Forkhead box P3-positive (Foxp3 + )-inducible Tregs (iTregs) are readily generated by TGF-β1 at low TCR signaling intensity. TGF-β1–mediated Foxp3 expression is further enhanced by retinoic acid (RA) and lactoferrin (LF). However, the intensity of TCR signaling required for induction of Foxp3 expression by TGF-β1 in combination with RA and LF is unknown. Here, we found that either RA or LF alone decreased TGF-β1–mediated Foxp3 expression at low TCR signaling intensity. In contrast, at high TCR signaling intensity, the addition of either RA or LF strongly increased TGF-β1–mediated Foxp3 expression. Moreover, decreased CD28 stimulation was more favorable for TGF-β1/LF–mediated Foxp3 expression. Lastly, we found that at high signaling intensities of both TCR and CD28, combined treatment with TGF-β1, RA, and LF induced robust expression of Foxp3, in parallel with powerful suppressive activity against responder T cell proliferation. Our findings that TGFβ/RA/LF strongly generate high affinity Ag-specific iTreg population would be useful for the control of unwanted hypersensitive immune reactions such as various autoimmune diseases.

Objective: : Stent-assisted coil embolization (SAC) has been increasingly used to treat various types of intracranial aneurysms. Delayed thromboembolic complications are major concerns regarding this procedure, so dual antiplatelet therapy with aspirin and clopidogrel is needed. However, clinicians vary the duration of dual antiplatelet therapy after SAC, and no randomized study has been performed. This study aims to compare the safety and efficacy of long-term (12 months) dual antiplatelet therapy and shortterm dual antiplatelet therapy (6 months) after SAC for patients with unruptured intracranial aneurysms (UIAs). Methods: : This is a prospective, randomized and multicenter trial to investigate the optimal duration of dual antiplatelet therapy after SAC in patients with UIAs. Subjects will receive dual antiplatelet therapy for 6 months (short-term group) or 12 months (longterm group) after SAC. The primary endpoint is the assessment of thromboembolic complications between 1 and 18 months after SAC. We will enroll 528 subjects (264 subjects in each group) and perform 1 : 1 randomization. This study will involve 14 topperforming, high-volume Korean institutions specializing in coil embolization. Results: : The trial will begin enrollment in 2022, and clinical data will be available after enrollment and follow-up. Conclusion : This article describes that the aim of this prospective randomized multicenter trial is to compare the effect of short-term (6 months) and long-term (12 months) dual antiplatelet therapy on UIAs in patients undergoing SAC, and to find the optimal duration.

Betaine derivatives are considered major ingredients of shampoos and are commonly used as antistatic and viscosity-increasing agents. Several studies have also suggested that betaine derivatives can be used as antimicrobial agents. However, the antifungal activity and mechanism of action of betaine derivatives have not yet been fully understood. In this study, we investigated the antifungal activity of six betaine derivatives against Malassezia restricta, which is the most frequently isolated fungus from the human skin and is implicated in the development of dandruff. We found that, among the six betaine derivatives, lauryl betaine showed the most potent antifungal activity. The mechanism of action of lauryl betaine was studied mainly using another phylogenetically close model fungal organism, Cryptococcus neoformans, because of a lack of available genetic manipulation and functional genomics tools for M. restricta. Our genome-wide reverse genetic screening method using the C. neoformans gene deletion mutant library showed that the mutants with mutations in genes for cell membrane synthesis and integrity, particularly ergosterol synthesis, are highly sensitive to lauryl betaine. Furthermore, transcriptome changes in both C. neoformans and M. restricta cells grown in the presence of lauryl betaine were analyzed and the results indicated that the compound mainly affected cell membrane synthesis, particularly ergosterol synthesis. Overall, our data demonstrated that lauryl betaine influences ergosterol synthesis in C. neoformans and that the compound exerts a similar mechanism of action on M. restricta.
Anti-Infective Agents ; Betaine ; Cell Membrane ; Cryptococcus ; Cryptococcus neoformans ; Dandruff ; Ergosterol ; Fungi ; Gene Deletion ; Genetic Testing ; Genomics ; Humans ; Malassezia ; Methods ; Skin ; Transcriptome

