Electroacupuncture alleviates ventilator-induced lung injury in mice by inhibiting the TLR4/NF-κB signaling pathway.

OBJECTIVE: This study was aimed to explore the protective effect of electroacupuncture (EA) pretreatment at Zusanli point (ST36) on ventilation-induced lung injury (VILI) and its potential anti-inflammatory mechanism. METHODS: High tidal volume ventilation was used to induce the VILI in mice, and EA pretreatment at ST36 was given for 7 consecutive days. The wet/dry ratio and pathological injury score of lung tissue, and total protein content of pulmonary alveolar lavage fluid (BALF) were detected after 4 h of mechanical ventilation (MV). Meanwhile, the expressions of TLR4 and NF- κB in lung tissue were evaluated by Western Blot, and the inflammatory factors in lung tissue were detected by ELISA. RESULTS: After four hours of mechanical ventilation, mice with ventilator-induced lung injury showed significant increases in lung wet/dry ratio, tissue damage scores, and protein content in bronchoalveolar lavage fluid. Pro-inflammatory cytokines (IL-6, IL-1ß, TNF-α) and TLR4/NF-κB expression levels in the lung were also markedly elevated (P < 0.05). Conversely, ST36 acupuncture point pre-treatment significantly reduced these parameters (P < 0.05). CONCLUSION: EA pretreatment at ST36 could alleviate the inflammatory response for VILI via inhibiting TLR4/NF- κB pathway.

A systematic review and network meta-analysis of virtual reality, audiovisuals and music interventions for reducing dental anxiety related to tooth extraction.

BACKGROUND: Tooth extraction is a common procedure performed by oral and maxillofacial surgeons or dentists, often resulting in dental fear and anxiety. The use of relaxing music, audiovisuals, and virtual reality (VR) technologies has been employed to reduce dental anxiety. This network meta-analysis (NMA) aimed to assess the comparative effectiveness of relaxing music, audiovisuals, and VR in reducing dental anxiety associated with tooth extraction. METHODS: Four electronic databases were searched up to March 8, 2023, to identify randomized controlled trials (RCTs) evaluating different multimedia interventions, including the application of using relaxing music, audiovisuals, and VR technologies for dental anxiety. Studies utilizing various anxiety scales for tooth extraction were considered eligible. The pooled standard mean difference (SMD) and 95% confidence interval (CI) of anxiety scale scores were analyzed using Bayesian NMA. RESULTS: A total of 11 RCTs were included in this NMA. The Bayesian NMA results demonstrated that relaxing music (SMD = -0.64, 95% CI: -1.04, -0.25) and VR (SMD = -0.54, 95% CI: -1.08, -0.02) were associated with a reduction in dental anxiety, while audiovisuals (SMD = -0.34, 95% CI: -0.97, 0.33) required further consideration. Ranking probabilities indicated that relaxing music might be the most acceptable method for individuals with dental anxiety. The frequentist NMA yielded consistent rankings in a sensitivity analysis. CONCLUSIONS: Relaxing music shows the greatest potential for reducing dental anxiety related to tooth extraction when compared to other multimedia interventions.

Attenuation of allergic responses following treatment with resveratrol in anaphylactic models and IgE-mediated mast cells.

Resveratrol exists widely in plant species and has a variety of anti-oxidant, anti-inflammatory, and immunomodulatory properties. However, there have been few reports regarding its anti-food allergic activity. In this study, we demonstrated that resveratrol (isolated from Abies georgei) could decrease the release of ß-hexosaminidase and histamine in rat basophilic leukemia-2H3 cells. Resveratrol was not only found to suppress the development of diarrhea, up-regulate the rectal temperature of ovalbumin-allergic mice, and decrease the serum level of specific immunoglobulin E, mouse mast cell protease-1 and histamine, but also found to decrease the population of dendritic cells, B cells and mast cells of ovalbumin -allergic mice in the spleen or mesenteric lymph node. Furthermore, resveratrol inhibited the release of ß-hexosaminidase and histamine in bone marrow-derived cells and alleviated mast cell-mediated passive cutaneous anaphylaxis reactions. These findings indicated that resveratrol isolated from Abies georgei might have the potential to alleviate food hypersensitivity or allergic disease.

