Protective Effects of Hemp (Cannabis sativa) Root Extracts against Insulin-Deficient Diabetes Mellitus In Mice.

The pharmacological potential of industrial hemp (Cannabis sativa) has been widely studied. However, the majority of studies have focused on cannabidiol, isolated from the inflorescence and leaf of the plant. In the present study, we evaluated the anti-diabetic potential of hemp root water (HWE) and ethanol extracts (HEE) in streptozotocin (STZ)-induced insulin-deficient diabetic mice. The administration of HWE and HEE ameliorated hyperglycemia and improved glucose homeostasis and islet function in STZ-treated mice (p < 0.05). HWE and HEE suppressed ß-cell apoptosis and cytokine-induced inflammatory signaling in the pancreas (p < 0.05). Moreover, HWE and HEE normalized insulin-signaling defects in skeletal muscles and apoptotic response in the liver and kidney induced by STZ (p < 0.05). Gas chromatography-mass spectrometry analysis of HWE and HEE showed possible active compounds which might be responsible for the observed anti-diabetic potential. These findings indicate the possible mechanisms by which hemp root extracts protect mice against insulin-deficient diabetes, and support the need for further studies geared towards the application of hemp root as a novel bioactive material.

Interpreting auditory brainstem evoked responses and distortion product otoacoustic emissions in diabetic patients with normal hearing.

OBJECTIVE: Hearing impairment is a reported late complication of diabetes mellitus (DM). Previous studies have suggested that microangiopathic complications may cause cochlear nerve function deterioration. We evaluated the auditory brainstem evoked responses (ABRs) and distortion product otoacoustic emission (DPOAE) results according to the presence of DM in subjects with normal hearing. METHODS: A cross-sectional comparative study was conducted from January 2016 to January 2018. Auditory function tests including ABR and DPOAE were performed for outpatients complaining of unilateral tinnitus. All of analyses were conducted in ears without tinnitus on contralateral side of tinnitus ears. We included subjects showing hearing thresholds within 25 dB at 0.5, 1k, 2k, and 4k on pure tone audiometry. 45 ears in patients with type 2 diabetes mellitus and 85 ears in non-diabetic patients were finally enrolled in our study. RESULTS: Diabetic subjects showed significantly more prolonged absolute peak latencies (I, III, V) and inter-peak latencies (I-V, III-V) than non-diabetic subjects. However, there was no significant difference in the inter-peak latency (I-III) between these two groups. Diabetic subjects also showed significantly lower amplitudes at f2 frequencies of 1001, 1200, 1587, 4004, 5042, and 6348 Hz than non-diabetic subjects. Additionally, the prevalence of a DPOAE response, defined as 3 dB above the noise floor, was significantly lower in diabetic subjects than that in non-diabetic subjects. CONCLUSION: Diabetic patients with normal hearing can still have abnormal ABR and DPOAE results due to diabetic neuroangiopathy. ABR and DPOAE assessments can help in detecting subclinical auditory dysfunction, which precedes the manifestation of hearing impairment in diabetic patients.

3D Bioprinted Osteogenic Tissue Models for In Vitro Drug Screening.

Metabolic bone disease affects hundreds of millions of people worldwide, and as a result, in vitro models of bone tissue have become essential tools to help analyze bone pathogenesis, develop drug screening, and test potential therapeutic strategies. Drugs that either promote or impair bone formation are in high demand for the treatment of metabolic bone diseases. These drugs work by targeting numerous signaling pathways responsible for regulating osteogenesis such as Hedgehog, Wnt/ß-catenin, and PI3K-AKT. In this study, differentiated bone marrow-derived mesenchymal stem cell (BM-MSC) scaffold-free 3D bioprinted constructs and 2D monolayer cultures were utilized to screen four drugs predicted to either promote (Icariin and Purmorphamine) or impair osteogenesis (PD98059 and U0126). Osteogenic differentiation capacity was analyzed over a four week culture period by evaluating mineralization, alkaline phosphatase (ALP) activity, and osteogenesis related gene expression. Responses to drug treatment were observed in both 3D differentiated constructs and 2D monolayer cultures. After four weeks in culture, 3D differentiated constructs and 2D monolayer cultures treated with Icariin or Purmorphamine showed increased mineralization, ALP activity, and the gene expression of bone formation markers (BGLAP, SSP1, and COL1A1), signaling molecules (MAPK1, WNT1, and AKT1), and transcription factors (RUNX2 and GLI1) that regulate osteogenic differentiation relative to untreated. 3D differentiated constructs and 2D monolayer cultures treated with PD98059 or U0126 showed decreased mineralization, ALP activity, and the expression of the aforementioned genes BGLAP, SPP1, COL1A1, MAPK1, AKT1, RUNX2, and GLI1 relative to untreated. Differences in ALP activity and osteogenesis related gene expression relative to untreated cells cultured in a 2D monolayer were greater in 3D constructs compared to 2D monolayer cultures. These findings suggest that our bioprinted bone model system offers a more sensitive, biologically relevant drug screening platform than traditional 2D monolayer in vitro testing platforms.

