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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.
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Objective:To evaluate the relationship between hippocampal miR-3065-5p and insulin-like growth factor-1/phosphatidylinositol 3-kinase/protein kinase B(IGF-1/PI3K/Akt)signaling pathway in a mouse model of perioperative neurocognitive disorder (PND).Methods:Eighty clean-grade healthy male C75BL/6 mice, aged 12-14 weeks, weighing 20-30 g, were divided them into 4 groups ( n=20 each) using the random number table method: control group (C group), PND group, miR-3065-5p agonist group (Ag group) and miR-3065-5p agonist negative control group (Ag-NC group). PND model was prepared by internal fixation of tibial fracture under anesthesia with 1.5% isoflurane. Two days before developing the model, miR-3065-5p agomir 2 μl was injected into the lateral ventricle in Ag group, miR-3065-5p agomir negative control 2 μl was injected into the lateral ventricle in Ag-NC group. Morris water maze test and open field test were performed at 7 days after surgery. The mice were sacrificed after the end of test, and hippocampal tissues were obtained for determination of the expression of miR-3065-5p, IGF-1 mRNA and Bcl-2 mRNA (by quantitative real-time polymerase chain reaction) and expression of IGF-1, phosphorylated Akt (p-Akt), phosphorylated glycogen synthase kinase-3β (p-GSK3β) and Bcl-2 (by Western blot). Results:There was no significant difference in each parameter in the open field test among the four groups ( P>0.05). Compared with group C, the postoperative escape latency was significantly prolonged, the percentage of time of stay at the target quadrant was decreased, the number of crossing the original platform was reduced, the expression of miR-3065-5p was up-regulated, and the expression of IGF-1 mRNA, Bcl-2 mRNA, IGF-1, p-Akt, p-GSK3β and Bcl-2 was down-regulated in the other three groups ( P<0.05). Compared with PND group and Ag-NC group, the postoperative escape latency was significantly prolonged, the percentage of time of stay at the target quadrant was decreased, the number of crossing the original platform was reduced, the expression of miR-3065-5p was up-regulated, and the expression of IGF-1 mRNA, Bcl-2 mRNA, IGF-1, p-Akt, p-GSK3β and Bcl-2 was down-regulated in Ag group ( P<0.05). Conclusions:Up-regulation of miR-3065-5p can inhibit the activation of IGF-1/PI3K/Akt signaling pathway, which might be one of the mechanisms of PND developed in mice.
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Objective:To investigate the correlation between serum insulin-like growth factor 1 (IGF-1), thyroid stimulating hormone (TSH), degree of insulin resistance and thyroid nodule imaging reporting and data system (TI-RADS) grading in patients with type 2 diabetes mellitus (T2DM).Methods:The clinical data of 120 patients with T2DM from February 2020 to November 2021 in Kunshan Hospital of Integrated Traditional Chinese and Western Medicine were retrospectively analyzed. Among them, 56 patients had no thyroid nodules (non-thyroid nodule group), all patients were TI-RADS grade 1; 64 patients had thyroid nodules (thyroid nodule group), including 7 cases of TI-RADS grade 2, 12 cases of TI-RADS grade 3, 20 cases of TI-RADS grade 4, and 25 cases of TI-RADS grade 5. The levels of IGF-1 and TSH were measured by automated biochemical analyzer, the homeostatic model assessment insulin resistance index (HOMA-IR) was calculated. Spearman method was used for correlation analysis; multivariate Logistic regression was used to analyze the independent risk factors of TI-RADS grading in patients with T2DM combined with thyroid nodules; the receiver operating characteristic (ROC) curve was drawn to analyze the efficacy of IGF-1, TSH and HOMA-IR in predicting TI-RADS grading in patients with T2DM combined with thyroid nodules.Results:The IGF-1, TSH and HOMA-IR in thyroid nodule group were significantly higher than those in non-thyroid nodule group: (185.35 ± 45.08) ng/L vs. (168.36 ± 30.25) ng/L, (2.98 ± 0.85) mU/L vs. (2.69 ± 0.35) mU/L and 3.25 ± 0.75 vs. 2.95 ± 0.44, and there were statistical differences ( P<0.05 or <0.01). In patients with T2DM combined with thyroid nodules, with the increase of TI-RADS classification, the IGF-1, TSH and HOMA-IR gradually increased, and there were statistical differences ( P<0.05). Spearman correlation analysis result showed that the levels of IGF-1, TSH and HOMA-IR were positive correlation with TI-RADS grading ( r = 0.918, 0.906 and 0.920; P<0.05). Multivariate Logistic regression analysis result showed that the IGF-1, TSH and HOMA-IR were independent risk factors for TI-RADS grading in patients with T2DM combined with thyroid nodule ( OR = 1.684, 1.044 and 1.851; 95% CI 0.674 to 6.665, 0.032 to 0.055 and 1.212 to 2.298; P<0.01 or <0.05). ROC curve analysis result show that the area under the curve of IGF-1, TSH and HOMA-IR for predicting the TI-RADS grading patients with T2DM combined with thyroid nodule were 0.946, 0.983 and 0.975, with all sensitivity of 100.00%, and specificity of 82.14%, 91.07% and 89.29%. Conclusions:There is a correlation between IGF-1, TSH, HOMA-IR and TI-RADS grading in patients with T2DM combined with thyroid nodule, which has some guiding value for clinical monitoring of thyroid nodule changes.
