ABSTRACT
Background: Retinoblastoma is currently the most common malignant tumor seen in newborns and children's eyes worldwide, posing a life-threatening hazard. Chemotherapy is an integral part of retinoblastoma treatment. However, the chemotherapeutic agents used in clinics often lead to drug resistance. Thus there is a need to investigate new chemotherapy-targeted agents. VEGFR3 inhibitors are anti-tumour-growth and could be used to develop novel retinoblastoma-targeted agents. Objective: To predict drug activity, discover influencing factors and design new drugs by building 2D, 3D-QSAR models. Method: First, linear and non-linear QSAR models were built using heuristic methods and gene expression programming (GEP). The comparative molecular similarity indices analysis (COMISA) was then used to construct 3D-QSAR models through the SYBYL software. New drugs were designed by changing drug activity factors in both models, and molecular docking experiments were performed. Result: The best linear model created using HM had an R2, S2, and R2cv of 0.82, 0.02, and 0.77, respectively. For the training and test sets, the best non-linear model created using GEP had correlation coefficients of 0.83 and 0.72 with mean errors of 0.02 and 0.04. The 3D model designed using SYBYL passed external validation due to its high Q2 (0.503), R2 (0.805), and F-value (76.52), as well as its low standard error of SEE value (0.172). This demonstrates the model's reliability and excellent predictive ability. Based on the molecular descriptors of the 2D model and the contour plots of the 3D model, we designed 100 new compounds using the best active compound 14 as a template. We performed activity prediction and molecular docking experiments on them, in which compound 14.d performed best regarding combined drug activity and docking ability. Conclusion: The non-linear model created using GEP was more stable and had a more substantial predictive power than the linear model built using the heuristic technique (HM). The compound 14.d designed in this experiment has the potential for anti-retinoblastoma treatment, which provides new design ideas and directions for retinoblastoma-targeted drugs.
ABSTRACT
Introduction: Tissue-resident stem cells (TRSCs) have the ability to self-renew and differentiate throughout an individual's lifespan, and they utilize both mechanisms to maintain homeostasis and regenerate damaged tissues. Several studies suggest that these stem cells can serve as a potential source for cell-replacement-based therapy by promoting differentiation or expansion. In recent years, low-intensity pulsed ultrasound (LIPUS) has been demonstrated to effectively stimulate stem cell proliferation and differentiation, promote tissue regeneration, and inhibit inflammatory responses. Aims: To present a comprehensive overview of current application and mechanism of LIPUS on tissue resident stem cells. Methods: We searched PubMed, Web of Science for articles on the effects of LIPUS on tissue resident stem cells and its application. Results: The LIPUS could modulate cellular activities such as cell viability, proliferation and differentiation of tissue resident stem cells and related cells through various cellular signaling pathways. Currently, LIPUS, as the main therapeutic ultrasound, is being widely used in the treatment of preclinical and clinical diseases. Conclusion: The stem cell research is the hot topic in the biological science, while in recent years, increasing evidence has shown that TRSCs are good targets for LIPUS-regulated regenerative medicine. LIPUS may be a novel and valuable therapeutic approach for the treatment of ophthalmic diseases. How to further improve its efficiency and accuracy, as well as the biological mechanism therein, will be the focus of future research.
Subject(s)
Stem Cells , Ultrasonic Therapy , Cell Differentiation , Ultrasonic Waves , Cells, CulturedABSTRACT
Aim: Targeted retinal photocoagulation (TRP) is an emerging laser technology for retinal targeted therapy. TRP can specifically act on unperfused retinal capillaries and retinal intermediate ischemic areas, reduce damage to tissue perfusion areas and panretinal photocoagulation (PRP) complications or adverse events. In this regard, this review discusses the treatment options, efficacy, and latest progress of TRP for diabetic retinopathy (DR) based on randomized controlled trial (RCT), meta-analysis, case review, and other existing studies. Methods: In-depth research was conducted on articles about the proposal and development of TRP, its simple application in DR, and combined therapy. In order to review the new progress, application methods, effects, and prospects of TRP in the treatment of DR, the articles related to TRP in the databases of PubMed and Web Of Science since this century were comprehensively analyzed. Results: TRP is effective in treating DR and may become a substitute for PRP in the future. In addition, the treatment regimen of TRP combined with intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs can also be used as a new therapeutic approach to expand the treatment regimen for the treatment of DR, and this combination therapy also has effects on other retinal vascular diseases. Conclusions: With the advancement of technology, TRP has been continuously applied in clinical practice, and its potential benefits have opened up broad prospects for the treatment of DR. The combination therapy of TRP and anti-VEGF is expected to become a new option for patients with DR an retinal diseases.
