Vibration and Sound Response of Glass-Fiber-Reinforced Polyamide 6 Using Microcellular-Foaming-Process-Applied Injection Molding Process.

In this study, the vibration and sound response characteristics of composites produced via injection molding applied with a microcellular foaming process (MCPs) were improved. The study was conducted using PA6 and glass fiber composites, which are representative thermoplastic engineering plastics. Two types of specimens were used: a plate specimen to confirm the basic sound and vibration characteristics, and a large roof-rack specimen from an actual vehicle with a complex shape. The frequency response function curve was calculated by conducting an impact test, and natural frequency and damping ratio were measured based on the curve. The results confirmed that, in the case of a specimen manufactured through the injection molding process to which MCPs were applied, the natural frequency was lowered, and the damping ratio decreased. The degree of change in the natural frequency and damping ratio was confirmed. To determine the cause of the change in the natural frequency and damping ratio, the mode shape at the natural frequency of each specimen was measured and the relationship was confirmed by measuring the density and the elastic modulus of the composite. In addition, the usability of the specimens to which MCPs were applied was verified by conducting impact strength and tensile strength tests.

Long-Term Outcomes of Nasoseptal Perforation Repair Using Anterior Maxillary Sinus Wall as an Interpositional Graft.

BACKGROUND: Various graft materials have been used to repair nasoseptal perforation, but there is no standardized treatment method. The anterior maxillary sinus wall is flattened in appearance and can be easily obtained in a sufficient amount for a large-sized nasoseptal perforation. OBJECTIVES: The aim of this study is to determine whether the anterior maxillary sinus wall is suitable as an interpositional graft in the surgical repair of septal or nasoseptal perforation. METHODS: This is a retrospective review of 21 patients who underwent repair of nasoseptal perforation using anterior maxillary sinus wall as an interpositional graft. The etiology, pre- and post-operative NOSE and GBI score, and perforation size were reviewed. The surgical outcome was considered successful if total closure was achieved after postoperative follow-up. RESULTS: 19 of the 21 perforations were successfully repaired with anterior maxillary sinus wall. Failure of the repair was found in 2 patients. Causal etiology of perforation was previous septoplasty in 10 patients, and electrocautery in 1 case, but not identified in 10 cases. The largest size was 2.7 × 2.2 cm. The most common symptoms were epistaxis, crusting, and nasal obstruction. Closure of septal perforation resulted in improved subjective symptoms and quality of life which were evaluated with NOSE and GBI score. CONCLUSION: Anterior maxillary sinus wall as interpositional graft between mucoperichondrial flaps can be used to reliably repair nasoseptal perforations.

Reproducible Large-Scale Isolation of Exosomes from Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells and Their Application in Acute Kidney Injury.

Acute kidney injury (AKI) is a fatal medical episode caused by sudden kidney damage or failure, leading to the death of patients within a few hours or days. Previous studies demonstrated that exosomes derived from various mesenchymal stem/stromal cells (MSC-exosomes) have positive effects on renal injuries in multiple experimental animal models of kidney diseases including AKI. However, the mass production of exosomes is a challenge not only in preclinical studies with large animals but also for successful clinical applications. In this respect, tangential flow filtration (TFF) is suitable for good manufacturing practice (GMP)-compliant large-scale production of high-quality exosomes. Until now, no studies have been reported on the use of TFF, but rather ultracentrifugation has been almost exclusively used, to isolate exosomes for AKI therapeutic application in preclinical studies. Here, we demonstrated the reproducible large-scale production of exosomes derived from adipose tissue-derived MSC (ASC-exosomes) using TFF and the lifesaving effect of the ASC-exosomes in a lethal model of cisplatin-induced rat AKI. Our results suggest the possibility of large-scale stable production of ASC-exosomes without loss of function and their successful application in life-threatening diseases.

Botanical preparation HX109 inhibits macrophage-mediated activation of prostate epithelial cells through the CCL4-STAT3 pathway: implication for the mechanism underlying HX109 suppression of prostate hyperplasia.

Benign prostatic hyperplasia (BPH) is one of the most frequently observed diseases in the elderly male population worldwide. A variety of factors such as aging, hormonal imbalance, chronic inflammation, and oxidative stress play an important role in its pathogenesis. We have previously shown that HX109, an ethanol extract prepared from 3 plants (Taraxacum officinale, Cuscuta australis, and Nelumbo nucifera), alleviates prostate hyperplasia in the BPH rat model and suppresses AR signaling by upregulating Ca2+/CAMKKß and ATF3. In this study, we used macrophage cell lines to examine the effects of HX109 on inflammation, which is considered an important causative factor in BPH pathogenesis. In the co-culture system involving macrophage-prostate epithelial cells, HX109 inhibited macrophage-induced cell proliferation, migration and epithelial-mesenchymal transition (EMT) by inhibiting the expression of CCL4 and the phosphorylation of STAT3. Furthermore, HX109 inhibited the expression of inflammatory cytokines and the phosphorylation of p65 NF-κB in a concentration dependent manner. Taken together, our results suggested that HX109 could regulate macrophage activation and its crosstalk with prostate cells, thereby inhibiting BPH.

