scholarly journals Towards Precision Dermatology: Emerging Role of Proteomic Analysis of the Skin

Dermatology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Gabriella Fredman ◽  
Lone Skov ◽  
Matthias Mann ◽  
Beatrice Dyring-Andersen

<b><i>Background:</i></b> The skin is the largest organ in the human body and serves as a multilayered protective shield from the environment as well as a sensor and thermal regulator. However, despite its importance, many details about skin structure and function at the molecular level remain incompletely understood. Recent advances in liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomics have enabled the quantification and characterization of the proteomes of a number of clinical samples, including normal and diseased skin. <b><i>Summary:</i></b> Here, we review the current state of the art in proteomic analysis of the skin. We provide a brief overview of the technique and skin sample collection methodologies as well as a number of recent examples to illustrate the utility of this strategy for advancing a broader understanding of the pathology of diseases as well as new therapeutic options. <b><i>Key Messages:</i></b> Proteomic studies of healthy skin and skin diseases can identify potential molecular biomarkers for improved diagnosis and patient stratification as well as potential targets for drug development. Collectively, efforts such as the Human Skinatlas offer improved opportunities for enhancing clinical practice and patient outcomes.

The Oxford Handbook of the Auditory Brainstem provides an in-depth reference to the organization and function of ascending and descending auditory pathways in the mammalian brainstem. Individual chapters are organized along the auditory pathway, beginning with the cochlea and ending with the auditory midbrain. Each chapter provides an introduction to the respective area and summarizes our current knowledge before discussing the disputes and challenges that the field currently faces.The handbook emphasizes the numerous forms of plasticity that are increasingly observed in many areas of the auditory brainstem. Several chapters focus on neuronal modulation of function and plasticity on the synaptic, neuronal, and circuit level, especially during development, aging, and following peripheral hearing loss. In addition, the book addresses the role of trauma-induced maladaptive plasticity with respect to its contribution in generating central hearing dysfunction, such as hyperacusis and tinnitus.The book is intended for students and postdoctoral fellows starting in the auditory field and for researchers of related fields who wish to get an authoritative and up-to-date summary of the current state of auditory brainstem research. For clinical practitioners in audiology, otolaryngology, and neurology, the book is a valuable resource of information about the neuronal mechanisms that are currently discussed as major candidates for the generation of central hearing dysfunction.


2021 ◽  
Vol 10 (4) ◽  
pp. 175-179
Author(s):  
Magdalena Daszkiewicz ◽  

Nowadays it is known that many dermatological diseases are associated with a poor diet and unhealthy lifestyle. Some nutrients can exacerbate the disease, while others aid in their treatment. The aim of the study was to present the current state of knowledge on the influence of nutrients on the course of skin diseases such as acne, atopic dermatitis and urticaria. Providing the body with the necessary ingredients and eliminating those that favor the development or worsening of symptoms are an important element in the treatment of many skin diseases.


Author(s):  
Gordon L. Clark ◽  
Adam D. Dixon

This chapter unpacks the concepts of trust and legitimacy as they pertain to sovereign funds in the global political economy. Its argument is divided into three parts. First, the importance of trust in finance and geopolitics, and the critical role of transparency, and how this relates to sovereign funds. Second, the legitimacy of sovereign funds at home and abroad in general with particular reference to how the regulatory regime surrounding public institutional investors in developed democracies is emulated in the Santiago Principles, and why it is significant for understanding the legitimacy of sovereign funds. Third, the current state of trust and legitimacy for sovereign funds is evaluated, with an explanation of why the continued opacity of some sovereign funds has not reduced trustworthiness. The chapter concludes on a speculative note, suggesting that the expected institutional form and function of sovereign funds may be at odds with the long-term interests of their state-sponsors.


1979 ◽  
Vol 58 (2_suppl) ◽  
pp. 684-694 ◽  
Author(s):  
R.M. Frank

Important progress has been made relative to the growth, structure and function of enamel. Better understanding of the epithelial mesenchymal interactions during odontogenesis has been gained through tissue culture, and the predominant role of the dental papilla has been established. Differences between rodent and human amelogenesis have been demonstrated. With radioautography and cytochemistry, a significant amount of new information has been obtained on the metabolism of the ameloblasts, concerning the synthesis of proteins, glycoproteins and proteoglycans, as well as calcium transport. Numerous biochemical investigations have been devoted to developing and mature enamel matrix. The organic components of human adult enamel are mainly constituted of lipids and proteins, but further investigations are still needed to elucidate their precise nature. The so-called key-hole configuration of adult enamel can be questioned when amelogenesis is considered since the tissue does not develop in a prismatic head-tail fashion. The most important results have probably been obtained in the field of individual enamel apatite crystals shape and ultrastructure as well as in the description of the precise patterns of their carious dissolution which bears great similarities to the dissolution of synthetic apatites in acids.


