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.

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.

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.

Organoclay-assisted interfacial polymerization for microfluidic production of monodisperse PEG-microdroplets and in situ encapsulation of E. coli.

We developed a novel one-pot synthetic strategy for preparing monodisperse polyethylene glycol diacrylate (PEGDA) microdroplets via organoclay-assisted interfacial polymerization approach for Escherichia coli encapsulation. Based on the mechanism of spontaneous and rapid polymerization of PEGDA precursor solution with Mg-organoclay, the prepared PEGDA microdroplets have uniform size and fine round shape, with size range of 74-118 µm. The size of microdroplets can be controlled through the changing continuous phase flow rate. Organoclay-assisted polymerization method provides a unique environment to produce non-toxic ways of fabricating microorganism encapsulated microdroplets and to prohibit microdroplets merge during the processes. Furthermore, we successfully carried out to entrap E. coli inside of the PEGDA microdroplets. E. coli expressing a green fluorescent protein shows a good viability inside the PEGDA microdroplets. The in situ microfluidic synthetic method provides a novel approach for the preparation of monodisperse PEGDA microdroplets via a one-pot route.

Porphyromonas gingivalis exacerbates the progression of fatty liver disease via CD36-PPARγ pathway.

Periodontal diseases have been reported to have a multidirectional association with metabolic disorders. We sought to investigate the correlation between periodontitis and diabetes or fatty liver disease using HFD-fed obese mice inoculated with P. gingivalis. Body weight, alveolar bone loss, serological biochemistry, and glucose level were determined to evaluate the pathophysiology of periodontitis and diabetes. For the evaluation of fatty liver disease, hepatic nonalcoholic steatohepatitis (NASH) was assessed by scoring steatosis, inflammation, hepatocyte ballooning and the crucial signaling pathways involved in liver metabolism were analyzed. The C-reactive protein (CRP) level and NASH score in P. gingivalis-infected obese mice were significantly elevated. Particularly, the extensive lobular inflammation was observed in the liver of obese mice infected with P. gingivalis. Moreover, the expression of metabolic regulatory factors, including peroxisome proliferator-activated receptor γ (Pparγ) and the fatty acid transporter Cd36, was up-regulated in the liver of P. gingivalis-infected obese mice. However, inoculation of P. gingivalis had no significant influence on glucose homeostasis, insulin resistance, and hepatic mTOR/AMPK signaling. In conclusion, our results indicate that P. gingivalis can induce the progression of fatty liver disease in HFD-fed mice through the upregulation of CD36-PPARγ axis. [BMB Reports 2021; 54(6): 323-328].

Implication of Porphyromonas gingivalis in colitis and homeostasis of intestinal epithelium.

Emerging evidences have reported that periodontitis can be a risk factor for the pathogenesis of various systemic diseases. Porphyromonas gingivalis (Pg), one of the crucial pathogens in chronic periodontitis, has been spotlighted as a potential cause for the promotion and acceleration of periodontitis-associated systemic disorders. To investigate the association between Pg and intestinal disease or homeostasis, we treated Pg-derived lipopolysaccharide (LPS) in murine colitis model or intestinal organoid, respectively. Pg-derived LPS (Pg LPS) was administrated into chemically induced murine colitis model and disease symptoms were monitored compared with the infusion of LPS derived from E. coli (Ec LPS). Organoids isolated and cultured from mouse small intestine were treated with Pg or Ec LPS and further analyzed for the generation and composition of organoids. In vivo observations demonstrated that both Pg and Ec LPS exerted slight protective effects against murine colitis. Pg LPS did not affect the generation and growth of intestinal epithelial organoids. Among subtypes of epithelial cells, markers for stem cells, goblet cells or Paneth cells were changed in response to Pg LPS. Taken together, these results indicate that Pg LPS leads to partial improvement in colitis and that its treatment does not significantly affect the self-organization of intestinal organoids but may regulate the epithelial composition.

Surfactant-enhanced electrokinetic removal of phenanthrene from kaolinite.