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With the progress of perinatal medicine, the survival rate of premature infants has been greatly improved, but the incidence of preterm related complications has also increased, including growth retardation, premature brain injury, retinopathy of prematurity, bronchopulmonary dysplasia and necrotizing enterocolitis.Insulin-like growth factor-1(IGF-1)specifically binds to IGF-1 receptor to activate intracellular signaling pathways, so that can promote cell growth, proliferation and differentiation, and inhibit apoptosis.IGF-1 is involved in the development of the heart, brain, lung, and other important organs and promotes tissue growth, so it plays an important role in fetal intrauterine development and neonatal extrauterine growth.At present, some clinical trials have found that recombinant IGF-1 and its binding protein-3 can play a role in the prevention and treatment of retinopathy of prematurity and bronchopulmonary dysplasia, bringing hope for the prevention and treatment of these refractory complications of prematurity.In this review, the function of IGF-1 and its role in preterm related complications are reviewed.
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Objective:To analyzed clinical characteristics of pituitary growth hormone(GH) adenomas patients with different responses to oral glucose inhibitory GH test.Methods:The clinical data of 50 patients with pituitary GH adenomas newly diagnosed with complete test data and case data in the Department of Endocrinology of Chinese PLA General Hospital was retrospectively analyzed from 2016 to 2021. The cases were divided into two groups according to the cutoff point of GH elevating to 50% of basaline during oral glucose test: abnormal elevation group(A group, n=16) and non-elevation group(B group, n=34). The clinical features, biochemistry, iconography, and immunohistochemistry of the two groups were analyzed. Results:The serum total cholesterol(TC)[(3.9±0.8) vs (4.6±0.9)mmol/L], 120 minutes insulin after glucose loading [11.2(4.4, 25.0) vs 92.0(10.8, 311.8)mU/L], long [1.0(0.4, 2.1) vs 1.5(0.5, 7.3) cm] and short[0.6(0.3, 1.3) vs 1.0(0.5, 5.8)cm] diameters of adenomas in A group were less than those in B group(all P<0.05) while insulin-like growth factor Ⅰ(IGF-Ⅰ) level was higher [(908.2±233.7) vs (743.1±273.1) ng/mL, P<0.05]. There were no significant differences in sex, age, disease course, clinical features, random GH, homeostasis model assessment of insulin resistance index(HOMA-IR), pituitary adenoma site, and invasive properties between the two groups. The immunohistochemical positive rates of ACTH(33% vs 0%) and prolactin(100% vs 28.6%)in A group were higher than those in B group( P<0.05). Conclusion:Pituitary GH adenomas patients with a paradoxical GH response pattern display lower serum TC and 120 minutes insulin levels as well as higher IGF-Ⅰ concentration and proportion of pituitary microadenomas. " Pure" growth hormone tumors may represent entities of a particular class of diseases in acromegaly.