OBJECTIVE: To evaluate the clinical efficacy and safety following percutaneous disc decompression, using navigable disc decompression device for cervical herniated nucleus pulposus (HNP). METHODS: Twenty subjects diagnosed with cervical HNP and refractory to conservative management were enrolled for the study. The herniated discs were decompressed under fluoroscopic guidance, using radiofrequency ablation device with navigable wand. The sagittal and axial plain magnetic resonance images of the clinically significant herniated disc, decided the space between the herniated base and outline as the target area for ablation. Clinical outcome was determined by Numeric Rating Scale (NRS), Neck Disability Index (NDI), and Bodily Pain scale of Short Form-36 (SF-36 BP), assessed after 48 weeks. After the procedure, we structurally matched the magnetic resonance imaging (MRI) and C-arm images through bony markers. The wand position was defined as being ‘correct’ if the tip was placed within the target area of both AP and lateral views; if not, the position was stated as ‘incorrect’. RESULTS: The average NRS fell from 7 to 1 at 48 weeks post procedure (p<0.05). In addition, statistically significant improvement was noted in the NDI and SF-36BP (p<0.05). The location of the wand tip resulted in 16 correct and 4 incorrect placements. Post-48 weeks, 3 of the incorrect tip cases and 1 correct tip case showed unsuccessful outcomes. CONCLUSION: The study demonstrated the promising results and safety of the procedure. Thus, focal plasma ablation of cervical HNP with navigable wand can be another effective treatment option.
Catheter Ablation ; Decompression* ; Humans ; Intervertebral Disc Displacement ; Magnetic Resonance Imaging ; Neck ; Neck Pain ; Plasma ; Treatment Outcome*

Correction for incorrect control groups (A, B, and C) at a Fig. 3. and Fig. 4. respectively. NPS 2014 20(4): 251-257.

Immunoglobulin G4 (IgG4)-related disease is a newly recognized condition characterized by fibroinflammatory lesions with dense lymphoplasmacytic infiltration, storiform-type fibrosis and obliterative phlebitis. The pathogenesis is not fully understood but multiple immune-mediated mechanisms are believed to contribute. This rare disease can involve various organs and pleural involvement is even rarer. We report a case of IgG4-related disease involving pleura. A 66-year-old man presented with cough and sputum production for a week. Chest radiography revealed consolidation and a pleural mass at right hemithorax. Treatment with antibiotics resolved the consolidation and respiratory symptoms disappeared, but the pleural mass was unchanged. Video-assisted thoracoscopic surgery was performed. Histopathology revealed dense lymphoplasmacytic infiltration and storiform fibrosis with numerous IgG4-bearing plasma cells. The serum IgG4 level was also elevated. Further examination ruled out the involvement of any other organ. The patient was discharged without further treatment and there is no evidence of recurrence to date.
Aged ; Anti-Bacterial Agents ; Autoimmune Diseases ; Cough ; Fibrosis ; Humans ; Immunoglobulin G ; Immunoglobulins* ; Phlebitis ; Plasma Cells ; Pleura ; Pleural Neoplasms ; Radiography ; Rare Diseases ; Recurrence ; Sputum ; Thoracic Surgery, Video-Assisted ; Thorax

TGF-beta induces IgA class switching by B cells. We previously reported that Smad3 and Smad4, pivotal TGF-beta signal-transducing transcription factors, mediate germline (GL) alpha transcription induced by TGF-beta1, resulting in IgA switching by mouse B cells. Post-translational sumoylation of Smad3 and Smad4 regulates TGF-beta-induced transcriptional activation in certain cell types. In the present study, we investigated the effect of sumoylation on TGF-beta1-induced, Smad3/4-mediated GLalpha transcription and IgA switching by mouse B cell line, CH12F3-2A. Overexpression of small ubiquitin-like modifier (SUMO)-1, SUMO-2 or SUMO-3 did not affect TGF-beta1-induced, Smad3/4-mediated GLalpha promoter activity, expression of endogenous GLalpha transcripts, surface IgA expression, and IgA production. Next, we tested the effect of the E3 ligase PIASy on TGF-beta1-induced, Smad3/4-mediated GLalpha promoter activity. We found that PIASy overexpression suppresses the GLalpha promoter activity in cooperation with histone deacetylase 1. Taken together, these results suggest that SUMO itself does not affect regulation of GLalpha transcription and IgA switching induced by TGF-beta1/Smad3/4, while PIASy acts as a repressor.
Animals ; B-Lymphocytes* ; Cell Line ; Histone Deacetylase 1 ; Immunoglobulin A ; Immunoglobulin Class Switching ; Mice ; Small Ubiquitin-Related Modifier Proteins* ; SUMO-1 Protein* ; Sumoylation ; Transcription Factors ; Transcriptional Activation ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; Ubiquitin-Protein Ligases

