Recent ucsdsom_derm_oapdeposits items

Clinical utility of 23-gene expression profiling and concordance with PRAME immunohistochemistry in melanocytic neoplasms: a retrospective diagnostic accuracy study

Thu, 21 May 2026 00:00:00 +0000

Clinical utility of 23-gene expression profiling and concordance with PRAME immunohistochemistry in melanocytic neoplasms: a retrospective diagnostic accuracy study

Acral Speckled Lentiginous Nevus

Thu, 21 May 2026 00:00:00 +0000

Speckled lentiginous nevus (SLN), also referred to as nevus spilus, is a common benign melanocytic neoplasm typically occurring as a small, café-au-lait-colored "speckled" patch studded with numerous darkly pigmented macules or papules. Herein, we present a unique case of SLN arising on the sole of the right foot in a young woman, which was reported to be gradually enlarging since a pregnancy two years prior. The lesion was removed by shave biopsy, and histopathology confirmed the diagnosis and ruled out atypical features. While SLN is quite common, the occurrence on acral skin is extremely rare. SLN is considered a mosaic RASopathy due to its embryological development through a postzygotic activating HRAS genetic variant. Although small lesions usually remain isolated, underlying SLN syndrome should be considered in extensive cases with associated neurologic or musculoskeletal abnormalities. Secondary melanocytic neoplasms commonly arise within SLN, but overall, small lesions...

Auricular discoid lupus erythematosus

Thu, 9 Apr 2026 00:00:00 +0000

Auricular discoid lupus erythematosus

The transcription elongation factors Spt4 and Spt6 promote dermal adipocyte differentiation

Thu, 9 Apr 2026 00:00:00 +0000

Regulation of adipogenesis has classically been viewed through the lens of transcription initiation driven by lineage defining transcription factors. In this study, we uncover transcription elongation as a critical and previously underappreciated regulatory layer controlling adipocyte cell fate. We demonstrate that the elongation factors Spt4 and Spt6 are indispensable for adipogenic differentiation, as their depletion severely impairs adipogenic gene induction and perilipin expression. Spt4 and Spt6 directly regulate the genes coding for core adipogenic transcription factors, including Cebpa, Pparg, Krox20, and Stat3, by promoting RNA polymerase II (Pol II) progression through their gene bodies. In the absence of these factors, Pol II becomes stalled at the transcriptional start sites of these adipogenic genes. These data support a post transcription initiation requirement for Spt4 and Spt6 in productive elongation rather than promoter loading. Our findings identify transcription...

Part I. The role of Staphylococcus aureus in the pathophysiology of dermatologic disease

Thu, 12 Mar 2026 00:00:00 +0000

In this first part of a two-part continuing medical education series, we examine the impact of Staphylococcus aureus (S. aureus) resistance and its pathogenic mechanisms, such as toxins, virulence factors, superantigens, quorum sensing, and biofilm formation. Next, we explore how S. aureus infection contributes to delayed wound healing, impetigo, and staphylococcal scalded skin syndrome. Additionally, S. aureus plays a crucial role in the pathophysiology of dermatologic diseases that goes beyond infection, including atopic dermatitis, cutaneous T-cell lymphoma, epidermolysis bullosa, and others. Understanding S. aureus will help dermatologists better understand and more effectively treat various skin conditions.

Part II. Targeting Staphylococcus aureus to treat dermatologic disease

Thu, 12 Mar 2026 00:00:00 +0000

In Part I of our CME series, we reviewed the pathogenic factors of Staphylococcus aureus (S. aureus) and outlined its role in various dermatologic diseases. Part II reviews the established and emerging therapeutic mechanisms targeting S. aureus in these diseases. We also discuss current antibiotic recommendations for treating S. aureus in the context of current resistance rates. Dermatologists should be familiar with the wide spectrum of topical and systemic antibiotics available for treating S. aureus, bullous impetigo and staphylococcal scalded skin syndrome, and the emerging clinical therapies that target S. aureus in atopic dermatitis and cutaneous T-cell lymphoma.

Splicing Factor 3a Subunit 1 Promotes Colorectal Cancer Growth via Anti-Apoptotic Effects of Syntaxin12.

Thu, 19 Feb 2026 00:00:00 +0000

RNA dysregulation mediated by aberrant RNA-binding proteins (RBPs) is closely associated with tumorigenesis. However, the tumorigenic mechanisms of each RBP remained unclear. In this study, we demonstrate that downregulation of Splicing factor 3A1 (SF3A1) markedly suppressed the proliferation of colorectal cancer (CRC) cells, with minimal cytotoxicity observed in non-cancerous epithelial cells. The tumor-promoting function of SF3A1 was further validated in an HCT116 xenograft mouse model. Multiple apoptosis assays-including TdT-mediated dUTP nick end labeling (TUNEL) staining, poly-ADP-ribose polymerase (PARP) immunoblotting, and caspase-3/7 activity measurements-showed that SF3A1 inhibited apoptotic signaling in CRC cells. Transcriptome analysis, combined with RNA-immunoprecipitation (RIP), identified Syntaxin 12 (STX12) as a downstream effector of SF3A1. Knockdown of STX12 induced apoptosis in CRC cells but had no effect on the viability of non-cancerous HCEC-1CT epithelial...

