BSA/Silver Nanoparticle-Loaded Hydrogel Film for Local Photothermal Treatment of Skin Cancer.

PURPOSE: To develop a hydrogel film containing bovine serum albumin (BSA)-coated silver nanoparticles (BSA/AgNP) and evaluate its applicability for topical photothermal treatment (PTT) of skin cancer. METHODS: BSA/AgNP-loaded hydrogel films were prepared and their swelling, bioadhesive, mechanical, and photothermal properties were characterized in vitro and in vivo. RESULTS: The synthesized BSA/AgNP exhibited a narrow size distribution with good size stability and, notably, possessed great photothermal activity that could stably maintain through repetitive laser irradiation. The BSA/AgNP-loaded hydrogel films showed favorable swelling, bioadhesive, tensile, and photothermal properties. Based on these results, when tested the anti-cancer effects in B16F10 s.c. tumor-bearing mice, the PTT with the topical treatment of BSA/AgNP-loaded hydrogel films could significantly inhibit the tumor growth by a single treatment with no apparent toxicity. CONCLUSIONS: Overall, the results of this study demonstrated that the BSA/AgNP-loaded hydrogel films may serve as an effective but safe topical PTT agent for the treatment of skin cancer.

Development and characterization of a superabsorbing hydrogel film containing Ulmus davidiana var. Japonica root bark and pullulan for skin wound healing.

Ulmus davidiana var. japonica (UD) has widely been used in Korean traditional medicine for the treatment of various types of diseases including inflammation and skin wounds. The UD root bark powders possess gelling activity with an excellent capacity for absorbing water. This distinct property could make the UD root bark powders to be a great material for manufacturing a gel film specifically for the healing of large and highly exudating wounds (e.g., pressure sores and diabetic ulcers). In this research, we separated the UD root bark powder into 4 different samples based on their sizes and then tested their water absorption capacity and flowability. Based on these results, 75-150 µm sized and below 75 µm sized samples of UD root bark powders were chosen, and UD gel films were prepared. The UD gel films showed good thermal stability and mechanically improved properties compared with pullulan only gel film with excellent swelling capacity and favorable skin adhesiveness. Further, in the animal studies with the skin wound mice model, the UD gel films exhibited significant therapeutic effects on accelerating wound closure and dermal regeneration. Overall, this study demonstrated the applicability of UD root bark powders for hydrogel wound dressing materials, and the potential of UD gel films to be superior wound dressings to currently available ones.

A comparison of the chemical composition and antioxidant activity of several new early- to mid-season apple cultivars for a warmer climate with traditional cultivars.

BACKGROUND: New early- to mid-season apple cultivars are being developed to help address warmer growing seasons due to climate change. Free sugars, organic acids, total phenolic content, total flavonoid content, antioxidant activity and phenolic composition were determined in the pulp and peel of six new and six traditional apple cultivars. In addition, the phenolic profiles of apple peels were characterized using high-resolution mass spectrometry. Forty-eight polyphenol compounds were identified, by accurate mass, in apple peel. RESULTS: Compared to Fuji apples, a new apple cultivar, Decobell, contained 2.6- and 1.4-fold higher levels of the sum of individual polyphenol levels in the peel and the pulp, respectively. Decobell apples showed similar sugar-to-acid ratio (0.27) to Fuji apples (0.25). CONCLUSIONS: The results indicate that the Decobell cultivar could have the best quality characteristics in terms of sugar-to-acid ratios and health-promoting activities due to the phenolic profiles. © 2019 Society of Chemical Industry.

Multivariate Statistical Optimization of Tablet Formulations Incorporating High Doses of a Dry Herbal Extract.

The development of oral tablet formulation for herbal medicines has been restricted by large drug loadings and the poor physicochemical and mechanical properties of dry herbal extracts (DHEs). Herein, statistical experimental designs were applied to herbal tablet formulation development and optimization using Wuzi Yanzong dry extract (WYE). The tablet disintegration time and hardness were identified as the critical quality attributes (CQAs) of the product. The tablet formulation was designed to achieve a high drug loading (50% or higher of WYE), shorter tablet disintegration time (less than 30 minutes), and suitable hardness (6.0 to 7.5 kp). A D-optimal mixture design was used to evaluate the effects of excipients on CQAs to minimize the risk compression failure and improve the tabletability in formulations containing WYE at 50% and 65% by weight. A partial least squares model was used to elucidate the multivariate relationships between a large number of formulation variables and product CQAs, and determine the maximum possible WYE loading. From overlaid plots of the effects of formulation variables on CQAs, it was found that a maximum WYE loading of 67% in tablet formulation satisfied the acceptance criteria of CQAs. In conclusion, this study shows that multivariate statistical tools are useful for developing tablet formulations containing high doses of herbal extracts and establishing control strategies that ensure product quality.

Lichen Secondary Metabolite, Physciosporin, Inhibits Lung Cancer Cell Motility.