[Effects of Electric Stimulation and Biofeedback for Pelvic Floor Muscle Exercise in Women with Vaginal Rejuvenation Women].

PURPOSE: The purpose of this study was to investigate the effects of pelvic floor muscle exercise using electric stimulation and biofeedback on maximum pressure of vaginal contraction, vaginal contraction duration and sexual function in women who have had vaginal rejuvenation. METHODS: The research design was a non-equivalent control group non-synchronized design study. Participants in this study were women who had vaginal rejuvenation at C obstetrics and gynecology hospital. The 15 participants in the experimental group were given pelvic floor muscle exercise using electric stimulation and biofeedback and the 15 participants in the control group received self pelvic floor muscle exercise. RESULTS: For maximum pressure of vaginal contraction, the experimental group showed a statistically significant increase compared to than the control group (t=5.96, p<.001). For vaginal contraction duration, the experimental group also showed a statistically significant increase compared to the control group (t=3.23, p=.003). For women's sexual function, the experimental group showed a significant increase when compared to the control group in total sexual function scores (t=3.41, p=.002). CONCLUSION: The results indicate that pelvic floor muscle exercise with electric stimulation and biofeedback after vaginal rejuvenation is effective in strengthening vaginal contraction pressure, vaginal contraction and that it also positively functions to increase women's sexual function.

Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer.

OBJECTIVE: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. PATIENTS AND METHODS: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (-). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. RESULTS: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (-), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). CONCLUSIONS: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

A prospective, split-face, randomized study of the efficacy and safety of a novel fractionated intense pulsed light treatment for melasma in Asians.

BACKGROUND: Intense pulsed light (IPL) has been reported to effectively treat melasma in previous studies, but an aggravation of pigmentation was noted. Fractionated IPL is a novel technique in which microsecond-domain fractionated pulses are delivered to the target area. OBJECTIVE: To compare the safety and efficacy of low-fluency, frequently scheduled fractionated IPL and conventional IPL for melasma treatment. MATERIALS AND METHODS: This was a 14-week, split-face study in which 30 Asian women were treated with weekly fractionated IPL on one side of the face and biweekly conventional IPL on the other side. RESULTS: The non-inferiority of a weekly fractionated IPL regimen to a biweekly conventional IPL regimen was verified by a lower margin of the 95% confidence interval for the difference in the Melasma Area and Severity Index (MASI) change from baseline of 2.61 for each side. This value was greater than the previously determined non-inferiority margin of -2.68 (P < 0.025). On the fractionated IPL side, the modified MASI score decreased continuously, but in the conventional IPL group, the MASI score rebounded during the treatment course. CONCLUSION: Fractionated IPL shows moderate efficacy as a melasma treatment and is therefore a good alternative to conventional IPL as there is no indication of melasma exacerbation. Fractionated IPL can also be used as a maintenance treatment for melasma.

Topical Application of Chrysanthemum indicum L. Attenuates the Development of Atopic Dermatitis-Like Skin Lesions by Suppressing Serum IgE Levels, IFN-γ, and IL-4 in Nc/Nga Mice.

Chrysanthemum indicum L. (CIL) is widely used as an anti-inflammatory agent in Asia and our preliminary study revealed that CIL reduced interleukin (IL)-4 and IL-13 in 2,4-dinitrochlorobenzene (DNCB)-treated HaCaT cells, a human keratinocyte cell line. We investigated the atopic dermatitis (AD) effect of topically applied CIL in mice with AD-like symptoms. After topical application of 1,3-butylen glycol (control), CIL-Low (5%), CIL-High (30%), or 0.1% hydrocortisone (HC) on the AD-like skin lesions in DNCB-treated NC/Nga mice for 5 weeks, the ear thickness, mast cell infiltration, and serum immunoglobulin E (IgE), IgG1, IL-4 and interferon (IFN)-γ were measured. The gene expressions of IL-4, IL-13, and IFN-γ in the dorsal skin were assayed. CIL treatment dosedependently reduced severity of clinical symptoms of dorsal skin, ear thickness, and the number of mast cells and eosinophils. CIL-High significantly decreased serum IgE, IgG1, IL-4, and IFN-γ levels and reduced mRNA levels of IFN-γ, IL-4, and IL-13 in dorsal skin lesion. The improvement by CIL-High was similar to HC, but without its adverse effects such as skin atrophy maceration, and secondary infection. In conclusion, CIL may be an effective alternative substance for the management of AD.

Anti-obesity effects of Chang-Chul-Eui-Ee-In-Tang [see text] in female rats with diet-induced obesity.

