TGFß4 alleviates the phenotype of Charcot-Marie-Tooth disease type 1A.

The duplication of the peripheral myelin protein 22 (PMP22) gene causes a demyelinating type of neuropathy, commonly known as Charcot-Marie-Tooth disease type 1A (CMT1A). Development of effective drugs for CMT1A still remains as an unmet medical need. In the present study, we assessed the role of the transforming growth factor beta 4 (TGFß4)/Nodal axis in the pathogenesis of CMT1A. First, we identified PMP22 overexpression-induced Nodal expression in Schwann cells, which might be one of the downstream effectors in CMT1A. Administration of Nodal protein at the developmental stage of peripheral nerves induced the demyelinating phenotype in vivo. Second, we further isolated TGFß4 as an antagonist that could abolish Nodal-induced demyelination. Finally, we developed a recombinant TGFß4-fragment crystallizable (Fc) fusion protein, CX201, and demonstrated that its application had promyelinating efficacy in Schwann cells. CX201 administration improved the demyelinating phenotypes of CMT1A mouse models at both pre-symptomatic and post-symptomatic stages. These results suggest that the TGFß4/Nodal axis plays a crucial role in the pathogenesis of CMT1A and might be a potential therapeutic target for CMT1A.

The impact of writing on academic performance for medical students.

BACKGROUND: Writing is a useful learning activity that promotes higher-order thinking, but there are limited studies that prove its effectiveness. In previous research, researchers tested the effect of summary writing on students' comprehension and found no significant difference from that of re-studying texts. The purpose of this study, therefore, is to expand previous findings and investigate the effect of two types of writing tasks on medical students' academic performance, specifically in the transfer of knowledge. METHODS: An experiment was conducted with 139 medical students from Seoul National University College of Medicine. They were randomly assigned to three study conditions: self-study (SS), expository writing (EW), and argumentative writing (AW) group. Each group studied the given material by the method they were assigned, and they were tested on their comprehension and transfer of knowledge using rote-memory type items and transfer type items respectively. RESULTS: The results showed that the two writing groups displayed better performance than the SS group in transfer type items, while there was no difference in scores between the EW and AW group. However, the three groups showed no significant difference in their scores for rote-memory type items. Also, there was a positive correlation between the writing scores and transfer type item scores in the AW group. CONCLUSIONS: This study provides empirical evidence for writing to be adopted in medical education for greater educational benefits. Our findings indicate that writing can enhance learning and higher-order thinking, which are critical for medical students.

Superoxide Dismutase 3-Transduced Mesenchymal Stem Cells Preserve Epithelial Tight Junction Barrier in Murine Colitis and Attenuate Inflammatory Damage in Epithelial Organoids.

Superoxide dismutase 3 (SOD3), also known as extracellular superoxide dismutase, is an enzyme that scavenges reactive oxygen species (ROS). It has been reported that SOD3 exerts anti-inflammatory abilities in several immune disorders. However, the effect of SOD3 and the underlying mechanism in inflammatory bowel disease (IBD) have not been uncovered. Therefore, in the present study, we investigated whether SOD3 can protect intestinal cells or organoids from inflammation-mediated epithelial damage. Cells or mice were treated with SOD3 protein or SOD3-transduced mesenchymal stem cells (MSCs). Caco-2 cells or intestinal organoids stimulated with pro-inflammatory cytokines were used to evaluate the protective effect of SOD3 on epithelial junctional integrity. Dextran sulfate sodium (DSS)-induced colitis mice received SOD3 or SOD3-transduced MSCs (SOD3-MSCs), and were assessed for severity of disease and junctional protein expression. The activation of the mitogen-activated protein kinase (MAPK) pathway and elevated expression of cytokine-encoding genes decreased in TNF-α-treated Caco-2 cells or DSS-induced colitis mice when treated with SOD3 or SOD3-MSCs. Moreover, the SOD3 supply preserved the expression of tight junction (ZO-1, occludin) or adherence junction (E-cadherin) proteins when inflammation was induced. SOD3 also exerted a protective effect against cytokine- or ROS-mediated damage to intestinal organoids. These results indicate that SOD3 can effectively alleviate enteritis symptoms by maintaining the integrity of epithelial junctions and regulating inflammatory- and oxidative stress.

Therapeutic Functions of Stem Cells from Oral Cavity: An Update.

