Two new isoarylbenzofuran diglucosides from the root bark of Morus alba.

Two new arylbenzofuran diglucopyranosides, (2″R)-(-)-moracin-O-5',3″-ß-D-diglucopyranoside (1) and (2″R)-(-)-moracin-P-5',2″-ß-d-diglucopyranoside (2), along with known arylbenzofurans, moracin M 6-ß-D-glucopyranoside (3), and an isomeric mixture of R-(-)-moracin O (4) and R-(-)-moracin P (5), were isolated from the root bark of Morus alba L. The structure of the compounds was elucidated based on mass spectrometry, infrared, 1D and 2D nuclear magnetic resonance spectroscopic data.

Long-term utility and durability of the therapeutic effects of bimatoprost 0.03% for eyelash augmentation in healthy Asian subjects.

BACKGROUND: Eyelashes of Asians differ from those of Caucasians in morphology and growth characteristics. Ethnic differences also exist for the tolerability profile of prostaglandin analogues. OBJECTIVE: To evaluate the long-term utility and durability of bimatoprost 0.03% in eyelash augmentation in Asian females. METHODS: One cohort received bimatoprost 0.03% for 36 weeks and another for 20 weeks, with the latter cohort followed for 16 weeks after treatment cessation. The primary endpoint was the percent change in eyelash length at week 20. Secondary measures included percent change in eyelash thickness and darkness, physician's Global Eyelash Assessment and patient satisfaction. RESULTS: At week 20, eyelash length was enhanced in a time-dependent manner, with maximum improvement achieved (19.3%; p < 0.0001). Significant improvements in thickness and darkness were also achieved (22.9%, 6.0%; p < 0.0001). 77.8% of subjects improved by ≥1 grade on Global Eyelash Assessment, with 83.1% satisfied/very satisfied. Improvements were maintained with ongoing treatment to 36 weeks, while these effects were progressively lost with discontinuation. CONCLUSION: Bimatoprost 0.03% safely enhanced eyelashes in Asian females, maintained with ongoing treatment. Cessation of treatment was associated with progressive loss of effects.

Postbiotic potential of Bacillus velezensis KMU01 cell-free supernatant for the alleviation of obesity in mice.

Attention toward the preventive effects of postbiotics on metabolic diseases has increased because of greater stability and safety over probiotics. However, studies regarding the bioactive effects of postbiotics, especially from probiotic Bacillus strains, are relatively limited. The anti-obesity effects of the cell-free culture supernatant of Bacillus velezensis KMU01 (CFS-B.vele) were evaluated using high-fat-diet (HFD)-induced mice. HFD-induced mice (n = 8 per group) received equal volumes of (1) CFS-B.vele (114 mg/kg) in PBS, (2) Xenical in PBS, or (3) PBS alone by oral gavage daily for 13 weeks. The results demonstrated that CFS-B.vele changed the gut microbiota and showed anti-obesity effects in HFD-induced obese mice. The elevated Firmicutes/Bacteroidota ratio induced by HFD was decreased in the CFS-B.vele group compared to the other groups (p < 0.05). The CFS-B.vele intervention led to the enrichment of SCFA-producers, such as Roseburia and Eubacterium, in the cecum, suggesting their potential involvement in the amelioration of obesity. Due to these changes, the various obesity-related biomarkers (body weight, fat in tissue, white adipose tissue weight and size, serum LDL-cholesterol level, hepatic lipid accumulation, and adipogenesis/lipogenesis-related gene/protein expression) were improved. Our findings suggest that CFS-B.vele has potential as a novel anti-obesity agent through modulation of the gut microbiota.

Neolignans from the fruits of Magnolia obovata and their inhibition effect on NO production in LPS-induced RAW 264.7 cells.

