Effects on keratinocytes of the traditional combination of herb extract (Royal Oji Complex) implicated the improvement of young children's skin moisture and barrier.

BACKGROUND: Natural products are often friendly and can be used on children's skin after systematic and careful research. Therefore, in this study, the Royal Oji Complex (ROC), a product with natural ingredients, was used to study their effectiveness on keratinocytes taken from the skin of children from 0 to 3 years old. METHOD: Normal human epidermal keratinocytes and tissue-isolated keratinocytes (TIKC) from young donors were treated with three different concentrations of ROC: 0.1, 1, and 10 ppm. The mRNA expression of the epidermal barrier's essential genes, such as hyaluronic acid synthase 3 (Has3), involucrin (IVL), loricrin (LOR), and claudin-1 (CLD1) was investigated using qRT-PCR. Ceramide content was measured by ELISA, with retinoic acid (R.A.) and amarogentin (AMA) serving as positive controls. RESULTS: ROC significantly elevated HAS3 gene expression in HEKn cells, especially at 10 ppm, indicating potential advantages for skin hydration in young infants. IVL increased at first but decreased as ROC concentrations increased. LOR was upregulated at lower ROC concentrations but reduced at higher doses. CLD1 gene expression increased considerably in HEKn but reduced with increasing ROC doses. Ceramide concentration increased somewhat but not significantly at 10 ppm. CONCLUSION: ROC shows potential in altering keratinocyte gene expression, with unique responses in HEKn and TIKC from young donors. While changes in ceramide content were insignificant, these results help to comprehend ROC's multiple effects on young children's skin.

An evaluation of the effectiveness of 'ULTRACOL 200' in enhancing nasolabial fold wrinkles through cutaneous repair.

BACKGROUND: Injectable filler, a nonsurgical beauty method, has gained popularity in rejuvenating sagging skin. In this study, polydioxanone (PDO) was utilized as the main component of the ULTRACOL200 filler that helps stimulate collagenesis and provide skin radiant effects. The study aimed to evaluate and compare the effectiveness of ULTRACOL200 with other commercialized products in visually improving dermatological problems. METHODS: Herein, 31 participants aged between 20 and 59 years were enrolled in the study. 1 mL of the testing product, as well as the quantity for the compared groups was injected into each participants face side individually. Subsequently, skin texture and sunken volume of skin were measured using ANTERA 3D CS imaging technology at three periods: before the application, 4 weeks after the initial application, and 4 weeks after the 2nd application of ULTRACOL200. RESULTS: The final results of skin texture and wrinkle volume evaluation consistently demonstrated significant enhancement. Consequently, subjective questionnaires were provided to the participants to evaluate the efficacy of the testing product, illustrating satisfactory responses after the twice applications. CONCLUSION: The investigation has contributed substantially to the comprehension of a PDO-based filler (ULTRACOL200) for skin enhancement and provided profound insight for future clinical trials.

Zirconium-Based Metal-Organic Framework Capable of Binding Proinflammatory Mediators in Hydrogel Form Promotes Wound Healing Process through a Multiscale Adsorption Mechanism.

The regulation of proinflammatory mediators has been explored to promote natural healing without abnormal inflammation or autoimmune response induced by their overproduction. However, most efforts to control these mediators have relied on pharmacological substances that are directly engaged in biological cycles. It is believed that functional porous materials removing target mediators provide a new way to promote the healing process using their adsorption mechanisms. In this study, the Zr-based metal-organic frameworks (MOF)-808 (Zr6 O4 (OH)4 (BTC)2 (HCOO)6 ) crystals are found to be effective at removing proinflammatory mediators, such as nitric oxide (NO), cytokines, and reactive oxygen species (ROS) in vitro and in vivo, because of their porous structure and surface affinity. The MOF-808 crystals are applied to an in vivo skin wound model as a hydrogel dispersion. Hydrogel containing 0.2 wt% MOF-808 crystals shows significant improvement in terms of wound healing efficacy and quality over the corresponding control. It is also proven that the mode of action is to remove the proinflammatory mediators in vivo. Moreover, the application of MOF-808-containing hydrogels promotes cell activation, proliferation and inhibits chronic inflammation, leading to increased wound healing quality. These findings suggest that Zr-based MOFs may be a promising drug-free solution for skin problems related to proinflammatory mediators.

Development of predictive models for lymphedema by using blood tests and therapy data.