Mesenchymal Stem/Stromal Cell-Derived Exosomes for Immunomodulatory Therapeutics and Skin Regeneration.

Exosomes are nano-sized vesicles that serve as mediators for cell-to-cell communication. With their unique nucleic acids, proteins, and lipids cargo compositions that reflect the characteristics of producer cells, exosomes can be utilized as cell-free therapeutics. Among exosomes derived from various cellular origins, mesenchymal stem cell-derived exosomes (MSC-exosomes) have gained great attention due to their immunomodulatory and regenerative functions. Indeed, many studies have shown anti-inflammatory, anti-aging and wound healing effects of MSC-exosomes in various in vitro and in vivo models. In addition, recent advances in the field of exosome biology have enabled development of specific guidelines and quality control methods, which will ultimately lead to clinical application of exosomes. This review highlights recent studies that investigate therapeutic potential of MSC-exosomes and relevant mode of actions for skin diseases, as well as quality control measures required for development of exosome-derived therapeutics.

Exosomes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Promote Epidermal Barrier Repair by Inducing de Novo Synthesis of Ceramides in Atopic Dermatitis.

Atopic dermatitis (AD) is a multifactorial, heterogeneous disease associated with epidermal barrier disruption and intense systemic inflammation. Previously, we showed that exosomes derived from human adipose tissue-derived mesenchymal stem cells (ASC-exosomes) attenuate AD-like symptoms by reducing multiple inflammatory cytokine levels. Here, we investigated ASC-exosomes' effects on skin barrier restoration by analyzing protein and lipid contents. We found that subcutaneous injection of ASC-exosomes in an oxazolone-induced dermatitis model remarkably reduced trans-epidermal water loss, while enhancing stratum corneum (SC) hydration and markedly decreasing the levels of inflammatory cytokines such as IL-4, IL-5, IL-13, TNF-α, IFN-γ, IL-17, and TSLP, all in a dose-dependent manner. Interestingly, ASC-exosomes induced the production of ceramides and dihydroceramides. Electron microscopic analysis revealed enhanced epidermal lamellar bodies and formation of lamellar layer at the interface of the SC and stratum granulosum with ASC-exosomes treatment. Deep RNA sequencing analysis of skin lesions demonstrated that ASC-exosomes restores the expression of genes involved in skin barrier, lipid metabolism, cell cycle, and inflammatory response in the diseased area. Collectively, our results suggest that ASC-exosomes effectively restore epidermal barrier functions in AD by facilitating the de novo synthesis of ceramides, resulting in a promising cell-free therapeutic option for treating AD.

Effects of Gas Adsorption on the Mechanical Properties of Amorphous Polymer.

This study investigates the properties of a polymer-gas mixture formed through diffusion, based on the changes in the partial pressure and observed changes in the impact and tensile strengths owing to the gas dissolution. The high-pressure gas dissolves into a solid-state polymer through diffusion based on the difference in the partial pressure. This dissolved gas is present in the amorphous region within the polymeric material temporarily, which results in the polymer exhibiting different mechanical properties, while the gas remains dissolved in the polymer. In this study, the mechanical properties of amorphous polyethylene terephthalate (APET) specimens prepared by dissolving CO2 using a high-pressure vessel were investigated, and the resulting impact and tensile strengths were measured. These experiments showed that the increase in sorption rate of CO2 caused an increase in the impact strength. At 2.9% CO2 absorption, the impact strength of APET increased 956% compared to that of the reference specimen. Furthermore, the tensile strength decreased by up to 71.7% at 5.48% CO2 sorption; the stress-strain curves varied with the gas sorption rate. This phenomenon can be associated with the change in the volume caused by CO2 dissolution. When the APET absorbed more than 2.0% CO2 gas, sample volume increased. A decrease in the network density can occur when the volume is increased while maintaining constant mass. The CO2 gas in the polymer acted as a cushion in impact tests which have sorption rates above 2%. In addition to the reduction in the network density in the polymer chain, Van Der Waals forces are decreased causing a decrease in tensile strength only while CO2 is present in the APET. These observations only occur prior to CO2 desorption from the polymer.

Warpage Reduction of Glass Fiber Reinforced Plastic Using Microcellular Foaming Process Applied Injection Molding.

