Psoriasis is a chronic, immune‐mediated disease affecting more than 100 million people worldwide and up to 2.2% of the UK population. The aetiology of psoriasis is thought to originate from an ...interplay of genetic, environmental, infectious and lifestyle factors. The manner in which genetic and environmental factors interact to contribute to the molecular disease mechanisms has remained elusive. However, the interleukin 23 (IL‐23)/T‐helper 17 (TH17) immune axis has been identified as a major immune pathway in psoriasis disease pathogenesis. Central to this pathway is the cytokine IL‐23, a heterodimer composed of a p40 subunit also found in IL‐12 and a p19 subunit exclusive to IL‐23. IL‐23 is important for maintaining TH17 responses, and levels of IL‐23 are elevated in psoriatic skin compared with non‐lesional skin. A number of agents that specifically inhibit IL‐23p19 are currently in development for the treatment of moderate‐to‐severe plaque psoriasis, with recent clinical trials demonstrating efficacy with a good safety and tolerability profile. These data support the role of this cytokine in the pathogenesis of psoriasis. A better understanding of the IL‐23/TH17 immune axis is vital and will promote the development of additional targets for psoriasis and other inflammatory diseases that share similar genetic aetiology and pathogenetic pathways.
Macrophages are endowed with a variety of receptors for lineage-determining growth factors, T helper (Th) cell cytokines, and B cell, host, and microbial products. In tissues, macrophages mature and ...are activated in a dynamic response to combinations of these stimuli to acquire specialized functional phenotypes. As for the lymphocyte system, a dichotomy has been proposed for macrophage activation: classic vs. alternative, also M1 and M2, respectively. In view of recent research about macrophage functions and the increasing number of immune-relevant ligands, a revision of the model is needed. Here, we assess how cytokines and pathogen signals influence their functional phenotypes and the evidence for M1 and M2 functions and revisit a paradigm initially based on the role of a restricted set of selected ligands in the immune response.
Inductively coupled plasma mass spectrometry (ICP-MS) is an analytical technique that can be used to measure elements at trace levels in biological fluids. Although older techniques such as atomic ...absorption and atomic emission are still in use by some laboratories, there has been a slow shift toward ICP-MS, particularly in the last decade. As this shift is likely to continue, clinical scientists should be aware of the analytical aspects of ICP-MS, as well as the potential for both spectroscopic and non-spectroscopic interference, and strategies that can be employed to eliminate or mitigate these issues.
All living organisms depend on primary and secondary membrane transport for the supply of external nutrients and removal or sequestration of unwanted (toxic) compounds. Due to the chemical diversity ...of cellular molecules, it comes as no surprise that a significant part of the proteome is dedicated to the active transport of cargo across the plasma membrane or the membranes of subcellular organelles. Transport against a chemical gradient can be driven by, for example, the free energy change associated with ATP hydrolysis (primary transport), or facilitated by the potential energy of the chemical gradient of another molecule (secondary transport). Primary transporters include the rotary motor ATPases (F-, A-, and V-ATPases), P-type ATPases and a large family of integral membrane proteins referred to as "ABC" (ATP binding cassette) transporters. ABC transporters are widespread in all forms of life and are characterized by two nucleotide-binding domains (NBD) and two transmembrane domains (TMDs). ATP hydrolysis on the NBD drives conformational changes in the TMD, resulting in alternating access from inside and outside of the cell for unidirectional transport across the lipid bilayer. Common to all ABC transporters is a signature sequence or motif, LSGGQ, that is involved in nucleotide binding. Both importing and exporting ABC transporters are found in bacteria, whereas the majority of eukaryotic family members function in the direction of export. Recent progress with the X-ray crystal structure determination of a variety of bacterial and eukaryotic ABC transporters has helped to advance our understanding of the ATP hydrolysis-driven transport mechanism but has also illustrated the large structural and functional diversity within the family.
Literature review is part and parcel of scholarly research. Though many literature review guides are available, they remain limited because they do not adequately account for the different types of ...literature review. Noteworthily, literature reviews can manifest as part of conceptual or empirical studies, or as independent studies, in which the latter may be curated in various ways. Moreover, despite its importance and popularity, literature reviews, particularly as independent studies, continue to attract unfair criticism and remain scarce in service research. To address the aforementioned gaps, this article endeavors to provide an overview and guidelines for writing literature reviews. Specifically, this article explains (1) what a literature review is and is not, (2) why literature reviews are valuable, and (3) how to conduct a literature review, as well as (4) the areas of service research and (5) the innovative ways in which literature reviews can be curated in the future.
Deep learning (DL) is a branch of machine learning and artificial intelligence that has been applied to many areas in different domains such as health care and drug design. Cancer prognosis estimates ...the ultimate fate of a cancer subject and provides survival estimation of the subjects. An accurate and timely diagnostic and prognostic decision will greatly benefit cancer subjects. DL has emerged as a technology of choice due to the availability of high computational resources. The main components in a standard computer-aided design (CAD) system are preprocessing, feature recognition, extraction and selection, categorization, and performance assessment. Reduction of costs associated with sequencing systems offers a myriad of opportunities for building precise models for cancer diagnosis and prognosis prediction. In this survey, we provided a summary of current works where DL has helped to determine the best models for the cancer diagnosis and prognosis prediction tasks. DL is a generic model requiring minimal data manipulations and achieves better results while working with enormous volumes of data. Aims are to scrutinize the influence of DL systems using histopathology images, present a summary of state-of-the-art DL methods, and give directions to future researchers to refine the existing methods.
Skin barrier dysfunction, a defining feature of atopic dermatitis (AD), arises from multiple interacting systems. In AD, skin inflammation is caused by host–environment interactions involving ...keratinocytes as well as tissue-resident immune cells such as type 2 innate lymphoid cells, basophils, mast cells, and T helper type 2 cells, which produce type 2 cytokines, including IL-4, IL-5, IL-13, and IL-31. Type 2 inflammation broadly impacts the expression of genes relevant for barrier function, such as intracellular structural proteins, extracellular lipids, and junctional proteins, and enhances Staphylococcus aureus skin colonization. Systemic anti‒type 2 inflammation therapies may improve dysfunctional skin barrier in AD.
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