OBJECTIVE: To investigate the effects of Chang-Chul-Eui-Ee-In-Tang ([see text], CCEET), modififi ed CCEET (MCCEET), and Semen Coicis (SC, a major component of CCEET) on energy and glucose homeostasis. The possible mechanism of action of CCEET was also determined. METHODS: A total of 100 Sprague Dawley female rats were randomly assigned to 5 groups, with 20 in each group. Rats in 4 groups were fed with a high fat diet supplementation (2 g/kg body weight), and water extracts of CCEET, MCCEET, SC, and cellulose (negative control), respectively. The last group was fed with a low-fat diet as a positive control. RESULTS: CCEET and MCCEET decreased body weight and body fat (mesenteric and retroperitoneal fat) more than SC. This decrease was due to decreased energy intake and increased energy expenditure and fat oxidation. The improvement in energy homeostasis was associated with the enhancement of the hypothalamic leptin signalling pathway involving potentiating the phosphorylation of the signal transducer and activator of transcription-3, as well as attenuating the phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK). Both CCEET and MCCEET improved glucose tolerance without changing serum insulin levels during an oral glucose tolerance test but MCCEET had a better effect than CCEET. CONCLUSIONS: Both CCEET and MCCEET safely exerted anti-obesity effects by enhancing energy balance in female rats with diet-induced obesity; MCCEET showed a better effect on glucose homeostasis.

Validation of the Korean Integrative Medicine Attitude Questionnaire (IMAQ).

BACKGROUND: To develop a Korean version of the Integrative Medicine Attitude Questionnaire (IMAQ) in order to evaluate physician attitudes toward integrative medicine/complementary and alternative medicine (CAM). METHODS: We developed a Korean IMAQ through careful translation of the 28-item questionnaire developed by Schmidt et al. A web-based survey was sent via email to 118 primary care physicians in Korea. The complete respose rate wasa 52.5%. The questionnaire's reliability and validity were verified using Cronbach's α, factor analysis, and discriminant analysis. RESULTS: Although the Korean IMAQ exhibited excellent internal consistency, its validity was insufficient. Our results suggest that Western and Korean physicians may have different understandings of CAM and the concept of holism, as factor analysis showed that incorrectly classified items were mainly part of the holism conceptual domain. Furthermore, the sum of the items within the holism conceptual domain was not significantly different for physicians who had previously received CAM education. CONCLUSION: This study developed and tested the first Korean IMAQ. We found that this version of the questionnaire lacks sufficient validity and requires further modification.

Wickerhamomyces ochangensis sp. nov., an ascomycetous yeast isolated from the soil of a potato field.

A novel ascomycetous yeast, designated strain N7a-Y2(T), was isolated from soil collected in a potato field in Ochang, Korea, and its taxonomic position was studied. A neighbour-joining tree based on the D1/D2 domain of large-subunit rRNA gene sequences revealed that the isolate was a member of the Wickerhamomyces clade and that it was closely related to Wickerhamomyces bisporus, Candida quercuum, Candida ulmi and Wickerhamomyces alni. Strain N7a-Y2(T) formed Saturn-shaped ascospores in unconjugated and persistent asci. D1/D2 domain 26S rRNA gene sequence divergences of 11.0-21.1 % between strain N7a-Y2(T) and other members of the Wickerhamomyces clade indicate that the strain represents a novel species of the genus Wickerhamomyces, for which the name Wickerhamomyces ochangensis sp. nov. is proposed. The type strain is N7a-Y2(T) ( = KCTC 17870(T)  = CBS 11843(T)).

Extract of Punica granatum inhibits skin photoaging induced by UVB irradiation.

BACKGROUND: Punica granatum (pomegranate) is kind of a fruit consumed fresh or in beverage. It has been widely used in traditional medicine in various parts of the world. In this study, we examined the efficacy of a Punica granatum (PG) extract in protecting skin against UVB-induced damage using cultured human skin fibroblasts. METHODS: A Korean red PG sample was used, and its effects classified according to if the PG source originated from the rind, seed and fruit. The polyphenol content of PG, which is known to prevent other adverse cutaneous effects of UV irradiation, was measured by GC-MS. The protective effects of PG on UVB-induced skin photoaging were examined by determining the level of procollagen type I and MMP-1 after UVB irradiation. RESULTS: Based on the GC-MS quantitative analysis, catechin, quercetin, kaempferol, and equol were the predominant compounds detected in PG. In the changes of expression of procollagen type I and MMP-1 in UV irradiated human skin fibroblasts treated PG, especially extract prepared from rind, the synthesis of collagen was increased and the expression of MMP-1 was decreased. CONCLUSION: The major polyphenols in PG, particularly catechin, play a significant role in its photoprotective effects on UVB-induced skin damage.

