Treatment of dermal ulcer with autologous fibrin glue: Two case reports of an exploratory prospective pilot study.

INTRODUCTION: The healing of recurrent and refractory skin ulcers requires a long time, during which there is risk of infection, and hospital admission is occasionally required for surgical or daily conservative treatment. Therefore, the development of promising treatments that promote faster, uneventful healing is a must. Composed of cryoprecipitate and thrombin, fibrin glue has a history of surgical use for preventing bleeding and spinal fluid leakage. Moreover, in-house cryoprecipitates contain higher concentrations of coagulation factors and cytokines that may enhance wound healing than commercially available products. However, the efficacy of completely autologous fibrin glue (AFG) in tissue repair has not yet been fully demonstrated. PATIENT CONCERNS: This study aimed to evaluate the efficacy of AFG in the treatment of refractory skin ulcers in comparison with the conventional treatment. DIAGNOSIS: Two patients with skin ulcer on their lower extremities due to trauma or scleroderma who showed resistance to conventional treatment were included in the study. Both study participants were diagnosed with refractory skin ulcer and were ineligible for autologous skin transplantation. INTERVENTIONS: AFG was prepared following autologous blood donation using a Cryoseal® system. Subsequently, AFG was administered to 50% of the area of each ulcer and observed for 4 weeks in comparison with recombinant basic fibroblast growth factor with bucladesine sodium treatment that was administered to the rest of the ulcer. OUTCOMES: The skin ulcer after trauma in participant 1 showed better improvement in the AFG-treated area. Although AFG did not show superiority regarding the ulcer area of a patient with scleroderma, it guarded the continuous exudation from the edge of the swollen skin surrounding the ulcer. CONCLUSION: AFG showed effective and beneficial results for wound healing of refractory skin ulcer and prevented exudation without any severe adverse events.

Damages of DNA in tritiated water.

Tritium is a radioisotope of hydrogen emitting low energy ß-rays in disintegration to 3He. DNA molecules are damaged mainly by ß-ray irradiation, and additional damages can be induced by break of chemical bond by nuclear transmutation to inert 3He. Deep knowledges of the mechanisms underlying DNA damages lead to better understanding of biological effects of tritium. This chapter reviews recent experimental and computer simulation activities on quantitative evaluation of damage rates by ß-ray irradiation and nuclear transmutation. The rate of DNA double-strand breaks in tritiated water has been examined using a single molecule observation method. The effects of ß-ray irradiation were not noticeable at the level of tritium concentration of ∼kBq/cm3, while the irradiation effects were clear at tritium concentrations of ∼MBq/cm3. The factors affecting on the DSB rate are discussed. A new image processing method for the automatic measurement of DNA length using OpenCV and deep learning is also introduced. The effects of tritium transmutation on hydrogen bonds acting between the two main strands of DNA have been examined using molecular dynamics simulations. The study showed that the collapsing of DNA structure by the transmutation can be quantitatively evaluated using the root mean square deviation of atomic positions.

Fas-FasL interaction in cytotoxic T cell-mediated vitiligo: The role of lesional expression of tumor necrosis factor-α and interferon-γ in Fas-mediated melanocyte apoptosis.

Vitiligo is an acquired skin depigmentation disorder resulting from the selective loss of epidermal melanocytes, and previous studies have suggested that a T lymphocyte-mediated mechanism has a role in melanocyte loss. Although Fas-Fas ligand (FasL) interactions are important for T lymphocytes to mediate cytotoxicity, there are only few reports examining the involvement of the Fas-FasL pathway in vitiligo using in vivo mouse models. In addition, there have been no reports concerning Fas-mediated apoptosis in human melanocytes in vitro. In this study, we found that the Fas-mediated pathway is involved in cytotoxic T lymphocyte (CTL)-dependent vitiligo in a mouse model and FasL-induced apoptosis of human melanocytes. Tumor necrosis factor (TNF)-α and interferon (IFN)-γ, the expression levels of which have been reported to be elevated in lesional skin of patients with vitiligo, synergistically upregulated Fas expression on human melanocytes but inhibited the Fas-mediated apoptosis. Treatment with TNF-α and IFN-γ synergistically upregulated the expression of the anti-apoptotic genes, c-IAP2, c-FLIP and MCL1. A siRNA knock-down study showed that c-FLIP and MCL1, but not c-IAP2, were involved in inducing synergistic inhibitory effects on Fas-mediated apoptosis. Furthermore, we found that FasL and TNF-related apoptosis-inducing ligand (TRAIL) synergistically induced apoptosis on human melanocytes. In conclusion, our results suggest that the Fas-FasL pathway is involved in CTL-dependent vitiligo and the elevated expression levels of TNF-α and IFN-γ in lesional skin may act synergistically on melanocytes to suppress Fas-mediated apoptosis.

