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Allotransplantation, performed using an acellular dermal matrix (ADM), plays a significant role in the cultivation of constituted and damaged organs in clinical. Herein, we fabricated an innovative ADM for allografting derived from decellularized human skin by utilizing the supercritical fluid of carbon dioxide to eliminate immunogenic components. By using histological staining, the ADM product demonstrated the successful removal of cellular constituents without exerting any harmful influence on the extracellular matrix. The results from DNA electrophoresis also supported this phenomenon by showing the complete DNA removal in the product, accompanied by the absence of Major Histocompatibility Complex 1, which suggested the supercritical fluid is an effective method for cellular withdrawal. Moreover, the mechanical property of the ADM products, which showed similarity to that of native skin, displayed great compatibility for using our human-derived ADM as an allograft in clinical treatment. Specifically, the cell viability demonstrated the remarkable biocompatibility of the product to human bio-cellular environment which was noticeably higher than that of other products. Additionally, the significant increase in the level of growth factors such as vascular endothelial growth factor, urokinase-type plasminogen activator receptor, granulocyte-macrophage colony-stimulating factor suggested the ability to stimulate cellular processes, proving the products to be innovative in the field of regeneration when applied to clinical in the future. This study provides a thoroughly extensive analysis of the new ADM products, enabling them to be applied in industrial and clinical treatment.

Background/Aim: Hypertrophic scars (HS) are the result of pathological wound healing characterized by a red, raised scar formation. The goal of this research was development of a new method for treatment of HS formation. Materials and Methods: A tranilast-loaded microneedle (TMN) was developed and applied in a rabbit ear model to treat an induced HS. Scar elevation index, the thickness of dorsal skin by hematoxylin and eosin staining, collagen deposition by Masson trichrome staining and expression of myofibroblast biomarker proteins were evaluated. Results: The 12×12 array of the TMN containing 2.9 μg tranilast per needle released more than 80% of the drug within 30 min. During the procedure, control, non-loaded MN and TMN loaded with three different doses of tranilast (low: 2.5-3, medium: 25-30, and high: 100-150 μg) were applied to the HS in rabbit ears. High-level TMN led to a clear and natural appearance of skin, a decrease in scar elevation index by 47% and decline in the thickness of the epidermis from 69.27 to 15.92 μm when compared to the control group. Moreover, the collagen density also decreased in groups treated with medium- or high-level TMNs, by 10.2% and 9.06%, respectively. Furthermore, the expression of transforming growth factor-β, collagen-1, and α-smooth muscle actin proteins was reduced in TMN-treated HSs compared to the control. Conclusion: The findings show the overall efficacy of TMNs in inhibiting HS. Thus, use of TMN is a simple and cosmetic remedy for HS, with good protection and reliability.

Background/Aim: Silicone implants are widely used biomaterials in surgeries owing to their physiological inertness and low toxicity. However, capsular contracture is a severe complication caused by the insertion of breast implants, which can endanger the health of patients. In this study, twelve different silicone breast implants were tested to determine which could lead to a lower incidence of capsular contracture. Materials and Methods: For in vivo experiments, these silicone implants were implanted into 60 rats (i.e., five implants per rat). The implants were explanted eight weeks after the operation. Samples were analyzed and measured by using hematoxylin and eosin staining, Masson’s trichrome staining, and immunofluorescence staining methods. We compared twelve samples for their differences in the thickness of capsular formation, number of inflammatory cells, collagen expression, fibroblast intensity (i.e., Vimentin and α-SMA), and inflammatory cytokines (i.e., IL-8, CD68, MCP-1, and F4/80). Results: Different surface textures of breast implants gave different effects on capsular thickness, collagen formation, fibroblast formation, and potential inflammation. Samples that had smooth textures such as SEBBIN, HANS, and Mentor showed higher collagen formation than other samples. SEBBIN Texture, Motiva Micro, HANS Smooth I, and HANS Micro exhibited higher fibroblast formation (i.e., α-SMA, Vimentin). SEBBIN Smooth and samples in HANS group displayed lower expression of inflammation cytokines (IL-8, CD68, MCP-1, and F4/80). Conclusion: These findings provide preliminary reports on the surface texture effect and support a selection of breast silicone implants in breast reconstruction to avoid the formation of capsular contracture after implantation.