Three new neolignans, named 9-methoxyobovatol (6), magnobovatol (7), and 2-hydroxyobovaaldehyde (9), along with six known ones, magnolol (1), honokiol (2), isomagnolol (3), obovatol (4), obovatal (5), and obovaaldehyde (8), were isolated from the fruits of Magnolia obovata using silica gel and ODS column chromatography. From the results of spectroscopic data including EIMS, IR, 1H- and 13C-NMR, DEPT, and 2D-NMR (gCOSY, gHSQC, gHMBC), the chemical structures were determined. All isolated compounds were evaluated for inhibition activity on nitric oxide production in LPS-induced RAW 264.7 cells, and compounds 1-4, 6, 7, and 9 showed significant activity with IC50 values of 15.8 ± 0.3, 3.3 ± 1.2, 14.1 ± 0.9, 6.2 ± 1.2, 14.8 ± 2.3, 14.2 ± 1.2, and 14.8 ± 3.2 µM, respectively, without any visible toxic effect.

Anti-Inflammatory Effect and Signaling Mechanism of Glycine max Hydrolyzed with Enzymes from Bacillus velezensis KMU01 in a Dextran-Sulfate-Sodium-Induced Colitis Mouse Model.

The purpose of this study was to investigate the effect that Glycine max hydrolyzed with enzymes from Bacillus velezensis KMU01 has on dextran-sulfate-sodium (DSS)-induced colitis in mice. Hydrolysis improves functional health through the bioconversion of raw materials and increase in intestinal absorption rate and antioxidants. Therefore, G. max was hydrolyzed in this study using a food-derived microorganism, and its anti-inflammatory effect was observed. Enzymatically hydrolyzed G. max (EHG) was orally administered once daily for four weeks before DSS treatment. Colitis was induced in mice through the consumption of 5% (w/v) DSS in drinking water for eight days. The results showed that EHG treatment significantly alleviated DSS-induced body weight loss and decreased the disease activity index and colon length. In addition, EHG markedly reduced tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 production, and increased that of IL-10. EHG improved DSS-induced histological changes and intestinal epithelial barrier integrity in mice. Moreover, we found that the abundance of 15 microorganisms changed significantly; that of Proteobacteria and Escherichia coli, which are upregulated in patients with Crohn's disease and ulcerative colitis, decreased after EHG treatment. These results suggest that EHG has a protective effect against DSS-induced colitis and is a potential candidate for colitis treatment.

Postbiotics Enhance NK Cell Activation in Stress-Induced Mice through Gut Microbiome Regulation.

Recent studies have revealed that probiotics and their metabolites are present under various conditions; however, the role of probiotic metabolites (i.e., postbiotics in pathological states) is controversial. Natural killer (NK) cells play a key role in innate and adaptive immunity. In this study, we examined NK cell activation influenced by a postbiotics mixture in response to gut microbiome modulation in stress-induced mice. In vivo activation of NK cells increased in the postbiotics mixture treatment group in accordance with Th1/Th2 expression level. Meanwhile, the Red Ginseng treatment group, a reference group, showed very little expression of NK cell activation. Moreover, the postbiotics mixture treatment group in particular changed the gut microbiome composition. Although the exact role of the postbiotics mixture in regulating the immune system of stress-induced mice remains unclear, the postbiotics mixture-induced NK cell activation might have affected gut microbiome modulation.

The effect of smartphone uses on gait and obstacle collision during walking.

OBJECTIVE: This study aims to investigate the impact of obstacle collision according to the presence or absence of light and the change of gait when using smartphones while walking. STUDY DESIGN/SETTING: A cross-sectional study. SUBJECTS: 24 healthy young people. METHODS: Obstacle collision was measured in participants as they passed through four obstacles at different heights (eyes, waist, knees, ankle level), with the lights turned on. The same was measured with the lights turned off. To measure spatiotemporal variables, GAITRite was used. Obstacle collision was used in the frequency analysis, and the spatiotemporal variables were assessed using one-way ANOVA test. The post-hoc Tukey's test was used to detect spatiotemporal variables differences (p < 0.05). RESULTS: Obstacle collision was the highest at eye level when playing games and messaging while walking. It was also higher when lights were turned off rather than when lights were on. Gait function decreased while walking when messaging or playing games on a smartphone as compared to when walking without a smartphone. CONCLUSION: Understanding the collision rate of various obstacles encountered when using smartphones while walking could contribute to the prevention of accidents.

