In Vitro Anti-Inflammatory and Antioxidant Activities of pH-Responsive Resveratrol-Urocanic Acid Nano-Assemblies.

Inflammatory environments provide vital biochemical stimuli (i.e., oxidative stress, pH, and enzymes) for triggered drug delivery in a controlled manner. Inflammation alters the local pH within the affected tissues. As a result, pH-sensitive nanomaterials can be used to effectively target drugs to the site of inflammation. Herein, we designed pH-sensitive nanoparticles in which resveratrol (an anti-inflammatory and antioxidant compound (RES)) and urocanic acid (UA) were complexed with a pH-sensitive moiety using an emulsion method. These RES-UA NPs were characterized by transmission electron microscopy, dynamic light scattering, zeta potential, and FT-IR spectroscopy. The anti-inflammatory and antioxidant activities of the RES-UA NPs were assessed in RAW 264.7 macrophages. The NPs were circular in shape and ranged in size from 106 to 180 nm. The RES-UA NPs suppressed the mRNA expression of the pro-inflammatory molecules inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in a concentration-dependent manner. Incubation of LPS-stimulated macrophages with RES-UA NPs reduced the generation of reactive oxygen species (ROS) in a concentration-dependent manner. These results suggest that pH-responsive RES-UA NPs can be used to decrease ROS generation and inflammation.

Tannylated Calcium Carbonate Materials with Antacid, Anti-Inflammatory, and Antioxidant Effects.

Calcium carbonate (CaCO3)-based materials have received notable attention for biomedical applications owing to their safety and beneficial characteristics, such as pH sensitivity, carbon dioxide (CO2) gas generation, and antacid properties. Herein, to additionally incorporate antioxidant and anti-inflammatory functions, we prepared tannylated CaCO3 (TA-CaCO3) materials using a simple reaction between tannic acid (TA), calcium (Ca2+), and carbonate (CO32-) ions. TA-CaCO3 synthesized at a molar ratio of 1:75 (TA:calcium chloride (CaCl2)/sodium carbonate (Na2CO3)) showed 3-6 µm particles, comprising small nanoparticles in a size range of 17-41 nm. The TA-CaCO3 materials could efficiently neutralize the acid solution and scavenge free radicals. In addition, these materials could significantly reduce the mRNA levels of pro-inflammatory factors and intracellular reactive oxygen species, and protect chondrocytes from toxic hydrogen peroxide conditions. Thus, in addition to their antacid property, the prepared TA-CaCO3 materials exert excellent antioxidant and anti-inflammatory effects through the introduction of TA molecules. Therefore, TA-CaCO3 materials can potentially be used to treat inflammatory cells or diseases.

Efficacy of a povidone-iodine foam dressing (Betafoam) on diabetic foot ulcer.

This study aimed to assess the efficacy of a new povidone-iodine (PVP-I) foam dressing (Betafoam) vs foam dressing (Medifoam) for the management of diabetic foot ulcers. This study was conducted between March 2016 and September 2017 at 10 sites in Korea. A total of 71 patients (aged ≥19 years) with type 1/2 diabetes and early-phase diabetic foot ulcers (Wagener classification grade 1/2) were randomised to treatment with PVP-I foam dressing or foam dressing for 8 weeks. Wound healing, wound infection, patient satisfaction, and adverse events (AEs) were assessed. The PVP-I foam and foam dressing groups were comparable in the proportion of patients with complete wound healing within 8 weeks (44.4% vs 42.3%, P = .9191), mean (±SD) number of days to complete healing (31.00 ± 15.07 vs 33.27 ± 12.60 days; P = .6541), and infection rates (11.1% vs 11.4%; P = 1.0000). Median satisfaction score (scored from 0 to 10) at the final visit was also comparable between groups (10 vs 9, P = .2889). There was no significant difference in AE incidence (27.8% vs 17.1%, P = .2836), and none of the reported AEs had a causal relationship with the dressings. The results of this study suggest that PVP-I foam dressing has wound-healing efficacy comparable with foam dressing, with no notable safety concerns. This study was funded by Mundipharma Korea Ltd and registered at ClinicalTrials.gov (identifier NCT02732886).

Exploring the In Vivo Anti-Inflammatory Actions of Simvastatin-Loaded Porous Microspheres on Inflamed Tenocytes in a Collagenase-Induced Animal Model of Achilles Tendinitis.