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Objective:To investigate the effects of vagus nerve stimulation on postoperative cognitive dysfunction and the role of hippocampal insulin growth factor 1 signaling pathway in aged mice.Methods:Seventy-five clean-grade C57 mice of both sexes, aged 21-23 months, weighing 28-34 g, were divided into 5 groups ( n=15 each) using a random number table method: sham operation group (group S), operation group (group O), operation + vagus nerve stimulation group (group O+ V), operation + IGF-1 siRNA group (group O+ I) and operation + vagus nerve stimulation + IGF-1 siRNA group (group O+ V+ I). Group O underwent exploratory laparotomy.Group O+ V received a 30-min electrical stimulation of the vagus nerve (intensity 0.5 mA, frequency 20 Hz, time 30 s, 6 times, interval 5 min) after the end of exploratory laparotomy.Group O+ I underwent exploratory laparotomy and inhaled IGF-1 siRNA solution 10 μl intranasally at 24 h before surgery and 24 and 48 h after surgery.Group O+ V+ I underwent electrical vagus nerve stimulation after exploratory laparotomy and inhaled IGF-1 siRNA solution 10 μl intranasally at 24 h before surgery and 24 and 48 h after surgery.Morris water maze tests were performed on 14-18 days after operation.On day 7 after operation, the mice were sacrificed and the hippocampus was obtained for determination of the expression of Bax, ionized calcium-binding adapter molecule 1 (Iba-1), insulin-like growth factor 1 (IGF-1), insulin-like growth factor 1 receptor (IGF1R), phosphorylated IGF1R (p-IGF1R), interleukin-1beta (IL-1β) and activated caspase-3 by Western blot. Results:Compared with group S, the escape latency was significantly prolonged on days 16-18 after operation, the frequency of crossing the platform was reduced, the time spent in the target quadrant was shortened, the expression of IGF-1 and p-IGF1R was down-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was up-regulated in group O ( P<0.05). Compared with group O, the escape latency was significantly shortened on days 16-18 after operation, the frequency of crossing the platform was increased, the time spent in the target quadrant was prolonged, the expression of IGF-1 and p-IGF1R was up-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was down-regulated in group O+ V ( P<0.05), and no significant change was found in the parameters mentioned above in group O+ I ( P>0.05). Compared with group O+ V, the escape latency was significantly prolonged on days 16-18 after operation, the frequency of crossing the platform was reduced, the time spent in the target quadrant was shortened, the expression of IGF-1 and p-IGF1R was down-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was up-regulated in group O+ V+ I ( P<0.05). There was no significant difference in the expression of IGF1R among the four groups ( P>0.05). Conclusions:Vagus nerve stimulation can reduce postoperative cognitive dysfunction, and the mechanism is related to activation of IGF-1 signaling pathway and reduction of hippocampal neuroinflammation and neuronal apoptosis in aged mice.
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Objective:To evaluate the effect of intrathecal insulin-like growth factor-1 (IGF-1) on chemotherapy-induced neuropathic pain (NP) in mice.Methods:Forty clean-grade healthy male C57 mice, aged 7-9 weeks, weighing 22-24 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), chemotherapy-induced NP group (group CIPN), low-dose IGF-1 group (group I1) and high-dose IGF-1 group (group I2). In CIPN, I1 and I2 groups, oxaliplatin 5 mg/kg was intraperitoneally injected for 5 consecutive days to establish chemotherapy-induced NP model.Normal saline 0.2 ml was given in group C. After measurement of the pain threshold at 10 days after establishment of the model, IGF-1 0.5 and 1.0 μg were intrathecally injected in group I1 and group I2, respectively.Normal saline 5 μl was intrathecally injected in C and CINP groups.Mechanical withdrawal threshold (MWT) was measured at 3, 5, 8, 10, 11, 13 and 15 days after establishment of the model.After measurement of the pain threshold at 15 days after establishment of the model, the expression of spinal IGF-1, IGF-1receptor (IGF-1R), interleukin (IL)-17A, IL-1β and tumor necrosis factor (TNF)-α was detected, and IGF-1 positive cells were counted using immunofluorescence. Results:Compared with group C, MWT was significantly decreased, the expression of spinal IGF-1 was down-regulated, the count of IGF-1 positive cells was decreased, and expression of IL-17A, IL-1β and TNF-α was up-regulated at 3-25 days after establishment of the model in CINP, I1 and I2 groups ( P<0.05). Compared with group CIPN, MWT was significantly increased at 15 days after establishment of the model in group I1, and MWT was increased, the expression of spinal IGF-1 was up-regulated, the count of IGF-1 positive cells was increased, and expression of IL-17A, IL-1β and TNF-α was down-regulated at 13 and 15 days after establishment of the model in group I2 ( P<0.05). Compared with group I1, the count of IGF-1 positive cells in spinal dorsal horn was increased in group I2 ( P<0.05). There was no significant difference in the expression of spinal IGF-1R among the 4 groups ( P>0.05). Conclusion:Intrathecal IGF-1 can alleviate chemotherapy-induced NP, and the mechanism may be related to inhibiting the inflammatory responses in spinal cord of mice.