Adult stem cells have been developed as therapeutics for tissue regeneration and immune regulation due to their self-renewing, differentiating, and paracrine functions. Recently, a variety of adult stem cells from the oral cavity have been discovered, and these dental stem cells mostly exhibit the characteristics of mesenchymal stem cells (MSCs). Dental MSCs can be applied for the replacement of dental and oral tissues against various tissue-damaging conditions including dental caries, periodontitis, and oral cancers, as well as for systemic regulation of excessive inflammation in immune disorders, such as autoimmune diseases and hypersensitivity. Therefore, in this review, we summarized and updated the types of dental stem cells and their functions to exert therapeutic efficacy against diseases.

Echinochrome A Reduces Colitis in Mice and Induces In Vitro Generation of Regulatory Immune Cells.

Echinochrome A (Ech A), a natural pigment extracted from sea urchins, is the active ingredient of a marine-derived pharmaceutical called 'histochrome'. Since it exhibits several biological activities including anti-oxidative and anti-inflammatory effects, it has been applied to the management of cardiac injury and ocular degenerative disorders in Russia and its protective role has been studied for other pathologic conditions. In the present study, we sought to investigate the therapeutic potential of Ech A for inflammatory bowel disease (IBD) using a murine model of experimental colitis. We found that intravenous injection of Ech A significantly prevented body weight loss and subsequent lethality in colitis-induced mice. Interestingly, T cell proliferation was significantly inhibited upon Ech A treatment in vitro. During the helper T (Th) cell differentiation process, Ech A stimulated the generation regulatory T (Treg) cells that modulate the inflammatory response and immune homeostasis. Moreover, Ech A treatment suppressed the in vitro activation of pro-inflammatory M1 type macrophages, while inducing the production of M2 type macrophages that promote the resolution of inflammation and initiate tissue repair. Based on these results, we suggest that Ech A could provide a beneficial impact on IBD by correcting the imbalance in the intestinal immune system.

Active learning through discussion: ICAP framework for education in health professions.

BACKGROUND: The ICAP framework based on cognitive science posits four modes of cognitive engagement: Interactive, Constructive, Active, and Passive. Focusing on the wide applicability of discussion as interactive engagement in medical education, we investigated the effect of discussion when it was preceded by self-study and further investigated the effect of generating questions before discussions. METHODS: This study was conducted in the second semester of 2018 and was participated in by 129 students majoring in health professions, including medicine, dentistry, veterinary medicine, and nursing. The students were assigned to four different trial groups and were asked to fill out a Subjective Mental Effort Questionnaire after completing each session. Their performance in posttest scores was analyzed using Bonferroni test, and mental effort was analyzed using mediation analysis. RESULTS: These results indicated that the self-study and question group had the highest performance and that the lecture and summary group had the lowest performance when comparing the total score. Using the analysis of mental effort, it was confirmed that the relationship between different study conditions and post-test performance was mediated by mental effort during test. CONCLUSIONS: Our findings support the ICAP framework and provide practical implications for medical education, representing the fact that students learn more when they are involved in active learning activities, such as self-study and question generation, prior to discussions.

Carbon balance of major volatile fatty acids (VFAs) in recycling algal residue via a VFA-platform for reproduction of algal biomass.

The feasibility of a carbon recycling system that transforms algal residue to volatile fatty acids (VFAs) for re-cultivating microalgae was evaluated based on a carbon balance analysis of major VFAs consisting of acetate (HAc), propionate (HPr), and butyrate (HBu). This system largely involves two processes: (i) bioconversion of algal residue to VFAs by anaerobic fermentation, and (ii) cultivation of microalgae using the produced VFAs. The carbon balance for each unit process was examined to assess how much carbon in algal residue can be converted to these major VFAs and then assimilated to microalgae biomass. First, the yield and the profile of VFAs from raw algae (RA) and lipid-extracted algae (LEA) at psychrophilic (15 °C), mesophilic (35 °C), and thermophilic conditions (55 °C) were compared. When digesting the LEA under the thermophilic condition, the highest conversion yield, 0.36 (g carbon in VFAs/g carbon in biomass), with a compositional ratio of 6:1:3 (HAc: HPr: HBu) was obtained. Consumption of VFAs for microalgal growth reached a maximum value of 0.66 (g VFAs assimilated to biomass/g VFAs provided) at the compositional ratio of 6:1:3. Consequently, the maximum total carbon recycling ratio was 23.8% when fermenting LEA at the thermophilic condition. Our findings comprehensively revealed that establishing conditions that convert LEA to higher content of acetate is a decisive factor. It was estimated that around 40% of the total carbon from the LEA can be recovered for the production of algal biomass, when increasing the VFA conversion yield beyond 60% by adopting pretreatment methods.