Micronized, Heat-Treated Lactobacillus plantarum LM1004 Alleviates Cyclophosphamide-Induced Immune Suppression.

The present study investigated the immunomodulatory activity and associated mechanisms of heat-treated Lactobacillus plantarum LM1004 (HT-LM1004) in a cyclophosphamide (CTX)-induced mouse model of immunosuppression. HT-LM1004 induced phagocytic activity and nitric oxide production in RAW264.7 macrophages and stimulated the release of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, and IL-12p70. In mice with CTX-induced immunosuppression, oral HT-LM1004 administration restored thymus and spleen indices, including spleen weight. Consistent with the in vitro results, HT-LM1004 increased TNF-α, IFN-γ, IL-2, and IL-12p70 levels in mice after 14 days of treatment and enhanced the natural killer (NK) cell activity of splenocytes from mice with CTX-induced immunosuppression against YAC-1 lymphoma cells. The method of HT-LM1004 generation influenced this activity: L. plantarum LM1004 grown in a membrane bioreactor, which reduced the size of the cells to <1.0 µm through physical stress (micronization), promoted NK cell cytotoxicity to a greater extent than LM1004 subjected to heat treatment alone. These findings indicate that HT-LM1004 without or with micronization can reverse CTX-induced immunosuppression without adverse side effects by potentiating NK cell function.

Homologous U-box E3 Ubiquitin Ligases OsPUB2 and OsPUB3 Are Involved in the Positive Regulation of Low Temperature Stress Response in Rice (Oryza sativa L.).

Rice U-box E3 Ub ligases (OsPUBs) are implicated in biotic stress responses. However, their cellular roles in response to abiotic stress are poorly understood. In this study, we performed functional analyses of two homologous OsPUB2 and OsPUB3 in response to cold stress (4°C). OsPUB2 was up-regulated by high salinity, drought, and cold, whereas OsPUB3 was constitutively expressed. A subcellular localization assay revealed that OsPUB2 and OsPUB3 were localized to the exocyst positive organelle (EXPO)-like punctate structures. OsPUB2 was also localized to the nuclei. OsPUB2 and OsPUB3 formed a hetero-dimeric complex as well as homo-dimers in yeast cells and in vitro. OsPUB2/OsPUB3 exhibited self-ubiquitination activities in vitro and were rapidly degraded in the cell-free extracts with apparent half-lives of 150-160 min. This rapid degradation of OsPUB2/OsPUB3 was delayed in the presence of the crude extracts of cold-treated seedlings (apparent half-lives of 200-280 min). Moreover, a hetero-dimeric form of OsPUB2/OsPUB3 was more stable than the homo-dimers. These results suggested that OsPUB2 and OsPUB3 function coordinately in response to cold stress. OsPUB2- and OsPUB3-overexpressing transgenic rice plants showed markedly better tolerance to cold stress than did the wild-type plants in terms of survival rates, chlorophyll content, ion leakage, and expression levels of cold stress-inducible marker genes. Taken together, these results suggested that the two homologous rice U-box E3 Ub ligases OsPUB2 and OsPUB3 are positive regulators of the response to cold stress.

CaPUB1, a Hot Pepper U-box E3 Ubiquitin Ligase, Confers Enhanced Cold Stress Tolerance and Decreased Drought Stress Tolerance in Transgenic Rice (Oryza sativa L.).

