Search

Interleukin-17A therapeutic inhibitors are among the most effective treatment methods for moderate-to-severe plaque psoriasis (PP). Reflectance confocal microscopy is a non-invasive imaging technique already documented to be beneficial in evaluating the follow-up of PP under treatment with topical actives and phototherapy. This study aimed to assess the epidermal and dermal changes associated with psoriasis and its treatment with RCM during systemic secukinumab treatment in patients with moderate-to-severe PP. A pilot study was conducted to evaluate RCM as a non-invasive tool for monitoring secukinumab treatment in patients with PP. For patients receiving secukinumab treatment, lesional skin was selected for RCM imaging, which were recorded at all scheduled times. The RCM evaluation criteria were established based on the histopathological diagnostic criteria for psoriasis. The clinical severity of psoriasis was assessed utilizing the psoriasis area severity index. A total of 23 patients with PP were included in the study. Each patient received 300 mg of subcutaneous secukinumab as induction therapy at baseline and weeks 1–4, followed by maintenance therapy every four weeks. Microscopic confocal changes were observed during the treatment. The results identified early microscopic evidence of the anti-inflammatory activity of secukinumab, which was not detected during the clinical examination. RCM findings correlating with the PASI were used to observe the patient's response to treatment and were identified as follows: acanthosis and parakeratosis, presence of epidermal and dermal inflammatory cells, presence of non-edge dermal papillae, and vascularization in the papillary dermis. This study is the first to demonstrate the use of RCM as an effective tool for non-invasive monitoring of secukinumab therapeutic response at a cellular level in a clinical or research setting. Early detection of RCM parameters associated with secukinumab activity may facilitate the identification of an early treatment response. RCM appears to be capable of providing practical and helpful information regarding follow-up in patients with PP undergoing secukinumab treatment. RCM may also provide novel perspectives on the subclinical evaluation of PP's response to biological therapy. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) is rare in young individuals and reported to possess different pathogenetic, clinical and histological features from late-onset BCC. However, the dermoscopic variability of BCC according to age of onset has not been investigated. Anatomic location was revealed to be associated with dermoscopic variation of BCC in Western population, but whether it applies to Asian population remains unknown. We evaluated the clinical and dermoscopic features of 448 BCCs and compared each feature by age of onset (age < 50/ > 50 years) and anatomic location. Early-onset BCCs occurred more frequently on non-sun-exposed sites (OR 3.28, P = 0.001) and were less pigmented than late-onset BCCs (P = 0.003). Blue–gray globules (OR 1.74, P = 0.037) and no vessels (OR 2.04, P = 0.021) were independently associated with early-onset BCCs, whereas arborizing telangiectasia (OR 0.30, P < 0.001), large blue–gray ovoid nests (OR 0.38, P < 0.001) and ulceration (OR 0.33, P < 0.001) were less common in early-onset BCCs. Scalp BCCs were significantly more pigmented than BCCs located elsewhere (P = 0.022). Superficial subtype (OR 5.90, P < 0.001), spoke-wheel areas (OR 4.78, P = 0.034), superficial erosions (OR 4.69, P = 0.003) and polymorph vessels (OR 6.86, P = 0.001) were independently associated with trunk BCCs, whereas nodular subtype (OR 5.48, P < 0.001) and arborizing telangiectasias (OR 3.64, P < 0.001) with BCCs on face and neck. Our findings suggest that age of onset and anatomic location are independent factors affecting the dermoscopic appearance of BCC. [ABSTRACT FROM AUTHOR]

Copyright of Frontiers of Information Technology & Electronic Engineering is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

DNA phosphorothioate (PT) modification, with a nonbridging phosphate oxygen substituted by sulfur, represents a widespread epigenetic marker in prokaryotes and provides protection against genetic parasites. In the PT-based defense system Ssp, SspABCD confers a single-stranded PT modification of host DNA in the 5′-CPSCA-3′ motif and SspE impedes phage propagation. SspE relies on PT modification in host DNA to exert antiphage activity. Here, structural and biochemical analyses reveal that SspE is preferentially recruited to PT sites mediated by the joint action of its N-terminal domain (NTD) hydrophobic cavity and C-terminal domain (CTD) DNA binding region. PT recognition enlarges the GTP-binding pocket, thereby increasing GTP hydrolysis activity, which subsequently triggers a conformational switch of SspE from a closed to an open state. The closed-to-open transition promotes the dissociation of SspE from self PT-DNA and turns on the DNA nicking nuclease activity of CTD, enabling SspE to accomplish self-nonself discrimination and limit phage predation, even when only a small fraction of modifiable consensus sequences is PT-protected in a bacterial genome.SspABCD–SspE is a phosphorothioation-sensing bacterial defence system. Here, authors find that SspE exploits DNA phosphorothioation-binding preference to modulate its biochemical activities for the self/nonself discrimination and phage resistance. [ABSTRACT FROM AUTHOR]

Psoriasis is a common, chronic, and relapsing skin disease characterized by hyperproliferation of keratinocytes and apoptosis delay. However, the molecular mechanisms underlying the progression of psoriasis remain elusive. MicroRNAs (miRNAs) are single-stranded, small non-coding RNAs that play a crucial role in the development of psoriasis by promoting targeted mRNA degradation or translational inhibition. Here, we report that miR-214-3p, one of the downregulated miRNAs identified in the skin of psoriatic patients and imiquimod (IMQ)-induced mouse models, can negatively regulate the expression of forkhead box M1 (FOXM1). miR-214-3p inhibition leads to hyperproliferation and increased apoptosis of keratinocytes in vitro. Moreover, we show that miR-214-3p inhibition causes an arrest of the cell cycle at the S stage by elevating the expression of NEK2, KIF20A, CENP-A, CENP-F, and Cyclin B1 and by reducing the expression of Cyclin D1 in HaCaT cells. In vivo, the administration of miR-214-3p attenuates the psoriasis-like phenotype in IMQ-induced mice. Collectively, our results suggest that miR-214-3p/FOXM1 axis in keratinocytes could be a novel target in the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