Bis(phenylsulfone) as a strong electron acceptor of thermally activated delayed fluorescent emitters.

Bis(phenylsulfone) was developed as a strong electron acceptor of thermally activated delayed fluorescent emitters. The connection of two electron withdrawing phenylsulfone moieties through meta-position of phenyl produced the bis(phenylsulfone) acceptor and the strong electron acceptor strength of bis(phenylsulfone) enabled preparation of sky-blue and green thermally activated delayed fluorescent emitters in combination with weak carbazole donors. The bis(phenylsulfone) acceptor and carbazole donor combined organic materials performed as thermally activated delayed fluorescent emitters with a high quantum efficiency of 18.3%.

Correlation of the molecular structure of host materials with lifetime and efficiency of blue phosphorescent organic light-emitting diodes.

Bicarbazole derivatives, 9,9'-bis(dibenzo[b,d]thiophen-2-yl)-9H,9'H-3,3'-bicarbazole (BCzDBT), 9,9'-bis(dibenzo[b,d]furan-2-yl)-9H,9'H-3,3'-bicarbazole (BCzDBF), and 9,9'-di([1,1'-biphenyl]-3-yl)-9H,9'H-3,3'-bicarbazole (BCzBP), were designed and examined as the hole transport type host materials of the tris[1-(2,4-diisopropyldibenzo[b,d]furan-3-yl)-2-phenylimidazole] (Ir(dbi)3) blue triplet emitter. BCzDBT performed better than BCzDBF and BCzBP as the hosts of Ir(dbi)3 and could demonstrate 24.8% quantum efficiency and long lifetime in the blue phosphorescent devices. Strong hole carrying properties of the bicarbazole derivatives were proposed as the main factors for the high quantum efficiency of the BCzDBT devices, and thermal and chemical stability of BCzDBT were suggested as crucial factors for the long lifetime of the BCzDBT devices.

Identification of novel genes responsible for salt tolerance by transposon mutagenesis in Saccharomyces cerevisiae.

Saccharomyces cerevisiae strains tolerant to salt stress are important for the production of single-cell protein using kimchi waste brine. In this study, two strains (TN-1 and TN-2) tolerant of up to 10 % (w/v) NaCl were isolated by screening a transposon-mediated mutant library. The determination of transposon insertion sites and Northern blot analysis identified two genes, MDJ1 and VPS74, and revealed disruptions of the open reading frame of both genes, indicating that salt tolerance can be conferred. Such tolerant phenotypes reverted to sensitive phenotypes on the autologous or overexpression of each gene. The two transposon mutants grew faster than the control strain when cultured at 30 °C in rich medium containing 5, 7.5 or 10 % NaCl. The genes identified in this study may provide a basis for application in developing industrial yeast strains.

Simultaneous treatment of food-waste recycling wastewater and cultivation of Tetraselmis suecica for biodiesel production.

There is an increasing interest in the use of cultivated microalgae to simultaneously produce biodiesel and remove nutrients from various wastewaters. For this purpose, Tetraselmis suecica was cultivated in flasks and fermenters using diluted food-waste recycling wastewater (FRW). The effect of FRW dilution on T. suecica growth and nutrient removal was initially tested in flasks. The maximal microalgal concentration after 14 days was in medium with a twofold dilution (28.3 × 10(6) cells/mL) and a fivefold dilution (25.5 × 10(6) cells/mL). When fivefold diluted medium was used in fermenters, the final dry cell weight of T. suecica was 2.0 g/L. The removal efficiencies of ammonium and phosphate in the fermenters were 99.0 and 52.3%, respectively. In comparison with the results of previous studies, the growth data of T. suecica in the FRW medium indicate that microalgal cultivation system incorporating removal of nutrients in FRW is feasible at the field level.

A simple method for decomposition of peracetic acid in a microalgal cultivation system.

A cost-efficient process devoid of several washing steps was developed, which is related to direct cultivation following the decomposition of the sterilizer. Peracetic acid (PAA) is known to be an efficient antimicrobial agent due to its high oxidizing potential. Sterilization by 2 mM PAA demands at least 1 h incubation time for an effective disinfection. Direct degradation of PAA was demonstrated by utilizing components in conventional algal medium. Consequently, ferric ion and pH buffer (HEPES) showed a synergetic effect for the decomposition of PAA within 6 h. On the contrary, NaNO3, one of the main components in algal media, inhibits the decomposition of PAA. The improved growth of Chlorella vulgaris and Synechocystis PCC6803 was observed in the prepared BG11 by decomposition of PAA. This process involving sterilization and decomposition of PAA should help cost-efficient management of photobioreactors in a large scale for the production of value-added products and biofuels from microalgal biomass.

