Complete genome sequence of pectin-degrading Flavobacteriaceae bacterium GSB9.

Pectic oligosaccharides, which are considered to be potential prebiotics, may be generated by pectin-degrading enzymes. Here, we report the complete genome sequence of the pectin-degrading marine bacterium, Flavobacteriaceae bacterium GSB9, which was isolated from seawater of South Korea. The complete genome sequence revealed that the chromosome was 3,630,376 bp in size, had a G + C content of 36.6 mol%, and was predicted to encode 3100 protein-coding sequences (CDSs), 40 tRNAs, and six 16S-23S-5S rRNAs. Genome sequence analysis revealed that this strain possesses multiple genes predicted to encode pectin-degrading enzymes. Our analysis may facilitate the future application of this strain against pectin in various industries.

Co-delivery of curcumin and miRNA-144-3p using heart-targeted extracellular vesicles enhances the therapeutic efficacy for myocardial infarction.

Curcumin exerts therapeutic effects in heart disease, but has limited bioavailability. Extracellular vesicles (EVs) have gained attention as nanovehicles; however, the poor targeting ability of systemically administered EVs still remains a crucial issue. Herein, we generated heart-targeted EVs (CTP-EVs) by functionalizing EVs surface with cardiac targeting peptide (CTP) using genetic modification of EVs-secreting cells, and further loaded curcumin into CTP-EVs (CTP-EVs-Cur). Consequently, CTP-EVs were able to specifically deliver curcumin to the heart. In addition, curcumin-loaded CTP-EVs possess improved bioavailability, and are fully functional with a high cardioprotective efficiency. Moreover, we loaded miR-144-3p in CTP-EVs-Cur following validation of miR-144-3p as a major contributor in curcumin-mediated therapeutic effects. The simultaneous packing of curcumin and miR-144-3p in CTP-EVs not only retains the active heart-targeting ability but also achieves enhanced cardioprotective effects both in vitro and in vivo, indicating the possibility of combining and sustaining their therapeutic potential by simultaneously loading in CTP-EVs. Therefore, CTP-EVs could be a potential and effective strategy for the delivery of therapeutic molecules, thereby providing a promising nanomedicine for MI therapy.

Effect of nintedanib on airway inflammation in a mouse model of acute asthma.

Objective: New treatments are needed for cases of asthma that are refractory to traditional therapies. In this study, we examined the effect of oral nintedanib, an intracellular inhibitor of tyrosine kinases, on airway hyper-responsiveness (AHR) and airway smooth muscle cells, using a mouse model of experimental asthma. Methods: Asthma was experimentally induced in mice via subcutaneous injection of ovalbumin (OVA). A group of saline-injected mice served as a control group. The OVA mice were then divided into four treatment groups according to the dose of nintedanib. AHR was examined via exposure to vaporized methacholine. Airway inflammation was assessed via bronchoalveolar lavage fluid (BALF) cell counts and Th2 cytokine concentrations. Results: Baseline levels of AHR and airway inflammation were higher in OVA mice than in the control group. Treatment with nintedanib lowered AHR, BALF cell counts and BALF cytokine levels in a dose-dependent fashion. The effect of nintedanib was comparable to that of dexamethasone. In particular, treatment with nintedanib lowered the expression of transforming growth factor-ß1 and inhibited the expression and phosphorylation of platelet-derived growth factor receptor-ß, vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR2, fibroblast growth factor receptor 2 (FGFR2), FGFR3, and extracellular signal-regulated kinase. Conclusions: Nintedanib lowered AHR and the expression of factors associated with airway inflammation and remodeling in a mouse model of experimental asthma. Our results suggest that nintedanib may be useful in the treatment of asthma.

Social Network Types, Health, and Health-Care Use Among South Korean Older Adults.

This study examines the associations among social network types, multiple health conditions, and various health-care use. Data came from the 2006 and 2008 wave of the Korean Longitudinal Study of Aging. A two-step cluster analytical approach was used to identify social network types. Regression models determined associations between social network types, health changes, and health-care use, including checkups, outpatient service, traditional medicine use, and hospitalization. Four social network types (restricted, couple focused, friend, and diverse) were found. Compared with the restricted type, individuals in the couple-focused type were more likely to use traditional medicine and outpatient care; members in the diverse type were more likely to use traditional medicine. The interaction model revealed varying associations between health change and social network on health-care use. Findings reveal the culturally contextualized association among multiple health conditions and how social network type moderates the relationship with health-care use.

