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International Journal of Molecular... Mar 2023Skin is a major administration route for drugs, and all transdermal formulations must be tested for their capability to overcome the cutaneous barrier. Therefore,...
Skin is a major administration route for drugs, and all transdermal formulations must be tested for their capability to overcome the cutaneous barrier. Therefore, developing highly reliable skin models is crucial for preclinical studies. The current in vitro models are unable to replicate the living skin in all its complexity; thus, to date, excised human skin is considered the gold standard for in vitro permeation studies. However, skin explants have a limited life span. In an attempt to overcome this problem, we used an innovative bioreactor that allowed us to achieve good structural and functional preservation in vitro of explanted human skin for up to 72 h. This device was then used to set up an in vitro inflammatory model by applying two distinct agents mimicking either exogenous or endogenous stimuli: i.e., dithranol, inducing the contact dermatitis phenotype, and the substance P, mimicking neurogenic inflammation. Our in vitro system proved to reproduce inflammatory events observed in vivo, such as vasodilation, increased number of macrophages and mast cells, and increased cytokine secretion. This bioreactor-based system may therefore be suitably and reliably used to simulate in vitro human skin inflammation and may be foreseen as a promising tool to test the efficacy of drugs and cosmetics.
Topics: Humans; Hydrodynamics; Skin; Administration, Cutaneous; Skin Absorption; Inflammation; Pharmaceutical Preparations
PubMed: 37047256
DOI: 10.3390/ijms24076284 -
International Journal of Dermatology Jan 2023
Topics: Humans; Anthralin; Skin; Psoriasis; Staining and Labeling; Face
PubMed: 36073242
DOI: 10.1111/ijd.16405 -
Frontiers in Microbiology 2020Influenza virus RNA-dependent RNA polymerase (vRdRp) does not have capping activity and relies on the capped RNAs produced by the host RNA polymerase II (RNAPII). The...
Influenza virus RNA-dependent RNA polymerase (vRdRp) does not have capping activity and relies on the capped RNAs produced by the host RNA polymerase II (RNAPII). The viral polymerases process the capped RNAs to produce short capped RNA fragments that are used as primers to initiate the transcription of viral mRNAs. This process, known as cap-snatching, can be targeted by antiviral therapeutics. Here, anthralin was identified as an inhibitor against influenza a virus (IAV) infection by targeting the cap-snatching activity of the viral polymerase. Anthralin, an FDA-approved drug used in the treatment of psoriasis, shows antiviral activity against IAV infection and . Importantly, anthralin significantly reduces weight loss, lung injury, and mortality caused by IAV infection in mice. The mechanism of action study revealed that anthralin inhibits the cap-binding function of PB2 subunit and endonuclease activity of PA. As a result, viral mRNA transcription is blocked, leading to the decreases in viral RNA replication and viral protein expression. In conclusion, anthralin has been demonstrated to have the potential of an alternative antiviral against influenza virus infection. Also, targeting the captive pocket structure that includes the N-terminus of PA endonuclease domain and the C-terminal of PB2 cap-binding domain of IAV RdRp may be an excellent strategy for developing anti-influenza drugs.
PubMed: 32132985
DOI: 10.3389/fmicb.2020.00178 -
Analytical Methods : Advancing Methods... Feb 2022In the analysis of polystyrene nanoplastics (PSNs), a nonpolar polymer (NP), using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry...
In the analysis of polystyrene nanoplastics (PSNs), a nonpolar polymer (NP), using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), silver salts were used as cationization reagents and simultaneously brought the potential problems of silver clusters that interfered with the PSN signal of MS. To detect PSNs, silver trifluoroacetate (AgTFA) and silver nitrate (AgNO) were mixed with five polar matrices, namely 2-(4-hydroxyphenylazo) benzoic acid (HABA), dithranol (DI), sinapic acid (SA), -3-indoleacrylic acid (IAA), and 2,5-dihydroxybenzoic acid (DHB), and three nonpolar matrices, namely pyrene (PRN), anthracene (ATH) and acenaphthene (ACTH). The results showed that silver salt cluster ions were detected in the range of / 1000-4000. Five polar matrices with silver salts produced silver clusters, which interfered with the signals in the mass spectrum of PSNs, but the combination of these matrices with copper II chloride (CuCl) salt did not produce copper-related clusters. However, the use of nonpolar matrices such as PRN, ATH or ACTH significantly decreased the signals of silver salt cluster ions, and this alteration of matrix types is considered a promising optimization approach for silver cluster ions. The nonpolar matrix conditions were optimized without producing silver cluster ions and the optimal detection conditions were found to be under nonpolar matrices (, pyrene) with silver salts (, AgTFA). The results suggest that when polar matrices, such as HABA, DI, SA, IAA, and DHB, are combined with silver salts in MALDI-TOF-MS analysis, silver-related clusters are detected in the range of / 1000-4000. Inhibition of the production of silver cluster ions can be achieved by the use of a nonpolar matrix (, PRN) or polar matrix (, DHB) with copper salts.
Topics: Ions; Microplastics; Polymers; Polystyrenes; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 35112122
DOI: 10.1039/d1ay02219a -
ELife Jun 2020Despite the introduction of biologics, topical dithranol (anthralin) has remained one of the most effective anti-psoriatic agents. Serial biopsies from human psoriatic...