Background: Lymphedema is a disease thatrefers to tissue swelling caused by an accumulation of protein-rich fluid that is usually drained through the lymphatic system. Detection of lymphedema is often based on expensive diagnoses such as bioimpedance spectroscopy, shear wave elastography, computed tomography, etc. Applications of data science and machine learning in predicting medical conditions offered support for medical doctors and patients in the early detection of diseases. Although current studies proposed machine learning models to predict lymphedema by using symptoms reported by patients, there might be uncertaintyinpatient-input data. In this study, we proposed to usemore reliable input data such as complete blood count, serum, and therapy data to develop predictive models for lymphedema. Methods: We collected data from 2137 patients, including 356 patients having lymphedema and 1781 patients not having lymphedema. The lymphedema status of each patient was confirmed by clinicians. Data of each patient includes: 1) complete blood count (CBC) test, 2) serum test, and 3) therapy information. We used machine learning algorithms (i.e., random forest, gradient boosting, support vector machine, decision tree and artificial neural network) to develop predictive models on training dataset (i.e., 80% of the data) and tested the models on the test dataset (i.e., 20% of the data). After choosing the best predictive models, we developed web application for medical doctors and clinicians to use our models for quick screening lymphedema patients. Results: A dataset of 2137 patients was collected from Seoul National University Bundang Hospital. Predictive models based on random forest algorithm showed satisfactory performance (balanced accuracy = 86.7 ± 0.9%, sensitivity = 84.3 ± 0.6%, specificity = 89.1 ± 1.5%, precision = 97.4 ± 0.4%, F1 score = 90.4 ± 0.4%, and AUC = 0.931 ± 0.007). A web application was made to assist medical doctors in quick screening lymphedema: https://snubhtxt.shinyapps.io/SNUBH_Lymphedema. Conclusions: Our study would provide a tool for the early detection of lymphedema and be the basement for future studies predicting lymphedema stages.

Background Autologous fat grafts are commonly used in cosmetic and reconstructive surgery, and various methods are used to improve their viability. Low-level laser therapy (LLLT) can enhance the proliferation, growth, and differentiation of various cell lines, including stem cells. Our study investigated and compared the effects of LLLT and the addition of adipose-derived stem cells (ADSCs) on the viability of fat grafts.Methods Twenty nude mice were divided into four groups: control (group 1), LLLT irradiation (group 2), ADSC addition (group 3), and LLLT irradiation+ADSC addition (group 4). ADSCs were combined with the fat tissue. LLLT irradiation was performed once daily for 1 week from the day of grafting. After 8 weeks, the weight, volume, histology, and Western blot findings of the grafted fat tissues were evaluated.Results The retention rate and volume of the fat tissue in groups 2, 3, and 4 were higher than that of group 1, but the difference was not statistically significant. The number of capillaries, histological parameters, and immunofluorescence staining analyses for CD68, CD31, fibroblast growth factor, and vascular endothelial growth factor (VEGF) showed no significant differences among the four groups. The expression level of VEGF was higher in group 2 than in the other groups, but not to a statistically significant level.Conclusions LLLT and ADSCs did not significantly improve the viability of autologous fat grafts. Therefore, further study is necessary to develop safe and effective methods to improve the viability of these grafts for clinical application.

Background/Aim: The skin plays an important role in protecting the body from mechanical damage, microbial infection, ultraviolet radiation, and extreme temperatures. Many products as well as ongoing studies have focused on skin injury and repair; however, unlimited challenges are still being faced. Furthermore, the drugs that are currently on the market are not adequate to meet the increasing medical needs. This study aimed to discover whether our new product can efficiently promote wound repair and skin restoration. Materials and Methods: In this study, we applied a new AIMP1-derived peptide (AdP), NeoPep S, administered in two dose types (1 ppm and 3 ppm), and determined their effect on skin wound repair in rat models. Cell proliferation and inflammatory responses were assessed using immunofluorescence (IF) staining and ELISA assay. Results: As expected, our results showed more rapid and satisfactory progress in wound closure upon treatment with NeoPep S 3 ppm than with NeoPep S 1 ppm. The 3 ppm peptide derived from AIMP1 protein, harmoniously interacted with the wound to promote re-epithelialization and collagen regeneration, as well as the down-regulation of several types of cytokines and chemokines, such as TNF-α, IL-6, IL-8, IL-1β, MCP-1, and F4/80. Moreover, it was demonstrated to promote fibroblast proliferation, migration, and differentiation by TGF-β1 and TGF-β3 modulation, as well as nitrite and reactive oxygen species scavenging. Conclusion: The novel peptide NeoPep S 3 ppm showed high effectiveness and safety in wound healing.

Bacterial biofilms have been implicated with breast implant complications including capsular contracture, double-capsule formation, and breast implant-associated anaplastic large cell lymphoma. However, the relationship between implant surface texture and microbial biofilm formation is insufficiently evaluated. In the present study, we examined the antimicrobial activities of different types of silicone breast implant. The growth of bacterial including Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa was compared using implants with various surface textures, including Hans Smooth, Hans SmoothFine, Allergan Smooth, Eurosilicone Smooth, Eurosilicone Texture, Sebbin Smooth, Sebbin Micro, Sebbin Texture, and Motiva Smooth. Microbial investigation revealed the increased growth of S. aureus on breast implants after 48 h, except Eurosilicone Smooth, Eurosilicone Texture, Hans SmoothFine and Sebbin Smooth material. At 48 hours, there was no major difference between the S. aureus attachment on smooth and textured implants. The results of S. epidermis attachment on the implant after 48 h showed that their growth decreased on surfaces of Motiva Smooth, Sebbin Smooth, and Eurosilicone Smooth. These results indicated that S. epidermis was unable to survive on these breast implants. Eventually, P. aeruginosa count had showed decrease of bacterial count after 48 hours compared to 24 hours in most of the implants except for Eurosilicone Texture, Sebbin Smooth and Sebbin Micro, where the count of P. aeruginosa slightly increased. This indicated that P. aeruginosa was unable to exist on the smooth surfaces. Our results show that the in vitro assay revealed no significant difference between smooth and textured surfaces and showed variable interactions and needed further molecular analysis to assess their adherence nature.