Lymphedema is a disease that refers 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. In current machine learning models for lymphedema prediction, reliance on observable symptoms reported by patients introduces the possibility of errors in patient-input data. Moreover, these symptoms are often absent during the initial stages of lymphedema, creating challenges in its early detection. Identifying lymphedema before these observable symptoms manifest would greatly benefit patients by potentially minimizing the discomfort caused by these symptoms. In this study, we propose to use new data, such as complete blood count, serum, and therapy data, to develop predictive models for lymphedema. This approach aims to compensate for the limitations of using only observable symptoms data. We collected data from 2137 patients, including 356 patients with lymphedema and 1781 patients without lymphedema, with the lymphedema status of each patient confirmed by clinicians. The data for each patient included: (1) a complete blood count (CBC) test, (2) a serum test, and (3) therapy information. We used various machine learning algorithms (i.e. random forest, gradient boosting, decision tree, logistic regression, and artificial neural network) to develop predictive models on the training dataset (i.e. 80% of the data) and evaluated the models on the external validation dataset (i.e. 20% of the data). After selecting the best predictive models, we created a web application to aid medical doctors and clinicians in the rapid screening of lymphedema patients. A dataset of 2137 patients was assembled from Seoul National University Bundang Hospital. Predictive models based on the random forest algorithm exhibited satisfactory performance (balanced accuracy = 87.0 ± 0.7%, sensitivity = 84.3 ± 0.6%, specificity = 89.1 ± 1.5%, precision = 97.4 ± 0.7%, F1 score = 90.4 ± 0.4%, and AUC = 0.931 ± 0.007). We developed a web application to facilitate the swift screening of lymphedema among medical practitioners: https://snubhtxt.shinyapps.io/SNUBH_Lymphedema . Our study introduces a novel tool for the early detection of lymphedema and establishes the foundation for future investigations into predicting different stages of the condition.

In situ photo-crosslinkable hyaluronic acid-based hydrogel embedded with GHK peptide nanofibers for bioactive wound healing.

A versatile hydrogel was developed for enhancing bioactive wound healing by introducing the amphiphilic GHK peptide (GHK-C16) into a photo-crosslinkable tyramine-modified hyaluronic acid (HA-Ty). GHK-C16 self-assembled into GHK nanofibers (GHK NF) in HA-Ty solution, which underwent in situ gelation after the wound area was filled with precursor solution. Blue light irradiation (460-490 nm), with riboflavin phosphate as a photoinitiator, was used to trigger crosslinking, which enhanced the stability of the highly degradable hyaluronic acid and enabled sustained release of the nanostructured GHK derivatives. The hydrogels provided a microenvironment that promoted the proliferation of dermal fibroblasts and the activation of cytokines, leading to reduced inflammation and increased collagen expression during wound healing. The complexation of Cu2+ into GHK nanofibers resulted in superior wound healing capabilities compared with non-lipidated GHK peptide with a comparable level of growth factor (EGF). Additionally, nanostructured Cu-GHK improved angiogenesis through vascular endothelial growth factor (VEGF) activation, which exerted a synergistic therapeutic effect. Furthermore, in vivo wound healing experiments revealed that the Cu-GHK NF/HA-Ty hydrogel accelerated wound healing through densely packed remodeled collagen in the dermis and promoting the growth of denser fibroblasts. HA-Ty hydrogels incorporating GHK NF also possessed improved mechanical properties and a faster wound healing rate, making them suitable for advanced bioactive wound healing applications. STATEMENT OF SIGNIFICANCE: By combining photo-crosslinkable tyramine-modified hyaluronic acid with self-assembled Cu-GHK-C16 peptide nanofibers (Cu-GHK NF), the Cu-GHK NF/HA-Ty hydrogel offers remarkable advantages over conventional non-structured Cu-GHK for wound healing. It enhances cell proliferation, migration, and collagen remodeling-critical factors in tissue regeneration. The incorporation of GHK nanofibers complexed with copper ions imparts potent anti-inflammatory effects, promoting cytokine activation and angiogenesis during wound healing. The Cu-GHK NF/hydrogel's unique properties, including in situ photo-crosslinking, ensure high customization and potency in tissue regeneration, providing a cost-effective alternative to growth factors. In vivo experiments further validate its efficacy, demonstrating significant wound closure, collagen remodeling, and increased fibroblast density. Overall, the Cu-GHK NF/HA-Ty hydrogel represents an advanced therapeutic option for wound healing applications.

Investigating the Anti-Aging Effects of Caviar Oil on Human Skin.