Tendon rupture induces an inflammatory response characterized by release of pro-inflammatory cytokines and impaired tendon performance. This study sought to investigate the therapeutic effects of simvastatin-loaded porous microspheres (SIM/PMSs) on inflamed tenocytes in vitro and collagenase-induced Achilles tendinitis in vivo. The treatment of SIM/PMSs in lipopolysaccharide (LPS)-treated tenocytes reduced the mRNA expressions of pro-inflammatory cytokines (Matrix metalloproteinase-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)). In addition, the local injection of SIM/PMSs into the tendons of collagenase-induced Achilles tendinitis rat models suppressed pro-inflammatory cytokines (MMP-3, COX-2, IL-6, TNF-α, and MMP-13). This local treatment also upregulated anti-inflammatory cytokines (IL-4, IL-10, and IL-13). Furthermore, treatment with SIM/PMSs also improved the alignment of collagen fibrils and effectively prevented collagen disruption in a dose-dependent manner. Therefore, SIM/PMSs treatment resulted in an incremental increase in the collagen content, stiffness, and tensile strength in tendons. This study suggests that SIM/PMSs have great potential for tendon healing and restoration in Achilles tendinitis.

Versatile Chemical Derivatizations to Design Glycol Chitosan-Based Drug Carriers.

Glycol chitosan (GC) and its derivatives have been extensively investigated as safe and effective drug delivery carriers because of their unique physiochemical and biological properties. The reactive functional groups such as the amine and hydroxyl groups on the GC backbone allow for easy chemical modification with various chemical compounds (e.g., hydrophobic molecules, crosslinkers, and acid-sensitive and labile molecules), and the versatility in chemical modifications enables production of a wide range of GC-based drug carriers. This review summarizes the versatile chemical modification methods that can be used to design GC-based drug carriers and describes their recent applications in disease therapy.

Intra-articular injection of stigmasterol-loaded nanoparticles reduce pain and inhibit the inflammation and joint destruction in osteoarthritis rat model: A pilot study.

Stigmasterol, a plant-derived sterol, sharing structural similarity with cholesterol, has demonstrated anti-osteoarthritis (OA) properties, attributed to its antioxidant and anti-inflammatory capabilities. Given that OA often arises in weight bearing or overused joints, prolonged localized treatment effectively targets inflammatory aspects of the disease. This research explored the impact of stigmasterol-loaded nanoparticles delivered via intra-articular injections in an OA rat model. Employing mesoporous silica nanomaterials (MSNs) combined with ß-cyclodextrin (ß-CD) as a vehicle, stigmasterol was loaded in conjunction with tannic acid, forming stigmasterol/ß-CD-MSNs to facilitate a sustained stigmasterol release. The study employed RAW 264.7 cells to examine the in vitro cytotoxicity and anti-inflammatory effect of stigmasterol/ß-CD-MSNs. For in vivo experimentation, we used healthy control rats and monosodium iodoacetate (MIA)-induced OA rats, separated into five groups, varying the injection substances. In vitro findings indicated that stigmasterol/ß-CD-MSNs suppressed the mRNA expression of key pro-inflammatory mediators such as interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-3 in a dose-dependent manner. In vivo experiments revealed a substantial decrease in the mRNA levels of pro-inflammatory factors in the stigmasterol(50 µg)/ß-CD-MSN group compared to the others. Macroscopic, radiographic, and histological evaluations established that intra-articular injections of stigmasterol/ß-CD-MSNs inhibited cartilage degeneration and subchondral bone deterioration. Therefore, in a chemically induced OA rat model, intra-articular stigmasterol delivery was associated with reduction in both local and systemic inflammatory responses, alongside a slowdown in joint degradation and arthritic progression.

Light-enhanced molecular polarity enabling multispectral color-cognitive memristor for neuromorphic visual system.

