ABSTRACT
Background: Early-onset myopia increases the risk of irreversible high myopia. Methods: This study systematically evaluated the efficacy and safety of low-dose atropine for myopia control in children with premyopia through meta-analysis using random-effects models. Effect sizes were calculated using risk ratios (RRs) with 95% confidence intervals (CIs). Comprehensive searches of PubMed, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov were conducted until 20 December 2023, without language restrictions. Results: Four studies involving 644 children with premyopia aged 4-12 years were identified, with atropine concentrations ranging from 0.01% to 0.05%. The analysis focused on myopia incidence and atropine-related adverse events. Lower myopia incidence (RR, 0.62; 95% CI, 0.40-0.97 D/y; p = 0.03) and reduction in rapid myopia shift (≥0.5 D/1y) (RR, 0.50; 95% CI, 0.26-0.96 D/y; p < 0.01) were observed in the 12-24-month period. Spherical equivalent and axial length exhibited attenuated progression in the atropine group. No major adverse events were detected in either group, whereas the incidence of photophobia and allergic conjunctivitis did not vary in the 12-24-month period. Conclusions: Our meta-analysis supports atropine's efficacy and safety for delaying myopia incidence and controlling progression in children with premyopia. However, further investigation is warranted due to limited studies.
Subject(s)
Abdominal Pain , Anesthetics, Local , Female , Humans , Abdominal Pain/diagnostic imaging , Abdominal Pain/etiologySubject(s)
Genital Diseases, Male , Skin Diseases , Male , Humans , Genital Diseases, Male/diagnostic imaging , Pain/etiologyABSTRACT
BACKGROUND/AIM: AZD8055 is an inhibitor of mammalian target of rapamycin (mTOR) that can suppress both mTOR complex 1 (mTORC1) and mTORC2. This study investigated the antitumor effects of AZD8055 on colon cancer. MATERIALS AND METHODS: The effects of AZD8055 on proliferation, apoptosis, and cell cycle of colon cancer cells, and tumor growth in a mouse colon cancer model were studied. RESULTS: AZD8055 significantly inhibited proliferation and induced apoptosis of colon cancer cells (p<0.05). The phosphorylation of both AKT and S6 kinase 1 (S6K1) was suppressed by AZD8055. AZD8055 also induced G0/G1 cell-cycle arrest, reduced cyclin D1 and increased p27 expression, and suppressed the levels of phospho-cyclin-dependent kinase 2 and phospho-retinoblastoma. Compared to the control, oral administration of AZD8055 significantly suppressed tumor growth in mice (p<0.05). CONCLUSION: AZD8055 induces cytotoxicity, apoptosis, and cell-cycle arrest of colon cancer cells, and exerts an antitumor effect in mice. It also inhibits the mTOR signaling pathway and mTOR-dependent cell-cycle progression.
Subject(s)
Colonic Neoplasms/drug therapy , G1 Phase Cell Cycle Checkpoints/drug effects , Morpholines/pharmacology , TOR Serine-Threonine Kinases/antagonists & inhibitors , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , HCT116 Cells , Humans , Male , Mice, Inbred BALB C , Morpholines/administration & dosage , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , Tumor Burden/drug effectsABSTRACT
BACKGROUND/PURPOSE: Toll-like receptors (TLRs) are important regulators of innate immunity, and TLR4 pathway can regulate the survival, migration, and differentiation of stem cells, including intestinal stem cells (ISCs). Deferoxamine (DFO), a hypoxia-mimic compound, can activate the proliferation of ISCs. In this study, we investigated the response of TLR4 signaling to DFO-induced hypoxia in cultured ISCs in vitro. METHODS: After DFO treatment, the crypt organoid number was counted, and the expression levels of Lgr5, Hsp70, HMGB1, HIF-1α, TLR4, MyD88, TRIF, and TRAM in ISCs were examined using QPCR and Western blotting. The chemical inhibitors of different signaling molecules were then used to determine their role in DFO-induced change in ISCs. RESULTS: The expression levels of Lgr5, HIF-1α, TLR4, MyD88, and TRIF in ISCs increased after DFO treatment, with peak expression of these molecules 6h after DFO treatment. In addition, DFO-induced gene expression of Lgr5 and HIF-1α was partially reversed by pretreatment with the inhibitor of TLR4 or MyD88, but not TRIF inhibitor. Inhibition of HIF-1α also resulted in partial downregulation of DFO-induced elevation of Lgr5 and TLR4. CONCLUSIONS: These results demonstrated that DFO treatment activated HIF-1α and the TLR4-MyD88 signaling pathway, which might mediate the activation of ISCs.
