performance (R 2 = 0.853 and Q 2 = 0.738). CONCLUSION: Our case study elucidates the variation of C, N, O, and S stable isotope ratios in ginseng root depending on cultivation region. Hence, the analysis of stable isotope ratios is a suitable tool for discrimination between the regional origins of ginseng samples from Korea, with potential application to other countries.

The evaluation of changes in peripheral neuropathy and quality-of-life using low-frequency electrostimulation in patients treated with chemotherapy for breast cancer: a study protocol.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a progressive, enduring, and sometimes irreversible neurotoxic symptom that occurs in 30-40% of chemotherapy-treated cancer patients. CIPN negatively affects both the patient's abilities to perform daily activities and their health-related quality of life (HRQOL) after chemotherapy treatment. Although this neuropathy has been treated with duloxetine and/or gabapentin, limited therapeutic benefits have been reported, thereby necessitating the development of an integrated approach that combines pharmacological management and complementary methods such as acupuncture and electric nerve stimulation. Therefore, this study is designed to examine the effect of a portable, low-frequency electrostimulation (ES) device on CIPN symptoms and HRQOL of female patients diagnosed with CIPN immediately after chemotherapy for breast cancer. METHODS: This study is a single-center, randomized, placebo-controlled trial with two parallel groups and a 2-week follow-up. We will enroll 80 breast cancer patients who are newly diagnosed with CIPN after chemotherapy. Duloxetine or pregabalin will be prescribed to all participants from the initial assessment. Half of the patients will be assigned into the experimental group and the other half to the control group. The CarebandR (Piomed Inc., Seoul, Korea), a wearable wristband that generates low-frequency electrostimulation, will be administered only to the experimental group. Electrostimulation will be administered on the unilateral PC6 acupoint. A numerical rating scale will be used to assess the overall intensity of CIPN symptoms. The key secondary outcome variables include patient-reported CIPN symptom distress tested by a self-rated questionnaire, physician-rated symptom severity assessed by the Total Neuropathy Score, and HRQOL. DISCUSSION: It is expected that the combination of a low-frequency electrostimulation device and pharmacological intervention (duloxetine or pregabalin) will produce synergistic effects in breast cancer patients with CIPN after treatment. To our knowledge, this is the first study to investigate the beneficial effect of a new integrated approach for CIPN management after breast cancer treatment. The study findings can expand our knowledge and understanding of the occurrence of CIPN and the efficacy of integrated intervention efforts to ameliorate CIPN symptoms. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), Republic of Korea, ID: KCT0002357 . Registered retrospectively on 13 June 2017.

Deep Learning-Based Survival Analysis Identified Associations Between Molecular Subtype and Optimal Adjuvant Treatment of Patients With Gastric Cancer.

PURPOSE: Gastric cancer (GC) is the third-leading cause of cancer-related deaths. Several pivotal clinical trials of adjuvant treatments were performed during the previous decade; however, the optimal regimen for adjuvant treatment of GC remains controversial. PATIENTS AND METHODS: We developed a novel deep learning-based survival model (survival recurrent network [SRN]) in patients with GC by including all available clinical and pathologic data and treatment regimens. This model uses time-sequential data only in the training step, and upon being trained, it receives the initial data from the first visit and then sequentially predicts the outcome at each time point until it reaches 5 years. In total, 1,190 patients from three cohorts (the Asian Cancer Research Group cohort, n = 300; the fluorouracil, leucovorin, and radiotherapy cohort, n = 432; and the Adjuvant Chemoradiation Therapy in Stomach Cancer cohort, n = 458) were included in the analysis. In addition, we added Asian Cancer Research Group molecular classifications into the prediction model. SRN simulated the sequential learning process of clinicians in the outpatient clinic using a recurrent neural network and time-sequential outcome data. RESULTS: The mean area under the receiver operating characteristics curve was 0.92 ± 0.049 at the fifth year. The SRN demonstrated that GC with a mesenchymal subtype should elicit a more risk-adapted postoperative treatment strategy as a result of its high recurrence rate. In addition, the SRN found that GCs with microsatellite instability and GCs of the papillary type exhibited significantly more favorable survival outcomes after capecitabine plus cisplatin chemotherapy alone. CONCLUSION: Our SRN predicted survival at a high rate, reaching 92% at postoperative year 5. Our findings suggest that SRN-based clinical trials or risk-adapted adjuvant trials could be considered for patients with GC to investigate more individualized adjuvant treatments after curative gastrectomy.