Pharmacokinetic/Pharmacodynamic Evaluation of a Novel Aminomethylcycline Antibiotic, KBP-7072, in the Neutropenic Murine Pneumonia Model against Staphylococcus aureus and Streptococcus pneumoniae.

KBP-7072 is a novel aminomethylcycline antibiotic in clinical development for community-acquired pneumonia. The goal of present studies was to determine which pharmacokinetic/pharmacodynamic (PK/PD) parameter magnitude correlated with efficacy in the murine pneumonia infection model against Staphylococcus aureus and Streptococcus pneumoniae KBP-7072 pharmacokinetic measurements were performed in plasma and epithelial lining fluid (ELF) at 4-fold-increasing doses from 1 to 256 mg/kg of body weight subcutaneously. Pharmacokinetic parameters were calculated using a noncompartmental model and were linear over the dose range. Penetration into ELF ranged from 82% to 238% comparing ELF drug concentrations to plasma free drug concentrations. Twenty-four-hour dose-ranging efficacy studies were then performed in the neutropenic murine pneumonia model against 5 S. aureus (3 methicillin-resistant and 2 methicillin-susceptible) and 6 S. pneumoniae (2 Tetr and 2 Penr) strains. KBP-7072 demonstrated potent in vivo activity resulting in a 3- to 5-log10 kill in CFU burden compared to the start of therapy for all strains. The PK/PD index area under the concentration-time curve (AUC)/MIC corelated well with efficacy (R2, 0.80 to 0.89). Net stasis was achieved at plasma 24-h free drug AUC/MIC values of 1.13 and 1.41 (24-h ELF AUC/MIC values of 2.01 and 2.50) for S. aureus and S. pneumoniae, respectively. A 1-log10 kill was achieved at 24-h plasma AUC/MIC values of 2.59 and 5.67 (24-h ELF AUC/MIC values of 4.22 and 10.08) for S. aureus and S. pneumoniae, respectively. A 2-log10 kill was achieved at 24-h plasma AUC/MIC values of 7.16 and 31.14 (24-h ELF AUC/MIC values of 8.37 and 42.92) for S. aureus and S. pneumoniae, respectively. The results of these experiments will aid in the rational design of dose-finding studies for KBP-7072 in patients with community-acquired bacterial pneumonia (CAP).

Salvianolic acid B attenuates experimental skin fibrosis of systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterized mainly by fibrosis of skin and internal organs. Our previous study has shown that salvianolic acid B (SAB), a bioactive component extracted from Salvia miltiorrhiza (SM), was one of the essential ingredients in the traditional Chinese medicine Yiqihuoxue formula, which has been used to treat SSc-related dermal and pulmonary fibrosis. The aim of the present study was to evaluate the effect of SAB on skin fibrosis and explore its underlying anti-fibrotic mechanism. We found that SAB was capable of alleviating skin fibrosis in a bleomycin-induced SSc mouse model, alleviating skin thickness and reducing collagen deposition. in vitro studies indicated that SAB reduced SSc skin fibroblast proliferation and downregulated extracellular matrix gene transcription and collagen protein expression. TGF-ß/SMAD and MAPK/ERK pathway activation were also shown to be suppressed in SAB treated fibroblasts. Moreover, RNA-seq revealed that the anti-fibrotic effect of SAB might be related to antioxidant activity, the cell cycle, and the p53 signaling pathway. Taken together, our results suggest that SAB has the ability to alleviate SSc-related skin fibrosis both in vivo and in vitro.

Actinomadura hankyongense sp. nov. Isolated From Soil of Ginseng Cultivating Field.

