Real-time technique for conversion of skin temperature into skin blood flow: human skin as a low-pass filter for thermal waves

Monitoring of skin blood flow oscillations related with mechanical activity of vessels is a very useful modality during diagnosis of peripheral hemodynamic disorders. In this study, we developed a new model and technique for real-time conversion of skin temperature into skin blood flow oscillations, and vice versa. The technique is based on the analogy between the thermal properties of the human skin and electrical properties of the special low-pass filter. Analytical and approximated impulse response functions for the low- and high-pass filters are presented. The general algorithm for the reversible conversion of temperature into blood flow is described. The proposed technique was verified using simulated or experimental data of cold stress, deep inspiratory gasp, and post-occlusive reactive hyperaemia tests. The implementation of the described technique will enable to turn a temperature sensor into a blood flow sensor.     

Mesenchymal stem cell-derived exosomes: A novel and potential remedy for cutaneous wound healing and regeneration

Poor healing of cutaneous wounds is a common medical problem in the field of traumatology. Due to the intricate pathophysiological processes of wound healing, the use of conventional treatment methods, such as chemical molecule drugs and traditional dressings, have been unable to achieve satisfactory outcomes. Within recent years, explicit evidence suggests that mesenchymal stem cells (MSCs) have great therapeutic potentials on skin wound healing and regeneration. However, the direct application of MSCs still faces many challenges and difficulties. Intriguingly, exosomes as cell-secreted granular vesicles with a lipid bilayer membrane structure and containing specific components from the source cells may emerge to be excellent substitutes for MSCs. Exosomes derived from MSCs (MSC-exosomes) have been demonstrated to be beneficial for cutaneous wound healing and accelerate the process through a variety of mechanisms. These mechanisms include alleviating inflammation, promoting vascularization, and promoting proliferation and migration of epithelial cells and fibroblasts. Therefore, the application of MSC-exosomes may be a promising alternative to cell therapy in the treatment of cutaneous wounds and could promote wound healing through multiple mechanisms simultaneously. This review will provide an overview of the role and the mechanisms of MSC-derived exosomes in cutaneous wound healing, and elaborate the potentials and future perspectives of MSC-exosomes application in clinical practice.     

The role of microbicidal lipids in host defense against pathogens and their potential as therapeutic agents

Lipids such as fatty alcohols, free fatty acids and monoglycerides of fatty acids are known to be potent antimicrobial/microbicidal agents in vitro and to kill enveloped viruses, Gram-positive and Gram-negative bacteria and fungi on contact. For over half a century several studies have tried to answer the question of whether or not lipids play a role in the natural host defense against pathogens. A comprehensive review is given of these studies, particularly concerning infections in skin and in mucosal membranes of the respiratory tract, and of the role of lipids in the antimicrobial activity of breast milk. Based on studies of the microbicidal activities of lipids, both in vitro and in vivo, the possibility of using such lipids as active ingredients in prophylactic and therapeutic dosage forms is considered and examples are given of studies of such pharmaceutical dosage forms in experimental animal models and in clinical trials.     

Diseases of epidermal keratins and their linker proteins

Epidermal keratins, a diverse group of structural proteins, form intermediate filament networks responsible for the structural integrity of keratinocytes. The networks extend from the nucleus of the epidermal cells to the plasma membrane where the keratins attach to linker proteins which are part of desmosomal and hemidesmosomal attachment complexes. The expression of specific keratin genes is regulated by differentiation of the epidermal cells within the stratifying squamous epithelium. Progress in molecular characterization of the epidermal keratins and their linker proteins has formed the basis to identify mutations which are associated with distinct cutaneous manifestations in patients with genodermatoses. The precise phenotype of each disease apparently reflects the spatial level of expression of the mutated genes, as well as the types and positions of the mutations and their consequences at mRNA and protein levels. Identification of specific mutations in keratinization disorders has provided the basis for improved diagnosis and subclassification with prognostic implications and has formed the platform for prenatal testing and preimplantation genetic diagnosis. Finally, precise knowledge of the mutations is a prerequisite for development of gene therapy approaches to counteract, and potentially cure, these often devastating and currently intractable diseases.     

Overlapping and divergent localization of Frem1 and Fras1 and its functional implications during mouse embryonic development

Frem1 belongs to a family of structurally related extracellular matrix proteins of which Fras1 is the founding member. Mutations in Fras1 and Frem1 have been identified in mouse models for Fraser syndrome, which display a strikingly similar embryonic skin blistering phenotype due to impaired dermal-epidermal adhesion. Here we show that Frem1 originates from both epithelial and mesenchymal cells, in contrast to Fras1 that is exclusively derived from epithelia. However, both proteins are localized in an absolutely overlapping fashion in diverse epithelial basement membranes. At the ultrastructural level, Frem1 exhibits a clustered arrangement in the sublamina densa coinciding with fibrillar structures reminiscent of anchoring fibrils. Furthermore, in addition to its extracellular deposition, around E16, Frem1 displays an intracellular distribution in distinct epidermal cell types such as the periderm layer and basal keratinocytes. Since periderm cells are known to participate in temporary epithelial fusions like embryonic eyelid closure, defective function of Frem1 in these cells could provide a molecular explanation for the "eyes open at birth" phenotype, a feature unique for Frem1 deficient mouse mutants. Finally, we demonstrate loss of Frem1 localization in the basement membrane but not in periderm cells in the skin of Fras1(-/-) embryos. Taken together, our findings indicate that besides a cooperative function with Fras1 in embryonic basement membranes, Frem1 can also act independently in processes related to epidermal differentiation.     