Identification and quantification of flavonoids in yellow grain mutant of rice (Oryza sativa L.).

Flavonoids are naturally occurring phenolic compounds with potential health-promoting activities. Although anthocyanins and phenolic acids in coloured rice have been investigated, few studies have focused on flavonoids. Herein, we analysed flavonoids in a yellow grain rice mutant using UHPLC-DAD-ESI-Q-TOF-MS, and identified 19 flavonoids by comparing retention times and accurate mass measurements. Among them, six flavonoids, isoorientin, isoorientin 2″-O-glucoside, vitexin 2″-O-glucoside, isovitexin, isoscoparin 2″-O-glucoside and isoscoparin, were isolated and fully identified from the yellow grain rice mutant, and the levels were significantly higher than wild-type, with isoorientin particularly abundant in mutant embryo. Significant differences in total phenolic compounds and antioxidant activity were observed in mutant rice by DPPH, FRAP and TEAC assays. The results suggest that the representative six flavonoids may play an important role in colouration and antioxidant activity of embryo and endosperm tissue. The findings provide insight into flavonoid biosynthesis and the possibility of improving functionality in rice.

Extremely low-frequency electromagnetic field induces neural differentiation of hBM-MSCs through regulation of (Zn)-metallothionein-3.

Extremely low-frequency electromagnetic field (ELFEMF) can stimulate neural differentiation in human bone marrow-derived mesenchymal cells (hBM-MSCs), and this provides an opportunity for research on neurodegenerative diseases such as Alzheimer's disease (AD). Metallothionein-3 (MT3), an isoform of the metal-binding proteins, metallothioneins, involved in maintaining intracellular zinc (Zn) homeostasis and the deregulation of zinc homeostasis, has separately been implicated in AD. Here, we investigated the effect of ELFEMF-induced neural differentiation of hBM-MSCs on Zn-MT3 homeostatic interaction. Exposure to ELFEMF induced neural differentiation of hBM-MSCs, which was characterized by decreased proliferation and enhanced neural-like morphology. We observed expression of neuronal markers such as ß-tubulin3, pleiotrophin, and neurofilament-M at the mRNA level and MAP2 at the protein level. ELFEMF-induced neural differentiation correlated with decreased expression of metal-response element-transcription factor 1 and MT3, as well as decreased intracellular Zn concentration. In addition, upregulation of dihydropyrimidinase-related protein 2 was observed, but there was no change in γ-enolase expression. These data indicate a possible regulatory mechanism for MT3 during neural differentiation. Our findings provide considerable insight into molecular mechanisms involved in neural differentiation, which is useful for developing new treatments for neurodegenerative diseases. Bioelectromagnetics. 38:364-373, 2017. © 2017 Wiley Periodicals, Inc.

Overexpression of Panax ginseng sesquiterpene synthase gene confers tolerance against Pseudomonas syringae pv. tomato in Arabidopsis thaliana.

Sesquiterpenes are an abundant group belonging to the terpenoid family, with a C15 structure comprise of three isoprene units. Many sesquiterpenes are volatile compounds and it act as chemical messenger in plant signalling, particularly in the defense mechanism against biotic and abiotic stresses. Panax ginseng Meyer is important medicinal herbs with various reported pharmacological efficacies in which its triterpenoid saponins, called ginsenosides, were mostly studied. However, there have been few studies on volatile sesquiterpenes compounds regulation on P. ginseng. As slow-growing perennial plant, P. ginseng received many kind of stresses during its cultivation. The pathogen attack is one of the most devastated perturbation for ginseng yield. Thus, we aimed to analyze P. ginseng STS gene (PgSTS) expressions in ginseng organs as well as mono-, sesquiterpenes contents from ginseng seedlings treated with elicitors. qRT-PCR and GC-MS analysis showed that two elicitors- salicylic acid (SA) and methyl jasmonate (MeJA) triggered PgSTS expression at different time points and significantly induced mono-, sesquiterpene yield. Overexpression of PgSTS in Arabidopsis also induced high terpene content and conferred tolerance against Pseudomonas syringae pv. tomato infection. These results suggested that PgSTS transcripts are involved in terpenoid biosynthesis in response to environmental stress mediated by MeJA and SA elicitors; thus, generate tolerance against pathogen attack.