A Gram-positive, rod-shaped, non-spore-forming, and aerobic bacterium (Gsoil 556T) was isolated from soil of a ginseng field and subjected to its taxonomic position. Based on 16S rRNA gene sequence similarity, strain Gsoil 556T was shown to belong to the genus Actinomadura of the family Thermomonosporaceae and was closely related to A. montaniterrae CYP1-1BT (99.3%), A. nitritigenes DSM 44137T (98.7%), and A. rudentiformis HMC1T (98.5%), while it showed less than 98.4% sequence similarity to the other species of this genus. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that it is most closely related to A. rudentiformis HMC1T and A. nitritigenes DSM 44137T. The DNA G+C content was 73.1 mol%. The peptidoglycan was meso-diaminopimelic acid and the whole-cell sugar contained fucose, galactose, glucose, mannose, and ribose. The predominant menaquinone (KK) was MK-9(H8) [55%] and MK-9(H6) [45%]. The major cellular fatty acids were C14:0, C16:0, C18:1 ω9c and summed feature 3 (C16:1 ω6c/C16:1 ω7c). All these data supported the affiliation of strain Gsoil 556T to the genus Actinomadura. The DNA-DNA hybridization between strain Gsoil 556T and its phylogenetically closest relatives were less than 40%. Furthermore, the results of physiological and biochemical tests enabled strain Gsoil 556T to be differentiated genotypically and phenotypically from currently known Actinomadura species. Therefore, strain Gsoil 556T represents a novel species of the genus Actinomadura, for which the name Actinomadura hankyongense sp. nov. is proposed. The type strain Gsoil 556T (=KACC 19438T=LMG 30327T).

Bioremediation of petroleum-contaminated soil using aged refuse from landfills.

This study explored the effects and mechanisms of petroleum-contaminated soil bioremediation using aged refuse (AR) from landfills. Three treatments of petroleum-contaminated soil (47.28 mg·g-1) amended with AR, sterilized aged refuse (SAR) and petroleum-contaminated soil only (as a control) were tested. During 98 days of incubation, changes in soil physicochemical properties, residual total petroleum hydrocarbon (TPH), biodegradation kinetics, enzyme activities and the microbial community were investigated. The results demonstrated that AR was an effective soil conditioner and biostimulation agent that could comprehensively improve the quality of petroleum-contaminated soil and promote microbial growth, with an 74.64% TPH removal rate, 22.36 day half-life for SAR treatment, compared with the control (half-life: 138.63 days; TPH removal rate: 22.40%). In addition, the petroleum-degrading bacteria isolation results demonstrated that AR was also a petroleum-degrading microbial agent containing abundant microorganisms. AR addition significantly improved both the biotic and abiotic conditions of petroleum-contaminated soil without other additives. The cooperation of conditioner addition, biostimulation and bioaugmentation in AR treatment led to better bioremediation effects (half-life: 13.86 days; TPH removal rate: 89.83%). In conclusion, AR amendment is a cost-effective, easy-to-use method facilitating in situ large-scale application while simultaneously recycling huge amounts of AR from landfills.

Polaromonas ginsengisoli sp. nov., isolated from ginseng field soil.

A Gram-reaction-negative, strictly aerobic, milky-white and rod-shaped bacterium (designated Gsoil 115T) isolated from ginseng field soil was characterized by a polyphasic approach to clarify its taxonomic position. Strain Gsoil 115T grew optimally at 30 °C and at pH 7.0 on Reasoner's 2A agar medium. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain Gsoil 115T belongs to the genus Polaromonas and was most closely related to Polaromonaseurypsychrophila B717-2T (98.6 %), Polaromonasvacuolata 34-PT (98.3 %), Polaromonasjejuensis NBRC 106434T (98.1 %), Polaromonas aquatic CCUG 39402T (97.7 %) and Polaromonascryoconiti Cr4-35T (97.5 %). The DNA G+C content was 60.9 mol%. The DNA-DNA hybridization relatedness between strain Gsoil 115T and P. eurypsychrophila B717-2T, P. vacuolata 34-PT, P. jejuensis NBRC 106434T, P. aquatic CCUG 39402T and P. cryoconiti Cr4-35T were 31.2, 21.6, 16.9, 8.7 and 10.1 %, respectively. The major polar lipids were phosphatidylglycerol (PG), diphosphatidylglycerol (DPG) and phosphatidylethanolamine (PE). The sole respiratory quinone was Q-8. The major fatty acids were C16 : 0 and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), which supported the affiliation of strain Gsoil 115T to the genus Polaromonas. Moreover, the physiological, biochemical and low level of DNA-DNA relatedness value allowed the phenotypic and genotypic differentiation of strain Gsoil 115T from the recognized species of the genus Polaromonas. Therefore, strain Gsoil 115T represents a novel species of the genus Polaromonas, for which the name Polaromonas ginsengisoli sp. nov. is proposed, with the type strain Gsoil 115T (LMG 23393T=KCTC 12577T).