Agminated fibroblastic connective tissue nevus in a 1-year-old boy.

Fibroblastic connective tissue nevus (FCTN) is a benign cutaneous mesenchymal lesion characterized by proliferation of CD34-positive fibroblastic/myofibroblastic spindle-shaped cells. We report a case of agminated FCTN on the right lower abdomen of a 1-year-old boy.

Classification of 3097 patients from the Japanese melanoma study database using the American joint committee on cancer eighth edition cancer staging system.

BACKGROUND: The American Joint Committee on Cancer (AJCC) 8th Edition Cancer Staging System was implemented in 2018; however, it has not been validated in an Asian melanoma population. OBJECTIVE: The purpose of this study was to validate the new system using a cohort of Japanese melanoma patients. METHODS: The AJCC 7th and 8th Editions were used for TNM classification of patients in a database established by the Japanese Melanoma Study Group. Patient data with sufficient information to be applicable to the AJCC 8th staging were selected. The Kaplan-Meier method was used to estimate disease-specific survival and relapse-free survival. RESULTS: In total, data for 3097 patients were analyzed. The 5-year disease-specific survival according to the 7th and 8th Edition staging system were as follows: IA = 98.5%/97.9%; IB = 95.4%/96.2%; IIA = 94.2%/94.1%; IIB = 84.6%/84.4%; IIC = 72.2%/72.2%; IIIA = 76.2%/87.5%; IIIB = 60.7%/72.6%; IIIC = 42.0%/55.3% and IIID = none/26.0%. The 5-year relapse-free survival according to the 7th and 8th Edition staging was as follows: IA = 94.5%/92.7%; IB = 85.4%/85.3%; IIA = 80.1%/79.4%; IIB = 71.4%/70.6%; IIC = 56.8%/55.7%; IIIA = 56.8%/69.4%; IIIB = 42.6%/56.8%; IIIC = 20.0%/33.3% and IIID = none/6.5%. CONCLUSION: The results show that new staging system could efficiently classify our Japanese melanoma cohort. Although there was no difference in Stage I and II disease between the 7th and 8th Edition systems, we should be careful in managing Stage III disease since the survival curves of the 8th Edition staging were completely different from the 7th Edition. Moreover, our results indicate that adjuvant therapies for Stage IIB and IIC should be developed, since the relapse-free survival for these stages were equivalent to Stage IIIA and IIIB, respectively.

Clinical and histopathological characteristics and survival analysis of 4594 Japanese patients with melanoma.

BACKGROUND: The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large-scale Asian studies that include follow-up data have been reported. OBJECTIVES: To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. METHODS: Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan-Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease-specific survival in patients with invasive melanoma. RESULTS: In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5-year disease-specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. CONCLUSIONS: Our study revealed the characteristics of melanoma in the Japanese population. The 5-year disease-specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.

An accelerated united-atom molecular dynamics simulation on the fast crystallization of ring polyethylene melts.

To investigate crystallinities based on trans-structures, we determined the differences in the crystallization properties of ring and linear polymers by performing united-atom-model molecular dynamics (MD) simulations of homogeneous polyethylene melts of equal length, N, which refers to the number of monomers per chain. Modified parameters based on the DREIDING force field for the CH2 units were used in order to accelerate the crystallization process. To detect polymer crystallization, we introduced some local-order parameters that relate to trans-segments in addition to common crystallinities using neighboring bond orders. Through quenching MD simulations at 5 K/ns, we roughly determined temperature thresholds, Tth, at which crystallization is observed although it was hard to determine the precise Tth as observed in the laboratory time frame with the present computing resources. When N was relatively small (100 and 200), Tth was determined to be 320 and 350 K for the linear- and ring-polyethylene melts, respectively, while Tth was found to be 330 and 350 K, respectively, when N was 1000. Having confirmed that the crystallization of a ring-polyethylene melt occurs faster than that of the analogous linear melt, we conclude that the trans-segment-based crystallinities are effective for the analysis of local crystal behavior.

Gene Expression and Methylation Analysis in Melanomas and Melanocytes From the Same Patient: Loss of NPM2 Expression Is a Potential Immunohistochemical Marker for Melanoma.