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Objective@#To explore effects of dendritic epidermal T cells (DETCs) and Vγ4 T lymphocytes on proliferation and differentiation of mice epidermal cells and the effects in wound healing of mice.@*Methods@#(1) Six C57BL/6 male mice aged 8 weeks were collected and divided into control group and wound group according to random number table (the same grouping method below), with 3 mice in each group. A 4 cm long straight excision with full-thickness skin defect was cut on back of each mouse in wound group, while mice in control group received no treatment. On post injury day (PID) 3, mice in 2 groups were sacrificed, and skin within 5 mm from the wound margin on back of mice in wound group and normal skin on corresponding part of mice in control group were collected to make single cell suspensions. The percentage of Vγ4 T lymphocyte expressing interleukin-17A (IL-17A) and percentage of DETCs expressing insulin-like growth factor Ⅰ (IGF-Ⅰ) were detected by flow cytometer. (2) Ten C57BL/6 male mice aged 8 weeks were collected and divided into control group and Vγ4 T lymphocyte depletion group with 5 mice in each group. Mice in Vγ4 T lymphocyte depletion group were injected with 200 g Vγ4 T lymphocyte monoclonal neutralizing antibody of Armenian hamster anti-mouse intraperitoneally, and mice in control group were injected with the same amount of Armenian hamster Ig intraperitoneally. One hole with full-thickness skin defect was made on each side of spine of back of each mice. The wound healing was observed on PID 1-8, and percentage of remaining wound area was calculated. (3) Six C57BL/6 male mice aged 8 weeks were grouped and treated in the same way as in experiment (2), with 3 mice in each group. On PID 3, expressions of IL-17A and IGF-Ⅰ in epidermis on margin of wound were detected with Western blotting. (4) Thirty C57BL/6 male mice aged 3 days were sacrificed, and epidermal cells were extracted. The keratin 14 positive cell rate was examined by flow cytometer (the same detecting method below). (5) Another batch of mouse epidermal cells were collected and divided into control group, IGF-Ⅰ group, and IL-17A group, with 3 wells in each group (the same well number below). Cells in IGF-Ⅰ group and IL-17A group were added with 1 mL recombinant mouse IGF-Ⅰ and IL-17A with final mass concentration of 100 ng/mL respectively, while cells in control group were added with the same amount of sterile phosphate buffered saline (PBS). On post culture day (PCD) 5, keratin 14 negative cell rate was examined. Another batch of mouse epidermal cells were collected, grouped, and treated in the same way as aforementioned experiment, and keratin 10 positive cell rate was examined on PCD 10. (6) Another batch of mouse epidermal cells were collected and added with 4 mmol/L 5(6)-carboxyfluorescein diacetate N-succinimidyl ester (CFSE) solution, and divided into control 0 d group, control 7 d group, IGF-Ⅰ group, and IL-17A group. Cells in IGF-Ⅰ group and IL-17A group were treated in the same way as the corresponding groups in experiment (5), and cells in control 0 d group and control 7 d group were treated in the same way as the control group in experiment (5). The CFSE fluorescence peaks were examined on PCD 0 of control 0 d group and PCD 7 of the other 3 groups. (7) Another batch of mouse epidermal cells were collected and divided into control group and IGF-Ⅰ group. Cells in IGF-Ⅰ group were added with 1 mL recombinant mouse IGF-Ⅰ with final mass concentration of 100 ng/mL, and cells in control group were added with the same amount of sterile PBS. On PCD 5, cells were underwent keratin 14 staining and CFSE staining as aforementioned, and keratin 14 negative cell rate of CFSE positive cells was examined. Another batch of mouse epidermal cells were collected and divided into control group and IL-17A group. Cells in IL-17A group were added with 1 mL recombinant mouse IL-17A with final mass concentration of 100 ng/mL, and cells in control group were added with the same amount of sterile PBS. On PCD 5, keratin 14 negative cell rate of CFSE positive cells was examined. Data were processed with one-way analysis of variance and t test.@*Results@#(1) On PID 3, percentage of DETC expressing IGF-Ⅰ in normal epidermis of control group was (9.9±0.8)%, significantly lower than (19.0±0.6)% of epidermis around margin of wound group (t=8.70, P<0.01); percentage of Vγ4 T lymphocyte expressing IL-17A in normal epidermis of control group was (0.123±0.024)%, significantly lower than (8.967±0.406)% of epidermis around margin of wound group (t=21.77, P<0.01). (2) On PID 1-4, there was obvious inflammatory reaction around wounds of mice in control group, and on PID 5-8, the wound area was still large. On PID 1-4, there was slight inflammatory reaction around wounds of mice in Vγ4 T lymphocyte depletion group, and on PID 5-8, the wound area was significantly reduced. On PID 3-7, percentages of residual wound area in Vγ4 T lymphocyte depletion group were significantly lower than those in control group (t=5.92, 5.74, 7.17, 5.38, 5.57, P<0.01), while percentages of residual wound area in two groups on PID 1, 2, 6 were similar (t=1.46, 3.17, 3.10, P>0.05). (3) On PID 3, compared with those in control group, expression of IL-17A and IGF-Ⅰ in epidermis around wound margin of mice in Vγ4 T lymphocyte depletion group was markedly decreased and increased respectively (t=8.47, 19.24, P<0.01). (4) The keratin 14 positive cell rate of mouse epidermal cells was 94.7%. (5) On PCD 5, the keratin 14 negative cell rate of mice in control group was markedly higher than that of IGF-Ⅰ group, while significantly lower than that of IL-17A group (t=7.25, 5.64, P<0.01). On PCD 10, the keratin 10 positive cell rate of mice in control group was significantly higher than that of IGF-Ⅰ group, while significantly lower than that of IL-17A group (t=3.99, 10.82, P<0.05 or P<0.01). (6) Compared with that of control 0 d group, CFSE fluorescence peaks of mouse epidermal cells in control 7 d group, IGF-Ⅰ group, and IL-17A group on PCD 7 shifted to the left. Compared with that of control 7 d group, CFSE fluorescence peaks of mouse epidermal cells in IGF-Ⅰ group and IL-17A group on PCD 7 shifted to the left. (7) On PCD 5, keratin 14 negative cell rate of CFSE positive cells of mice in control group was significantly higher than that in IGF-Ⅰ group (t=9.91, P<0.01), and keratin 14 negative cell rate of CFSE positive cells of mice in control group was markedly lower than that in IL-17A group (t=6.49, P<0.01).@*Conclusions@#In the process of wound healing, IGF-Ⅰ secreted by DETC can promote the proliferation of mouse keratin 14 positive epidermal cells and inhibit their terminal differentiation, while IL-17A secreted by Vγ4 T lymphocyte can promote the proliferation and terminal differentiation of mouse keratin 14 positive epidermal cells, thus both IGF-Ⅰ and IL-17A can affect wound healing.