Mucilaginibacter hankyongensis sp. nov., isolated from soil of ginseng field Baekdu Mountain.

A Gram-negative, non-motile, aerobic, and rod-shaped bacterial strain designated as BR5-28T was isolated from the soil of a ginseng field at Baekdu Mountain Korea, and its taxonomic position was investigated using a polyphasic approach. Strain BR5-28T grew at 10-42°C (optimum temperature, 30°C) and pH 5.5-8.5 (optimum pH, 7.0) on R2A agar medium without additional NaCl supplementation. Strain BR5- 28T exhibited ß-glucosidase activity, which was responsible for its ability to transform the ginsenosides Rb1 and Rd (the two dominant active components of ginseng) to compound-K. Based on 16S rRNA gene phylogeny, the novel strain showed a new branch within the genus Mucilaginibacter of the family Sphingobacteriaceae, and formed clusters with Mucilaginibacter frigoritolerans FT22T (95.8%) and Mucilaginibacter gotjawali SA3-7T (95.7%). The G+C content of the genomic DNA was 45.1%. The predominant respiratory quinone was MK-7 and the major fatty acids were summed feature 3 (comprising C16:1 ω6c and/or C16:1 ω7c), iso-C15:0 and anteiso-C15:0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Strain BR5-28T was differentiated genotypically and phenotypically from the recognized species of the genus Mucilaginibacter. The isolate therefore represents a novel species, for which the name Mucilaginibacter hankyongensis sp. nov. is proposed, with the type strain BR5-28T (=KCTC 22274T =DSM 21151T).

Treatment effects of the traditional Chinese medicine Shenks in bleomycin-induced lung fibrosis through regulation of TGF-beta/Smad3 signaling and oxidative stress.

Pulmonary fibrosis is a kind of devastating interstitial lung disease due to the limited therapeutic strategies. Traditional Chinese medicine (TCM) practices have put forth Shenks as a promising treatment approach. Here, we performed in vivo study and in vitro study to delineate the anti-fibrotic mechanisms behind Shenks treatment for pulmonary fibrosis. We found that regardless of the prophylactic or therapeutic treatment, Shenks was able to attenuate BLM-induced-fibrosis in mice, down regulate extracellular matrix genes expression, and reduce collagen production. The aberrantly high Smad3 phosphorylation levels and SBE activity in TGF-ß-induced fibroblasts were dramatically decreased as a result of Shenks treatment. At the same time, Shenks was able to increase the expression of antioxidant-related genes, including Gclc and Ec-sod, while reduce the transcription levels of oxidative-related genes, such as Rac1 and Nox4 demonstrated by both in vivo and in vitro studies. Further investigations found that Shenks could decrease the oxidative productions of protein (3-nitrotyrosine) and lipid (malondialdehyde) and increase GSH content both in bleomycin treated mouse lungs and TGF-ß stimulated fibroblasts, as well as inhibit the production of ROS stimulated by TGF-ß to fight against oxidative stress. Overall, Shenks inhibited fibrosis by blocking TGF-ß pathway and modulating the oxidant/antioxidant balance.

Eucheuma cottonii Sulfated Oligosaccharides Decrease Food Allergic Responses in Animal Models by Up-regulating Regulatory T (Treg) Cells.