BACKGROUND/AIM: As the largest organ of the human body, the skin serves as a critical barrier against environmental damage. However, many factors, such as genetics, sun exposure, and lifestyle choices can lead to skin damage creating wrinkles, sagging, and loss of elasticity. The use of skincare products containing natural ingredients has become increasingly popular as a way to combat the signs of aging. Caviar oil is one such ingredient that has gained attention due to its rich composition of fatty acids, vitamins, and minerals. The objective of this study was to investigate the potential anti-aging effects of caviar oil and to develop a product, Cavi Balm, which could potentially reduce wrinkles and skin sagging. MATERIALS AND METHODS: An in vitro model using the 3T3-L1 cell line was employed to assess the effect of caviar oil on adipocyte differentiation. An ex vivo study using human skin tissue was conducted to investigate the impact of caviar oil on collagen and elastin formation and the expression of matrix metalloproteinase-1,2,9 (MMP-1, MMP-2, MMP-9). Furthermore, 102 participants were enrolled in five clinical studies to evaluate the anti-aging efficacy of our product, "Cavi Balm", in facial and neck wrinkles, facial and eye area lifting, and various skin parameters, such as skin moisture, skin elasticity, skin density, skin tightening relief, skin clarity, and skin turnover. RESULTS: In vitro, caviar oil enhanced adipocyte differentiation, and increased lipid accumulation inside the cells. The ex vivo analysis revealed that caviar oil reduced the expression levels of MMP-1, MMP-2, and MMP-9, and increased the formation of elastin and collagen I, III. Moreover, in the clinical study, Cavi Balm improved skin parameters after one-time use, with more significant effects observed after four weeks of usage. CONCLUSION: Caviar oil has a substantial impact on mitigating skin aging and holds potential for application in anti-aging products.

Enhancement of Wound Healing Efficacy by Chitosan-based Hydrocolloid on Sprague Dawley Rats.

BACKGROUND/AIM: Chitosan-based functional materials have attracted considerable attention worldwide for applications in wound healing, especially in skin wound healing, due to their efficiency in hemostasis, anti-bacterial, and skin regeneration. Various chitosan-based products have been developed for skin wound healing applications, but most of these face limitations in either efficacy or cost-effectiveness. Therefore, there is a need to develop a unique material that can handle all of these concerns and be utilized for acute and chronic wounds. This study investigated mechanisms of new chitosan-based hydrocolloid patches in inflammatory reduction and skin formation by using wound-induced Sprague Dawley Rats. MATERIALS AND METHODS: Our study combined a hydrocolloid patch with chitosan to achieve a practical and accessible medical patch that would enhance skin wound healing. Our chitosan-embedded patch has shown a significant influence by preventing wound expansion and inflammation increment on Sprague Dawley rat models. RESULTS: The chitosan patch significantly increased the wound healing rate and accelerated the inflammatory stage by suppressing pro-inflammatory cytokines activity (e.g., TNF-α, IL-6, MCP-1, and IL-1ß). Moreover, the product was effective in promoting skin regeneration, demonstrated by the increase in the number of fibroblasts through specific biomarkers (e.g., vimentin, α-SMA, Ki-67, collagen I, and TGF-ß1). CONCLUSION: Our study on the chitosan-based hydrocolloid patches not only elucidated mechanisms of reducing inflammation and enhancing proliferation, but also provided a cost-effective method for skin wound dressing.

Complementary combination of biomarkers for diagnosis of sarcopenia in C57BL/6J mice.

AIMS: 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. MATERIAL AND METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: A complementary combination of digital and chemical biomarkers covers multiple domains of sarcopenia to provide an effective strategy for the early diagnosis of sarcopenia.

Effective decellularization of human skin tissue for regenerative medicine by supercritical carbon dioxide technique.

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.

Comparison of Formation of Capsule Among Different Breast Silicone Implants.

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.

A Comprehensive Review of Natural Compounds for Wound Healing: Targeting Bioactivity Perspective.

Wound healing is a recovering process of damaged tissues by replacing dysfunctional injured cellular structures. Natural compounds for wound treatment have been widely used for centuries. Numerous published works provided reviews of natural compounds for wound healing applications, which separated the approaches based on different categories such as characteristics, bioactivities, and modes of action. However, current studies provide reviews of natural compounds that originated from only plants or animals. In this work, we provide a comprehensive review of natural compounds sourced from both plants and animals that target the different bioactivities of healing to promote wound resolution. The compounds were classified into four main groups (i.e., anti-inflammation, anti-oxidant, anti-bacterial, and collagen promotion), mostly studied in current literature from 1992 to 2022. Those compounds are listed in tables for readers to search for their origin, bioactivity, and targeting phases in wound healing. We also reviewed the trend in using natural compounds for wound healing.

Nanomicelle-generating Microneedles Loaded With Tranilast for Treatment of Hypertrophic Scars in a Rabbit Model.