An optoelectronic synapse having a multispectral color-discriminating ability is an essential prerequisite to emulate the human retina for realizing a neuromorphic visual system. Several studies based on the three-terminal transistor architecture have shown its feasibility; however, its implementation with a two-terminal memristor architecture, advantageous to achieving high integration density as a simple crossbar array for an ultra-high-resolution vision chip, remains a challenge. Furthermore, regardless of the architecture, it requires specific material combinations to exhibit the photo-synaptic functionalities, and thus its integration into various systems is limited. Here, we suggest an approach that can universally introduce a color-discriminating synaptic functionality into a two-terminal memristor irrespective of the kinds of switching medium. This is possible by simply introducing the molecular interlayer with long-lasting photo-enhanced dipoles that can adjust the resistance of the memristor at the light-irradiation. We also propose the molecular design principle that can afford this feature. The optoelectronic synapse array having a color-discriminating functionality is confirmed to improve the inference accuracy of the convolutional neural network for the colorful image recognition tasks through a visual pre-processing. Additionally, the wavelength-dependent optoelectronic synapse can also be leveraged in the design of a light-programmable reservoir computing system.

Association between First-Generation Antihistamine Use in Children and Cardiac Arrhythmia and Ischemic Heart Disease: A Case-Crossover Study.

Cardiotoxicity from first-generation H1-antihistamines has been debated since the 1990s. However, large-scale studies on this topic in a general pediatric population are lacking. This study aimed to assess the association between first-generation H1-antihistamine use and cardiovascular events in a nationwide pediatric population. In this case-crossover study, the main cohort included children with cardiovascular events from the National Health Insurance Service database (2008-2012 births in Korea) until 2018. The second cohort excluded children with specific birth histories or underlying cardiovascular diseases from the main cohort. Cardiovascular events of interest included cardiac arrhythmia and ischemic heart disease. Odds ratios (ORs) of cardiovascular events were estimated using conditional logistic regression models, comparing first-generation H1-antihistamine use during 0-15 days before cardiovascular events (hazard period) with use during 45-60 and 75-90 days before events (control periods). Among the participants, 1194 (59.9%) were aged 24 months to 6 years, and 1010 (50.7%) were male. Cardiovascular event risk was increased among users of first-generation H1-antihistamines (adjusted OR [aOR], 1.201; 95% confidence interval, 1.13-1.27). Significant odds of cardiovascular events persisted within 10 and 5 days (aOR, 1.25 and 1.25). In the second cohort, the association was comparable with that in the main cohort. Our findings indicate that cardiovascular event risk is increased in children who are administered first-generation H1-antihistamines.

Highly Reliable 3D Channel Memory and Its Application in a Neuromorphic Sensory System for Hand Gesture Recognition.

Brain-inspired neuromorphic computing systems, based on a crossbar array of two-terminal multilevel resistive random-access memory (RRAM), have attracted attention as promising technologies for processing large amounts of unstructured data. However, the low reliability and inferior conductance tunability of RRAM, caused by uncontrollable metal filament formation in the uneven switching medium, result in lower accuracy compared to the software neural network (SW-NN). In this work, we present a highly reliable CoOx-based multilevel RRAM with an optimized crystal size and density in the switching medium, providing a three-dimensional (3D) grain boundary (GB) network. This design enhances the reliability of the RRAM by improving the cycle-to-cycle endurance and device-to-device stability of the I-V characteristics with minimal variation. Furthermore, the designed 3D GB-channel RRAM (3D GB-RRAM) exhibits excellent conductance tunability, demonstrating high symmetricity (624), low nonlinearity (ßLTP/ßLTD ∼ 0.20/0.39), and a large dynamic range (Gmax/Gmin ∼ 31.1). The cyclic stability of long-term potentiation and depression also exceeds 100 cycles (105 voltage pulses), and the relative standard deviation of Gmax/Gmin is only 2.9%. Leveraging these superior reliability and performance attributes, we propose a neuromorphic sensory system for finger motion tracking and hand gesture recognition as a potential elemental technology for the metaverse. This system consists of a stretchable double-layered photoacoustic strain sensor and a crossbar array neural network. We perform training and recognition tasks on ultrasonic patterns associated with finger motion and hand gestures, attaining a recognition accuracy of 97.9% and 97.4%, comparable to that of SW-NN (99.8% and 98.7%).

Repair of rabbit ulna segmental bone defect using freshly isolated adipose-derived stromal vascular fraction.