This study analyzes the fundamental principles and characteristics of the microcellular foaming process (MCP) to minimize warpage in glass fiber reinforced polymer (GFRP), which is typically worse than that of a solid polymer. In order to confirm the tendency for warpage and the improvement of this phenomenon according to the glass fiber content (GFC), two factors associated with the reduction of the shrinkage difference and the non-directionalized fiber orientation were set as variables. The shrinkage was measured in the flow direction and transverse direction, and it was confirmed that the shrinkage difference between these two directions is the cause of warpage of GFRP specimens. In addition, by applying the MCP to injection molding, it was confirmed that warpage was improved by reducing the shrinkage difference. To further confirm these results, the effects of cell formation on shrinkage and fiber orientation were investigated using scanning electron microscopy, micro-CT observation, and cell morphology analysis. The micro-CT observations revealed that the fiber orientation was non-directional for the MCP. Moreover, it was determined that the mechanical and thermal properties were improved, based on measurements of the impact strength, tensile strength, flexural strength, and deflection temperature for the MCP.

PG102 Upregulates IL-37 through p38, ERK, and Smad3 Pathways in HaCaT Keratinocytes.

IL-37 is an immunomodulatory cytokine that suppresses inflammation in various cell types and disease models. However, its role in keratinocytes has not been clearly understood, and there has been no report on the agents that can increase the expression of IL-37 in keratinocytes. In this study, we investigated the effects of silencing IL37 in HaCaT keratinocytes and the molecular mechanisms involved in the upregulation of IL-37 by PG102, a water-soluble extract from Actinidia arguta. It was found that knockdown of IL37 resulted in the augmented expression of antimicrobial peptides (AMPs) in response to cytokine stimulation. PG102 increased the expression of IL-37 at both mRNA and protein levels presumably by enhancing the phosphorylation of Smad3, ERK, and p38. Indeed, when cells were treated with specific inhibitors for these signaling molecules, the expression level of IL-37 was reduced. PG102 also promoted colocalization of phospho-Smad3 and IL-37. Our results suggest that IL-37 inhibits the expression of AMPs and that PG102 upregulates IL-37 through p38, ERK, and Smad3 pathways in HaCaT cells.

A Water-Soluble Extract from Actinidia arguta Ameliorates Psoriasis-Like Skin Inflammation in Mice by Inhibition of Neutrophil Infiltration.

Psoriasis is a chronic inflammatory disease with complex etiology involving multiple factors. Current treatment methods are highly limited and there is a strong need for the development of safer and efficacious agents. We have previously shown that a water-soluble extract derived from hardy kiwifruit Actinidia arguta, called PG102, shows potent anti-inflammatory effects. Based on its reported biological activities, the effects of PG102 were examined on imiquimod-induced psoriasis-like skin inflammation. Our results showed that topical application of PG102 ameliorates clinical symptoms of psoriasis, reducing skin thickness and Interleukin (IL)-17A level in draining lymph nodes without causing any adverse effects. Treatment with PG102 on cytokine-stimulated HaCaT cells suppressed hyperproliferation and downregulated the expression of various chemokines and antimicrobial peptides known to induce neutrophil infiltration. These anti-inflammatory activities of PG102 were mediated via inhibition of NF-κB and signal transducer of activation (STAT) signaling. We also found decreased neutrophil chemotaxis both in vitro and in vivo. Taken together, PG102 has potential as a safe and effective reagent for the treatment of psoriasis.

Dehydrodiconiferyl Alcohol Inhibits Osteoclast Differentiation and Ovariectomy-Induced Bone Loss through Acting as an Estrogen Receptor Agonist.

Estrogen deficiency after menopause increases bone loss by activating RANKL-induced osteoclast differentiation. Dehydrodiconiferyl alcohol (DHCA), a lignan originally isolated from Cucurbita moschata, has been thought to be a phytoestrogen based on its structure. In this study, we tested whether DHCA could affect RANKL-induced osteoclastogenesis in vitro and ovariectomy-induced bone loss in vivo. In RAW264.7 cells, DHCA inhibited RANKL-induced differentiation of osteoclasts. Consistently, expression of the six osteoclastogenic genes induced by RANKL was down-regulated. DHCA was also shown to suppress the NF-κB and p38 MAPK signaling pathways by activating AMPK. Data from transient transfection assays suggested that DHCA might activate the estrogen receptor signaling pathway. Effects of DHCA on RANKL-induced osteoclastogenesis were reduced when cells were treated with specific siRNA to ERα, but not to ERß. Interestingly, DHCA was predicted from molecular docking simulation to bind to both ERα and ERß. Indeed, data from an estrogen receptor competition assay revealed that DHCA acted as an agonist on both estrogen receptors. In the ovariectomized (Ovx) mouse model, DHCA prevented Ovx-induced bone loss by inhibiting osteoclastogenesis. Taken together, our results suggest that DHCA may be developed as an efficient therapeutic for osteoporosis by regulating osteoclastogenesis through its estrogenic effects.