Background/Aim: Acellular dermal matrices (ADMs) have become popular in implant-based breast reconstruction. The aim of this study was to compare three commonly used ADM products in vivo in an animal model. Materials and Methods: The nucleic acid content (residual double-stranded DNA) and the levels of the remaining growth factors after decellularization were measured for each ADM. Cytocompatibility with ADMs was documented using NIH 3T3 mouse fibroblast cells. In vivo, the implanted ADMs were histologically evaluated at 1, 2, 3, and 6 months (n=5) using male 8-week-old Sprague-Dawley rats. Results: Fibroblasts grew in the SureDerm HD and DermACELL with no cytotoxicity. In a rat model, SureDerm HD and DermACELL incorporated more readily into the surrounding host tissue, as measured by rapid cell influx and collagen deposition, and showed more delayed tissue remodeling with decreased matrix metalloproteinases levels compared to AlloDerm. Conclusion: SureDerm HD and DermACELL can be used as biological materials for breast reconstruction.

Let $n$ be a nonnegative integer. For each composition $\alpha$ of $n$, Berg $\textit{et al.}$ introduced a cyclic indecomposable $H_n(0)$-module $\mathcal{V}_\alpha$ with a dual immaculate quasisymmetric function as the image of the quasisymmetric characteristic. In this paper, we study $\mathcal{V}_\alpha$'s from the homological viewpoint. To be precise, we construct a minimal projective presentation of $\mathcal{V}_\alpha$ and a minimal injective presentation of $\mathcal{V}_\alpha$ as well. Using them, we compute ${\rm Ext}^1_{H_n(0)}(\mathcal{V}_\alpha, {\bf F}_\beta)$ and ${\rm Ext}^1_{H_n(0)}( {\bf F}_\beta, \mathcal{V}_\alpha)$, where ${\bf F}_\beta$ is the simple $H_n(0)$-module attached to a composition $\beta$ of $n$. We also compute ${\rm Ext}_{H_n(0)}^i(\mathcal{V}_\alpha,\mathcal{V}_{\beta})$ when $i=0,1$ and $\beta \le_l \alpha$, where $\le_l$ represents the lexicographic order on compositions., Comment: 44 pages, to be published in Forum of Math: Sigma

Thymic stromal lymphopoietin (TSLP), a type I cytokine belonging to the IL-2 cytokine family, promotes Th2-mediated inflammatory responses. The aim of this study is to investigate whether TSLP increases inflammatory responses via induction of autophagy using a murine T cell lymphoma cell line, EL4 cells, and lipopolysaccharide (LPS)-injected mice. TSLP increased expression levels of autophagy-related factors, such as Beclin-1, LC3-II, p62, Atg5, and lysosome associated membrane protein 1/2, whereas these factors increased by TSLP disappeared by neutralization of TSLP in EL4 cells. TSLP activated JAK1/JAK2/STAT5/JNK/PI3K, while the blockade of JAK1/JAK2/STAT5/JNK/PI3K signaling pathways reduced the expression levels of Beclin-1, LC3-II, and p62 in TSLP-stimulated EL4 cells. In addition, TSLP simultaneously increased levels of inflammatory cytokines via induction of autophagy by activation of JAK1/JAK2/STAT5/JNK/PI3K signaling pathways. In an LPS-induced acute liver injury (ALI) mouse model, exogenous TSLP increased expression levels of Beclin-1 and LC3-II, whereas functional deficiency of TSLP by TSLP siRNA resulted in lower expression of Beclin-1, LC3-II, and inflammatory cytokines, impairing their ability to form autophagosomes in ALI mice. Thus, our findings show a new role of TSLP between autophagy and inflammatory responses. In conclusion, regulating TSLP-induced autophagy may be a potential therapeutic strategy for inflammatory responses.

The objective of this study is to provide a reliable strategy for the diagnosis of sarcopenia based on a complementary combination of biomarkers from various approaches.A total of 30 C57BL/6J mice were used for the experiment, in which 15 young mice (YM) at 24 weeks old and 15 aged mice (AM) at 88 weeks old. Extracted features-based digital biomarkers from the electromyography activity of tibialis anterior muscles were evaluated by using receiver operating characteristic analysis. Extracted tissular proteins and circulating hormones based chemical biomarkers were investigated by using immunoblotting and enzyme-linked immunosorbent assay.In terms of digital biomarkers, the feature-based classification of mice groups showed good performance (Feature A: AUC = 0.986, accuracy = 0.928) and (Feature B: AUC = 0.999, accuracy = 0.990). On the other hand, muscle-specific protein levels based chemical biomarkers (e.g. MuRF1, FoxO1, and perilipin2) were observed significantly increase with age. Pro-inflammatory cytokines based biomarkers extracted from muscle tissue and circulating plasma (e.g. TNF-α, IL-6, and IL-8) were significantly higher in case of AM group compared to YM group. Circulating hormone-based chemical biomarkers (e.g. cortisol/DHEA ratio and cathepsin D) presented a significant increase in concentrations with age. Circulating neurotransmitter based biomarkers (e.g. acetylcholine, serotonin, and histamine) also increased significantly in concentrations from YM to AM.A complementary combination of digital and chemical biomarkers covers multiple domains of sarcopenia to provide an effective strategy for the early diagnosis of sarcopenia.