In the present study, the anti-food allergy activity of Eucheuma cottonii sulfated oligosaccharide (ESO) was investigated. ESO was obtained by enzymatic degradation and purified by column chromatography. RBL-2H3 cells and BALB/c mouse model were used to test the anti-food allergy activity of ESO. The effects of ESO on the regulatory T (Treg) cells and bone marrow-derived mast cells (BMMCs) were investigated by flow cytometry. The results of in vivo assay showed that ESO decreased the levels of mast cell protease-1 and histamine and inhibited the levels of specific IgE by 77.7%. In addition, the production of interleukin (IL)-4 and IL-13 was diminished in the ESO groups compared to the non-ESO-treated group. Furthermore, ESO could up-regulate Treg cells by 22.2-97.1%. In conclusion, ESO decreased the allergy response in mice by reducing basophil degranulation, up-regulating Treg cells via Forkhead box protein 3 (Foxp3), and releasing IL-10. ESO may have preventive and therapeutic potential in allergic disease.

Salvianolic Acid B Attenuates Experimental Pulmonary Fibrosis through Inhibition of the TGF-ß Signaling Pathway.

Pulmonary fibrosis is a progressive and fatal disorder. In our previous study, we found that the Yiqihuoxue formula (YQHX), a prescription of Traditional Chinese Medicine, had a curative effect on scleroderma, a typical fibrotic disease. The aim of this study was to determine the key ingredient mediating the therapeutic effects of YQHX and to examine its effect on pulmonary fibrosis, including its mechanism. Luciferase reporter assays showed that the most important anti-fibrotic component of the YQHX was Salviae miltiorrhiza (SM). Experiments performed using a bleomycin-instilled mouse model of pulmonary fibrosis showed that Salvianolic acid B (SAB), the major ingredient of SM, had strong anti-inflammatory and anti-fibrotic effects through its inhibition of inflammatory cell infiltration, alveolar structure disruption, and collagen deposition. Furthermore, SAB suppressed TGF-ß-induced myofibroblastic differentiation of MRC-5 fibroblasts and TGF-ß-mediated epithelial-to-mesenchymal transition of A549 cells by inhibiting both Smad-dependent signaling and the Smad-independent MAPK pathway. Taken together, our results suggest that SM is the key anti-fibrotic component of the YQHX and that SAB, the major ingredient of SM, alleviates experimental pulmonary fibrosis both in vivo and in vitro by inhibiting the TGF-ß signaling pathway. Together, these results suggest that SAB potently inhibits pulmonary fibrosis.

Anti-Food Allergic Activity of Sulfated Polysaccharide from Gracilaria lemaneiformis is Dependent on Immunosuppression and Inhibition of p38 MAPK.

Polysaccharides from Gracilaria lemaneiformis in particular possess various bioactive functions, but their antiallergic activity remains incompletely defined. Sulfated polysaccharide from Gracilaria lemaneiformis (GLSP) was obtained by water extraction and ethanol precipitation followed by column chromatography. BALB/c mice, RBL-2H3, and KU812 cells were used for verifying the anti food allergic activity of GLSP. According to the results of mice experiment, GLSP was able to alleviate allergy symptoms, to reduce TM-specific IgE and IgG1, to suppress Th2 cell polarization, and to promote the function of regulatory T (Treg) cells. In addition, GLSP had the ability to inhibit the function of RBL-2H3 cells. Furthermore, GLSP inhibited the activation of KU812 via suppression of p38 mitogen-activated protein kinase (MAPK). In conclusion, immunosuppression as well as the reduction in the level of p38 MAPK may contribute to GLSP's putative activity against food allergy. GLSP may be used as a functional food component for allergic patients.

Marmoricola ginsengisoli sp. nov. and Marmoricola pocheonensis sp. nov. isolated from a ginseng-cultivating field.