Cultivation of Chlorella protothecoides in anaerobically treated brewery wastewater for cost-effective biodiesel production.

The use of wastewater has been investigated to overcome the economic challenge involved with a production of microalgae-based biodiesel. In this study, to achieve economical biodiesel production along with effective wastewater treatment at the same time, anaerobically treated brewery wastewater (ABWW) was utilized as a low-cost nutrient source, in the cultivation of Chlorella protothecoides. About 96 and 90 % of total nitrogen and phosphorus in ABWW were removed, respectively, while C. protothecoides was accumulating 1.88 g L(-1) of biomass. The C. protothecoides grown in ABWW showed increases in cell size and cell aggregation, resulting in a near 80 % enhanced harvesting efficiency within 20 min, as compared with only 4 % in BG-11. In addition, the total fatty acid content of the C. protothecoides grown in ABWW increased by 1.84-fold (35.94 ± 1.54 % of its dry cell weight), relative to that of BG-11.

Utilization of seawater for cost-effective cultivation and harvesting of Scenedesmus obliquus.

Microalgae hold great promise as a source of biofuels and biochemicals. The main obstacles to their industrial application are the high cultivation and downstream costs related to media and harvesting. In the work, we explored the multiple potentials of seawater to address key issues relating to the cultivation of Scenedesmus obliquus. Seawater can sufficiently replace some of the key elements in BG11 medium such as MgSO4, CaCl2, and NaCO3, and its use can significantly reduce the quantity of water required for the preparation of culture media. Among our results, the total chlorophyll content in cells grown in modified BG11 using 10 % (v/v) seawater was increased 1.47-fold without sacrificing biomass or lipid production. More than 70 % of the total algal biomass was auto-flocculated within one hour when cells were grown in seawater-supplemented media, which compares very favorably with a yield of only 3 % from cells grown in BG11.

Optimization of variables affecting the direct transesterification of wet biomass from Nannochloropsis oceanica using ionic liquid as a co-solvent.

Ionic liquids have many applications, one of which entails their utilization as powerful solvents. In the present study, various experimental conditions of ionic liquid-mediated direct transesterification were investigated in terms of lipid-extracting ionic liquids, catalyst, reaction time, reaction temperature and volume of methanol to achieve effective FAME conversion with wet microalgal feedstock, Nannochloropsis oceanica. With ionic liquid, [Bmim][CF3SO3], highest fatty acid methyl ester (FAME) yield was shown. Among many experimental parameters, the two most critical factors to enhance FAME conversion were characteristic of ionic liquids and volume of methanol. Optimized ionic liquid-mediated direct transesterification of wet N. oceanica, compared with a control experiment using chloroform and methanol, increased the FAME conversion yield by 11-fold.

Ginsenoside Rc promotes anti-adipogenic activity on 3T3-L1 adipocytes by down-regulating C/EBPα and PPARγ.

Panax ginseng and its major components, the ginsenosides, are widely used in oriental medicine for the prevention of various disorders. In the present study, the inhibitory activity of ginsenoside Rc on adipogenesis was investigated using the 3T3-L1 cell line. The results obtained showed that Rc reduced the proliferation and viability of 3T3-L1 preadipocytes in a dose-dependent manner. Treatment with Rc decreased the number of adipocytes and reduced lipid accumulation in maturing 3T3-L1 preadipocytes, demonstrating an inhibitory effect on lipogenesis. Moreover, it was found that Rc directly induced lipolysis in adipocytes and down-regulated the expression of major transcription factors of the adipogenesis pathway, such as PPARγ and C/EBPα. These findings indicate that Rc is capable of suppressing adipogenesis and therefore they seem to be natural bioactive factors effective in adipose tissue mass modulation.

Characterization of the spectrum of Korean inflammatory demyelinating diseases according to the diagnostic criteria and AQP4-Ab status.