Huang-Lian-Jie-Du-Tang supplemented with Schisandra chinensis Baill. and Polygonatum odoratum Druce improved glucose tolerance by potentiating insulinotropic actions in islets in 90% pancreatectomized diabetic rats.

We investigated to determine what effects, if any, the respective water extracts of Radix scutellariae (RS), Fructus schisandrae chinensis (FSC), Huang-Lian-Jie-Du-Tang (HLJDT), and HLJDT supplemented with FSC, and Rhizoma Polygonati odorati (HLJDT-M) would have on glucose tolerance by modulating glucose-stimulated insulin secretion, beta-cell mass, and morphometry in 90% pancreatectomized (Px) diabetic rats fed high-fat diets. Through the elevation of intracellular cAMP levels, FSC RS, HLJDT, and HLJDT-M increased insulin secretion in Min6 cells and GLP-1 secretion in NCI-H716 cells. After an 8-week period of treatment, it was found that HLJDT-M improved glucose tolerance in an oral glucose tolerance test in Px rats. HLJDT-M also potentiated first- and second-phase insulin secretion, but RS and HLJDT elevated only the second phase at hyperglycemic clamp. RS and HLJDT increased beta-cell mass by hyperplasia and hypertrophy, while HLJDT-M increased it only by hyperplasia. The rise in hyperplasia was associated with elevated IRS2 and PDX-1 expression in the islets. In conclusion, HLJDT-M worked as an anti-diabetic prescription by enhancing insulinotropic actions in diabetic rats.

The multi-herbal medicine Gongjin-dan enhances memory and learning tasks via NGF regulation.

Nerve growth factor (NGF) decreases degeneration of cholinergic neurons, improves memory loss, and increases long-term potentiation and learning tasks. Therefore, NGF mimetics or NGF inducers may be important targets for the treatment of various neurodegenerative disorders. Traditionally, Gongjin-dan (GJD) has been used clinically for the treatment of central nervous system disorders. In this study, we examined the effects of GJD on NGF mimetic activity in PC12 cells and the induction of NGF secretion in primary astrocytes. Moreover, we also measured neuron survival by MAP-2 staining in an immobilization stress rat model and induction of long-term potentiation by the MEA system in rat hippocampus slices treated with dexamethasone. The behavioral syndrome by novel object test was also performed in mice. GJD increased neurite outgrowth in PC12 cells and NGF secretion in primary astrocytes. Also, it reduced neuronal cell death and increased long-term potentiation in the rat hippocampus. Moreover, the number of entries, the time spent and the distance moved in the center area of the test region by the mice was increased by oral administration of GJD in comparison with the distance moved over the total area. These data suggest that administration of GJD may improve memory and learning tasks via NGF regulation, and that it may have a potential for multiple function neuroprotection via NGF regulation.

To compare the efficacy and safety of nifedipine sustained release with Ginkgo biloba extract to treat patients with primary Raynaud's phenomenon in South Korea; Korean Raynaud study (KOARA study).

This study examined the efficacy and safety of nifedipine sustained release (nifedipine SR) compared with Ginkgo biloba extract as treatment for primary Raynaud's phenomenon (RP) in Korea. Primary RP were screened and assigned to either the nifedipine SR group (Group N) or the Ginkgo biloba extract group (Group G) in the ratio of 2:1. After a run-in period of 2 weeks, patients received treatment for 8 weeks. We observed the percent improvement of the RP attack rate between before and after the 8-week treatment. Ninety-three subjects were randomly assigned. The percent improvement in Group N was 50.1% at 8 weeks after treatment, while it was 31.0% in Group G (p = 0.03). No serious adverse events occurred, and almost adverse events were mild and improved without specific treatment. nifedipine SR was more effective than Ginkgo biloba extract for treatment of primary RP in Korean patients. Both drugs were tolerable with primary RP patients.

The cancer preventive peptide lunasin from wheat inhibits core histone acetylation.

Lunasin is a unique 43-amino acid cancer preventive peptide initially reported in soybean and barley and has been shown to be chemopreventive in mammalian cells and in a skin cancer mouse model against oncogenes and chemical carcinogens. We report here the core histone H3- and H-acetylation inhibitory properties of lunasin from wheat, a new source of the peptide and from the livers of rats fed with lunasin-enriched wheat (LEW) to measure bioavailability. A non-radioactive histone acetyl transferase assay was used to measure inhibition of core histone acetylation. The presence of lunasin in wheat was established by Western blot and identified by liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). Lunasin isolated from wheat seeds at different stages of development inhibited core histone H3 and H4 acetylation in a dose-dependent manner. Lunasin extracted from liver of rats fed with lunasin-enriched wheat (LEW) also inhibited histone acetylation confirming that the peptide is intact and bioactive. The amounts of lunasin in the developing seeds and in the rat liver correlated extremely well with the extent of inhibition of core histone acetylation.