Granular cell tumor of the vulva: Case report and systematic review of the literature.

RATIONALE: Granular cell tumor (GCT) of the vulva is an exceptionally rare female genital tract tumor. The majority of these are benign and there are no standardized surgical techniques for the special site to reduce tension of the wound. PATIENT CONCERNS: A 47-years-old Chinese woman experienced a nodule on her right vulva with itch sometimes in late 2018. DIAGNOSES: Magnetic resonance imaging showed a high possibility of vulvar cancer. While Chest X-ray, abdominal sonography, and cystoscopy examination were unremarkable. INTERVENTIONS: The patient underwent local complete resection of vulvar tumor under general anesthesia on March 24, 2022. The resection scope was approximately 4 cm × 3 cm × 3 cm. Due to the large surgical incision, Z-plasty was performed to achieve the primary closure for decreasing wound tension and improving aesthetic reduction. OUTCOMES: The final pathological diagnosis was benign GCT of the vulva and surgical margins were uninvolved. At 8 months follow-up, no new lesions were detected. LESSONS: Surgery with negative resection margins is the mainstay for benign GCT of the vulva, while Z-plasty is appropriate for decreasing the tension of the wound and improving aesthetic reduction.

High-throughput screening campaign identifies a small molecule agonist of the relaxin family peptide receptor 4.

Relaxin/insulin-like family peptide receptor 4 (RXFP4) is a class A G protein-coupled receptor (GPCR), and insulin-like peptide 5 (INSL5) is its endogenous ligand. Although the precise physiological role of INSL5/RXFP4 remains elusive, a number of studies have suggested it to be a potential therapeutic target for obesity and other metabolic disorders. Since selective agonists of RXFP4 are scarcely available and peptidic analogs of INSL5 are hard to make, we conducted a high-throughput screening campaign against 52,000 synthetic and natural compounds targeting RXFP4. Of the 109 initial hits discovered, only 3 compounds were confirmed in secondary screening, with JK0621-D008 displaying the best agonism at human RXFP4. Its S-configuration stereoisomer (JK1) was subsequently isolated and validated by a series of bioassays, demonstrating a consistent agonistic effect in cells overexpressing RXFP4. This scaffold may provide a valuable tool to further explore the biological functions of RXFP4.

W2476 ameliorates ß-cell dysfunction and exerts therapeutic effects in mouse models of diabetes via modulation of the thioredoxin-interacting protein signaling pathway.

Recent evidence shows that high glucose levels recruit carbohydrate response element-binding protein, which binds the promoter of thioredoxin-interacting protein (txnip), thereby regulating its expression in ß-cells. Overexpression of txnip not only induces ß-cell apoptosis but also reduces insulin production. Thus, the discovery of compounds that either inhibit TXNIP activity or suppress its expression was the focus of the present study. INS-1E cells stably transfected with either a txnip proximal glucose response element connected to a luciferase reporter plasmid (BG73) or full-length txnip promoter connected to a luciferase reporter plasmid (CL108) were used in primary and secondary high-throughput screening campaigns, respectively. From 256 000 synthetic compounds, a small molecule compound, W2476 [9-((1-(4-acetyl-phenyloxy)-ethyl)-2-)adenine], was identified as a modulator of the TXNIP-regulated signaling pathway following the screening and characterized using a battery of bioassays. The preventive and therapeutic properties of W2476 were further examined in streptozotocin-induced diabetic and diet-induced obese mice. Treatment with W2476 (1, 5, and 15 µmol/L) dose-dependently inhibited high glucose-induced TXNIP expression at the mRNA and protein levels in INS-1E cells and rat pancreatic islets. Furthermore, W2476 treatment prevented INS-1E cells from apoptosis induced by chronic exposure of high glucose and enhanced insulin production in vitro. Oral administration of W2476 (200 mg·kg-1·d-1) rescued streptozotocin-induced diabetic mice by promoting ß-cell survival and enhancing insulin secretion. This therapeutic property of W2476 was further demonstrated by its ability to improve glucose homeostasis and insulin sensitivity in diet-induced obese mice. Thus, chemical intervention of the TXNIP-regulated signaling pathway might present a viable approach to manage diabetes.