Novel Methods to Generate Active Ingredients-Enriched Ashwagandha Leaves and Extracts.

Ashwagandha (Withania somnifera) is an Ayurvedic herb commonly used in world-renowned traditional Indian home medicine system. Roots of Ashwagandha have been traditionally known to possess a variety of therapeutic and health promoting potentials that have not been sufficiently supported by laboratory studies. Nevertheless, most, if not all, of the preventive and therapeutic potentials have been assigned to its bioactive components, steroidal alkaloids and lactones. In contrast to the traditional use of roots, we have been exploring bioactivities in leaves of Ashwagandha. Here, we report that the leaves possess higher content of active Withanolides, Withaferin-A (Wi-A) and Withanone (Wi-N), as compared to the roots. We also established, for the first time, hydroponic cultivation of Ashwagandha and investigated the effect of various cultivation conditions on the content of Wi-A and Wi-N by chemical analysis and bioassays. We report that the Withanone/Withaferin A-rich leaves could be obtained by manipulating light condition during hydroponic cultivation. Furthermore, we recruited cyclodextrins to prepare extracts with desired ratio of Wi-N and Wi-A. Hydroponically grown Ashwagandha and its extracts with high ratio of withanolides are valuable for cancer treatment.

Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX.

PURPOSE: Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients. MATERIALS AND METHODS: Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells. RESULTS: Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, -42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly. CONCLUSION: Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly.

GPR30 mediates anorectic estrogen-induced STAT3 signaling in the hypothalamus.

OBJECTIVE: Estrogen plays an important role in the control of energy balance in the hypothalamus. Leptin-independent STAT3 activation (i.e., tyrosine(705)-phosphorylation of STAT3, pSTAT3) in the hypothalamus is hypothesized as the primary mechanism of the estrogen-induced anorexic response. However, the type of estrogen receptor that mediates this regulation is unknown. We investigated the role of the G protein-coupled receptor 30 (GPR30) in estradiol (E2)-induced STAT3 activation in the hypothalamus. MATERIALS/METHODS: Regulation of STAT3 activation by E2, G-1, a specific agonist of GPR30 and G-15, a specific antagonist of GPR30 was analyzed in vitro and in vivo. Effect of GPR30 activation on eating behavior was analyzed in vivo. RESULTS: E2 stimulated pSTAT3 in cells expressing GPR30, but not expressing estrogen receptor ERα and ERß. G-1 induced pSTAT3, and G-15 inhibited E2-induced pSTAT3 in primary cultures of hypothalamic neurons. A cerebroventricular injection of G-1 increased pSTAT3 in the arcuate nucleus of mice, which was associated with a decrease in food intake and body weight gain. CONCLUSIONS: These results suggest that GPR30 is the estrogen receptor that mediates the anorectic effect of estrogen through the STAT3 pathway in the hypothalamus.

Aliphatic ß-nitroalcohols for therapeutic corneoscleral cross-linking: corneal permeability considerations.

PURPOSE: Our recent tissue cross-linking studies have raised the possibility of using aliphatic ß-nitroalcohols (BNAs) for pharmacologic, therapeutic corneal cross-linking. The present study was performed to determine the permeability of BNAs and to explore the use of permeability-enhancing agents. METHODS: Ex vivo rabbit corneas were mounted in a typical Franz diffusion chamber. BNA permeability was determined by assaying the recipient chamber over time using a modification of the Griess nitrite colorimetric assay. The apparent permeability coefficient (Ptot) was determined for 2 mono-nitroalcohols [2-nitroethanol (2ne) and 2-nitro-1-propanol (2nprop)], a nitrodiol [2-methyl-2-nitro-1,3-propanediol (MNPD)], and a nitrotriol [2-hydroxymethyl-2-nitro-1,3-propanediol (HNPD)]. Permeability-enhancing effects using benzalkonium chloride (BAC) (0.01% and 0.02%), ethylenediaminetetraacetic acid (0.05%), and a combination of 0.01% BAC + 0.5% tetracaine were also studied. RESULTS: The Ptot (±SE) values (in centimeters per second) were as follows: 4.33 × 10 (±9.82 × 10) for 2ne [molecular weight (MW) = 91 Da], 9.34 × 10 (±2.16 × 10) for 2nprop (MW = 105 Da), 4.37 × 10 (±1.86 × 10) for MNPD (MW = 135 Da), and 8.95 × 10 (±1.93 × 10) for HNPD (MW = 151 Da). Using the nitrodiol, permeability increased approximately 2-fold using 0.01% BAC, 5-fold using 0.02% BAC, and 5-fold using the combination of 0.01% BAC + 0.5% tetracaine. No effect was observed using 0.05% ethylenediaminetetraacetic acid. CONCLUSIONS: The results indicate that the corneal epithelium is permeable to BNAs, with the apparent permeability corresponding to MW. The findings are consistent with previous literature indicating that the small size of these compounds (<10Å) favors their passage through the corneal epithelium via the paracellular route. This information will help to guide dosing regimens for in vivo topical cross-linking studies.