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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.
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After binding to the specific insulin-like growth factor 1 receptor (IGF1R) on the surface of target tissue cells, IGF can regulate physiological processes such as apoptosis, proliferation and senescence, which are closely related to growth and development of the body, and occurrence and development of diseases. The binding between IGF1 and IGF1Rα can cause conformational changes of the beta subunit of IGF1R, lead to activation of receptor tyrosine kinase, initiation of the downstream phosphatidylinositol 3-kinase pathway and mitogen-activated protein kinase pathway, and finally participate in the occurrence of acne, psoriasis and other skin diseases. This review summarizes research advances in the role of the IGF1R signaling pathway in the pathogenesis of related skin diseases.
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Mter binding to the specific insulin-like growth factor 1 receptor (IGF1R) on the surface of target tissue cells,IGF can regulate physiological processes such as apoptosis,proliferation and senescence,which are closely related to growth and development of the body,and occurrence and development of diseases.The binding between IGF1 and IGF1Rα can cause conformational changes of the beta subunit of IGF1R,lead to activation of receptor tyrosine kinase,initiation of the downstream phosphatidylinositol 3-kinase pathway and mitogen-activated protein kinase pathway,and fina]ly participate in the occurrence of acne,psoriasis and other skin diseases.This review summarizes research advances in the role of the IGF1R signaling pathway in the pathogenesis of related skin diseases.
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Objective To evaluate the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) on insulin-like growth factor-Ⅰ (IGF-Ⅰ) and insulin-like growth factor-Ⅰ receptor (IGF-IR) expression after transcervical resection of polyp (TCRP).Methods 100 cases of endometrial polyps were selected.The control group (n =50) was treated with TCRP only,while the observation group (n =50) was treated with LNG-IUS after TCRP.The scores of pictorial blood loss assessment chart (PBCA),endometrial thickness,recurrence rate,mRNA expression of IGF-Ⅰ and IGF-IR in endometrial tissue were compared between the two groups.Results At 1,3,6,12 months follow-up,the PBAC score and endometrial thickness of observation group were significantly lower than control group (P ≤ 0.05).At 12 months after operation,the mRNA expression levels of IGF-Ⅰ and IGF-IR in the endometrium of the observation group were significantly lower than those of the control group (P ≤ 0.05).After 12 months of follow-up,the recurrence rates of the control group and the observation group were 16.0％ (8/50) and 4.0％ (2/50),respectively.The recurrence rate of the observation group was significantly lower than that of the control group (P ≤ 0.05).Conclusions TCRP combined with LNG-IUS treatment can significantly reduce EP recurrence,and down-regulation of the mRNA expression of IGF-Ⅰ and IGF-IR maybe its possible mechanism.
