ABSTRACT
Teprotumumab-trbw,a monoclonal antibody that acts on the insulin growth factor-Ⅰ receptor, was approved in 2020 for the treatment of thyroid-associated ophthalmopathy, but little is known about it in China. It is hoped to provide guidance for clinical use through the review of its molecular structure, pharmacokinetics, therapeutic mechanism, clinical research and safety. It inhibits immune inflammation by blocking thyroid-stimulating hormone receptor /insulin growth factor-Ⅰ receptor crosstalk signaling, so as to reduce the production of hyaluronic acid and inflammatory factors in response. It can also promote the apoptosis of retro-orbital fibroblasts/adipocytes and inhibit the expression of genes related to the synthesis of thyroid hormones, thereby significantly improving the clinical symptoms such as exophthalmos and diplopia. The common adverse reactions of Teprotumumab-trbw are muscle spasm, hyperglycemia, hearing loss and so on. Teprotumumab-trbw is effective and durable in the treatment of thyroid-associated ophthalmopathy, and patients with secondary treatment can also benefit from it, which provides a new way and hope for the treatment of thyroid-associated ophthalmopathy.
ABSTRACT
Objective@#To explore the effect of insulin-like growth factor-Ⅰ (IGF-Ⅰ) receptor on radiosensitivity of HepG2 cells and the underlying mechanism.@*Methods@#HepG2 cells were divided into the following groups: negative control group, siRNA group, irradiation group and combined group. HepG2 cells were transfected with IGF-Ⅰ receptor siRNA combined with irradiation therapy to investigate the effect on cell proliferation by methyl thiazolyl tetrazolium and cell cycle using flow cytometry. Expression of IGF-Ⅰ receptor, proliferating cell nuclear antigen (PCNA), cyclin-dependent kinases 1(CDK1) and Survivin were detected using Western blotting and Q-PCR.@*Results@#The expression of IGF-Ⅰ receptor in HepG2 cells was decreased significantly after siRNA transfection compared with the control group. After the combinational therapy, cell viability was decreased significantly according with control group [(1.02±0.08) vs. (1.08± 0.10) vs. (0.60±0.07)]; In addition, cell cycle was arrested in G2/M[(20.3±0.3)% vs. (22.6±0.4)% vs. (34.7±0.5)%] and CDK1 expression was reduced significantly. The relative expression of Survivin in siRNA group was lower than negative control group, the difference was statistically significant (P<0.05).@*Conclusion@#Inhibition of IGF-Ⅰ receptor can enhance the radiosensitivity of HepG2 cells through cell cycle arrest.
ABSTRACT
Objective To investigate the effect of subclinical hypothyroidism during pregnancy on hippocampus insulin-like growth factor Ⅰ (IGF-Ⅰ) signaling pathway in rat offspring.Methods A total of 60 female Wistar rats were evenly divided into control(CON),subclinical hypothyroidism(SCH),and clinical hypothyroidism (CH) groups.The hippocampus of progenies were collected on the postnatal day 3,postnatal day 7 to measure protein kinase B (Akt) and phosphorylated-Akt (p-Akt) by Western blot,IGF-Ⅰ and insulin-like growth factor Ⅰ receptor (IGF-Ⅰ R) by Elisa.Morris water maze and field excitatory postsynaptic potential long-term potentiation were measured at the postnatal 40 day.Results Western blot and Elisa revealed that levels of IGF-Ⅰ,IGF-Ⅰ R,and p-Akt of pups from SCH group were lower than that of CON group and were higher than CH group on day 3 (P ＜ 0.05).On day 7,the levels of IGF-Ⅰ,IGF Ⅰ R,and p-Akt of pups from SCH group were lower than CON group (P＜ 0.05),but no difference was observed in p-Akt and IGF-Ⅰ R level between SCH group and CH group (P ＞ 0.05).Latencies of all groups had shortened in Morris water maze test with increasing of training trials.The slope of field excitatory postsynaptic potenial was increased in all groups after Theta burst stimulation.The amplification percentage of slope of field excitatory postsynaptic potenial in SCH group's was lower than control group's but was higher than CH group's(all P values＜0.05).Conclusions Maternal subclinical hypothyroidism impairs long-term potentiation induction in hippocampus of rat might be associated with the levels of IGF-Ⅰ,IGF-Ⅰ R,and p-Akt.
ABSTRACT
Localization and expression of two subunits (IGF ⅠR? and IGF ⅠR?) of insulin like growth factor Ⅰ receptor and phosphorylated tyrosine proteins (P Tyr) in skins at different developmental stages were studied in order to explore their potential biological significance. Immunohistochemistry and pathological methods were used to detect the expression intensity and distribution of IGF ⅠR?, IGF ⅠR? and P Tyr in skins of 12 fetuses with different gestational ages and 8 adults. The results showed that positive immunohistochemical signals of IGF ⅠR?, IGF ⅠR? and P Tyr could be found in fetal and adult skins. Along with growth and development of the fetus, the positive cell rates of IGF ⅠR?, IGF ⅠR? and P Tyr in skins elevated progressively. In adult skins, IGF ⅠR was mainly located in the cell membrane of epidermal cells, while P Tyr was chiefly distributed in epidermal cells and some fibroblasts. These results suggested that IGF ⅠR and its mediating signaling pathway might be involved in cutaneous development at embryonic stage, in cutaneous structure and function maintenance, and in wound healing at postnatal stage.