A nationwide study of the incidence rate of herb-induced liver injury in Korea.

Discrepant incidence has been reported regarding the incidence of herb-induced liver injury (HILI). To address the growing worldwide concern of HILI, we evaluated the risk of HILI in a nationwide prospective study. Between April 2013 and January 2016, 1001 inpatients (360 males and 641 females) from 10 tertiary hospitals throughout South Korea were treated with herbal drugs and had their liver enzymes periodically measured. A total of six patients met the criteria for HILI with RUCAM scores ranging from 4 to 7. All these participants were women and developed the hepatocellular type of HILI. One HILI participant met the criteria for Hy's law; however, none of six cases presented clinical symptoms related to liver injury. This is the first nationwide prospective study that estimated the extent of the incidence of HILI [total: 0.60%, 95% confidence interval (CI) 0.12-1.08; women: 0.95%, 95% CI 0.19-1.68] and described its features in hospitalized participants.

A manual acupuncture treatment attenuates common cold and its symptoms: a case series report from South Korea.

OBJECTIVE: To investigate beneficial effects of manual acupuncture on common cold periods and its symptoms depended on the difference onset time of common cold, within 36 h or over than that. To prove effects of manual acupuncture on common cold, a retrospective chart review was conducted. METHODS: Chart data for patients with common cold who were treated with only manual acupuncture with fulfilling Jackson scales and satisfaction at the end of each treatment were collected via multi-centers of Oriental hospitals, Oriental medicine clinics and covalent hospital in South Korea. Totally 187 patients were divided into two groups, Group Ⅰ (115 patients, within 36 h) and Group Ⅱ (72 patients, onset time of cold over than 36 h). Finally 120 patients were observed until entire resolution of cold symptoms. RESULTS: Group Ⅰ showed significant decreases themediandurationsofcompletelyrecovery (3 days; 95% CI 3.0-4.0) as compared with Group Ⅱ (6 days; 95% CI 4.0-7.0, P < 0.001). The manual acupuncture beneficially worked for reduction rate of common cold symptoms by 50% after initial treatment, decreased cold symptoms, and reduced cold duration. CONCLUSION: Manual acupuncture beneficially affected common cold and its symptoms. Moreover it is more susceptibility on the early time of onset cold.

Moringa oleifera with promising neuronal survival and neurite outgrowth promoting potentials.

ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera Lam. (Moringaceae) by virtue of its high nutritional as well as ethnomedical values has been gaining profound interest both in nutrition and medicinal research. The leaf of this plant is used in ayurvedic medicine to treat paralysis, nervous debility and other nerve disorders. In addition, research evidence also suggests the nootropic as well as neuroprotective roles of Moringa oleifera leaf in animal models. The aim of the present study was to evaluate the effect of Moringa oleifera leaf in the primary hippocampal neurons regarding its neurotrophic and neuroprotective properties. MATERIALS AND METHODS: The primary culture of embryonic hippocampal neurons was incubated with the ethanol extract of Moringa oleifera leaf (MOE). After an indicated time, cultures were either stained directly with a lipophilic dye, DiO, or fixed and immunolabeled to visualize the neuronal morphology. Morphometric analyses for neurite maturation and synaptogenesis were performed using Image J software. Neuronal viability was evaluated using trypan blue exclusion and lactate dehydrogenase assays. RESULTS: MOE promoted neurite outgrowth in a concentration-dependent manner with an optimal concentration of 30 µg/mL. As a very initial effect, MOE significantly promoted the earlier stages of neuronal differentiation. Subsequently, MOE significantly increased the number and length of dendrites, the length of axon, and the number and length of both dendrite and axonal branches, and eventually facilitated synaptogenesis. The ß-carotene, one major compound of MOE, promoted neuritogensis, but the increase was not comparable with the effect of MOE. In addition, MOE supported neuronal survival by protecting neurons from naturally occurring cell death in vitro. CONCLUSIONS: Our findings indicate that MOE promotes axodendritic maturation as well as provides neuroprotection suggesting a promising pharmacological importance of this nutritionally and ethnomedically important plant for the well-being of nervous system.