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Objective To detect the levels of serum micro RNA (miRNA) -29b and insulin growth factor-1 (IGF-1) in patients with type 2 diabetes mellitus (T2DM) and depression, and to analyze their clinical significance. Methods 504 patients with T2DM admitted to our hospital from February 2016 to February 2018 were selected, among them, 264 patients without depression, the other 240 patients with de-pression were selected as the study group, and 200 patients with physical examination were selected as the control group. Serum triglyceride (TG), cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol ( HDL), glycosylated hemoglobin ( HbA1c), fasting blood glucose ( FPG) were measured by automatic biochemical analyzer. Levels of serum IGF-1 were measured by auto-matic chemiluminescence instrument in all subjects. The expression of miR-29b in serum was detected by quantitative real-time polymerase chain reaction ( Qrt-PCR ) . All subjects were scored with 24 Hamilton Scales (HAMD). Results The serum TC, TG, LDL, FPG, HbA1c, and HAMD scores of patients with depression in T2DM were significantly higher than those of control group and patients with T2DM ( P <0. 05);the serum TC, TG, FPG, HbA1c of patients with T2DM were significantly higher than those of the control group (P<0. 05). The levels of serum miR-29b in patients with T2DM and depression were signifi-cantly lower than those in patients with T2DM and control group (P<0. 05), while the level of IGF-1 was significantly higher than that in patients with T2DM and in control group (P<0. 05); the level of serum miR-29b in patients with T2DM was significantly lower than that in control group (P<0. 05), while the level of IGF-1 was significantly higher than that in control group (P<0. 05). The levels of serum miR-29b in patients with severe depression and T2DM were significantly lower than those in patients with mild or moderate depression (P<0. 05), while the level of IGF-1 showed the opposite (P<0. 05). There was a significant negative correlation between serum miR-29b and IGF-1 level in patients with T2DM and depres-sion (P<0. 05). Logistic regression analysis showed that high levels of serum HbA1c (≥11. 06％) and IGF-1 (≥25. 74 ng/ml) were risk factors for depression in patients with T2DM, and high level of serum miR-29b (≥0. 39) was protective (P<0. 05). Conclusions The serum levels of IGF-1 increased and miR-29b decreased in patients with type 2 diabetes mellitus and depression. Serum levels of miR-29b were negatively correlated with the levels of IGF-1. High levels of IGF-1 were risk factors for depression in pa-tients with type 2 diabetes mellitus, and high levels of miR-29b were protective factors.
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@#Objective To investigate the protective effect of insulin-like growth factor-1 (IGF-1) on 6-hydroxy dopamine (6-OHDA) induced oxidative damage in PC-12 cells. Methods PC12 cells were treated with 6-OHDA (concentrations of 25, 50, 100, 150 and 200 μmol/L). In order to select the optimal experimental concentration and treatment time, the activity of PC12 cells was detected by MTT at different time points of 12 h, 24 h and 48 h after treatment. PC12 cells were divided into three groups: control group, 6-OHDA group and IGF-1+6-OHDA group. The activity of PC12 cells was detected by MTT assay. Reactive oxygen species (ROS) level of PC12 cells was detected by immunofluorescence staining, and apoptosis was detected by Hoechst33342 / PI double staining method. Results With the increased concentration and the prolongation of the action time of 6-OHDA, the activity of PC12 cells decreased gradually. The concentration of 150 μmol/L and action time of 24 h of 6-OHDA were selected as the optimal experimental concentration and observation time for this study. Compared with 6-OHDA group, the activity of PC12 cells increased, the expression level of ROS and the apoptosis decreased in IGF-1+6-OHDA group. Conclusion IGF-1 pretreatment can reduce 6-OHDA induced oxidative damage and apoptosis of PC12 cells, also can increase cell activity, which can provide a potential strategy for the prevention and treatment of Parkinson’s disease.
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To determine the associations between expressions of insulin-like growth factor-Ⅰ( IGF-Ⅰ), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) 165 in serum, and the occurrence and development of diabetic retinopathy ( DR). A total of 129 patients diagnosed as DM in our hospital between September 2015 and September 2017 were randomly selected in the study, including 58 cases single DM, diabetes with non-proliferative retinopathy group ( 45 cases) and diabetic proliferative retinopathy group ( 26 cases). Meanwhile, 110 healthy examinees during the same period were collected as a normal control group. The severity of retinopathy was judged by fundus photography and fundus fluorescein angiography. Blood glucose, BMI, HbA1C , TC, TG, HDL-C, LDL-C, and VLDL-C were detected in all subjects. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the serum concentrations of IGF-Ⅰ, TNF-α, and VEGF165. The expressions of serum IGF-Ⅰ, TNF-α, and VEGF in DM patients were significantly higher than those in the control group (all P<0.05). As diabetic retinopathy worsened, the expressions of serum IGF-Ⅰ, TNF-α, and VEGF increased. Pearson correlation analysis showed that serum IGF-Ⅰ was positively correlated with TNF-α, TNF-α, and VEGF165, IGF-Ⅰ, and VEGF165(P<0.05). Logistic regression analysis showed that IGF-Ⅰ and VEGF165 were risk factors for DR (OR = 1.059, 1.165, all P<0.05). The sensitivity, specificity and diagnostic accuracy of IGF-Ⅰ, TNF-α, and VEGF165 were higher than IGF-Ⅰ, TNF-α, and VEGF165 alone(AUC = 0.968, 0.928, 0.792, 0.893, all P<0.05). The expression level of IGF-Ⅰ, TNF-α, and VEGF165 in serum was related to the severity of diabetic retinopathy. The diagnosis of diabetic retinopathy with combined IGF-Ⅰ, TNF-α, and VEGF165 measurements was better than the single index of IGF-Ⅰ, TNF-α, and VEGF165.