Proteomes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 23
Author(s):  
Marcus M. K. Hughes ◽  
Eva Aryal ◽  
Elnaz Safari ◽  
Biljana Mojsoska ◽  
Håvard Jenssen ◽  
...  

With a relatively large surface area (2 m2) and 15% of total body mass, the skin forms the largest organ of the human body. The main functions of the skin include regulation of body temperature by insulation or sweating, regulation of the nervous system, regulation of water content, and protection against external injury. To perform these critical functions, the skin encodes genes for transporters responsible for the cellular trafficking of essential nutrients and metabolites to maintain cellular hemostasis. However, the knowledge on the expression, regulation, and function of these transporters is very limited and needs more work to elucidate how these transporters play a role both in disease progression and in healing. Furthermore, SLC and ABC transporters are understudied, and even less studied in skin. There are sparse reports on relation between transporters in skin and sweat metabolites. This mini review focuses on the current state of SLC and ABC transporters in the skin and their relation to sweat metabolites and skin diseases.


2021 ◽  
Vol 22 (11) ◽  
pp. 6135
Author(s):  
Michelle D. Bagood ◽  
R. Rivkah Isseroff

Skin is innervated by a multitude of sensory nerves that are important to the function of this barrier tissue in homeostasis and injury. The role of innervation and neuromediators has been previously reviewed so here we focus on the role of the transient receptor potential cation channel, subfamily V member 1 (TRPV1) in wound healing, with the intent of targeting it in treatment of non-healing wounds. TRPV1 structure and function as well as the outcomes of TRPV1-targeted therapies utilized in several diseases and tissues are summarized. In skin, keratinocytes, sebocytes, nociceptors, and several immune cells express TRPV1, making it an attractive focus area for treating wounds. Many intrinsic and extrinsic factors confound the function and targeting of TRPV1 and may lead to adverse or off-target effects. Therefore, a better understanding of what is known about the role of TRPV1 in skin and wound healing will inform future therapies to treat impaired and chronic wounds to improve healing.


2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Roman N Rodionov ◽  
Jens Martens-Lobenhoffer ◽  
Silke Brilloff ◽  
Bernd Hohenstein ◽  
Norbert Weiss ◽  
...  

Background Multiple epidemiological studies demonstrated increased levels of an endogenous inhibitor of nitric oxide synthases asymmetric dimethylarginine (ADMA) in cardiovascular diseases. In addition to the well characterized pathway of ADMA hydrolysis by dimethylarginine dimethylaminohydrolase (DDAH) ADMA can also be metabolized through an alternative pathway by alanine:glyoxylate aminotransferase 2 (AGXT2), which converts ADMA to α-keto-δ-(N,N-dimethylguanidino)valeric acid (DMGV). The goal of this study was to better characterize the role of AGXT2 pathway in metabolism of ADMA in vivo using a recently developed assay for detection of DMGV in biological samples. Methods ADMA (250 μmol x kg-1 x d-1) was infused in C57/BL6 mice for 3 days using osmotic minipumps implanted intraperitoneally. We performed bilateral nephrectomy in some of the mice 24 hours before the end of ADMA infusion and sample collection. Urine was collected for 24 hours in metabolic cages. Blood was collected by cardiac puncture. Measurements of ADMA and DMGV were performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results Intraperitoneal infusion of ADMA for 3 days resulted in an increase in plasma ADMA levels from 0.46±0.045 to 1.57±0.40 μM (p<0.05) and in urine ADMA levels from 36.4±3.4 to 188.6±31.5 μmol / mmol creatinine (p<0.05). Elevation of ADMA concentration coincided with elevation of plasma DMGV levels from 0.21±0.025 to 0.61±0.14 μM (p<0.05) and urine DMGV levels from 41.4±3.2 to 162.5±32.9 μmol / mmol creatinine (p<0.05). Bilateral nephrectomy in the mice, which underwent ADMA infusion, lead to a 1.7 fold increase in plasma ADMA levels and a 17.6 fold increase in DMGV levels compared with the mice from the sham group. Conclusions Infusion of ADMA leads to increased flux through the AGXT2 pathway of ADMA metabolism in vivo. The observation that each 1 μmol / mmol creatinine increase in ADMA level in urine leads to a ~1 μmol / mmol creatinine increase in urine DMGV level suggests that AGXT2 is a major enzyme regulating ADMA levels in urine. The marked increase in DMGV levels in the mice lacking both kidneys suggests significant extrarenal production of DMGV in addition to absent renal excretion.