Two novel actinobacteria, designated strains Gsoil 097T and Gsoil 818T, isolated from soil of a ginseng field, South Korea, were characterized by a polyphasic approach to clarify their taxonomic positions. They were Gram-reaction-positive, aerobic, non-spore-forming and rod-shaped. Phylogenetic analysis based on 16S rRNA gene sequences indicated that both isolates belong to the genus Marmoricola and were related most closely to Marmicola solisilvae KIS18-7T (99.1 and 98.3 % similarity, respectively), Marmicola terrae JOS5-1T (97.9 and 97.9 %), Marmicola scoriae Sco-D01T (97.8 and 97.1 %) and Marmicola aequoreus SST-45T (97.5 and 97.0 %). The G+C content of the genomic DNA was 68.8 and 70.0 mol%, respectively. Both strains were characterized chemotaxonomically as having ll-2,6-diaminopimelic acid in the cell-wall peptidoglycan, MK-8(H4) as the predominant menaquinone and C17 : 1ω6c, C18 : 1ω9c, C18 : 0 10-methyl and iso-C16 : 0 as major fatty acids. These chemotaxonomic data supported the affiliation of both strains to the genus Marmoricola. However, levels of DNA-DNA relatedness between the two strains and closely related type strains of Marmoricola species were less than 30 %. Moreover, the results of physiological and biochemical tests allowed the phenotypic differentiation of strains Gsoil 097T and Gsoil 818T from other Marmoricola species with validly published names. Therefore, the two isolates represent two novel species, for which the names Marmoricola ginsengisoli sp. nov. (type strain Gsoil 097T = KACC 14267T = DSM 22772T) and Marmoricola pocheonensis sp. nov. (type strain Gsoil 818T = KACC 14275T = DSM 22773T) are proposed.

Flavisolibacter ginsenosidimutans sp. nov., with ginsenoside-converting activity isolated from soil used for cultivating ginseng.

A Gram-reaction-negative, aerobic, non-motile and rod-shaped bacterial strain designated Gsoil 636T was isolated from soil of a ginseng cultivation field in Pocheon Province, South Korea and its taxonomic position was investigated using a polyphasic approach. Gsoil 636T grew at 18-30 °C and at pH 6.0-8.0 on R2A medium. Gsoil 636T possessed ß-glucosidase activity, which was responsible for its ability to transform ginsenoside Rb1 (ones of the dominant active components of ginseng) to F2. On the basis of 16S rRNA gene sequence similarity, Gsoil 636T was shown to belong to the family Chitinophagaceae and to be related to Flavisolibacter ginsengiterrae Gsoil 492T (96.7 % sequence similarity), Flavisolibacter ginsengisoli Gsoil 643T (96.6 %) and Flavisolibacter rigui 02SUJ3T (96.6 %). The G+C content of the genomic DNA was 48.9 %. The predominant respiratory quinone was MK-7 and the major fatty acids were iso-C15 : 0, summed feature 3 (comprising C16 : 1ω6c and/or C16 : 1ω7c) and iso-C17 : 0 3-OH. DNA and chemotaxonomic data supported the affiliation of Gsoil 636T to the genus Flavisolibacter. Gsoil 636T could be differentiated genotypically and phenotypically from the species of the genus Flavisolibacter with validly published names. The isolate therefore represents a novel species, for which the name Flavisolibacter ginsenosidimutans sp. nov. is proposed, with the type strain Gsoil 636T (KCTC 22818T = JCM 18197T = KACC 14277T).