Abiotic stresses such as drought and low temperature critically restrict plant growth, reproduction, and productivity. Higher plants have developed various defense strategies against these unfavorable conditions. CaPUB1 (Capsicum annuum Putative U-box protein 1) is a hot pepper U-box E3 Ub ligase. Transgenic Arabidopsis plants that constitutively expressed CaPUB1 exhibited drought-sensitive phenotypes, suggesting that it functions as a negative regulator of the drought stress response. In this study, CaPUB1 was over-expressed in rice (Oryza sativa L.), and the phenotypic properties of transgenic rice plants were examined in terms of their drought and cold stress tolerance. Ubi:CaPUB1 T3 transgenic rice plants displayed phenotypes hypersensitive to dehydration, suggesting that its role in the negative regulation of drought stress response is conserved in dicot Arabidopsis and monocot rice plants. In contrast, Ubi:CaPUB1 progeny exhibited phenotypes markedly tolerant to prolonged low temperature (4°C) treatment, compared to those of wild-type plants, as determined by survival rates, electrolyte leakage, and total chlorophyll content. Cold stress-induced marker genes, including DREB1A, DREB1B, DREB1C, and Cytochrome P450, were more up-regulated by cold treatment in Ubi:CaPUB1 plants than in wild-type plants. These results suggest that CaPUB1 serves as both a negative regulator of the drought stress response and a positive regulator of the cold stress response in transgenic rice plants. This raises the possibility that CaPUB1 participates in the cross-talk between drought and low-temperature signaling pathways.

Overcoming HSP27-mediated resistance by altered dimerization of HSP27 using small molecules.

Heat shock protein 27 (HSP27, HSPB1) is an anti-apoptotic protein characterized for its tumorigenic and metastatic properties, and now referenced as a major therapeutic target in many types of cancer. The biochemical properties of HSP27 rely on a structural oligomeric and dynamic organization that is important for its chaperone activity. Down-regulation by small interfering RNA or inhibition with a dominant-negative mutant efficiently counteracts the anti-apoptotic and protective properties of HSP27. However, unlike other HSPs such as HSP90 and HSP70, small molecule approaches for neutralization of HSP27 are not well established because of the absence of an ATP binding domain. Previously, we found that a small molecule, zerumbone (ZER), induced altered dimerization of HSP27 by cross linking the cysteine residues required to build a large oligomer, led to sensitization in combination with radiation. In this study, we identified another small molecule, a xanthone compound, more capable of altering dimeric HSP27 than ZER and yielding sensitization in human lung cancer cells when combined with HSP90 inhibitors or standard anticancer modalities such as irradiation and cytotoxic anticancer drugs. Therefore, altered dimerization of HSP27 represents a good strategy for anticancer therapy in HSP27-overexpressing cancer cells.

Germacrane sesquiterpenes isolated from the rhizome of Curcuma xanthorrhiza Roxb. inhibit UVB-induced upregulation of MMP-1, -2, and -3 expression in human keratinocytes.

Four sesquiterpenes were isolated from the rhizome of Curcuma xanthorrhiza Roxb.: furanodiene (1), germacrone (2), furanodienone (3), and 13-hydroxygermacrone (4). Importantly, this was the first time compounds 1 and 4 were isolated from this plant. The chemical structures of these compounds were determined using 1D- and 2D-nuclear magnetic resonance, infrared spectroscopy, and electron ionization mass spectrometry analyses. Among the isolated compounds, compounds 2 and 4 inhibited UVB-induced upregulation of the mRNA and protein expression levels of MMP-1, MMP-2, and MMP-3 in human keratinocytes (HaCaT). Moreover, this upregulation occurred in a dose-dependent manner over the range of 1-10 µM for each compound.

Lignan and flavonoids from the stems of Zea mays and their anti-inflammatory and neuroprotective activities.