DNA methylation is considered the primary epigenetic mechanism underlying the development of malignant melanoma. Since DNA methylation can be influenced by environmental factors, it is preferable to compare cancer and normal cells from the same patient. In order to compare the methylation status in melanoma tissues and melanocytes from the same individuals, we employed a novel epidermal sheet cultivation technique to isolate normal melanocytes from unaffected sites of melanoma patients. We also analyzed primary and metastatic melanoma samples, three commercially available melanocytes, and four melanoma cell lines. Cluster analysis of DNA methylation data classified freshly isolated melanomas and melanocytes into the same group, whereas the four melanoma cell lines were clustered together in a distant clade. Moreover, our analysis discovered methylation at several novel loci (KRTCAP3, AGAP2, ZNF490), in addition to those identified in previous studies (COL1A2, GPX3); however, the latter two were not observed in fresh melanoma samples. Subsequent studies revealed that NPM2 was hypermethylated and downregulated in melanomas, which was consistent with previous reports. In many normal melanocytes, NPM2 showed distinct immunohistochemical staining, while its expression was lost in malignant melanoma cells. In particular, intraepithelial lesions of malignant melanoma, an important challenge in clinical practice, could be distinguished from benign nevi. The present findings indicate the importance of using fresh melanoma samples, not melanoma cell lines and melanocytes in epigenetic studies. In addition, NPM2 immunoreactivity could be used to differentiate melanomas from normal melanocytes or benign disease.

Exacerbation and Prolongation of Psoriasiform Inflammation in Diabetic Obese Mice: A Synergistic Role of CXCL5 and Endoplasmic Reticulum Stress.

Accumulating evidence suggests that psoriasis is frequently accompanied by metabolic disorders, such as obesity and diabetes. However, the mechanisms underlying the association between increased psoriasis severity and concomitant metabolic syndrome have not been fully clarified. Herein, we show that imiquimod-induced psoriasiform inflammation was exacerbated and prolonged in diabetic obese mice compared to that in control mice, accompanied by remarkably increased lesional expressions of Cxcl5 and Il-1b. Notably, a large number of CXCL5+ Ly6G+ cells infiltrated the dermis and subcutaneous fat tissue of the diabetic obese mice. Most macrophages in the subcutaneous fat tissues of the diabetic obese mice were positive for expression of IL-1ß and GRP78/Bip, an endoplasmic reticulum stress marker. Depletion of Ly6G+ cells and macrophages diminished the imiquimod-induced psoriasiform inflammation. Further, CXCL5 potentiated the secretion of IL-1ß from macrophages and palmitic acid, a fatty acid released from subcutaneous adipocytes, further enhanced IL-1ß secretion via endoplasmic reticulum stress induction. Combined with the fact that the serum levels of both CXCL5 and palmitic acid are significantly elevated in patients with metabolic syndrome, our results suggest a role for CXCL5 and endoplasmic reticulum stress in the increase of psoriasis severity of patients with concomitant metabolic syndrome.

Novel serum metabolomics-based approach by gas chromatography/triple quadrupole mass spectrometry for detection of human skin cancers: Candidate biomarkers.

Skin cancer incidence rates are continuing to rise; however, if detected at an early stage, they can be cured with minimally invasive treatment. Therefore, the identification of novel and robust biomarkers for the early detection of skin cancer is required to improve the quality of life of the patient after treatment. In the present study, we aimed to identify novel biomarkers of skin cancers. We carried out serum metabolomics using gas chromatography/triple quadrupole mass spectrometry for two types of skin cancer: squamous cell carcinoma and melanoma. The changes in the expression of metabolites compared with healthy volunteers were analyzed by principal component analysis. Among all 118 metabolites, 27 in patients with squamous cell carcinoma and 33 in patients with melanoma showed significant changes in comparison with healthy volunteers. Principal component analysis showed that both skin cancer groups could be distinguished from the healthy volunteers group. We further investigated the specific metabolites most useful for these distinctions. In the squamous cell carcinoma group, these metabolites were glycerol, 4-hydroxybenzoic acid, sebacic acid, fucose and suberic acid. In the melanoma group, these metabolites were glutamic acid, sebacic acid, suberic acid, 4-hydroxybenzoic acid and phenylalanine. The present study identified several metabolites that were distinct for certain skin cancer types, which could potentially be used as diagnostic biomarkers leading to novel clinical management strategies.