Breast reconstruction is achieved using silicone implants, which are currently associated with major complications. Several strategies have been considered to overcome the existing limitations as well as to improve their performance. Recently, surface modification has proved to be an effective clinical approach to prevent bacterial adhesion, reduce capsular thickness, prevent foreign body reactions, and reduce other implant-associated problems. This review article summarizes the ongoing strategies for the surface modification of silicone implants in breast reconstruction applications. The article mostly discusses two broad categories of surface modification: drug-mediated and polymer-based. Different kinds of drugs have been applied with silicone that are associated with breast reconstruction. Initially, this article discusses studies related to drugs immobilized on silicone implants, focusing on drug-loading methods and their effects on capsule contracture. Moreover, the pharmacological action of drugs on fibroblast cells is considered in this section. Next, the polymeric modification of the silicone surface is introduced, and we discuss its role in reducing capsule thickness at the cellular and biological levels. The polymeric modification techniques, their chemistry, and their physical properties are described in detail. Notably, polymer activities on macrophages and inflammation are also briefly discussed. Each of the reviewed articles is summarized, highlighting their discussion of capsular thickness, foreign body reactions, and bacterial attachment. The aim of this review is to provide the main points of some research articles regarding the surface modification of silicon, which can lead to a decrease in capsular thickness and provides better patient compliance.

Breast augmentations with silicone implants can have adverse effects on tissues that, in turn, lead to capsular contracture (CC). One of the potential ways of overcoming CC is to control the implant/host interaction using immunomodulatory agents. Recently, a high ratio of anti-inflammatory (M2) macrophages to pro-inflammatory (M1) macrophages has been reported to be an effective tissue regeneration approach at the implant site. In this study, a biofunctionalized implant was coated with interleukin (IL)-4 to inhibit an adverse immune reaction and promoted tissue regeneration by promoting polarization of macrophages into the M2 pro-healing phenotype in the long term. Surface wettability, nitrogen content, and atomic force microscopy data clearly showed the successful immobilization of IL-4 on the silicone implant. Furthermore, in vitro results revealed that IL-4-coated implants were able to decrease the secretion of inflammatory cytokines (IL-6 and tumor necrosis factor-α) and induced the production of IL-10 and the upregulation of arginase-1 (mannose receptor expressed by M2 macrophage). The efficacy of this immunomodulatory implant was further demonstrated in an in vivo rat model. The animal study showed that the presence of IL-4 diminished the capsule thickness, the amount of collagen, tissue inflammation, and the infiltration of fibroblasts and myofibroblasts. These results suggest that macrophage phenotype modulation can effectively reduce inflammation and fibrous CC on a silicone implant conjugated with IL-4.

Cosmetic silicone implants for breast reconstruction often lead to medical complications, such as abnormally excessive fibrosis driven by foreign body granulomatous inflammation. The purpose of this study was to develop a silicone breast implant capable of local and controlled release of a glucocorticoid drug triamcinolone acetonide (TA) for the prevention of silicone-breast-implant-induced fibrosis in a Yorkshire pig model (in vivo). Implants were dip-coated in a TA solution to load 1.85 μg/cm2 of TA in the implant shell, which could release the drug in a sustained manner for over 50 days. Immunohistochemical analysis for 12 weeks showed a decline in tumor necrosis factor-α expression, capsule thickness, and collagen density by 82.2%, 55.2%, and 32.3%, respectively. Furthermore, the counts of fibroblasts, macrophages, and myofibroblasts in the TA-coated implants were drastically reduced by 57.78%, 48.8%, and 64.02%, respectively. The TA-coated implants also lowered the expression of vimentin and α-smooth muscle actin proteins, the major profibrotic fibroblast and myofibroblast markers, respectively. Our findings suggest that TA-coated silicone breast implants can be a promising strategy for safely preventing fibrosis around the implants.

Background and purpose As an osteoclast differentiation factor, receptor activator of NF-κB ligand (RANKL) is produced by various immune cells and may be involved in the pathogenesis of osteoporosis and inflammation. Although RANKL is expressed in most immune cells and tissues, it is not clear how this might affect allergic inflammation. Experimental approach The roles of RANKL in allergic rhinitis (AR) were analysed in an ovalbumin (OVA)-induced animal model, human subjects, and a human mast cell line (HMC-1). Small interfering RNA experiments were performed in an OVA-induced AR model. Key results RANKL and RANKL receptor (RANK) were up-regulated in serum or nasal mucosal tissues of AR patients and AR mice. RANKL and RANK were colocalised in mast cells of nasal mucosa tissue. Depletion of RANKL by RANKL siRNA ameliorated AR symptoms and reduced AR-related biomarkers, including thymic stromal lymphopoietin (TSLP), IgE, histamine, and inflammatory cell infiltration, whereas recombinant RANKL increased AR responses and TSLP levels. In addition, functional deficiency of TSLP decreased AR responses induced by RANKL. In human mast cells, interaction of RANKL with RANK increased production of TSLP and inflammatory cytokines. Production of TSLP by RANKL stimulation was mediated through activation of the PI3K, MAPK, caspase-1, and NF-κB pathways. Furthermore, dexamethasone alleviated RANKL-induced inflammatory reactions in AR models. Conclusion and implications Collectively, these data suggest that RANKL may induce development of AR through up-regulation of TSLP.