The stems of Zea mays L., otherwise known as cornstalks, were extracted with 80 % aqueous MeOH, and the concentrated extract was successively partitioned with ethyl acetate (EtOAc), normal butanol, and water. From the EtOAc fraction, a new lignan along with three known flavonoids, tricin (1), salcolin A (2), and salcolin B (3), were isolated. The chemical structure of the lignan was determined to be tetrahydro-4,6-bis(4-hydroxy-3-methoxyphenyl)-1H,3H-furo[3,4-c]furan-1-one (4) through spectroscopic data analyses including NMR, MS, and IR. All compounds were isolated for the first time from this plant. The isolated compounds were evaluated for their inhibitory activity against NO production in Lipopolysaccharide-induced RAW 264.7 cells and their protective activity in glutamate-induced cell death in HT22 cells. The compounds 1, 2 and 4 showed anti-inflammatory effects with IC50 values of 2.63, 14.65, and 18.91 µM, respectively, as well as neuroprotective effects with EC50 values of 25.14, 47.44, and >80 µM, respectively.

A new flavonoid glycoside from the root bark of Morus alba L.

A new guibourtinidol glycoside, (2R,3S)-guibourtinidol-3-O-α-d-apiofuranosyl-(1 → 6)-O-ß-D-glucopyranoside (1), and three known compounds, quercetin 7-O-ß-D-glucopyranoside (2), syringaresinol-4-O-ß-D-glucopyranoside (3) and dehydrodiconiferyl alcohol 4,9'-di-O-ß-D-glucopyranoside (4), were isolated from the root bark of Morus alba L. through repeated silica gel, octadecyl silica gel and Sephadex LH-20 column chromatography for the n-BuOH fraction. The chemical structure of the compounds was elucidated based on MS, infrared, 1D and 2D NMR spectroscopic data. Compounds 2-4 were also isolated for the first time from the root bark of M. alba L. in this study.

Re-evaluation of physicochemical and NMR data of triol ginsenosides Re, Rf, Rg2, and 20-gluco-Rf from Panax ginseng roots.

Ginseng roots were extracted with aqueous methanol, and extracts were suspended in water and extracted successively with ethyl acetate and n-butanol. Column chromatography using the n-butanol fraction yielded four purified triol ginseng saponins: the ginsenosides Re, Rf, Rg2, and 20-gluco-Rf. The physicochemical, spectroscopic, and chromatographic characteristics of the ginsenosides were measured and compared with reports from the literature. For spectroscopic analysis, two-dimensional nuclear magnetic resonance (NMR) methods such as (1)H-(1)H correlation spectroscopy, nuclear Overhauser effect spectroscopy, heteronuclear single quantum correlation, and heteronuclear multiple bond connectivity were employed to identify exact peak assignments. Some peak assignments for previously published (1)H- and (13)C-NMR spectra were found to be inaccurate. This study reports the complete NMR assignment of 20-gluco-Rf for the first time.

Clinical and histopathological analysis of specific lesions of cutaneous sarcoidosis in Korean patients.

BACKGROUND: Sarcoidosis is a multi-systemic, non-caseating, granulomatous disorder of unknown origin. OBJECTIVE: The purpose of our investigation was to describe the clinicopathological characteristics of specific lesions of cutaneous sarcoidosis and treatment outcomes in Korean patients. METHODS: A retrospective review was made of 31 patients who were diagnosed with sarcoidosis at Severance Hospital, Yonsei University Health System in Korea between 2000 and 2008; these patients were enrolled in this study. The diagnosis of cutaneous sarcoidosis was made in 17 of the patients. They were confirmed by histopathologic examinations. The clinical features were analyzed through review of medical records, and histopathologic and radiologic examinations. RESULTS: The patients' primary complaints were cutaneous symptoms (51.6%) and respiratory symptoms (32.3%). The most common presentation of cutaneous sarcoidal lesions was the nodule-plaque form (41.2%) and systemic organ involvement was observed in six cases (35.3%). Treatment modalities included steroid, hydroxychloroquine, cyclosporine, topical tacrolimus, and pulsed dye laser. In our series, five patients (30%) achieved complete resolution of the cutaneous lesions and 10 patients (60%) showed partial resolution after corticosteroid treatment. Also, patients without extracutaneous symptoms responded better to corticosteroid treatment compared to patients with systemic involvement. CONCLUSIONS: These data reveal the diversity of clinical and histopathologic findings of cutaneous sarcoidosis in Korea.