BACKGROUND AIMS: Stromal vascular fractions (SVF) from adipose tissue have heterogeneous cell populations, and include multipotent adipose-derived stem cells. The advantages of using of SVF include the avoidance of an additional culture period, a reduced risk of extensive cell contamination, and cost-effectiveness. METHODS: Unilateral 20-mm mid-diaphyseal segmental defects in rabbit ulna were treated with one of the following: polylactic glycolic acid (PLGA) scaffold alone (group 1, control), a PLGA scaffold with undifferentiated SVF cells (group 2), or a PLGA scaffold with osteogenically differentiated SVF cells (group 3). At 8 weeks after implantation, five rabbits in each treatment group were killed to assess bone defect healing by plain radiography, quantitative microcomputed tomography and histology. RESULTS: The SVF cells were well grown on PLGA scaffolds and expressed type I collagen and alkaline phosphatase (ALP). The intensity of ALP and OPN gene expressions in osteogenic medium culture were increased from 14 days to 28 days. In vivo evaluations at 8 weeks showed that treatment of SVF cells with or without osteogenic differentiation resulted in more bone formation in the critically sized segmental defects than PLGA scaffold alone. Osteogenically differentiated SVF cells significantly enhanced bone healing compared with undifferentiated SVF cells. CONCLUSIONS: Adipose-derived stromal SVF showed osteogenic potential in vitro. Accordingly, SVF could provide a cell source for bone tissue engineering. However, treatment with uncultured SVF cells on bone healing was not satisfactory in the in vivo animal model.

The effect of bone morphogenic protein-2-coated tri-calcium phosphate/hydroxyapatite on new bone formation in a rat model of femoral distraction osteogenesis.

BACKGROUND AIMS: Distraction osteogenesis (DO) is an increasingly popular technique used to stimulate new bone formation to treat orthopedic disorders resulting from bone defects and deficits. Because of various possible complications that can occur during the long consolidation period, the development of procedures to accelerate regenerated ossification is clearly desirable. The purpose of this study was to evaluate the effect of single insertions of bone morphogenic protein-2 (BMP-2), delivered by tri-calcium phosphate (TCP)/hydroxyapatite (HA), administered at osteotomy sites, on the rate of new bone formation during DO in a rat model. METHODS: Thirty-six male Sprague-Dawley rats, aged 12 weeks and weighing a mean (± standard deviation) of 401 ± 14 g, were used in this study. The animals were randomized into three groups of 12 rats each. Group I served as a control, group II was treated with only TCP/HA, and group III was treated with recombinant human (rh) BMP-2-coated TCP/HA. Materials were inserted into the medullary canal at the femoral osteotomy site at the end of the lengthening period. After a 7-day latent phase, distraction was commenced on day 0 at a rate of 0.50 mm every 6 h for 5 days (2 mm daily), resulting in a total of 10 mm of lengthening by day 5. At two different time-points [at 4 weeks (day 33) and 8 weeks (day 61) after cessation of distraction], the progress of bone formation was determined with microcomputed tomography (micro-CT), histology and real-time polymerase chain reaction (PCR). The mean and standard deviation of the values obtained from the experiment were computed and statistical analyses performed using anova. Statistical significance was established at P < 0.05. Results. Radiographically, all group III rat femurs exhibited bridging callus formation 8 weeks after cessation of distraction, whereas group II rat femurs demonstrated non-bridging callus formation. None of the group I rat femurs showed callus in the central zone of the distraction gap. For micro-CT, bone formation and remodeling of the distraction regeneration with beta-TCP/HA coated with rhBMP-2 had greater values than the control sides at all time-points. Two-dimensional quantitative analysis of the distraction regeneration showed that the bone volume of group III had higher values than groups I and II at 4 weeks (P < 0.05). This difference was also evident at 8 weeks. With hematoxylin and eosin (H&E) staining, the control group (group I) did not show any bone tissue at the distraction site. In group II at 4 weeks, abundant fibrous tissue surrounding the particles was visible with some areas of woven bone. At 8 weeks, the woven bone covered the particles but not the whole circumference. In group III at 4 weeks, much of the woven bone surrounded the particle with some fibrocartilagenous materials. At 8 weeks, woven bone covering the whole circumference of the particles was visible. CONCLUSIONS: Application of rhBMP-2, at the end of the rather rapid distraction period, as a single bolus significantly increased the osteogenic process, while beta-TCP/HA behaved effectively as a sustained delivery system for this osteoinductive protein.

Dermoscopy-guided Mohs micrographic surgery in post-laser basal cell carcinomas: is dermoscopy helpful for demarcation of the surgical margin?