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-ß, 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.

Anaplastic Large Cell Lymphoma: Molecular Pathogenesis and Treatment.

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.

Evaluation of the Performance of a ZnO-Nanoparticle-Coated Hydrocolloid Patch in Wound Healing.

Hydrocolloid dressings are an important method for accelerating wound healing. A combination of a hydrocolloid and nanoparticles (NPs), such as gold (Au), improves the wound healing rate, but Au-NPs are expensive and unable to block ultraviolet (UV) light. Herein, we combined zinc oxide nanoparticles (ZnO-NPs) with hydrocolloids for a less expensive and more effective UV-blocking treatment of wounds. Using Sprague-Dawley rat models, we showed that, during 10-day treatment, a hydrocolloid patch covered with ZnO-NPs (ZnO-NPs-HC) macroscopically and microscopically stimulated the wound healing rate and improved wound healing in the inflammation phase as shown by reducing of pro-inflammatory cytokines (CD68, IL-8, TNF-α, MCP-1, IL-6, IL-1ß, and M1) up to 50%. The results from the in vitro models (RAW264.7 cells) also supported these in vivo results: ZnO-NPs-HCs improved wound healing in the inflammation phase by expressing a similar level of pro-inflammatory mediators (TNF-α and IL-6) as the negative control group. ZnO-NPs-HCs also encouraged the proliferation phase of the healing process, which was displayed by increasing expression of fibroblast biomarkers (α-SMA, TGF-ß3, vimentin, collagen, and M2) up to 60%. This study provides a comprehensive analysis of wound healing by measuring the biomarkers in each phase and suggests a cheaper method for wound dressing.

Silicone Implants Immobilized with Interleukin-4 Promote the M2 Polarization of Macrophages and Inhibit the Formation of Fibrous Capsules.

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.

Functionalization of Silicone Surface with Drugs and Polymers for Regulation of Capsular Contracture.

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.

In Vivo Comparison of Three Human Acellular Dermal Matrices for Breast Reconstruction.

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.

Silicone Breast Implant Coated with Triamcinolone Inhibited Breast-Implant-Induced Fibrosis in a Porcine Model.

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.

Mutational analysis of critical residues of FAD-independent catabolic acetolactate synthase from Enterococcus faecalis V583.

Catabolic acetolactate synthase (cALS) from Enterococcus faecalis is a FAD-independent enzyme, which catalyzes the condensation of two molecules of pyruvate to produce acetolactate. Mutational and kinetic analyses of variants suggested the importance of H111, Q112, and Q411 residues for catalysis in cALS. The wild-type and variants were expressed as equally soluble proteins and co-migrated to a size of 60 kDa on SDS-PAGE. Importantly, H111 in cALS, which is widely present as phenylalanine in many other ThDP-dependent enzymes, plays a crucial role in substrate binding. Interestingly, the H111 variants, H111R and H111F, demonstrated altered specific activity of H111 variants with 17- and 26-fold increases in Km, respectively, compared to wild-type cALS. Furthermore, Q112 variants, Q112E, Q112N, and Q112V, exhibited significantly lower specific activity with 70-, 15-, and 10-fold higher Ks for ThDP, respectively. In the case of Q411, the variant Q411E showed a 10-fold rise in Km and a 20-fold increase in Ks for ThDP. Further, the molecular docking results indicated that the binding mode of ThDP was slightly affected in the variants of cALS. Based on these results, we suggest that H111 plays a role in substrate binding, and further suggest that Q112 and Q411 might be involved in ThDP binding of cALS.

The family-wide structure and function of human dual-specificity protein phosphatases.

Dual-specificity protein phosphatases (DUSPs), which dephosphorylate both phosphoserine/threonine and phosphotyrosine, play vital roles in immune activation, brain function and cell-growth signalling. A family-wide structural library of human DUSPs was constructed based on experimental structure determination supplemented with homology modelling. The catalytic domain of each individual DUSP has characteristic features in the active site and in surface-charge distribution, indicating substrate-interaction specificity. The active-site loop-to-strand switch occurs in a subtype-specific manner, indicating that the switch process is necessary for characteristic substrate interactions in the corresponding DUSPs. A comprehensive analysis of the activity-inhibition profile and active-site geometry of DUSPs revealed a novel role of the active-pocket structure in the substrate specificity of DUSPs. A structure-based analysis of redox responses indicated that the additional cysteine residues are important for the protection of enzyme activity. The family-wide structures of DUSPs form a basis for the understanding of phosphorylation-mediated signal transduction and the development of therapeutics.