FSP1 and histone deacetylases suppress cancer persister cell ferroptosis

Fri, 16 Jan 2026 00:00:00 +0000

Cancer persister cells which survive oncogene targeted therapies are sensitized to ferroptosis, but mechanistic understanding of this vulnerability remains limited. Here, we found that while levels of iron, glutathione, and various ferroptosis-suppressing enzymes vary among persister cell types, ferroptosis suppressor protein 1 (FSP1) is down-regulated in multiple persister cell types, and persister cells which survive glutathione peroxidase 4 (GPX4) inhibition rely on residual FSP1 to survive. Furthermore, persister cells which survive GPX4 inhibition down-regulate oxidative phosphorylation, a key source of mitochondrial reactive oxygen species which are required for persister cell ferroptosis. We also found that persister cell treatment with histone deacetylase inhibitors induces reactive oxygen species and sensitizes multiple persister cell types to GPX4 inhibition. Together, these findings reveal that FSP1 and histone deacetylases suppress persister cell ferroptosis.

DNA fragmentation factor B suppresses interferon to enable cancer persister cell regrowth

Fri, 16 Jan 2026 00:00:00 +0000

Oncogene-targeted cancer therapies can provide deep responses but frequently suffer from acquired resistance. Therapeutic approaches to treat tumours that have acquired drug resistance are complicated by continual tumour evolution and multiple co-occurring resistance mechanisms. Rather than treating resistance after it emerges, it may be possible to prevent it by inhibiting the adaptive processes that initiate resistance, but these are poorly understood. Here we report that residual cancer persister cells that survive oncogene-targeted therapy are growth arrested by drug stress-induced intrinsic type I interferon signalling. To escape growth arrest, persister cells leverage apoptotic machinery to transcriptionally suppress interferon-stimulated genes (ISGs). Mechanistically, persister cells sublethally engage apoptotic caspases to activate DNA endonuclease DNA fragmentation factor B (also known as caspase-activated DNase), which induces DNA damage, mutagenesis and stress response...

Dual dysregulation of TNF/interferon signaling and classical monocytes are implicated in Reactive Infectious Mucocutaneous Eruptions

Thu, 4 Dec 2025 00:00:00 +0000

Dual dysregulation of TNF/interferon signaling and classical monocytes are implicated in Reactive Infectious Mucocutaneous Eruptions

Chronological age estimation from human microbiomes with transformer-based Robust Principal Component Analysis

Thu, 4 Dec 2025 00:00:00 +0000

Deep learning for microbiome analysis has shown potential for understanding microbial communities and human phenotypes. Here, we propose an approach, Transformer-based Robust Principal Component Analysis(TRPCA), which leverages the strengths of transformer architectures and interpretability of Robust Principal Component Analysis. To investigate benefits of TRPCA over conventional machine learning models, we benchmarked performance on age prediction from three body sites(skin, oral, gut), with 16S rRNA gene amplicon(16S) and whole-genome sequencing(WGS) data. We demonstrated prediction of age from longitudinal samples and combined classification and regression tasks via multi-task learning(MTL). TRPCA improves age prediction accuracy from human microbiome samples, achieving the largest reduction in Mean Absolute Error for WGS skin (MAE: 8.03, 28% reduction) and 16S skin (MAE: 5.09, 14% reduction) samples, compared to conventional approaches. Additionally, TRPCA’s MTL approach achieves...

PolyIC as an adjuvant outperforms anti-VEGF in combination with anti-PD-L1 therapy in mouse liver tumor models

Fri, 12 Sep 2025 00:00:00 +0000

BACKGROUND: Immune checkpoint inhibitors combined with antiangiogenic therapy have become the standard of care for advanced HCC, albeit with limited therapeutic benefit. Our previous studies demonstrated the immunomodulatory and antitumor effects of polyIC, a synthetic dsRNA. Here, we compared the efficacy of anti-programmed death ligand 1 (αPD-L1) plus polyIC versus αPD-L1 plus anti-vascular endothelial growth factor (αVEGF) in mouse tumor models. METHODS: We established a primary liver tumor model using hydrodynamic tail vein injection of Ras/Myc oncogenes and a metastasized tumor model via intrasplenic injection of colon cancer cells. Flow cytometry and gene expression analysis were performed to assess immune profiles across treatment groups. Key factors contributing to antitumor efficacy were explored. RESULTS: In both models, αPD-L1 plus polyIC demonstrated superior antitumor effects relative to αPD-L1 plus αVEGF. Unlike αVEGF, polyIC enhanced the immune response to αPD-L1...

Genetic and pharmacological targeting of nicotinic acetylcholine receptor action blocks tumor progression in mouse models of breast cancer

Thu, 31 Jul 2025 00:00:00 +0000

Effective small molecule therapies are a major unmet need in triple-negative breast cancer. Therefore, we examined the mechanism of action of a novel cancer therapeutic target in preclinical mouse models focusing on the α7 nicotinic acetylcholine receptor (CHRNA7). E0771 breast tumor cells were implanted into CHRNA7KO mice to determine the role of CHRNA7, which is expressed in tumor-associated myeloid immune cells. We observed that tumor-bearing CHRNA7KO mice had decreased survival and increased tumor burden linked to a CHRNA7-mediated reduction in immune cell activation. Based on the tumor permissive phenotype of CHRNA7KO mice, we tested the effect of a small molecule agonist of CHRNA7, AR-R17779, in several mouse models of breast cancer. For example, in both the E0771 tumor model and PyMT tumor models, treatment with AR-R17779 increased survival. In the 4T1 breast tumor model, treatment with AR-R17779 also increased survival, with a well-defined reduction in primary tumor burden...

Capivasertib-induced polymorphous lichenoid exanthem: report of a novel AKT kinase inhibitor-related drug eruption

Thu, 17 Jul 2025 00:00:00 +0000

Capivasertib-induced polymorphous lichenoid exanthem: report of a novel AKT kinase inhibitor-related drug eruption

Depression and Anxiety Associated With Systemic Lupus Erythematosus: A Nested, Case–Control Study in the All of Us Database