Reproduction ◽  
2009 ◽  
Vol 138 (2) ◽  
pp. 371-382 ◽  
Author(s):  
S E Ulbrich ◽  
K Schulke ◽  
A E Groebner ◽  
H D Reichenbach ◽  
C Angioni ◽  
...  

Prostaglandins (PGs) are important regulators of reproductive processes including early embryonic development. We analyzed the most relevant PG in bovine uteri at different preimplantation pregnancy stages when compared with non-pregnant controls. Additionally, endometrium and trophoblast tissues were examined regarding specific enzymes and receptors involved in PG generation and function. Simmental heifers were artificially inseminated or received seminal plasma only. At days 12, 15, or 18, post-estrus uteri were flushed for PG determination by liquid chromatography–tandem mass spectrometry. Endometrium and trophoblast tissues were sampled for RNA extraction and quantitative real-time PCR analysis. At all days and points of time examined, the concentration of 6-keto PGF1α (stable metabolite of PGI2) was predominant followed by PGF2α>PGE2>PGD2≈TXB2 (stable metabolite of TXA2). At days 15 and 18, PG increased from overall low levels at day 12, with a much more pronounced increase during pregnancy. The PGF2α/PGE2 ratio was not influenced by status. The highest PG concentration was measured at day 15 with 6-keto PGF1α (6.4 ng/ml) followed by PGF2α (1.1 ng/ml) and PGE2 (0.3 ng/ml). Minor changes in endometrial PG biosynthesis enzymes occurred due to pregnancy. Trophoblasts revealed high transcript abundance of general and specific PG synthases contributing to uterine PG. As PGI2 and PGF2α receptors were abundantly expressed by the trophoblast, abundant amounts of PGI2 and PGF2α in the uterine lumen point towards an essential role of PG for the developing embryo. High amounts of PG other than PGE2 in the preimplantation uterus may be essential rather than detrimental for successful reproduction.


2018 ◽  
Vol 7 (12) ◽  
pp. 511 ◽  
Author(s):  
Tonia Woodberry ◽  
Sophie Bouffler ◽  
Alicia Wilson ◽  
Rebecca Buckland ◽  
Anne Brüstle

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a strong autoimmune, neurodegenerative, and neuroinflammatory component. Most of the common disease modifying treatments (DMTs) for MS modulate the immune response targeting disease associated T and B cells and while none directly target neutrophils, several DMTs do impact their abundance or function. The role of neutrophils in MS remains unknown and research is ongoing to better understand the phenotype, function, and contribution of neutrophils to both disease onset and stage of disease. Here we summarize the current state of knowledge of neutrophils and their function in MS, including in the rodent based MS model, and we discuss the potential effects of current treatments on these functions. We propose that neutrophils are likely to participate in MS pathogenesis and their abundance and function warrant monitoring in MS.


2020 ◽  
Vol 21 (10) ◽  
pp. 3552 ◽  
Author(s):  
Alicja Frączek ◽  
Agnieszka Owczarczyk-Saczonek ◽  
Waldemar Placek

Vitiligo is the most common hypopigmentation disease affecting both the skin and mucous membranes. The pathogenesis of this disorder is complex and involves the influence of genetic and environmental factors, oxidative stress, and autoimmune responses. Recent studies have indicated that skin lesions observed in vitiligo tend to recur in the same places where they were found before treatment. This phenomenon is explained by the presence of recently discovered tissue-resident memory T cells (TRM), whose primary function is to provide antiviral and antibacterial protection in non-lymphoid tissues. TRM cells show the presence of CD49a, CD69, and CD103 markers on their surface, although not all of them express these particles. Due to their ability to produce and secrete perforin, IFN-γ, and granzyme B, TRM cells demonstrate a cytotoxic effect on melanocytes, thus inducing depigmented lesions in the course of the vitiligo. It has been proved that the occurrence of TRM cells largely depends on IL-15, which promotes the TRM function ex vivo. The findings above, as well as their reference to the pathogenesis of autoimmune skin diseases will have a considerable influence on the development of new therapeutic strategies in the near future. This article presents an up-to-date review of information regarding the role of TRM cells in the development and progression of vitiligo.


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