Granular parakeratosis (GP) is a rare, idiopathic, and benign skin condition that presents classically as erythematous to brown hyperkeratotic papules that can coalesce into plaques. Axillary GP was initially observed by Northcutt and colleagues and has since been described in various other areas of the body including other intertriginous and non-intertriginous sites. The term "granular parakeratosis" is now used to describe not only the skin condition, but also a distinctive histological reactive pattern on biopsy specimens that are either regarded as the disease itself, or merely as an incidental finding. Upon review of the current findings, opinions, and associations of this entity, we propose the reappraisal of GP as a reactive pattern, rather than a distinct entity.
Perioperative pain is a significant issue among patients undergoing pelvic exenteration. One in three patients require high-dose opiates preoperatively that is associated with worse pain outcomes. Potential areas to improve pain outcomes in these complex patients could include increased use of regional anesthesia, antineuropathic agents, and opiate-sparing techniques. See Video Abstract at http://links.lww.com/DCR/A572.
Imiquimod is a TLR7/8 agonist that has anti-cancer therapeutic efficacy in the treatment of pre-cancerous skin lesions and certain non-melanoma skin cancers. To test our hypothesis that imiquimod enhances DNA repair as a mechanism for its anticancer activity, the nucleotide excision repair genes were studied in bone marrow derived cells. Imiquimod enhanced the expression of XPA and other DNA repair genes (qPCR analysis), and resulted in an increased nuclear localization of the DNA repair enzyme XPA. This was dependent on MyD88, as bone marrow derived cells from MyD88−/− mice did not increase XPA gene expression, and did not enhance the survival of MyD88−/− derived bone marrow derived cells after UVB exposure as was observed in bone marrow derived cells from MyD88+/+ mice. Imiquimod also enhanced DNA repair of UVL irradiated gene expression constructs, and accelerated the resolution of cyclobutane pyrimidine dimers (CBPD) after UVL exposures in P388 and XS52. Lastly, topical treatment of mouse skin with 5% imiquimod cream prior to UVL irradiation resulted in a decrease in the number of cyclobutane pyridimine dimer positive, APC that were found in local lymph nodes 24 hours after UVL irradiation in both wild type and IL-12 gene targeted mice. In total, these data support the idea that TLR7 agonists such as imiquimod enhance DNA repair in bone marrow derived cells. This property is likely to be an important mechanism for its anti-cancer effects, because it protects cutaneous APC from the deleterious effects of UVL.
Existing methods often fail to recognize the conversions for the biological roles of the pairs of genes and microRNAs (miRNAs) between the tumor and normal samples. We have developed a novel cluster scoring method to identify messenger RNA (mRNA) and miRNA interaction pairs and clusters while considering tumor and normal samples jointly. Our method has identified 54 significant clusters for 15 cancer types selected from The Cancer Genome Atlas project. We also determined the shared clusters across tumor types and/or subtypes. In addition, we compared gene and miRNA overlap between lists identified in our liver hepatocellular carcinoma (LIHC) study and regulatory relationships reported from human and rat nonalcoholic fatty liver disease studies (NAFLD). Finally, we analyzed biological functions for the single significant cluster in LIHC and uncovered a significantly enriched pathway (phospholipase D signaling pathway) with six genes represented in the cluster, symbols: DGKQ, LPAR2, PDGFRB, PIK3R3, PTGFR and RAPGEF3.
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