BACKGROUND: The relative frequencies of demyelinating diseases among Korean patients with idiopathic inflammatory demyelinating disease of the central nervous system (IIDD) have not been sufficiently studied. We therefore describe a cohort of 203 patients with IIDD from three centers in Korea whose syndromes were identified precisely according to international clinical criteria and autoantibody to aquaporin 4 (AQP4-Ab) status. METHODS: In total, 260 consecutive patients were screened and 203 were included from three hospitals in Korea. All were tested for AQP4-Ab by using a cell-based assay. Patients who met the criteria for definite neuromyelitis optica (NMO) or had a positive AQP4-Ab test result were defined as the NMO group. Among the others, patients were assessed if they had acute disseminated encephalomyelitis, multiple sclerosis (MS), acute transverse myelitis, optic neuritis, or other demyelinating disease as a clinically isolated syndrome of the brain. RESULTS: Eighteen percent of patients were classified as the NMO group, 2% as acute disseminated encephalomyelitis, 18% as MS, 41% as acute transverse myelitis, 11% as optic neuritis, and 8% as other clinically isolated syndrome of the brain. AQP4-Ab was positive in 18% of patients and the relative frequency of NMO to MS (NMO/MS ratio) was 1.06. The mean duration of follow up in our patients was 64 months. CONCLUSIONS: Among Korean patients with idiopathic inflammatory demyelinating diseases, the incidence of NMO may be similar to that of MS, and the overall positivity of AQP4-Ab could be lower than previously reported. In addition, acute transverse myelitis that is not associated with MS or NMO can be relatively common in these patients. Further population-based studies with AQP4-Ab are needed to determine the exact incidence of NMO and other idiopathic inflammatory demyelinating diseases in Korea.

Continuous harvest of marine microalgae using electrolysis: effect of pulse waveform of polarity exchange.

Advances in harvesting of microalgae are needed for the efficient and economical production of microalgal biodiesel. In addition to improvements in recovery efficiency, developments in harvest technology should focus on reducing the adverse impact of subsequent processes, and should also allow water recycling. We investigated a continuous electrochemical approach for microalgal biodiesel production. Instead of conventional DC, pulsed DC was applied as a method of polarity exchange and its performance was analyzed in terms of recovery efficiency, electricity consumption, and residual Al concentration. Under optimized pulsed-DC conditions, 32 % less electricity was required and 7 % less Al was remained after continuous harvesting and there was no decrease in recovery efficiency compared to the continuous harvesting by conventional DC. We also examined the effect of this new protocol on biodiesel quality and water reusability. There were no differences in the microalgal oil composition before and after electrolytic harvesting. In addition, the harvested oil quality, based on four key parameters, was superior to that produced by other terrestrial crops. Lastly, there was no retardation of growth in recycled medium relative to that in fresh medium.

Use of extracts from oyster shell and soil for cultivation of Spirulina maxima.

Calcium ion and trace metals play important roles in various metabolisms of photosynthetic organisms. In this study, simple methods were developed to extract calcium ion and micronutrients from oyster shell and common soil, and the prepared extracts were tested as a replacement of the corresponding chemicals that are essential for growth of microalgae. The oyster shell and soil were treated with 0.1 M sodium hydroxide or with 10 % hydrogen peroxide, respectively. The potential application of these natural sources to cultivation was investigated with Spirulina maxima. When compared to standard Zarrouk medium, the Spirulina maxima cultivated in a modified Zarrouk media with elements from oyster shell and soil extract exhibited increases in biomass, chlorophyll, and phycocyanin by 17, 16, and 64 %, respectively. These results indicate that the extracts of oyster shell and soil provide sufficient amounts of calcium and trace metals for successful cultivation of Spirulina maxima.

Effects of molten-salt/ionic-liquid mixture on extraction of docosahexaenoic acid (DHA)-rich lipids from Aurantiochytrium sp. KRS101.

In this study, lipid extraction from Aurantiochytrium sp. was performed using a molten-salt/ionic-liquid mixture. The total fatty acid content of Aurantiochytrium sp. was 478.8 mg/g cell, from which 145 mg/g cell (30.3% of total fatty acids) of docosahexaenoic acid (DHA) was obtained. FeCl3·6H2O showed a high lipid extraction yield (207.9 mg/g cell), when compared with that of [Emim]OAc, which was only 118.1 mg/g cell; notably however, when FeCl3·6H2O was mixed with [Emim]OAc (5:1, w/w), the yield was increased to 478.6 mg/g cell. When lipid was extracted by the FeCl3·6H2O/[Emim]OAc mixture at a 5:1 (w/w) blending ratio under 90 °C, 30 min reaction conditions, the fatty acid content of the extracted lipid was a high purity 997.7 mg/g lipid, with most of the DHA having been extracted (30.2% of total fatty acids). Overall, lipid extraction from Aurantiochytrium sp. was enhanced by the synergistic effects of the molten-salt/ionic-liquid mixture with different ions.