Effects of berberine on hippocampal neuronal damage and matrix metalloproteinase-9 activity following transient global cerebral ischemia.

Berberine, an isoquinoline alkaloid with a long history of use in Chinese medicine, has several important pharmacological effects. Several studies have revealed that berberine has neuroprotective and neuropsychiatric effects. However, there are few reports regarding the protective effect of berberine against neuronal damage following transient global cerebral ischemia. In this study, mice were subjected to 20 min of global brain ischemia and sacrificed 72 hr later. Berberine was administered for 7 days prior to ischemia and daily until sacrifice. Mice treated with berberine showed reduced matrix metalloproteinase-9 (MMP-9) activity. Berberine inhibited gelatinase activity directly in in situ zymography and reduced neuronal damage following global ischemia. Laminin expression and NeuN expression were markedly reduced in CA1 and CA2 areas after ischemia, and berberine reduced the laminin degradation and neuronal loss. In the TUNEL assay, damaged neurons were also apparent in the CA1 and CA2 areas, and berberine reduced TUNEL-positive cells. These data demonstrate that berberine, a plant alkaloid, may protect from hippocampal neuronal damage following transient global ischemia by reducing MMP-9 activity.

Nutritional status of vitamin D and the effect of vitamin D supplementation in Korean breast-fed infants.

We investigated the vitamin D status and the effect of vitamin D supplementation in Korean breast-fed infants. The healthy term newborns were divided into 3 groups; A, formula-fed; B, breast-fed only; S, breast-fed with vitamin D supplementation. We measured serum concentrations of vitamin D (25OHD3), calcium (Ca), phosphorus (P), alkaline phosphatase (AP), intact parathyroid hormone (iPTH) and bone mineral density (BMD) at 6 and 12 months of age. Using questionnaires, average duration of sun-light exposure and dietary intake of vitamin D, Ca and P were obtained. At 6 and 12 months of age, 25OHD3 was significantly higher in group S than in group B (P<0.001). iPTH was significantly lower in group S than in group B at 6 months (P=0.001), but did not differ at 12 months. Regardless of vitamin D supplementation, BMD was lower in group B and S than in group A (P<0.05). Total intake of vitamin D differed among 3 groups (P<0.001, A>S>B), but total intake of Ca and P were higher in group A than in group B and S (P<0.001). In conclusion, breast-fed infants show lower vitamin D status and bone mineralization than formula-fed infants. Vitamin D supplementation (200 IU/day) in breast-fed infants increases serum 25-OH vitamin D(3), but not bone mineral density.

Effect of ionizing radiation on the physiological activities of ethanol extract from hizikia fusiformis cooking drips.

Although the byproduct from Hizikia fusiformis industry had many nutrients, it is being wasted. In this study, the physiological activities of cooking drip extracts from H. fusiformis (CDHF) were determined to investigate the effect of a gamma and an electron beam irradiations. DPPH radical scavenging activity and tyrosinase and ACE inhibition effects of the gamma and electron beam irradiated CDHF extracts were increased with increasing irradiation dose. These were reasoned by the increase in the content of the total polyphenolic compound of CDHF by the gamma and electron beam irradiation. There were no differences for the radiation types. These results show that ionizing radiation could be used for enhancing the functional activity of CDHF which is a major by-product in Hizikia fusiformis processing, in various applications.