ABSTRACT
BACKGROUND: Bladder urothelial carcinoma (BLCA) is a prevalent malignant tumor of the urinary system and, ranks 13th worldwide. Its incidence and mortality rates are consistently increasing, posing a significant threat to the physical and mental well-being of patients. METHODS: We conducted a literature search in the field of BLCA from 2010 to 2023 using the Web of Science Core Collection (WoSCC) database. CiteSpace 6.2.R4 and VOSviewer 1.6.19 were utilized to visually represent the annual publications, countries, institutions, authors, journals, keywords, and references in the literature. RESULTS: A total of 10,378 articles were included in this study. Since 2010, the number of published articles has been increasing. The countries and institutions that contributed the most were the USA and Medical University Vienna. The most frequently cited author was Bellmunt J, with 2551 citations. Shariat Shahrokh F holds the record for most published articles with 445. The journal "Urologic Oncology-Seminars and Original Investigations" had the largest number of publications, while "Eur Urol" was the most frequently cited journal. "survival" and "radical cystectomy" were identified as the most frequent keywords in recent years. Burst detection analysis revealed that the keyword with the highest intensity value was "Transitional-Cell Carcinoma," and the reference with the highest intensity value was Babjuk M, 2013. CONCLUSION: This study aimed to analyze and predict the research hotspots and trends in BLCA to provide reference value for further research in this field. The findings of this study can contribute to the research progress in BLCA.
Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Urinary Bladder , Bibliometrics , CystectomyABSTRACT
Diabetic keratopathy, commonly associated with a hyperactive inflammatory response, is one of the most common eye complications of diabetes. The peptide hormone fibroblast growth factor-21 (FGF-21) has been demonstrated to have anti-inflammatory and antioxidant properties. However, whether administration of recombinant human (rh) FGF-21 can potentially regulate diabetic keratopathy is still unknown. Therefore, in this work, we investigated the role of rhFGF-21 in the modulation of corneal epithelial wound healing, the inflammation response, and oxidative stress using type 1 diabetic mice and high glucose-treated human corneal epithelial cells. Our experimental results indicated that the application of rhFGF-21 contributed to the enhancement of epithelial wound healing. This treatment also led to advancements in tear production and reduction in corneal edema. Moreover, there was a notable reduction in the levels of proinflammatory cytokines such as TNF-α, IL-6, IL-1ß, MCP-1, IFN-γ, MMP-2, and MMP-9 in both diabetic mouse corneal epithelium and human corneal epithelial cells treated with high glucose. Furthermore, we found rhFGF-21 treatment inhibited reactive oxygen species production and increased levels of anti-inflammatory molecules IL-10 and SOD-1, which suggests that FGF-21 has a protective role in diabetic corneal epithelial healing by increasing the antioxidant capacity and reducing the release of inflammatory mediators and matrix metalloproteinases. Therefore, we propose that administration of FGF-21 may represent a potential treatment for diabetic keratopathy.
Subject(s)
Corneal Diseases , Diabetes Complications , Diabetes Mellitus, Experimental , Epithelium, Corneal , Fibroblast Growth Factors , Inflammation Mediators , Oxidative Stress , Wound Healing , Animals , Humans , Mice , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Corneal Diseases/complications , Corneal Diseases/drug therapy , Corneal Diseases/metabolism , Diabetes Complications/drug therapy , Diabetes Complications/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Epithelium, Corneal/drug effects , Fibroblast Growth Factors/pharmacology , Fibroblast Growth Factors/therapeutic use , Glucose/adverse effects , Glucose/metabolism , Inflammation Mediators/metabolism , Matrix Metalloproteinases/metabolism , Oxidative Stress/drug effects , Wound Healing/drug effectsABSTRACT
Introduction: Recombinant human fibroblast growth factor 21 (FGF-21) is a potential therapeutic agent for multiple metabolic diseases. However, little is known about the toxicokinetic characteristics of FGF-21. Methods: In the present study, we investigated the toxicokinetics of FGF-21 delivered via subcutaneous injection in vivo. Twenty cynomolgus monkeys were injected subcutaneously with different doses of FGF-21 for 86 days. Serum samples were collected at eight different time points (0, 0.5, 1.5, 3, 5, 8, 12, and 24 h) on day 1, 37 and 86 for toxicokinetic analysis. The serum concentrations of FGF-21 were measured using a double sandwich Enzyme-linked immunosorbent assay. Blood samples were collected on day 0, 30, 65, and 87 for blood and blood biochemical tests. Necropsy and pathological analysis were performed on d87 and d116 (after recovery for 29 days). Results: The average AUC(0-24h) values of low-dose FGF-21 on d1, d37, and d86 were 5253, 25268, and 60445 µg h/L, and the average AUC(0-24h) values of high-dose FGF-21 on d1, d37, and d86 were 19964, 78999, and 1952821 µg h/L, respectively. Analysis of the blood and blood biochemical indexes showed that prothrombin time and AST content in the high-dose FGF-21 group increased. However, no significant changes in other blood and blood biochemical indexes were observed. The anatomical and pathological results showed that continuous subcutaneous injection of FGF-21 for 86 days did not affect organ weight, the organ coefficient, and histopathology in cynomolgus monkeys. Discussion: Our results have guiding significance for the preclinical research and clinical use of FGF-21.