A traditional herbal formula, Hyangsa-Pyeongwi san (HPS), improves quality of life (QoL) of the patient with functional dyspepsia (FD): randomized double-blinded controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyangaa-Pyeongwi san is the most well known description in Traditional Chinese Medicine for treating functional gastrointestinal disorders. Functional dyspepsia (FD) is a main concern of intimidating quality of life (QoL) in recent days. Although many medicines have been developed to improve FD symptoms as well as QoL, there are no potential drugs and treatments for FD. The aim of this study is to investigate the effects of Hyangaa-Pyeongwi san (HPS) on QoL of patients with FD. METHODS: This study was designed as a randomized, double blinded, placebo controlled, and parallel group trial. Participants received either placebo or HPS (9.68g of HPS at once, three times daily) for 4-weeks, and the efficacy evaluations were performed by assessing the Nepean Dyspepsia Index (NDI) and functional dyspepsia-quality of life (FD-QoL) at 0-, 4- and 8-weeks. RESULTS: Total of 170 patients participated and were randomly allocated into placebo or HPS groups. Total symptom score of NDI decreased after 4-weeks trial in both groups (p>0.05). HPS significantly improved QoL scores, especially in the area of 'interference and eat/drink' in NDI (p=0.0031) as well as 'liveliness status', 'role-functioning status', and total score in FD-QoL (p=0.026 for liveliness status and p=0.035 for role-functioning status). This significant improvement of FD-QoL had lasted for 4-weeks. CONCLUSION: HPS treatment is markedly effective in improving QoL in patients with FD. Moreover, we observed that this improvement had lasted for 4 weeks after finishing the trial through the follow-up study.

The marine alga Gelidium amansii promotes the development and complexity of neuronal cytoarchitecture.

Neurotrophic factors are vital not only to support neuronal development but also to protect mature neurons from atrophy in neurodegenerative diseases. As an effort to explore natural sources that possess neurotrophic activity, we screened common marine algae for their neuritogenic activity in the developing rat hippocampal neurons in culture. Of the 22 seaweed species examined, ethanol extracts of Gelidium amansii (GAE) exhibited potent neuritogenic activity, followed by Undaria pinnatifida and Sargassum fulvellum extracts. The effects of GAE were dose dependent with an optimum concentration of 15 µg/mL. The GAE significantly promoted the initial neuronal differentiation from the stage I into the stage II and increased the indices of axonal and dendritic development such as the length, the numbers of primary processes, and branching frequencies by a minimum of twofold compared with the vehicle control. These results show that marine algae are promising candidates for neurotrophic potentials.

Antiviral activities of flavonoids isolated from the bark of Rhus verniciflua stokes against fish pathogenic viruses In Vitro.

An 80% methanolic extract of Rhus verniciflua Stokes bark showed significant anti-viral activity against fish pathogenic infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV) in a cell-based assay measuring virus-induced cytopathic effect (CPE). Activity-guided fractionation and isolation for the 80% methanolic extract of R. verniciflua yielded the most active ethyl acetate fraction, and methyl gallate (1) and four flavonoids: fustin (2), fisetin (3), butin (4) and sulfuretin (5). Among them, fisetin (3) exhibited high antiviral activities against both IHNV and VHSV showing EC(50) values of 27.1 and 33.3 µM with selective indices (SI = CC(50)/EC(50)) more than 15, respectively. Fustin (2) and sulfuretin (5) displayed significant antiviral activities showing EC50 values of 91.2-197.3 µM against IHNV and VHSV. In addition, the antiviral activity of fisetin against IHNV and VHSV occurred up to 5 hr post-infection and was not associated with direct virucidal effects in a timed addition study using a plaque reduction assay. These results suggested that the bark of R. verniciflua and isolated flavonoids have significant anti-viral activity against IHNV and VHSV, and also have potential to be used as anti-viral therapeutics against fish viral diseases.