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Objective To evaluate the effects of pretreatment with exogenous insulin-like growth factor-1 (IGF-1) on lung injury in rats undergoing cardiopulmonary bypass (CPB).Methods Seventy-two SPF healthy male Sprague-Dawley rats,weighing 350-500 g,were divided into 4 groups (n =18 each) using a random number table:sham operation group (group S),CPB group,CPB plus left lung ischemia-reperfusion group (group LI) and IGF-1 group.The chest was only opened,and the rats underwent no CPB in group S.Only the CPB model was established in group CPB.The model of left lung ischemia-reperfusion injury was established based on the CPB model in group LI.The model of CPB and left lung ischemia-reperfusion injury was established,and IGF-1 30 μg/kg was intravenously injected at 10 min before clamping the hilum of lung and immediately after opening the hilum of lung in group IGF-1.Six rats were selected before operation (T1),10 min after opening the left hilum (T2) and at the end of operation (T3),and blood samples were collected from the femoral artery for blood gas analysis.The oxygenation index (OI) and respiratory index (RI) were calculated.Serum was obtained from blood,and the concentrations of interleukin-6 (IL-6),IL-1β and tumor necrosis factor-alpha (TNF-α) in serum were measured using enzyme-linked immunosorbent assay.The left upper lung tissues were removed for examination of the pathological changes which were scored with a light microscope.Results Compared with the baseline at T1,OI was significantly decreased,and RI,concentrations of IL-6,IL-1β and TNF-α in serum and pathological scores of lung tissues were increased at T3 in CPB,LI and IGF-1 groups (P＜0.05).Compared with group S,OI was significantly decreased,and RI,concentrations of IL-6,IL-1β and TNF-α in serum and pathological scores of lung tissues were increased at T3 in CPB,LI and IGF-1 groups (P＜0.05).Compared with group CPB,OI was significantly decreased,and RI,concentrations of IL-6,IL-1β and TNF-α in serum and pathological scores of lung tissues were increased at T3 in group LI (P＜0.05).Compared with group LI,OI was significantly increased,RI,concentrations of IL-6 and IL-1β in serum and pathological scores of lung tissues were decreased at T3,and the concentration of serum TNF-α was increased at T3 in group IGF-1 (P＜0.05).Conclusion IGF-1 pretreatment can reduce lung injury in rats undergoing CPB,and the mechanism is related to inhibiting inflammatory responses.
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Objective To observe the effectiveness of long-acting octreotide in the treatment of acromegaly patients who did not achieve biochemical control after neurosurgery or gamma knife therapy of growth hormone-secreting pituitary adenoma. Methods Six acromegaly patients who received long-acting octreotide treatment regularly were included. Five patients had received prior trans-sphenoidal surgery and 1 patient had received prior gamma knife therapy before admission. All patients were admitted monthly for evaluation of pituitary-target gland function and octreotide therapy. Data of treatment with octreotide for 6 months were retrospectively summarized. Results Symptoms were reported to be alleviated. Two patients achieved biochemical control of the disease. Two patients had fasting growth hormone level less than 2.5 μg/L,but insulin-like growth factor-1(IGF-1)level was still higher than the age-adjusted normal range.Another 2 patients had decreased growth hormone and IGF-1 level, but both still higher than the normal range. Compared with baseline, IGF-1 level was decreased after treatment:(371.83 ± 217.46)μg/L vs.(713.33 ± 198.29)μg/L,and there was statistical difference (P = 0.017). There were no statistical differences in glycated hemoglobin and fasting plasma glucose before and after octreotide treatment (P > 0.05). Conclusions For acromegaly patients who do not achieve biochemical control after neurosurgery or gamma knife therapy, long-acting octreotide can effectively control IGF-1 level and increase the biochemical control rate of the disease.
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Objective To evaluate the effects of exogenous insulin like growth factor 1(IGF-1) on postoperative cognitive function in aged rats. Methods One hundred and twenty pathogen-free healthy male Sprague-Dawley rats, aged 18-20 months, weighing 500-600 g, were divided into 4 groups(n=30)using a random number table: control group(group C), sham operation group(group S), opera-tion group(group O)and exogenous IGF-1 group(group I). Splenectomy was performed, IGF-1 50 μg∕kg was subcutaneously injected at the same time point every day for 7 consecutive day starting from the end of surgery on the day of surgery in group I, and splenectomy was performed, and the equal volume of normal saline was given instead in group O. Morris water maze test was performed on 1, 3 and 7 days after surgery, and the escape latency and swimming distance were recorded. The rats were sacrificed after the end of Morris water maze test, and hippocampi were isolated for determination of the expression of amyloid-β(Aβ), amyloid precusor protein(APP)and β-secretase 1(BACE-1)using immunohistochemistry and Western blot methods. Results Compared with group C, the escape latency and swimming distance were significantly prolonged at 1, 3 and 7 days after surgery, and the expression of Aβ, BACE-1 and APP was up-regulated in O and I groups(P<005), and no significant change was found in the parameters mentioned above in group S(P>005). Compared with group O, the escape latency and swimming dis-tance were significantly shortened at 1, 3 and 7 days after surgery, and the expression of Aβ, BACE-1 and APP was down-regulated in group I(P<005). Conclusion Exogenous IGF-1 can improve postoperative cognitive function in aged rats.