Removal of hydrophobic organic contaminants (HOCs) using surfactant-enhanced electrokinetic (EK) method was studied in a model system. Kaolinite and phenanthrene were selected as a model clay soil and a representative HOC, respectively. Three different types of surfactants: APG (alkyl polyglucoside), Brij30 (polyoxyethylene-4-lauryl ether), and SDS (sodium dodecyl sulfate), were used to enhance the solubility of HOC. Characteristics of surfactants, such as surface tension, HOC solubility, and biodegradability were measured. In the case of Brij30 solution, phenanthrene solubility was higher than that of others. After 4 days, APG and Brij30 were degraded by 65% and 26% of the initial amount, respectively. However, degradation of SDS was hardly detected. Electroosmotic flow (EOF) of Brij30 solution was lower than others when the 0.1M NaCl was used as electrolyte. Addition of the acetate buffer solution increased the EOF of Brij30 solution and enhanced removal of phenanthrene. Among three different surfactants tested, APG showed the highest removal efficiency.

Silicone emulsion-enhanced recovery of chlorinated solvents: batch and column studies.

Batch and column experiments were conducted to investigate the feasibility of flushing with silicone oil emulsion for the removal of chlorinated solvents, including trichloroethylene (TCE), perchloroethylene (PCE) and 1,2-dichlorobenzene (DCB). In the batch experiments, solubilization potentials of emulsion and effects of surfactants as additives were examined. The emulsion prepared with 2% (v/v) silicone oil could solubilize 90.7% of 10,000 ppm TCE, 97.3% of 4000 ppm PCE and 99.7% of 7,800 ppm DCB. Results of one-dimensional column studies indicated that aqueous solubility and sorption of contaminants determined the flushing efficiency. The addition of surfactants below their critical micelle concentration (CMC) did not affect the removal of chlorinated solvents in batch and column experiments. The results of this study show that flushing with oil-based emulsion can be applied to treat the chlorinated solvents.

A Simple, Cost-Efficient Method to Separate Microalgal Lipids from Wet Biomass Using Surface Energy-Modified Membranes.

For the efficient separation of lipid extracted from microalgae cells, a novel membrane was devised by introducing a functional polymer coating onto a membrane surface by means of an initiated chemical vapor deposition (iCVD) process. To this end, a steel-use-stainless (SUS) membrane was modified in a way that its surface energy was systemically modified. The surface modification by conformal coating of functional polymer film allowed for selective separation of oil-water mixture, by harnessing the tuned interfacial energy between each liquid phase and the membrane surface. The surface-modified membrane, when used with chloroform-based solvent, exhibited superb permeate flux, breakthrough pressure, and also separation yield: it allowed separation of 95.5 ± 1.2% of converted lipid (FAME) in the chloroform phase from the water/MeOH phase with microalgal debris. This result clearly supported that the membrane-based lipid separation is indeed facilitated by way of membrane being functionalized, enabling us to simplify the whole downstream process of microalgae-derived biodiesel production.

Synthesis of chitosan-based polymeric surfactants and their adsorption properties for heavy metals and fatty acids.

Chitosan-based polymeric surfactants (CBPSs) were prepared by N-acylation of chitosans (chitosan 10 and 500) with several acid anhydrides such as hexanoic (C6), lauric (C12), and palmitic (C16) anhydrides. Among the CBPS samples, CBPSs having a good solubility at pH 4.0 were selected and observed for viscosity, surface tension, and adsorption of heavy metals (Cd2+, Co2+, Cr2O7(2-), and Pb2+) as well as the fatty acid (n-octanoic acid). The 1H NMR spectrum of chitosan 10 modified with C16 at the substitution ratio of 0.4 (CBPS10-C16,0.4) showed 85% of acylation in 1% DCl/D2O solutions. CBPS10 with the substitution ratio less than 0.4 showed a good solubility because of shorter repeating units and lesser amounts of hydrophobic substituents. The intrinsic viscosity of CBPS10 was slightly increased, while that of CBPS500 was decreased. As the substitution ratio and length of the carbon chain increased, the surface tension of CBPS10 tended to decrease. CBPS10-C16,0.2 had high adsorption ability for cationic metal ions such as Cd2+, Co2+, and Pb2+ comparable to chitosan. Interestingly, CBPS(10)-C(16,0.2) showed a unique pH optimum for the anionic metal ion such as Cr2O7(2-). In addition, CBPS10-C16,0.2 exhibited the highest adsorption ability for n-octanoic acid among the tested CBPS10 with different carbon chains.

Competitive extraction of multi-component contaminants in water by Carboxen-polydimethylsiloxane fiber during solid-phase microextraction.