BellaGel SmoothFine® implant is a novel nanotextured silicone breast implant. The objective of this study was to characterize differences of BellaGel SmoothFine® surfaces with commercial available implant surfaces in terms of texture, topography, and wettability as well as the behavior of capsular contracture. The surface textures of breast implants from two different manufacturers (Hans Biomed and Motiva) were evaluated. The implants utilized in this study were BellaGel Smooth®, BellaGel Textured®, BellaGel SmoothFine® or Motiva SilkSurface®. The shell textures of these implants were characterized using a scanning electron microscopy, three dimensional confocal laser scanning microscope, and contact angle goniometer. Silicone breast implants were emplaced beneath the panniculus carnosus muscle on the dorsum of Sprague Dawley rats and observed for up to 8 weeks postoperative days. The fibrous capsules around silicone implants were explanted for histological examination. BellaGel SmoothFine® exhibits a relatively flat, with little or no depth in the texturing, 5.96 ± 0.41 μm surface roughness, and a contact angle of 103.14 ± 2.06 BellGel SmoothFine® implant resulted in significant decreases in capsule thickness (P P ® and BellaGel Textured® implant groups. Significant (P ®. Fibrous tissue formation markers (Vimentin and alpha-smooth muscle actin) were significantly reduced in BellaGel SmoothFine® surfaces versus BellaGel Smooth® surfaces (P ® groups (P ® implant is associated with less breast implant derived capsular contracture than other surfaces.

Most allergic disease studies have focused on postnatal chemical or microbial exposure. Recent studies have indicated that allergic diseases are associated with the immunological interaction between the mother and her offspring, but the relevant mechanisms are unclear. The aim of this study was to assess whether maternal exposure to allergens during pregnancy could affect allergic rhinitis (AR) in the offspring. Compared with offspring of naive mothers, offspring of ovalbumin (OVA)-exposed mothers exhibited a significant reduction in AR clinical symptoms and levels of histamine, IgE, T helper type-2(Th2) cytokines, thymic stromal lymphopoietin, cyclooxygenase-2, chemokines, infiltration of inflammatory cell, and activity of caspase-1. Interestingly, we observed that offspring of OVA-exposed mothers regulated OVA-induced Th2 responses by inducing autophagy in mast cells. Our data demonstrated that maternal exposure to OVA during pregnancy decreased allergic sensitivity in offspring, suggesting that the vertical transmission of maternal immune responses may be involved. These findings have important implications in the regulation of AR. Furthermore, we propose that the autophagy of mast cells may be a potential target for AR prevention or treatment.

Introduction: Recipient site preparation using external volume expansion (EVE) increases graft survival in large-volume fat grafting. To improve patient compliance with using the device, we tested a new cyclic high negative-pressure (CHNP) mode that involves 1 h/day at −55 mm Hg, cycled between 1-second negative-pressure activation, followed by a 2-second deactivation period in an animal model. Material and Method: A miniaturized EVE device was applied to 30 8-week-old male Sprague-Dawley rats. The rats were assigned to 3 groups (no pressure for the control group, conventional −25 mm Hg for 8 h/day for conventional EVE, and CHNP mode for the CHNP group). After 28 days, micro-computed tomography was performed and skin biopsy specimens were obtained. Results: The CHNP group showed a 6.6-fold increase and the conventional EVE group showed a 4.4-fold increase in volume compared to the control group. Hematoxylin and eosin staining showed a similar increase in subcutaneous tissue thickness in both EVE groups, compared to the control group. Masson's trichome and proliferating cell nuclear antigen staining showed significantly higher collagen deposition and subdermal adipocytes in EVE groups. Immunohistochemistry against platelet endothelial cell adhesion molecule 1 showed 2.5- and 2.7-times higher vessel density in the conventional and CHNP EVE groups, respectively. There was no statistically significant difference in subcutaneous tissue thickness, collagen deposition, subdermal adipocyte proliferation, and vessel density between the 2 EVE groups. Conclusion: CHNP produced comparable results in recipient site preparation (subcutaneous tissue thickening and angiogenesis) compared to the conventional protocol, while markedly reducing the daily wear-time from 8 hours to 1 hour. Although further clinical data must be acquired, our new pressure setting seems promising and provides a more patient-friendly pre-expansion environment.