Lichens produce various unique chemicals that can be used for pharmaceutical purposes. To screen for novel lichen secondary metabolites showing inhibitory activity against lung cancer cell motility, we tested acetone extracts of 13 lichen samples collected in Chile. Physciosporin, isolated from Pseudocyphellaria coriacea (Hook f. & Taylor) D.J. Galloway & P. James, was identified as an effective compound and showed significant inhibitory activity in migration and invasion assays against human lung cancer cells. Physciosporin treatment reduced both protein and mRNA levels of N-cadherin with concomitant decreases in the levels of epithelial-mesenchymal transition markers such as snail and twist. Physciosporin also suppressed KITENIN (KAI1 C-terminal interacting tetraspanin)-mediated AP-1 activity in both the absence and presence of epidermal growth factor stimulation. Quantitative real-time PCR analysis showed that the expression of the metastasis suppressor gene, KAI1, was increased while that of the metastasis enhancer gene, KITENIN, was dramatically decreased by physciosporin. Particularly, the activity of 3'-untranslated region of KITENIN was decreased by physciosporin. Moreover, Cdc42 and Rac1 activities were decreased by physciosporin. These results demonstrated that the lichen secondary metabolite, physciosporin, inhibits lung cancer cell motility through novel mechanisms of action.

Novel drug combination for Mycobacterium abscessus disease therapy identified in a Drosophila infection model.

OBJECTIVES: Mycobacterium abscessus is known to be the most drug-resistant Mycobacterium and accounts for ∼80% of pulmonary infections caused by rapidly growing mycobacteria. This study reports a new Drosophila melanogaster-M. abscessus infection model that can be used as an in vivo efficacy model for anti-M. abscessus drug potency assessment. METHODS: D. melanogaster were challenged with M. abscessus, and infected flies were fed with a fly medium containing tigecycline, clarithromycin, linezolid, clofazimine, moxifloxacin, amikacin, cefoxitin, dinitrobenzamide or metronidazole at different concentrations (0, 100 and 500 mg/L). The survival rates of infected flies were plotted and bacterial colonization/dissemination in fly bodies was monitored by cfu determination and green fluorescent protein epifluorescence. RESULTS: The D. melanogaster-M. abscessus model enabled an assessment of the effectiveness of antibiotic treatment. Tigecycline was the best drug for extending the lifespan of M. abscessus-infected Drosophila, followed by clarithromycin and linezolid. Several different combinations of tigecycline, linezolid and clarithromycin were tested to determine the best combination. Tigecycline (25 mg/L) plus linezolid (500 mg/L) was the best drug combination and its efficacy was superior to conventional regimens, not only in prolonging infected fly survival but also against M. abscessus colonization and dissemination. CONCLUSIONS: This D. melanogaster-M. abscessus infection/curing methodology may be useful for the rapid evaluation of potential drug candidates. In addition, new combinations using tigecycline and linezolid should be considered as possible next-generation combination therapies to be assessed in higher organisms.

Mycobacterium marinum infection in Drosophila melanogaster for antimycobacterial activity assessment.

OBJECTIVES: The major advantages of Drosophila melanogaster are a well-characterized immune system and high degree of susceptibility to tuberculosis caused by Mycobacterium marinum. The D. melanogaster-M. marinum infection model is gaining momentum as a screening tool because it is genetically amenable, low priced, rapid, technically convenient and ethically acceptable. In this context, the aim of this study was to develop a new, effective D. melanogaster-M. marinum in vivo efficacy model for antimycobacterial drug discovery. METHODS: D. melanogaster were challenged with intra-abdominal injections of M. marinum and infected flies were fed with a fly medium containing isoniazid, rifampicin, ethambutol, pyrazinamide, amikacin, dinitrobenzamide or ampicillin dissolved in DMSO at different concentrations (0, 100 and 500 mg/L). Bacterial dissemination in flies was monitored by fluorescence microscopy/cfu counts and a fly survival curve was plotted. RESULTS: The D. melanogaster-M. marinum model allowed assessment of the effectiveness of antibiotic treatment not only with conventional drugs, but also with newly discovered antimycobacterial agents. Rifampicin, dinitrobenzamide, amikacin and isoniazid effectively extended the life span of infected flies and ethambutol showed slightly improved survival. However, M. marinum infection was not cured by ampicillin or pyrazinamide. CONCLUSIONS: This D. melanogaster-M. marinum infection/curing methodology may be valuable in the rapid evaluation of the activity of new antimycobacterial agents in drug discovery.

A Case of Linear IgA Bullous Dermatosis of Childhood / 대한피부과학회지

Linear IgA bullous dermatoses(LABD) occurring in childhood is considered to be a childhood counterpart of LABD,rather than chronic bullous dermatosis of childhood. This disease characteristically involves the perioral area,lower trunk,pelvic region and the lower extremities. Immunopathologically,it is characterized by the linear deposits of IgA at the dermoepidermal junction of the perilesional skin. A 20-month-old female infant presented with multiple pruritic tense bullae on the face, lower trunk, both extremities and pelvic region of 2 weeks duration. She had no oral lesions or any specific signs or symptoms referable to the disease of the gastrointestinal tract. A skin biopsy revealed subepidermal blisters infiltrated with many neutrophils and a few eosinophils. Direct immunofluorescence demonstrated linear deposition of IgA at the dermoepidermal junction. An indirect immunofluorescence study using NaC1-split skin as the substrate revealed fluorescence for IgA in a linear pattern on the roof of the split at a titer of 1:40. The clinical diagnosis of LABD of childhood was confirmed and we started with a combined remedy of dapsone and corticosteroids; 10 weeks later almost all of the lesions had disappeared.