A headspace analysis for groundwater contaminated with BTEX (benzene, toluene, ethylbenzene, and xylenes) was employed to investigate the feasibility and limitations of Carboxen-PDMS (polydimethylsiloxane) fiber during SPME (solid-phase microextraction). Although the response of the Carboxen-PDMS fiber was much higher than that of conventional PDMS fiber, a reduction of the extracted amount was also observed under multi-component conditions due to competitive replacement. The general affinity of analytes to the fiber was high in the order xylene>ethylbenzene>toluene> benzene. The behavior of the Carboxen-PDMS fiber was examined more precisely at constant compositional ratio, because the analysis of contaminants using Carboxen-PDMS fiber was reported to be possible at known composition. The relative affinity of each component was shown to differ according to the total amount of analytes. Furthermore, the extracted amounts of benzene and toluene did not show a consistent tendency as the concentration of each component increased. These results indicate that caution should be exercised if Carboxen-PDMS fibers are used for the analysis of BTEX in groundwater samples.

Removal characteristics of anionic metals by micellar-enhanced ultrafiltration.

Surfactant-based separation of Fe(CN)(6)(3-) and CrO(4)(2-) using regenerated cellulose membrane was studied in order to assess the potential of micellar-enhanced ultrafiltration for the remediation of wastewater or groundwater polluted with ferriccyanide and chromate. In the ferriccyanide/octadecylamine acetate (ODA) and chromate/ODA systems, removal of ferriccyanide increased from 73 to 92% and to 98%, and that of chromate from 64 to 97% and to >99.9% as the molar ratio of ODA to ferriccyanide and to chromate increased from 1 to 2 and to 3, respectively. In the ferriccyanide/chromate/ODA system, while the removal of ferriccyanide increased from 62 to 72% and to 93%, the removal of chromate from 20 to 38% and to 68% as the molar ratio of ferriccyanide:chromate:ODA increased from 1:1:1 to 1:1:2 and to 1:1:4, respectively. With the molar ratio of 1:1:6, the removal was >99.9 and 98% for chromate and ferriccyanide, respectively. Ferriccyanide ions were more easily bound to ODA micelles because the binding power of ferriccyanide was greater than that of chromate.

Separation of galactose, 5-hydroxymethylfurfural and levulinic acid in acid hydrolysate of agarose by nanofiltration and electrodialysis.

A two-stage membrane process for the separation of galactose, 5-hydroxymethylfurfural (5-HMF) and levulinic acid (LA) has been proposed. The first step of nanofiltration (NF) is to remove 5-HMF and LA from galactose solution obtained by the hydrolysis of agarose, the main component of red algal galactan for the reduction of its microbial toxicity. 5-HMF and LA are inhibitory to fermentation but at the same time useful compounds themselves with many applications. The second step of electrodialysis (ED) is to separate 5-HMF and LA in the permeate from NF. More than 91% of 5-HMF and up to 62% of LA could be removed from agarose hydrolysate, while galactose was almost completely retained by NF. Further removal of LA was expected to be possible with no loss of galactose by operating the NF process in a diafiltration mode. 5-HMF and LA could be effectively separated from each other by ED.

Mass transfer of polyaromatic hydrocarbons (PAHs) in a two-liquid-phase system.

Studies were conducted to observe the solubility of phenanthrene, anthracene, and pyrene in four water-immiscible liquids (WILs) and the mass transfer of PAH in a two-liquid-phase (TLP) system. The order of solubility in WILs for three different PAHs was phenanthrene > pyrene >> anthracene. Among the WILs tested in a TLP system, paraffine oil did not affect the mass transfer of three PAHs, while silicone oil reduced the mass transfer of anthracene significantly because paraffine oil had a higher solubilizing capacity for anthracene than silicone oil. When initial PAHs concentration increased up to 2500 mg PAHs/kg soil, the mass transfer of phenanthrene and pyrene were hardly influenced, while that of anthracene was reduced to 40%. As the amount of light paraffine oil decreased, the mass transfer of anthracene decreased significantly compared to that of phenanthrene and pyrene. Based on the present results, it was confirmed that the mass transfer of PAHs from soil to WIL was governed mainly by the solubilizing capacity of WIL for PAHs. This is the first report on the mass transfer of PAHs from soil to WIL, in which the mechanism of TLP process can be understood more clearly.