Anaplastic large cell lymphoma (ALCL) is an uncommon type of non-Hodgkin’s lymphoma (NHL), as well as one of the subtypes of T cell lymphoma, accounting for 1 to 3% of non-Hodgkin’s lymphomas and around 15% of T cell lymphomas. In 2016, the World Health Organization (WHO) classified anaplastic large cell lymphoma into four categories: ALK-positive ALCL (ALK+ALCL), ALK-negative ALCL (ALK−ALCL), primary cutaneous ALCL (pcALCL), and breast-implant-associated ALCL (BIA-ALCL), respectively. Clinical symptoms, gene changes, prognoses, and therapy differ among the four types. Large lymphoid cells with copious cytoplasm and pleomorphic characteristics with horseshoe-shaped or reniform nuclei, for example, are found in both ALK+ and ALK−ALCL. However, their epidemiology and pathogenetic origins are distinct. BIA-ALCL is currently recognized as a new provisional entity, which is a noninvasive disease with favorable results. In this review, we focus on molecular pathogenesis and management of anaplastic large cell lymphoma.

In the past, acellular dermal matrices (ADMs) have been used in implant-based breast reconstruction. Various factors affect the clinical performance of ADMs since there is a lack of systematic characterization of ADM tissues. This study used BellaCell HD and compared it to two commercially available ADMs&mdash, AlloDerm Ready to Use (RTU) and DermACELL&mdash, under in vitro settings. Every ADM was characterized to examine compatibility through cell cytotoxicity, proliferation, and physical features like tensile strength, stiffness, and the suture tensile strength. The BellaCell HD displayed complete decellularization in comparison with the other two ADMs. Several fibroblasts grew in the BellaCell HD with no cytotoxicity. The proliferation level of fibroblasts in the BellaCell HD was higher, compared to the AlloDerm RTU and DermACELL, after 7 and 14 days. The BellaCell HD had a load value of 444.94 N, 22.44 tensile strength, and 118.41% elongation ratio, and they were higher than in the other two ADMs. There was no significant discrepancy in the findings of stiffness evaluation and suture retention strength test. The study had some limitations because there were many other more factors useful in ADM&rsquo, s testing. In the study, BellaCell HD showed complete decellularization, high biocompatibility, low cytotoxicity, high tensile strength, high elongation, and high suture retention strengths. These characteristics make BellaCell HD a suitable tissue for adequate and safe use in implant-based breast reconstruction in humans.

Thymic stromal lymphopoietin (TSLP) derived by mast cells is recognized as a critical factor in many allergic inflammatory disorders. Cysteine is a well-known amino acid which exhibits anti-inflammatory activities. However, the effect and mechanism of cysteine on TSLP production have not been investigated. Thus, we hypothesized that cysteine may regulate TSLP production from mast cells. To test this hypothesis, the anti-inflammatory effects and signaling pathways of cysteine were investigated in phorbol 12-myristate 13-acetate 4 and calcium ionophore A23187 (PMACI)-stimulated human mast cell line HMC-1. Cysteine dramatically attenuated the levels of TSLP of both mRNA and protein without cytotoxicity. Moreover, cysteine suppressed caspase-1 activation and nuclear factor-κB translocation. The phosphorylation of p38 and c-Jun N-terminal kinase was downregulated in all cases in PMACI-stimulated HMC-1 cells treated with cysteine. In addition, cysteine decreased PMACI-induced proinflammatory cytokines in terms of both protein and mRNA levels. In conclusion, cysteine regulates TSLP production by blocking caspase-1, nuclear factor-κB, p38, and c-Jun N-terminal kinase-dependent pathways in activated HMC-1 cells, suggesting its potential as a regulator of allergic inflammatory diseases.

Vanillic acid, which is well known as a benzoic acid derivative, has been used as a flavouring agent. Currently, we ascertained the therapeutic potential action of vanillic acid on allergic inflammatory reaction in human mast cell line, HMC-1. Treatment with vanillic acid resulted in a significant decrease in levels of thymic stromal lymphopoietin and pro-inflammatory cytokines compared to phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-treated HMC-1 cells. In PMACI-stimulated cells, treatment with vanillic acid also dramatically inhibited activities of caspase-1 and nuclear factor-kB (p65). Furthermore, treatment with vanillic acid suppressed phosphorylation of mitogen-activated protein kinases in PMACI-treated HMC-1 cells. Taken together, these findings suggest that vanillic acid has a beneficial effect on allergic inflammatory disorders.

Previously, we showed the inhibitory effects of β-eudesmol on mast cell-mediated allergic inflammatory responses. Stem cell factor (SCF) participates in allergic reactions through the differentiation and migration of mast cells. However, the effects of β-eudesmol on SCF-mediated allergic reactions are poorly understood. Herein, we showed that a treatment of rat peritoneal mast cells (RPMCs) with β-eudesmol markedly suppressed SCF-induced mast cell migration and morphological alterations in a concentration-dependent manner. β-eudesmol also reduced F-actin formation. The activation of Fyn kinase, Rac1 GTPase, and p38 mitogen-activated protein kinases as increased by SCF was reduced by β-eudesmol. Moreover, β-eudesmol significantly abolished SCF-induced tumor necrosis factor-α and intercellular adhesion molecule-1 production without cytotoxicity. These results demonstrate that β-eudesmol has an anti-allergic inflammatory effect through the inhibition of mast cell migration and inflammatory cytokine production.