Endobronchial mass developing 19 years after total thyroidectomy due to follicular thyroid carcinoma.

Endobronchial metastasis from thyroid follicular carcinoma is a rare manifestation. We describe a case of 62-year-old woman who underwent total thyroidectomy due to thyroid follicular carcinoma 19 years previously. Computerized tomography and bronchoscopy suggested an endobronchial enhancing nodule in the right bronchus intermedius, resulting in right middle lobe (RML) and right lower lobe (RLL) collapse. A biopsy specimen showed thyroid follicular carcinoma identical to that taken from a specimen previously. She underwent metastectomy and high-dose radioactive iodine ablation therapy. To our knowledge, this patient represents the first case of endobronchial metastasis with a long past history of thyroid follicular carcinoma.

Effects of the brown seaweed Undaria pinnatifida on erythematous inflammation assessed using digital photo analysis.

The brown seaweed Undaria pinnatifida (Harvey) Suringar produced potent inhibition of erythematous inflammation assessed using digital photo analysis. The analysis technique was validated by laser speckle flowgraphy and blood vessel contraction. The methanol extract suppressed erythema by 50% when applied within 1 h before or 15 min after application of phorbol myristate acetate. Erythema reduction to half-maximal values took 12 h with the extract, compared with 25 h with the vehicle. The blade part of the thallus showed the highest activity, while the northern type of U. pinnatifida had slightly higher activity than the southern type. The active constituents were stearidonic acid and eicosapentaenoic acid. These findings reinforce the claims of the health care industry and indigenous medicine that U. pinnatifida can be used as a health food and remedy for inflammation-related symptoms.

Isolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fatty acids from the brown seaweed Undaria pinnatifida.

Two anti-inflammatory omega-3 polyunsaturated fatty acids (PUFAs) of stearidonic acid (SA) and eicosapentaenoic acid (EPA) and one pro-inflammatory omega-6 PUFA of arachidonic acid (AA) were isolated from the edible brown seaweed Undaria pinnatifida. SA was active against mouse ear inflammation induced by phorbol myristate acetate, with IC50 values of 160, 314, and 235 microg per ear for edema, erythema, and blood flow, respectively. EPA was also active against edema, erythema, and blood flow, with IC50 values of 230, 462, and 236 microg per ear, respectively. Although AA at low concentrations showed anti-inflammatory activities when measured 10 h later, AA doses of more than 243 microg per ear induced inflammatory symptoms 1 h later. Mature thalli generally had larger amounts of PUFAs than young thalli. The algal blade contained more omega-3 PUFAs than were found in other parts, while the holdfast contained extremely high amounts of AA. Late-season thalli showed increased amounts of PUFAs, especially AA.

2',5,7-Trihydroxy-4',5'-(2,2-dimethylchromeno)-8-(3-hydroxy-3-methylbutyl) flavanone purified from Cudrania tricuspidata induces apoptotic cell death of human leukemia U937 cells.

Cellular DNA topoisomerase I is an important target in cancer chemotherapy. A chloroform extract of the root barks of Cudrania tricuspidata showed an inhibitory effect on mammalian DNA topoisomerase I. The topoisomerase I inhibitory compound was purified and identified as 2',5,7-trihydroxy-4',5'-(2,2-dimethylchromeno)-8-(3-hydroxy-3-methylbutyl) flavanone. The compound, temporarily designated as PKH-3, was shown to inhibit the activity of topoisomerase I with IC50 about 1.0 mM. Concentration of 10 microM PKH-3 caused 50% growth inhibition of human cancer cell U937. PKH-3-induced cell death was characterized with the cleavage of poly(ADP-ribose) polymerase (PARP) and pro-caspase 3. Furthermore, PKH-3 induced the fragmentation of DNA into multiples of 180 b.p. (an apoptotic DNA ladder), indicating that the inhibitor triggered apoptosis. This induction of apoptosis by PKH-3 was also confirmed using flow cytometry analysis. Taken together, these results suggest that PKH-3 may function by inhibiting oncogenic disease, at least in part, through the inhibition of topoisomerase I activity.