BACKGROUND: Mohs micrographic surgery (MMS) in cases where the tumor margin is poorly defined to the naked eye can lead to the need to take an increased number of Mohs stages. OBJECTIVE: To evaluate the usefulness of dermoscopy in determining MMS surgical margins of BCCs with a history of ablative laser treatment. METHODS: Patients were randomly allocated to naked eye (n = 69) or dermoscopy (n = 64) groups by the surgical margin detection method. Surgical outcomes of 133 post-laser BCC patients treated with MMS were analyzed. RESULTS: The lateral margin involvement rate at the first MMS stage was significantly lower in the dermoscopy group than in the naked eye group (4.7% vs. 29.0%; p < .001). However, the deep margin involvement rate at the first and mean MMS stages were not significantly different between the groups. The ablative laser treatment duration correlated to the number of MMS stages (p = .026). CONCLUSION: The results demonstrated that lateral margin was mostly controlled within the first MMS stage with dermoscopy. Dermatosurgeons could focus on the deep margin after the first MMS stage; thus, the performance of MMS could be improved with dermoscopic assistance in post-laser BCC patients.

Venous Insufficiency is a Clear Provoker of Pigmented Purpuric Dermatosis.

BACKGROUND: Pigmented purpuric dermatosis (PPD) is a chronic disorder characterized by distinct petechial hemorrhage and brownish pigmentation. The cause of PPD is unclear, but several underlying conditions are associated with it. Previous reports suggest that venous insufficiency (VI) might be related to PPD; however, a clear correlation remains unelucidated. OBJECTIVE: To elucidate the causal relationship between PPD and VI. METHODS: A total 118 patients diagnosed with PPD in the Department of Dermatology, Pusan National University Hospital from November 2006 to July 2019 were retrospectively reviewed. Doppler ultrasonography of the lower extremities was performed in 56 PPD patients, who were then divided into two groups: PPD with and without VI. We compared the clinical features between the two groups. In the PPD with VI group, we assessed the correspondence ratios between PPD and VI lateralities, and between the PPD distribution and the veins involved. RESULTS: VI was detected in 35 of the 56 patients (62.5%). The PPD with VI group was significantly associated with wider distribution, darker coloration and longer disease duration. There was a positive correlation of laterality between PPD and VI, and between PPD distribution and the vein involved. CONCLUSION: This findings suggest that VI is a clear provoker of PPD.

Intra-Articular Injection of Rebamipide-Loaded Nanoparticles Attenuate Disease Progression and Joint Destruction in Osteoarthritis Rat Model: A Pilot Study.

OBJECTIVE: Rebamipide has antioxidant effects and is a drug with a local rather than systemic mechanism of action. Oxidative stress and inflammation in chondrocytes are the major factors contributing to the development and progression of osteoarthritis (OA). Since OA is mainly developed in weight bearing or overused joints, the locally sustained therapy is effective for targeting inflammatory component of OA. We investigated the effects of intra-articular injection of rebamipide loaded nanoparticles (NPs) in OA rat model. DESIGN: We fabricated rebamipide-loaded methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG-PDLLA) and poly(D, L-lactide-co-glycolide) (PLGA) NPs that allow the sustained release of rebamipide. In vitro, chondrocytes from rat were used to investigate the cytotoxicity and anti-inflammatory effect of rebamipide-loaded NPs. In vivo, monosodium iodoacetate (MIA)-induced OA rats were divided into 7 groups, consisting of healthy control rats and rats injected with MIA alone or in combination with NPs, rebamipide (1 mg)/NPs, rebamipide (10 mg)/NPs, rebamipide (10 mg) solution, or oral administration. RESULTS: In vitro, rebamipide/NPs dose-dependently suppressed the mRNA levels of pro-inflammatory mediators, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, matrix metalloproteinase (MMP)-3, MMP-13, and cyclo-oxygenase-2. In vivo, the mRNA levels of pro-inflammatory components most markedly decreased in the intra-articularly injected rebamipide (10 mg)/NP group compared to other groups. Macroscopic, radiographic, and histological evaluations showed that the intra-articular injection of rebamipide/NPs inhibited cartilage degeneration more than rebamipide solution or rebamipide administration. CONCLUSIONS: Using a chemically induced rat model of OA, intra-articular delivery of rebamipide was associated with decreased local and systemic inflammatory response decreased joint degradation and arthritic progression.