Background Recently, we reported an anti-fatigue effect of fermented porcine placenta (FPP). Glycine-leucine (GL) and leucine-glycine (LG) dipeptides are main peptides of FPP. However, the therapeutic effects and underlying mechanisms of GL and LG dipeptides on fatigue are still unclear. Methods Herein, we examined the anti-fatigue properties of GL and LG dipeptides using RAW264.7 macrophages and forced swimming test (FST) animal model. Results Our data revealed that lipopolysaccharide (LPS)-induced interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 productions were markedly inhibited by GL or LG in RAW264.7 macrophages without inducing cytotoxicity. LPS-enhanced nitric oxide (NO) production and inducible nitric oxide synthase expression were inhibited by GL or LG, whereas superoxide dismutase (SOD) activities were significantly enhanced by GL or LG in LPS-stimulated RAW264.7 macrophages. The present study also figured out that these effects of GL and LG were mediated by blockade of caspase-1 and nuclear factor-κB activation. In FST-induced fatigue mouse model, the mice which received the GL or LG for 21 days showed significant decreases of IL-1β, IL-6, and NO serum levels. Treatment with GL or LG significantly enhanced levels of SOD and glycogen and significantly lowered levels of lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Conclusion Taken together, our results indicated that GL and LG dipeptides, active components of FPP, should be considered as candidate of anti-fatigue agents.

We investigate chromatic symmetric functions in the relation to the algebra $\Gamma$ of symmetric functions generated by Schur $Q$-functions. We construct natural bases of $\Gamma$ in terms of chromatic symmetric functions. We also consider the $p$-positivity of skew Schur $Q$-functions and find a class of $p$-positive ribbon Schur $Q$-functions, making a conjecture that they are \emph{all}. We include many concrete computational results that support our conjecture., Comment: 16 pages

We study the H n ( 0 ) -module S α σ due to Tewari and van Willigenburg, which was constructed using new combinatorial objects called standard permuted composition tableaux and decomposed into cyclic submodules. First, we show that every direct summand appearing in their decomposition is indecomposable and characterize when S α σ is indecomposable. Second, we find characteristic relations among S α σ 's and expand the image of S α σ under the quasi characteristic in terms of quasisymmetric Schur functions. Finally, we show that the canonical submodule of S α σ appears as a homomorphic image of a projective indecomposable module.

Receptor activator of NF-κB ligand (RANKL) as an osteoclast differentiation factor induces inflammatory reactions via production of thymic stromal lymphopoietin (TSLP). Epigallocatechin gallate (EGCG) is the major and the most active compound in green tea and has anti-inflammatory, anti-cancer, anti-oxidant, and neuroprotective effects. However, the effect and molecular mechanisms of EGCG are still unknown in RANKL-induced inflammatory reactions. Here we investigated the immuno-regulatory effects and its molecular mechanisms of epigallocatechin gallate (EGCG) in RANKL-stimulated human mast cell line, HMC-1 cells. In this study, EGCG prevented expression of PI3 Kinase and phosphorylation of mitogen-activated protein (MAP) Kinases in RANKL-stimulated HMC-1 cells. EGCG prevented caspase-1 activity and decreased transcriptional activity of nuclear factor (NF)-κB by suppressing inhibitory protein κBα phosphorylation in RANKL-stimulated HMC-1 cells. EGCG has been shown to prevent production and mRNA expression of TSLP, interleukin (IL)-1β, IL-6, and IL-8 by RANKL without cytotoxicity. Furthermore, EGCG prevented degranulation of mast cell in RANKL-stimulated HMC-1 cells. Overall, these results suggest that EGCG acts as a natural agent for preventing and treating RANKL-mediated inflammatory diseases by targeting PI3 Kinase, MAP Kinase, caspase-1, and NF-κB signaling cascade in mast cells.

This study investigated a salutary effect of atractylone (Atr) which is an active constituent of Pyeongwee-San (KMP6) on mast cell-mediated allergic reactions. Our previous report indicated that KMP6 regulated allergic reactions. Thus, this study sought to determine the potential of Atr in vitro models, compound 48/80-stimulated rat peritoneal mast cells (RPMCs), phorbol 12-myristate 13-acetate (PMA) plus A23187-stimulated human mast cell line (HMC-1) cells, and stem cell factor (SCF)-stimulated RPMCs as well as in vivo models, IgE-mediated passive cutaneous anaphylaxis (PCA), compound 48/80-induced systemic anaphylaxis, and compound 48/80-induced ear swelling. The results showed that Atr inhibited compound 48/80-induced RPMCs degranulation, intracellular calcium level, tryptase release, and histamine release. Atr inhibited the up-regulation of p56lck tyrosine kinase activity by compound 48/80. And Atr reduced tryptase and histamine releases from PMA plus A23187-stimulated HMC-1 cells. In addition, Atr decreased histidine decarboxylase activity and expression in the activated HMC-1 cells. Atr inhibited SCF-induced morphological alteration and filamentous actin formation in RPMCs. Atr improved IgE-induced PCA reaction by decreasing the levels of histamine, IgE, interleukin (IL)-4, IL-5, IL-6, vascular endothelial growth factor, and IL-13 in the serum of PCA-induced mice. Furthermore, Atr mitigated compound 48/80-induced systemic anaphylaxis and ear swelling. Taken together, these results of this study indicate that Atr regulates the degranulation of mast cell, proving its potential in the treatment of mast cell-mediated allergic reactions.