PURPOSE: The purpose of this study was to evaluate the surface characteristics and response of osteoblast-like cell at SLA surface treated with NaOH. MATERIALS AND METHODS: Three kinds of specimens were fabricated for the experiment groups. Control group was a machined surface, SLA group was a conventionally SLA treated surface, and SLA/NaOH gorup was SLA surface treated with NaOH. To evaluate the surface characteristics, the surface elemental composition (XPS), surface roughness and surface contact angle were evaluated in each group. And the cytotoxicity, cell adhesion, cell proliferation and ATP activity of osteoblast-like cells (MG-63 cells) were compared in each group for evaluatation of the cell responses. Statistical comparisons between groups were carried out via one-way ANOVA using the SPSS software (SPSS Inc., Chicago, USA), and then performed multiple comparisons. The differences were considered statistically significant at P<.05. RESULTS: SLA surface treated with NaOH (SLA / NaOH group) was changed to hydrophilic surface. All groups did not show the cytotoxicity to the MG-63. In cell adhesion studies, SLA / NaOH group showed the higher degree of adhesion than anothers (P<.05), Up to 7 days of incubation, the proliferation was showed the increasing tendency in all groups but SLA / NaOH group showed the highest cell proliferation between the three groups (P<.05). At 7 days of incubation, there was no difference in ALP activities between the three groups, but at 14 days, SLA / NaOH group showed significant increase in ALP activities (P<.05). CONCLUSION: In this study, SLA surface treated with NaOH promoted cell adhesion, proliferation and differentiation. It means that SLA/NaOH group is possible to promote osseointegration of implants.
Adenosine Triphosphate ; Cell Adhesion ; Cell Culture Techniques ; Cell Proliferation ; Osseointegration

BACKGROUND: Toll-like receptors (TLRs) have been extensively studied in recent years. However, functions of these molecules in murine B cell biology are largely unknown. A TLR4 stimulant, LPS is well known as a powerful polyclonal activator for murine B cells. METHODS: In this study, we explored the effect of a murine TLR9 stimulant, M6-395 (a synthetic CpG ODNs) on B cell proliferation and Ig production. RESULTS: First, M6-395 was much more potent than LPS in augmenting B cell proliferation. As for Ig expression, M6-395 facilitated the expression of both TGF-beta1-induced germ line transcript alpha (GLTalpha) and IL-4-induced GLTgamma1 as levels as those by LPS and Pam3CSK4 (TLR1/2 agonist) : a certain Ig GLT expression is regarded as an indicative of the corresponding isotype switching recombination. However, IgA and IgG1 secretion patterns were quite different--these Ig isotype secretions by M6-395 were much less than those by LPS and Pam3CSK4. Moreover, the increase of IgA and IgG1 production by LPS and Pam3CSK4 was virtually abrogated by M6-395. The same was true for the secretion of IgG3. We found that this unexpected phenomena provoked by M6-395 is attributed, at least in part, to its excessive mitogenic nature. CONCLUSION: Taken together, these results suggest that M6-395 can act as a murine polyclonal activator but its strong mitogenic activity is unfavorable to Ig isotype switching.
B-Lymphocytes ; Cell Proliferation ; Germ Cells ; Immunoglobulin A ; Immunoglobulin Class Switching ; Immunoglobulin G ; Oligodeoxyribonucleotides ; Recombination, Genetic ; Toll-Like Receptors

PURPOSE: To analyze the stress distribution of the implant and its supporting structures through 3D finite elements analysis for implants with different hexagon heights and to make the assessment of the mechanical stability and the effect of the elements. MATERIALS AND METHODS: Infinite elements modeling with CAD data was designed. The modeling was done as follows; an external connection type Phi 4.0 mm x11.5 mm Osste(R) USII (Osstem Co., Pusan, Korea) implant system was used, the implant was planted in the mandibular first molar region with appropriate prosthetic restoration, the hexagon (implant fixture's external connection) height of 0.0, 0.7, 1.2, and 1.5 mm were applied. ABAQUS 6.4 (ABAQUS, Inc., Providence, USA) was used to calculate the stress value. The force distribution via color distribution on each experimental group's implant fixture and titanium screw was studied based on the equivalent stress (von Mises stress). The maximum stress level of each element (crown, implant screw, implant fixture, cortical bone and cancellous bone) was compared. RESULTS: The hexagonal height of the implant with external connection had an influence on the stress distribution of the fixture, screw and upper prosthesis and the surrounding supporting bone. As the hexagon height increased, the stress was well distributed and there was a decrease in the maximum stress value. If the height of the hexagon reached over 1.2 mm, there was no significant influence on the stress distribution. CONCLUSION: For implants with external connections, a hexagon is vital for stress distribution. As the height of the hexagon increased, the more effective stress distribution was observed.
Dental Implants ; Molar ; Plants ; Prostheses and Implants ; Titanium