Dissection of the mechanism of traditional Chinese medical prescription-Yiqihuoxue formula as an effective anti-fibrotic treatment for systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue fibrotic disease for which there is no effective treatment. Traditional Chinese Medicine (TCM), such as the Yiqihuoxue formula used in Shanghai TCM-integrated Hospital, has shown the efficacy of anti-fibrosis in clinical applications. This study was aiming to dissect the anti-fibrotic mechanism of Yiqihuoxue treatment for SSc. METHODS: Bleomycin-induced mice and SSc dermal fibroblasts were treated with Yiqihuoxue decoction; NIH-3T3 fibroblasts were exposed to exogenous TGF-ß1, and then cultured with or without Yiqihuoxue decoction. Luciferase reporter gene assay was used to determine the activity of Smad binding element (SBE). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the mRNA levels of extracellular matrix (ECM) genes. The protein levels of type I collagen, Smad3 and phosphorylated-Smad3 (p-Smad3) were detected by western blotting. Student's t-tests were used to determine the significance of the results. RESULTS: Bleomycin-induced mice, SSc dermal fibroblasts and TGF-ß1-induced NIH/3T3 fibroblasts showed higher levels of ECM gene transcriptions and collagen production. In addition, the phosphorylation level of Smad3 and activity of SBE were significantly increased after exogenous TGF-ß1 induction. Whereas, Yiqihuoxue treatment could obviously attenuate fibrosis in bleomycin-induced mice, down regulate ECM gene expressions and collagen production in SSc dermal fibroblasts and TGF-ß1-induced NIH/3T3 fibroblasts. Furthermore, the aberrantly high phosphorylation level of Smad3 and activity of SBE in the TGF-ß1-induced NIH/3T3 fibroblasts were also dramatically decreased by Yiqihuoxue treatment. CONCLUSIONS: Yiqihuoxue treatment could effectively reduce collagen production via down-regulating the phosphorylation of Smad3 and then the activity of SBE, which are involved in the TGF-ß pathway and constitutively activated in the progression of SSc.

Mucilaginibacter ginsenosidivorax sp. nov., with ginsenoside converting activity isolated from sediment.

A Gram-reaction-negative, strictly aerobic, non-motile, non-spore-forming, and rod-shaped bacterial strain designated KHI28(T) was isolated from sediment in Gapcheon (river) and its taxonomic position was investigated using a polyphasic approach. Strain KHI28(T) grew at 10-42°C and at pH 5.5-8.5 on R2A and nutrient agar without additional NaCl as a supplement. Strain KHI28(T) possessed ß-glucosidase activity, which was responsible for its ability to transform ginsenosides Rb1 and Re (ones of the dominant active components of ginseng) to C-K and Rg2, respectively. On the basis of 16S rRNA gene sequence similarity, strain KHI28(T) was shown to belong to the family Sphingobacteriaceae and to be related to Mucilaginibacter dorajii DR-f4(T) (97.9% sequence similarity), M. polysacchareus DRP28(T) (97.3%), and M. lappiensis ANJLI2(T) (97.2%). The G+C content of the genomic DNA was 45.8%. The predominant respiratory quinone was MK-7 and the major fatty acids were summed feature 3 (comprising C16:1 ω6c and/or C16:1 ω7c), iso-C15:0 and C16:0. DNA and chemotaxonomic data supported the affiliation of strain KHI28(T) to the genus Mucilaginibacter. Strain KHI28(T) could be differentiated genotypically and phenotypically from the recognized species of the genus Mucilaginibacter. The isolate therefore represents a novel species, for which the name Mucilaginibacter ginsenosidivorax sp. nov. is proposed, with the type strain KHI28(T) (=KACC 14955(T) =LMG 25804(T)).

Mass production of the ginsenoside Rg3(S) through the combinative use of two glycoside hydrolases.

The ginsenoside Rg3(S), which is one of the exceptional components of Korean red ginseng extract, has been known to have anti-cancer, anti-metastatic, and anti-obesity effects. An enzymatic bioconversion method was developed to obtain the ginsenoside Rg3(S) with a high specificity, yield, and purity. Two glycoside hydrolases (BglBX10 and Abf22-3) were employed to produce Rg3(S) as a 100g unit. The conversion reaction transformed ginsenoside Rc to Rd using Abf22-3, followed by Rb1 and Rd to Rg3(S), using BglBX10. It was performed in a 10L jar fermenter at pH 6.0 and 37°C for 24h, with a high concentration of 50mg/ml of purified ginsenoside mixture obtained from ginseng roots. Finally, 144g of Rg3(S) was produced from 250g of root extract with 78±1.2% chromatographic purity. These results suggest that this enzymatic method would be useful in the preparation of ginsenoside Rg3(S) for the functional food and pharmaceutical industries.

Nocardioides panaciterrulae sp. nov., isolated from soil of a ginseng field, with ginsenoside converting activity.