Multifunctional Tannic Acid-Alendronate Nanocomplexes with Antioxidant, Anti-Inflammatory, and Osteogenic Potency.

In the current study, we fabricated tannic acid-alendronate (TA-ALN) nanocomplexes (NPXs) via self-assembly. These TA-ALNs were characterized by dynamic light scattering, zeta potential, transmission electron microscopy, and FT-IR spectroscopy. The TA-ALNs were evaluated for antioxidant, anti-inflammatory, and osteogenesis-accelerating abilities in osteoblast-like cells (MC3T3-E1 cells). All TA-ALNs displayed nano-sized beads that were circular in form. Treatment with TA-ALN (1:0.1) efficiently removed reactive oxygen species in cells and protected osteoblast-like cells from toxic hydrogen peroxide conditions. Moreover, TA-ALN (1:0.1) could markedly decrease the mRNA levels of pro-inflammatory mediators in lipopolysaccharide-stimulated cells. Furthermore, cells treated with TA-ALN (1:1) exhibited not only significantly greater alkaline phosphatase activity and calcium collection, but also outstandingly higher mRNA levels of osteogenesis-related elements such as collagen type I and osteocalcin. These outcomes indicate that the prepared TA-ALNs are excellent for antioxidant, anti-inflammatory, and osteogenic acceleration. Accordingly, TA-ALN can be used latently for bone renovation and regeneration in people with bone fractures, diseases, or disorders.

A comparative pilot study of oral diacerein and locally treated diacerein-loaded nanoparticles in a model of osteoarthritis.

Diacerein (DIA) is a slow-acting drug for osteoarthritis (OA). Oral DIA administration, however, exerts side effects including diarrhea and urine discoloration. We fabricated DIA-loaded poly(d,l-lactide-co-glycolide) nanoparticles (DIA/PLGA NPs) that allow sustained release of DIA. In vitro, rat synoviocytes were used to investigate the cytotoxicity and anti-inflammatory effects of DIA-loaded NPs. In vivo, monosodium iodoacetate (MIA)-induced OA rats were divided into seven groups that included non-treated healthy control rats and rats injected with MIA alone or in combination with NPs, DIA(5%) solution, DIA(1%)/NPs, DIA(5%)/NPs, or oral DIA. The in vitro studies revealed that DIA/PLGA NPs dose-dependently suppressed mRNA levels of pro-inflammatory cytokines and enzymes, including interleukin-1 (IL-1), IL-6, tumor necrosis factor-α, matrix metalloproteinase-3 (MMP-3), MMP-13, cyclo-oxygenase-2, and a disintegrin and metalloproteinase with thrombospondin motifs-5 in synoviocytes. The in vivo studies demonstrated that intra-articular treatment of OA rat models with DIA-loaded PLGA NPs markedly decreased mRNA levels of these pro-inflammatory factors and increased those of anti-inflammatory cytokines (IL-4 and IL-10). Micro-computed tomography and histological evaluations indicated that intra-articular injection of DIA-loaded NPs was effective in protecting against cartilage degradation. Administration of DIA/PLGA NPs via intra-articular injection is promising for inhibiting inflammation and protecting against cartilage degradation in OA.

Therapeutic Efficacy of Intratendinous Delivery of Dexamethasone Using Porous Microspheres for Amelioration of Inflammation and Tendon Degeneration on Achilles Tendinitis in Rats.

Achilles tendinitis caused by overuse, aging, or gradual wear induces pain, swelling, and stiffness of Achilles tendon and leads to tendon rupture. This study was performed to investigate the suppression of inflammation responses in interleukin-1ß- (IL-1ß-) stimulated tenocytes in vitro and the suppression of the progression of Achilles tendinitis-induced rat models in vivo using dexamethasone-containing porous microspheres (DEX/PMSs) for a sustained intratendinous DEX delivery. DEX from DEX/PMSs showed the sustained release of DEX. Treatment of IL-1ß-stimulated tenocytes with DEX/PMSs suppressed the mRNA levels for COX-2, IL-1ß, IL-6, and TNF-α. The intratendinous injection of DEX/PMSs into Achilles tendinitis rats both decreased the mRNA levels for these cytokines and increased mRNA levels for anti-inflammatory cytokines IL-4 and IL-10 in tendon tissues. Furthermore, DEX/PMSs effectively prevented tendon degeneration by enhancing the collagen content and biomechanical properties. Our findings suggest that DEX/PMSs show great potential as a sustained intratendinous delivery system for ameliorating inflammation responses as well as tendon degeneration in Achilles tendinitis.