Despite the introduction of biologics, topical dithranol (anthralin) has remained one of the most effective anti-psoriatic agents. Serial biopsies from human psoriatic lesions and both the c-Jun/JunB and imiquimod psoriasis mouse model allowed us to study the therapeutic mechanism of this drug. Top differentially expressed genes in the early response to dithranol belonged to keratinocyte and epidermal differentiation pathways and IL-1 family members (i.e. but not elements of the IL-17/IL-23 axis. In human psoriatic response to dithranol, rapid decrease in expression of keratinocyte differentiation regulators (e.g. involucrin, and ), antimicrobial peptides (e.g. ß-defensins like S100 proteins like ), chemotactic factors for neutrophils (e.g. ) and neutrophilic infiltration was followed with much delay by reduction in T cell infiltration. Targeting keratinocytes rather than immune cells may be an alternative approach in particular for topical anti-psoriatic treatment, an area with high need for new drugs.
Topics: Animals; Anthralin; Chemokines, CXC; Dermatologic Agents; Interleukin-1; Keratinocytes; Mice; Neutrophils; Pore Forming Cytotoxic Proteins; Psoriasis; Serpins; Signal Transduction; Skin
PubMed: 32484435
DOI: 10.7554/eLife.56991 -
Anais Brasileiros de Dermatologia 2021
Randomized Controlled Trial
Topics: Administration, Topical; Alopecia Areata; Anthralin; Cyclopropanes; Humans
PubMed: 33849753
DOI: 10.1016/j.abd.2020.06.018 -
World Journal of Plastic Surgery Mar 2022A 16-year-old female with psoriasis presented to our Plastic Surgery Department with a significant chemical burn to the neck, upper torso and left cheek (TBSA 6%). She...
A 16-year-old female with psoriasis presented to our Plastic Surgery Department with a significant chemical burn to the neck, upper torso and left cheek (TBSA 6%). She applied a concoction of cream prescribed by her dermatologist in her native country, Poland when she returned to the United Kingdom. A few hours after application she developed a burn with pH of 5. A review of the cream revealed a mixture of 19% dithranol and 5% salicylic acid. This combination is recognized for managing psoriasis, however the strength of dithranol in the combination given is of a high concentration (normally <3%). This alone can cause a burn to the skin if left for a prolonged period of time. Salicylic acid is an enhancer which augments the stability of dithranol and increases its penetration and efficacy. The concentration of 5% is also on the higher end. Our patient was admitted for pain relief and further irrigation till normalization of the pH which was achieved after 3 days. A worrying aspect in our patients' case is that she was given the cream to commence at home. High concentration preparation is normally commenced in a controlled setting under medical supervision.
PubMed: 35592224
DOI: 10.52547/wjps.11.1.138 -
NPJ Vaccines Jun 2023
PubMed: 37349361
DOI: 10.1038/s41541-023-00689-9 -
Dermatologic Therapy May 2020We present the results on retrospective analysis about the efficacy of Certolizumab pegol (CZP), an antitumor necrosis factor-alpha agent, as monotherapy on skin...
We present the results on retrospective analysis about the efficacy of Certolizumab pegol (CZP), an antitumor necrosis factor-alpha agent, as monotherapy on skin psoriasis (PsO) in patients affect both by psoriatic arthritis (PsA) and mild-severe PsO. To date, the CZP is authorized for the treatment of PsA, PsO beyond that rheumatoid arthritis, axial spondyloarthritis/ankylosing spondylitis, and Crohn's. Assessments included an evaluation of the Psoriasis Area and Severity Index (PASI). Twelve patients (9M and 3F mean age 57.8 ± 8 years) were enrolled in our study. Nine patients had been previously treated with others biologic agents, three patients were naïve. Clinical and laboratory evaluations including PASI, erythrosedimentation rate, and C-reactive protein were performed at baseline (BL), at Week 12 (W12), Week 24 (W24), and Week 52 (W52) of treatment. Although the combination between methotrexate and CZP is allowed, we included, in our study, patients treated only with CZP. In such a way as to be as specific as possible, topical corticosteroids, vitamin D derivatives, retinoid creams, anthralin derivatives as well as p-UVA or UV-B have been forbidden to enrolled patients. With the same purpose, all the patients used the identical moisturizing cream two times a day. Mean PASI score decreased from 18 (BL) to 0 (W52) as follows: 18 at BL, 4 at W12, 0 at W24, and 0 at W52. Severe adverse events were not reported. Safety evaluations were performed every 3 months: liver and renal functions were monitored in all patients during the treatment, and no patient presented abnormal values. To the best of our knowledge, this is the first report that highlights the efficacy of CZP as monotherapy in psoriasis with mild to severe cutaneous involvement. Although to date the drug is authorized only for PsA, our results demonstrate that CZP is safe and effective on both cutaneous and joint components representing, therefore, an effective option in the treatment of cutaneous symptoms of PsO. Limitations of our study are presented by the relatively short observation time (W52) and by numeric small study group. Long-term data with a larger number of enrolled patients are necessary in order to confirm our preliminary observations.
Topics: Aged; Antirheumatic Agents; Arthritis, Psoriatic; Certolizumab Pegol; Double-Blind Method; Humans; Immunosuppressive Agents; Middle Aged; Psoriasis; Retrospective Studies; Treatment Outcome
PubMed: 32291887
DOI: 10.1111/dth.13409 -
Dermatologic Therapy Sep 2022
A study examining the combination of methotrexate and leflunomide with topical anthralin in pediatric alopecia areata-a possible steroid-free regimen with diverse mechanistic actions.
Topics: Administration, Topical; Alopecia Areata; Anthralin; Child; Humans; Leflunomide; Methotrexate
PubMed: 35735053
DOI: 10.1111/dth.15662