A Gram-positive, coccoid to rod-shaped, non-spore-forming bacterium, designated Gsoil 958(T), was isolated from soil of a ginseng field located in Pocheon province in South Korea. This bacterium was characterized in order to determine its taxonomic position by using a polyphasic approach. Strain Gsoil 958(T) was observed to grow well at 25-30 °C and at pH 7.0 on R2A and nutrient agar without NaCl supplementation. Strain Gsoil 958(T) was determined to have ß-glucosidase activity and the ability to transform ginsenoside Rb1 (one of the dominant active components of ginseng) to F2 via gypenoside XVII and Rd. On the basis of 16S rRNA gene sequence similarity, strain Gsoil 958(T) was shown to belong to the family Nocardioidaceae and related most closely to Nocardioides koreensis MSL-09(T) (97.6 % 16S rRNA gene sequence similarity), Nocardioides aquiterrae GW-9(T) (97.0 %), and Nocardioides sediminis MSL-01(T) (97.0 %). The sequence similarities with other validly named species within the genus Nocardioides were less than 96.8 %. Strain Gsoil 958(T) was characterized chemotaxonomically as having LL-2,6-diaminopimelic acid in the cell-wall peptidoglycan, MK-8(H4) as the predominant menaquinone, and iso-C16:0, iso-C16:1 H, iso-C14:0, iso-C15:0 were identified as the major fatty acids. The G + C content of genomic DNA was determined to be 70.8 mol %. The chemotaxonomic properties and phenotypic characteristics supported the affiliation of strain Gsoil 958(T) to the genus Nocardioides. The results of both physiological and biochemical tests allowed for differentiation of strain Gsoil 958(T) from the recognized Nocardioides species. Therefore, strain Gsoil 958(T) is considered to represent a novel species of the genus Nocardioides, for which the name Nocardioides panaciterrulae sp. nov. is proposed, with the type strain Gsoil 958(T) (KACC 14271(T) = KCTC 19471(T) = DSM 21350(T)).

Sphingomonas ginsengisoli sp. nov. and Sphingomonas sediminicola sp. nov.

Two novel bacteria, designated strains Gsoil 634(T) and Dae 20(T), were isolated in South Korea from soil of a ginseng field and freshwater sediment, respectively and were characterized by a polyphasic approach to clarify their taxonomic positions. Phylogenetic analysis based on 16S rRNA gene sequences indicated that, although they probably represented two distinct species (indicated by a sequence similarity of 96.6 %), both strain Gsoil 634(T) and strain Dae 20(T) belonged to the genus Sphingomonas and were most closely related to 'Sphingomonas humi' PB323 (97.8 % and 96.7 % sequence similarity, respectively), Sphingomonas kaistensis PB56(T) (96.8 % and 96.7 %), Sphingomonas astaxanthinifaciens TDMA-17(T) (96.6 % and 95.4 %) and Sphingomonas jaspsi TDMA-16(T) (95.6 % and 95.8 %). For both novel strains, the major ubiquinone was Q-10, the major polyamine was homospermidine, the major cellular fatty acids included summed feature 7 (C(18 : 1)ω7c, C(18 : 1)ω9t and/or C(18 : 1)ω12t), C(17 : 1)ω6c and C(16 : 0), and the polar lipids included sphingoglycolipid. These chemotaxonomic data supported the affiliation of both strains to the genus Sphingomonas. However, the DNA-DNA relatedness value between strain Gsoil 634(T) and 'Sphingomonas humi' PB323(T) was 31 %. Moreover, the results of physiological and biochemical tests allowed the phenotypic differentiation of strains Gsoil 634(T) and Dae 20(T) from established members of the genus Sphingomonas. Based on these data, the two isolates represent two novel species in the genus Sphingomonas, for which the names Sphingomonas ginsengisoli sp. nov. (type strain Gsoil 634(T) = KCTC 12630(T) = DSM 18094(T) = LMG 23739(T)) and Sphingomonas sediminicola sp. nov. (type strain Dae 20(T)  = KCTC 12629(T) = DSM 18106(T) = LMG 23592(T)) are proposed.