Clinical and Dermoscopic Features of Fungal Melanonychia: Differentiating from Subungual Melanoma.

BACKGROUND: Fungal melanonychia (FM) is a rare nail disorder that presents as dark pigmentation in the nail plate because of fungal nail infection. The diagnosis of FM is occasionally confusing because its appearance is similar to melanonychia due to other causes including malignant melanoma. Dermoscopy could help increase the accuracy of diagnosing the cause of pigmented nail lesions. However, dermoscopic features of FM are not well elucidated. OBJECTIVE: This study aimed to investigate clinical and dermoscopic characteristics of FM. METHODS: The clinical features and dermoscopic findings of 20 patients diagnosed with FM and 14 patients diagnosed with subungual melanoma the Department of Dermatology of Pusan National University Hospitals (Busan and Yangsan) were retrospectively reviewed. RESULTS: FM mainly occurred as a solitary form in the toenail. Patients in the FM group were older than those in the subungual melanoma group. The most distinguishable general dermoscopic features in FM were a distal diffuse pattern, distal linear pattern, and light brown to yellowish color. FM-associated specific dermoscopic patterns such as the reverse triangular pattern, subungual hyperkeratosis, scale on the nail surface, and white or yellowish streaks were dominantly observed in the FM group compared to the subungual melanoma group. CONCLUSION: FM-associated dermoscopic patterns and distal diffuse and linear patterns could be helpful diagnostic clues for differential diagnosis of FM from subungual melanoma.

Identification of prognostic mRNAs in metastatic cutaneous melanoma.

Cutaneous melanoma is the most common cause of skin cancer-related deaths worldwide. There is an urgent need to identify prognostic biomarkers to facilitate decision-making for treatment of metastatic cutaneous melanoma. Gene expression microarrays and RNA-seq technology have recently improved or changed current prognostic and therapeutic strategies for several cancers. However, according to the current melanoma staging system, prognosis is almost entirely dependent on clinicopathological features. To identify novel prognostic biomarkers, we investigated gene expression and clinical data for patients with cutaneous melanoma from three cohorts of The Cancer Genome Atlas and Gene Expression Omnibus. Kaplan-Meier survival analysis using median values of each gene as cutoff value revealed that nine genes (ABCC3, CAPS2, CCR6, CDCA8, CLU, DPF1, PTK2B, SATB1, and SYNE1) were statistically significant prognostic biomarkers of metastatic cutaneous melanoma in all three independent cohorts. Low expression of two genes (CDCA8 and DPF1) and high expression of seven genes (ABCC3, CAPS2, CCR6, CLU, PTK2B, SATB1, and SYNE) were significantly associated with positive metastatic cutaneous melanoma prognoses. In conclusion, we suggest nine novel prognostic biomarkers for cutaneous metastatic melanoma.

Lactoferrin-Anchored Tannylated Mesoporous Silica Nanomaterials for Enhanced Osteo-Differentiation Ability.

In the present study, we created lactoferrin-anchored mesoporous silica nanomaterials with absorbed tannic acid (LF/TA-MSNs) and evaluated the effect of these LF/TA-MSNs on the in vitro osteo-differentiation ability of adipose-derived stem cells (ADSCs) by testing alkaline phosphatase (ALP) level, calcium accumulation, and expression of osteo-differentiation-specific genes, including osteocalcin (OCN) and osteopontin (OPN). Both bare MSNs and LF/TA-MSNs exhibited round nano-particle structures. The LF/TA-MSNs demonstrated prolonged LF release for up to 28 days. Treatment of ADSCs with LF (50 µg)/TA-MSNs resulted in markedly higher ALP level and calcium accumulation compared to treatment with LF (10 µg)/TA-MSNs or bare MSNs. Furthermore, LF (50 µg)/TA-MSNs remarkably increased mRNA levels of osteo-differentiation-specific genes, including OCN and OPN, compared to MSNs or LF (10 µg)/TA-MSNs. Together, these data suggest that the ability of LF/TA-MSNs to enhance osteo-differentiation of ADSCs make them a possible nanovehicle for bone healing and bone regeneration in patients with bone defect or disease.