PG201 protects mice from experimental autoimmune encephalomyelitis via suppression of effector T cell activation.

BACKGROUND: PG201 is a botanical formulation, approved as an ethical drug (ETC) phytomedicine for treatment of patients with osteoarthritis in Korea, following satisfactory phase II and phase III studies. This phytomedicine was previously been shown to possess significant anti-inflammatory activities, presumably via the control of Th1 and Th17 cells in animal models and in vitro cell culture systems. PURPOSE: In this study, the possibility of using PG201 to treat multiple sclerosis was explored. METHODS: In vitro, the effect of PG201 on the differentiation of CD4+ T cells was investigated. To test the effects of PG201 in vivo, a mouse experimental autoimmune encephalomyelitis (EAE) model was used. RESULTS: It was found that PG201 treatment decreased the frequency of both CD4+T-bet+ and CD4+RORγt+T cells. In addition, the production of interferon- gamma (IFN-γ) and interleukin-17 (IL-17) from respective Th cells was highly reduced. The data from western blots showed that the amount of phosphorylated c-Jun, but not that of p65, was decreased by PG201. Consistently, the level of luciferase activity was downregulated by PG201 in activator protein 1 (AP-1) reporter plasmid assays. In mice pretreated with PG201, the day of onset was delayed and clinical symptoms of EAE were significantly improved in a dose-dependent manner. Consistent with these results, the number of infiltrated cells and the expression level of pro-inflammatory molecules were decreased. CONCLUSION: These findings indicate that PG201 may exert strong immunomodulatory effects in the EAE model via suppression of T cell activation, and that PG201 is a therapeutic reagent for the treatment of multiple sclerosis.

Dehydrodiconiferyl alcohol promotes BMP-2-induced osteoblastogenesis through its agonistic effects on estrogen receptor.

Estrogen deficiency results in an imbalance between the levels of bone-resorping osteoclasts and bone-forming osteoblasts, eventually leading to overall bone loss. Dehydrodiconiferyl alcohol (DHCA), a lignan compound originally isolated from Cucurbita moschata, has been shown to bind to estrogen receptor, and indeed exhibits various activities of estrogen, such as anti-inflammatory and anti-oxidative stress effects. In this study, we tested whether synthetic DHCA could affect the BMP-2-induced osteoblastogenesis in vitro. In MC3T3-E1 cells, DHCA promoted BMP-2-induced differentiation of osteoblasts. Consistently, the expression of three osteoblastogenic genes known to be induced by BMP-2, ALP, osteocalcin and OPG, was up-regulated by DHCA treatment. DHCA was also shown to activate the production of RUNX2 by activating Smad1/5/9 and AMPK. Data from transient transfection assays suggested that DHCA might activate the estrogen receptor signaling pathway. Effects of DHCA on BMP-2-induced osteoblastogenesis were reduced when cells were treated with a specific siRNA to ERα or ERß. Taken together, our results suggest that DHCA may be developed as an efficient therapeutic for osteoporosis by regulating osteoblastogenesis through its estrogenic effects.

Survival of patients with advanced hepatocellular carcinoma: sorafenib versus other treatments.

BACKGROUND AND AIM: Although sorafenib is recommended for patients with advanced hepatocellular carcinoma (HCC), a substantial portion of HCC patients in Asia are still treated with other treatments, mainly due to the prohibitive cost of sorafenib. We aimed to evaluate the clinical outcome of patients treated with sorafenib and those treated with other modalities in a single-center cohort. METHODS: We reviewed the medical records of two groups of consecutive patients with advanced HCC, according to applied treatment modalities, between January 2007 and September 2009 as follows: patients who received sorafenib for 6 weeks or more (n=123) and patients who were treated with one or more of other treatments, including transarterial chemoembolization, radiation, and cytotoxic chemotherapy (n=253). RESULTS: Overall survival did not differ significantly between these two groups (8.4 vs 8.2 months; P=0.601). Significant prognostic factors were high α-fetoprotein (≥200 ng/mL), massive/infiltrative intrahepatic tumors, macrovascular invasion, extrahepatic spread, and higher tumor-node-metastasis stage. Subgroup analysis, according to these factors, showed that sorafenib resulted in superior survival in patients with extrahepatic spread (hazard ratio [HR]=0.539; P=0.003) and massive/infiltrative tumors (HR=0.680; P=0.036). In the absence of each prognostic factor, other treatments were better than sorafenib. CONCLUSIONS: Considering the survival benefit for sorafenib over other treatments in patients with extrahepatic spread and massive/infiltrative intrahepatic tumors, these characteristics might be regarded as compelling indications for sorafenib.