Unraveling the skin; a comprehensive review of atopic dermatitis, current understanding, and approaches.

Atopic dermatitis, also known as atopic eczema, is a chronic inflammatory skin disease characterized by red pruritic skin lesions, xerosis, ichthyosis, and skin pain. Among the social impacts of atopic dermatitis are difficulties and detachment in relationships and social stigmatization. Additionally, atopic dermatitis is known to cause sleep disturbance, anxiety, hyperactivity, and depression. Although the pathological process behind atopic dermatitis is not fully known, it appears to be a combination of epidermal barrier dysfunction and immune dysregulation. Skin is the largest organ of the human body which acts as a mechanical barrier to toxins and UV light and a natural barrier against water loss. Both functions face significant challenges due to atopic dermatitis. The list of factors that can potentially trigger or contribute to atopic dermatitis is extensive, ranging from genetic factors, family history, dietary choices, immune triggers, and environmental factors. Consequently, prevention, early clinical diagnosis, and effective treatment may be the only resolutions to combat this burdensome disease. Ensuring safe and targeted drug delivery to the skin layers, without reaching the systemic circulation is a promising option raised by nano-delivery systems in dermatology. In this review, we explored the current understanding and approaches of atopic dermatitis and outlined a range of the most recent therapeutics and dosage forms brought by nanotechnology. This review was conducted using PubMed, Google Scholar, and ScienceDirect databases.

Unsolved mystery of Fas: mononuclear cells may have trouble dying in patients with Sjögren's syndrome.

BACKGROUND: Patients with Sjögren's syndrome, like other patients with autoimmune disorders, display dysregulation in the function of their immune system. Fas and Fas Ligand (FasL) are among the dysregulated proteins. METHODS: We studied Fas and FasL on IL-2Rα+ cells and in serum of patients with Sjögren's syndrome (n = 16) and healthy individuals (n = 16); both from same ethnic and geographical background. We used flow cytometry and enzyme-linked immunosorbent for this purpose. We also measured the expression of Bcl-2 and Bax by reverse transcription quantitative real-time PCR (RT-qPCR) and percentage of apoptotic and dead cells using Annexin V and 7-AAD staining in lymphocytes. RESULTS: FasL was increased in patients' T and B cells while Fas was increased in patients' monocytes, T and B cells. No signs of increased apoptosis were found. sFas and sFasL in patients' serum were increased, although the increase in sFasL was not significant. We suspect an effect of non-steroidal anti-inflammatory therapy on B cells, explaining the decrease of the percentage Fas+ B cells found within our samples. In healthy individuals, there was a noticeable pattern in the expression of FasL which mutually correlated to populations of mononuclear cells; this correlation was absent in the patients with Sjögren's syndrome. CONCLUSIONS: Mononuclear cells expressing IL-2Rα+ had upregulated Fas in Sjögren's syndrome. However, the rate of apoptosis based on Annexin V staining and the Bcl-2/Bax expression was not observed in mononuclear cells. We suspect a functional role of abnormal levels of Fas and FasL which has not been cleared yet.

3D printed permeation module to monitor interaction of cell membrane transporters with exogenic compounds in real-time.

A new design of permeation module based on 3D printing was developed to monitor the interaction of exogenic compounds with cell membrane transporters in real-time. The fluorescent marker Rhodamine 123 (Rho123) was applied as a substrate to study the activity of the P-glycoprotein membrane transporter using the MDCKII-MDR1 genetically modified cell line. In addition, the inhibitory effect of verapamil (Ver), a prototype P-glycoprotein inhibitor, was examined in the module, demonstrating an enhanced Rho123 transfer and accumulation into cells as well as the applicability of the module for P-glycoprotein inhibitor testing. Inhibition was demonstrated for different ratios of Rho123 and Ver, and their competition in terms of interaction with the P-glycoprotein transporter was monitored in real-time. Employing the 3D-printed module, permeation testing was shortened from 8 h in the conventional module to 2 h and evaluation based on kinetic profiles in every 10 min was possible in both donor and acceptor compartments. We also show that monitoring Rho123 levels in both compartments enables calculate the amount of Rho123 accumulated inside cells without the need of cell lysis.