A comparative proteomic analysis of skin secretions of the tammar wallaby (Macropus eugenii) and the wombat (Vombatus ursinus)

The secretome of the pouch skin of the model marsupial the tammar wallaby, Macropus eugenii has been investigated using techniques of two-dimensional gel electrophoresis, in-gel trypsin digestion followed by nanoliquid chromatography coupled tandem mass spectrometry (LC-MS/MS). Differences in the patterns of secreted proteins were observed in the female pouch at three stages of maturity — reproductively immature; reproductively mature and active and mature, postreproductively active. Skin from the underarm area of mature females had a markedly different secreted protein profile. The greatest diversity of proteins was seen in the mature reproductive pouch and from an opportunistic sample collected from the pouch another mature female marsupial, the common wombat, Vombatus ursinus. A total of 20 proteins were confidently identified from the pouch skin secretions of the tammar wallaby and wombats, whilst 20 proteins were tentatively identified. In all skin secretomes, globins were the most abundant proteins whilst the antimicrobial, dermcidin was detected in the wombat sample. Some proteins such as keratin and actin could be sourced to sloughed and degraded skin cells. A number of proteins were present at such low concentrations that confident identification was not possible. This was compounded by the lack of a comprehensive database of marsupial proteins which constrains the reliability of automated identification protocols.     

Analysis of mouse skin reveals proteins that are altered in a diet-induced diabetic state: a new method for detection of type 2 diabetes

In this study, proteomic analysis was performed on the skin of C57BL/6J mice with type 2 diabetes and compared to nondiabetic controls. To induce obesity and subsequent diabetes, mice were placed on a high-fat diet for 16 wk. After 16 wk, both diabetic and nondiabetic control mice were sacrificed and their skin removed for analysis. Following 2-DE, proteomic profiles from the skin samples were quantified using PDQuest software. Out of more than 1000 distinct protein spots, 28 were shown to be significantly altered with 6 being decreased and 22 increased in the diabetic state compared to controls. The 28 protein spots were removed from the gels and analyzed by MALDI-TOF and MS/MS analyses. Protein identifications revealed that 17 of the 28 proteins were involved in energy metabolism (60.7% of changes observed). Collectively, none of the significantly altered proteins had been shown previously to be altered in diabetic skin. This study not only helps to identify proteins found in skin samples of obese mice with type 2 diabetes, but also shows that skin biopsies coupled with proteomic analysis may be useful as a noninvasive method for the diagnosis of hyperinsulinemia and diabetes.     

Huffmanela selachii n. sp. (Nematoda: Trichosomoididae: Huffmanelinae): A new species infecting the skin of the great hammerhead shark (Sphyrna mokarran) and the blacktip reef shark (Carcharhinus melanopterus) in the Arabian Gulf,off-shore Saudi Arabia

From January 2017 - December 2019, 75 out of 850 (8.8 %) great hammerhead sharks from the Arabian Gulf had skin lesions of black irregular discolorations on the ventral surface of the head. The lesions consisted of pencil-like lineations often advancing forward by about 2 mm in back-and-forth looped scribbles often forming a relatively linear bands of about 5–7 cm wide. Similar lesions were also found in the blacktip reef shark from the same area within the same period, and consisted of straight to irregular black lines, extended indiscriminately across the skin of the sharks. Microscopic examination of the skin revealed the presence of dark-brown eggs exhibiting the spindle or ellipsoidal eggs characteristic of Huffmanela sp. The morphometrics of eggs from both hosts were similar (62.9–89.9 μm long and 29.3–56.1 μm wide). The eggshells were smooth with polar plugs protruding or not, with an abruptly truncated crown-like or shoulder-like collar surrounding the plug. The eggs were only found in the epidermal layer of the skin. Based on the unique morphometrics of the eggs, we report a new species, named: Huffmanela selachii n. sp.. This appears to be the first report of Huffmanela from either the great hammerhead shark or the blacktip reef shark, and the third reported Huffmanela in sharks from the Arabian Gulf. It is also one of few species reported from connecting waters of the greater Indian Ocean. This new finding contributes to our understanding of the diversity and ubiquity of Huffmanela sp. in marine creatures.     

IL-33/HMGB-1与胎鼠皮肤伤口的瘢痕形成的相关性研究

摘要 目的：探究IL-33/HMGB-1在胎鼠伤口愈合中的作用。方法：构建小鼠伤口愈合模型,并随机分组为注射PBS组、注射重组蛋白IL-33组和重组蛋白HMGB-1组。通过免疫组织化学、DAB和苏木精复染方法检测IL-33/HMGB-1的表达及定位;结合Axiovision软件计算MOMA-2阳性巨噬细胞、波形蛋白阳性成纤维细胞和血管密度;通过Masson''s三色染色评估伤口胶原蛋白的沉积情况和愈合情况。结果：E15和E18胎鼠未损伤皮肤的基底角质形成细胞核均呈阳性染色;与E15胎鼠相比,E18胎鼠皮肤中HMGB-1和IL-33的表达水平升高（P<0.05）。处理0 h-48 h,E15和E18胎鼠伤口边缘附近角质形成细胞的核染色呈降低,IL-33和HMGB-1表达水平均降低（P<0.05）。Masson三色染色结果显示,与PBS组相比,当采取200 ng或400 ng HMGB-1或IL-33处理,E15胎鼠伤口愈合形成疤痕的数量均显著增加（P<0.05）,且疤痕大小呈剂量依赖性增加（P<0.05）。创伤后7 d,与PBS组相比,HMGB-1和IL-33处理的E15胎鼠伤口和瘢痕中波形蛋白阳性成纤维细胞、MOMA-2阳性巨噬细胞的数量和PECAM阳性血管密度均显著升高（P<0.01）。结论：IL-33/HMGB-1可以促进胎鼠伤口瘢痕的形成,其可能机制包括对成纤维细胞的直接刺激,以及与伤口中血管生成和巨噬细胞募集增加有关。