The objective of the present study was to investigate the differences in the proteomic profiles of sperm from infertile males with severe oligoasthenoteratozoospermia requiring intracytoplasmic sperm injection (ICSI) and normal control sperm from fertile males. Isobaric tag for relative and absolute quantitation labeling and liquid chromatography–tandem mass spectrometry was performed for identifying proteins in the sperm of infertile and fertile males. Differentially expressed proteins were analyzed via the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases through the Database for Annotation, Visualization, and Integrated Discovery, and protein–protein networks were produced using the Search Tool for Retrieval of Interacting Genes. Immunofluorescence and western blotting verified the differential expression of Y-box-binding protein 1(YBX1), adenylate kinase 1 (AK1), and aconitase 2, mitochondrial (ACO2) proteins. Altogether, 3444 proteins were identified in the sperm of infertile and fertile males, and 938 were differentially expressed between the two groups. Pairwise comparisons revealed that 226 and 712 proteins were significantly upregulated and downregulated in infertile males, respectively. These proteins were significantly enriched in metabolic pathways as per KEGG enrichment analysis. YBX1 expression was upregulated in the sperm heads of patients requiring ICSI treatment, whereas AK1 and ACO2, which are critical enzymes involved in energy metabolism, were downregulated in the sperm tails of the same patients. This result indicates that metabolism may have a crucial role in maintaining normal sperm function. Overall, our results provide insights that will further help in investigating the pathogenic mechanisms of infertility and possible therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: We aimed to analyze the results of 24-h multichannel intraluminal impedance and pH-monitoring (MII-pH) of the laryngopharynx and esophagus in asymptomatic volunteers. Moreover, we also aimed to gain insight into and establish a baseline for laryngopharyngeal reflux in the healthy population by quantitatively and qualitatively comparing the reflux and pH distribution in both the laryngopharynx and the esophagus. Methods: Healthy volunteers were recruited and observed; they underwent 24-h ambulatory combined MII-pH monitoring. The proximal sensor (pH1) was positioned approximately 1 cm above the upper esophageal sphincter with the aid of a solid-state high-resolution esophageal manometer. Laryngopharyngeal reflux events were detected and characterized by the incidence and property of reflux both in the laryngopharynx and the esophagus. Results: Thirty-eight asymptomatic volunteers who completed all the examinations were included in this study. The median pH detected by the proximal sensor was 6.6 (6.2, 7.0), with an average of 6.58 ± 0.74. A total of 814 laryngopharyngeal reflux events were detected, including 722 (89%) in the upright position and 92 (11%) in the supine position with incidence (0%) in the liquid state, 44 (5%) in the mixture, and 769 (95%) in the gaseous state. Furthermore, 5 incidences (1%) of acid reflux and 809 incidences of non-acid reflux (99%) were noted. A total of 5779 esophageal reflux events were detected, including 5020 (87%) in the upright position, 759 (13%) in the supine position, with 2051 (36%) in the liquid state, 2050 (35%) in the mixed condition, and 1678 (29%) in the gaseous state; adding up to 805 incidences (14%) of acid reflux and 4974 incidences (86%) of non-acid reflux. Conclusion: Non-acid reflux in the upright position is characteristic of laryngopharyngeal reflux. Acid reflux is almost undetectable in healthy subjects. Hence, the diagnostic indicators of gastroesophageal reflux disease are not suitable for laryngopharyngeal reflux disease. [ABSTRACT FROM AUTHOR]

Chronic hand eczema is a common chronic inflammatory skin disease that influences public health. Staphylococcus aureus colonization plays important roles in chronic hand eczema morbidity and progression, which also correlated to chronicity and severity of the disease. In this multicenter clinical trial, we aim to investigate the relationship between S. aureus colonization and chronic hand eczema. Eighty patient volunteers diagnosed with chronic hand eczema in 4 hospitals from 4 cities participated in this study. Staphylococcus aureus colonization was determined using Polymerase Chain Reaction and fluorescent labeling probe to rapidly detect the endemic thermostable nuclease gene nuc of S. aureus in clinical samples. All patients were treated with Halometasone Triclosan Cream for 2 weeks. The changes of clinical symptom scores were observed during the follow-up time. We found that the severity of chronic hand eczema was related to S. aureus colonization. Chronic hand eczema would remain severer than others if S. aureus colonization was not eliminated. Eliminating S. aureus colonization could provide good effectiveness in treatment of chronic hand eczema. Therefore, we make a proposal that detection and treatment of S. aureus should be considered in the clinical treatment of chronic hand eczema. [ABSTRACT FROM AUTHOR]

We report a case of subcutaneous phaeohyphomycosis due to Phialophora verrucosa in a 64-year-old Chinese farmer suffering from CD4+ lymphopenia. He presented with diffuse and infiltrated plaques involving the entire face including the eyes, neck, occiput, and extending to the dorsal regions of his torso. The patient is notable for the discrete multifocal nature of the illness in the absence of disseminated infection and rarity of P. verrucosa as a cause of subcutaneous phaeohyphomycosis. [ABSTRACT FROM AUTHOR]