Cucurbita moschata Duch. has long been used for traditional health food in many countries. However, to enhance the immune system of Cucurbita moschata Duch. and its major component, β-carotene is not clear. Here, we determined the immune enhancement effect of Cucurbita moschata Duch. and β-carotene in mouse splenocytes and RAW 264.7 macrophage cell line. We prepared baked Cucurbita moschata Duch. (Sweetme Sweet Pumpkin(TM), SSP) and steamed Cucurbita moschata Duch. (SC). Splenocytes isolated from the spleen of BALB/c mice were treated with SSP, SC, and β-carotene for 24 h. RAW 264.7 cells were stimulated with recombinant interferon-γ (rIFN-γ) for 6 h before treatment with SSP, SC, or β-carotene. SSP, SC and β-carotene significantly up-regulated the proliferation of splenocyte and mRNA expression of KI-67. The levels of interleukin-2 and IFN-γ were up-regulated by SSP, SC, or β-carotene in the splenocytes. SC and β-carotene also increased the levels of tumor necrosis factor-α (TNF-α) in the splenocytes. In addition, SSP, SC, or β-carotene significantly increased the levels of TNF-α through the nuclear translocation of the nuclear factor-κB and phosphorylation of IκBα in the rIFN-γ-primed RAW 264.7 cells. These data indicate that Cucurbita moschata Duch. and β-carotene may have an immune-enhancing effect through the production of Th1 cytokines by activation of splenocytes and macrophages.

Korean bamboo salt (BS) is known to have therapeutic effects in the treatment of diseases, including viral disease, dental plaque, diabetes, circulatory organ disorders, cancer and inflammatory disorders. However, the effect of BS on immune functions remains to be elucidated. The present study was designed to determine the immune‑enhancing effect of BS and its component, hydrogen sulfide, using RAW264.7 macrophages and a forced swimming test (FST) animal model. BS and sodium hydrosulfide (NaSH), a hydrogen sulfide donor, significantly increased the levels of tumor necrosis factor (TNF)‑α through the activation of nuclear factor‑κB in the RAW 264.7 cells. In an in vivo experiment, BS and NaSH were administered orally once a day for 28 days. After the 28 days, the immobility times in the FST were significantly decreased in the BS and NaSH‑fed groups, compared with the control group. In addition, BS and NaSH induced significant increases in the levels of interferon‑γ, interleukin‑2 and TNF‑α, compared with the control group. Taken together, these results indicated that BS and NaSH may improve immune function.

The amino acids in the placenta have multiple functions; however, the therapeutic effects of proline remain poorly for relief postmenopausal symptoms. The aim of present study was to evaluate the effects of proline in the treatment of menopause using in vitro and in vivo models. We assessed the therapeutic effects and regulatory mechanisms of proline by using MCF-7 estrogen-dependent cells, MG63 osteoblast cells, and ovariectomized mice model. An in vivo study was carried out in eight-week-old sham and ovariectomized group. The ovariectomized mouse was further subdivided into two groups administered orally with 17β-estradiol or proline (10 mg/kg/day) for eight weeks. Proline significantly increased cell proliferation and Ki-67 levels in MCF-7 cells and enhanced cell proliferation, alkaline phosphatase activity, extracellular signal-regulated kinase phosphorylation, and glutamyl-prolyl-tRNA synthetase activation in MG63 cells. The estrogen receptor-β and estrogen-response elements luciferase activity were significantly increased by proline in MCF-7 and MG63 cells. In ovariectomized mice, oral administration of proline (10 mg/kg/day) for eight weeks significantly reduced body and vaginal weights. Proline also significantly increased serum estradiol and alkaline phosphatase levels, whereas serum luteinizing hormone was decreased by proline. In addition, detailed microcomputed tomography analysis showed that the proline notably enhanced bone mineral density, trabecular bone volume, and trabecular number in ovariectomized mice. Those findings implied that proline can be a promising candidate for the treatment of menopause.

The surface of poly(dimethylsiloxane) (PDMS) is grafted with poly(acrylic acid) (PAA) layers via surface-initiated photopolymerization to suppress the capsular contracture resulting from a foreign body reaction. Owing to the nature of photo-induced polymerization, various PAA micropatterns can be fabricated using photolithography. Hole and stripe micropatterns ≈100-µm wide and 3-µm thick are grafted onto the PDMS surface without delamination. The incorporation of PAA micropatterns provides not only chemical cues by hydrophilic PAA microdomains but also topographical cues by hole or stripe micropatterns. In vitro studies reveal that a PAA-grafted PDMS surface has a lower proliferation of both macrophages (Raw 264.7) and fibroblasts (NIH 3T3) regardless of the pattern presence. However, PDMS with PAA micropatterns, especially stripe micropatterns, minimizes the aggregation of fibroblasts and their subsequent differentiation into myofibroblasts. An in vivo study also shows that PDMS samples with stripe micropatterns polarized macrophages into anti-inflammatory M2 macrophages and most effectively inhibits capsular contracture, which is demonstrated by investigation of inflammation score, transforming-growth-factor-β expression, number of macrophages, and myofibroblasts as well as the collagen density and capsule thickness.