Late-onset eccrine angiomatous hamartoma associated with a ganglion cyst on the sole of the foot.

Eccrine angiomatous hamartoma (EAH) is a benign, uncommon, combined vascular and eccrine malformation. Most cases of this disorder have been single or multiple nodules or plaques that appear red, yellow, blue, violaceous, or skin colored. EAH may be congenital or appear later in childhood; it rarely arises during puberty or adulthood. A 52-year-old female patient visited our department for tender subcutaneous cystic tumor on the right sole with a one month history. Histopathologic examination confirmed EAH. During excisional biopsy procedure, mucinous discharges were observed which were histopathologically diagnosed as ganglion.

A Case of Lichen Planus Pigmentosus-inversus in a Korean Patient.

Lichen planus pigmentosus-inversus is a rare variant of lichen planus pigmentosus. The eruption of lichen planus pigmentosus-inversus occurs mainly in the flexural regions and presents with brownish macules and patches. Here we describe the case of a 31-year-old Korean woman who presented with hyperpigmented lesions over her antecubital and popliteal area and groin. Physical examination revealed multiple brownish macules and patches on the intertriginous area without pruritis, and histologic findings showed a regressive pattern of lichen planus. These clinical and histological findings were consistent with a diagnosis of lichen planus pigmentosus-inversus.

A case of acrodermatitis enteropathica localized on the hands and feet with a normal serum zinc level.

Acrodermatitis enteropathica is classified as a congenital autosomal recessive type and an acquired transient type. This disease manifests as acral and periorificial dermatitis, alopecia, intractable diarrhea, and failure to thrive. Whereas the autosomal hereditary type is caused by malabsorption of zinc in the intestine, the acquired type is caused by low nutritional support or decreased peripheral release of zinc from blood. We experienced a case of a 5-month old, breast feeding, full-term female presenting with only acral bullous dermatitis without diarrhea, periorificial dermatitis and an abnormal serum zinc level.

IL-1α stimulation restores epidermal permeability and antimicrobial barriers compromised by topical tacrolimus.

In a previous study, we showed that barrier recovery was delayed after acute barrier disruption in the skin treated with topical calcineurin inhibitors. Tacrolimus decreases lipid synthesis and the expressions of antimicrobial peptide (AMP) and IL-1α in the epidermis. IL-1α is an important cytokine for improving barrier function, lamellar body (LB) production, and lipid synthesis in keratinocytes (KCs). We aimed to evaluate whether IL-1α stimulation could restore the barrier dysfunction observed in tacrolimus-treated skin. Topical imiquimod, an IL-1α inducer, restored the epidermal permeability barrier recovery that had been inhibited by tacrolimus treatment in human (n=15) and murine (n=10) skins, and improved stratum corneum integrity by restoring corneodosmosomes in murine skin (n=6). Imiquimod co-applied on the epidermis resulted in an increase in the production of LB and three major lipid synthesis-related enzymes, and in the expressions of mBD3, CRAMP, and IL-1α (n=5). Furthermore, intracutaneous injection of IL-1α restored permeability barrier recovery (n=6). In IL-1 type 1 receptor knockout mice, topical imiquimod was unable to restore permeability barrier recovery after tacrolimus treatment (n=21). In conclusion, IL-1α stimulation induced positive effects on epidermal permeability and antimicrobial barrier functions in tacrolimus-treated skin. These positive effects were mediated by an increase in epidermal lipid synthesis, LB production, and AMP expression.