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Objective To investigate the dynamic changes of serum insulin-like growth factor-1 (IGF-1) in acute traumatic brain injury (TBI) as well as their correlations with the initial severity of TBI and prognosis.Methods A total of 229 patients with acute TBI admitted from September 2014 to June 2016 were retrospectively studied.Patients were further classified as mild TBI group (GCS 13-15 points),moderate TBI group (GCS 9-12 points) and severe TBI group (GCS 3-8 points) according to Glasgow coma score (GCS).The control group consisted of 30 healthy subjects.The prognosis was evaluated by using Glasgow outcome scale (GOS) at 6 months after TBI.The IGF-1 levels were further tested at days 1,3,5,7 and 14 and their correlations with the initial GCS and GOS at 6 months after injury were evaluated.Results (1) The serum IGF-1 levels of mild,moderate and severe TBI group at all time points were significantly lower than those of the control group (P ＜ 0.05);the serum IGF-1 levels of severe and moderate TBI groups at all time points after injury were significantly lower than those of the mild TBI group (P ＜0.05);the serum IGF-1 levels of the severe group at days 1,3,5 and 7 d after injury were lower than those of the moderate TBI group (P＜0.05).(2) IGF-1 levels were significantly different between the two groups (P ＜ 0.05) at different time points during the follow-up of 6 months.(3)IGF-1 levels were positively correlated with both GCS and GOS at the acute stage of TBI and sub-acute stage following TBI (P ＜ 0.05).Conclusion The dynamic changes of serum IGF-1 levels in patients with acute TBI are related to both initial severity of TBI and the neurological outcomes and can be used as a reliable biomarker for early severity assessment and prognostic prediction of TBI.
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Objective To elucidate the function of phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway underlying the regulation of Na+-I-symporter (NIS) and the influence of different levels of iodine on PI3K-AKT signaling pathway in lactating breast cells.Methods The primary cultured mammary gland cells were divided into three groups:①control group [0 μmol/L LY294002 + 0 μg/L insulin-like growth factor Ⅰ (IGF-Ⅰ)];②stimulation group (50 μg/L IGF-Ⅰ);③inhibition group (40 μmo]/L LY294002 + 50 μg/L IGF-Ⅰ).In addition,the cells were treated with different iodine contents (0,5,50,1 000,3 000 μg/L) for low iodine groups 1 and 2,iodine group,high iodine groups 1 and 2,and IGF-Ⅰ (50 μg/L) was used to stimulate PI3K-AKT signaling pathway.The expressions of AKT and NIS mRNA and protein were determined by real-time quantitative PCR and Western blotting,respectively.Results The expression of AKT mRNA (1.497 ± 0.550) in stimulation group was higher than that in inhibition group (0.777 ± 0.108,P ＜ 0.05),while the expression of NIS mRNA and protein in stimulation group (0.783 ± 0.187,0.618 ± 0.103) was lower than those in inhibition group (2.430 ± 1.423,1.417 ± 0.250,all P ＜ 0.05).With the iodine concentration increasing,except high iodine group 1 (1.090 ± 0.356),the expression of AKT mRNA in low iodine groups 1 and 2,iodine group,high iodine group 2 (1.758 ± 0.893,1.320 ± 0.538,1.003 ± 0.006,0.745 ± 0.307) tended to decline;total AKT protein (0.640 ± 0.106,0.601 ± 0.081,0.583 ± 0.089,0.555 ± 0.097,0.532 ± 0.023) and NIS mRNA (2.259 ± 0.682,1.823 ± 0.332,1.409 ± 0.366,1.321 ± 0.405,1.150 ± 0.454) tended to decline in low iodine groups 1 and 2,iodine group,high iodine groups 1 and 2;except low iodine group 2 (0.484 ± 0.179),NIS protein expression tended to decline (0.556 ± 0.199,0.502 ± 0.179,0.455 ± 0.126,0.435 ± 0.138);however,except low iodine group 2 (0.076 ± 0.045),the p-AKT protein expressions (0.078 ± 0.049,0.079 ± 0.040,0.085 ± 0.055,0.095 ± 0.051) were on the rise.Conclusion PI3K-AKT signaling pathway may play an inhibition role in the expression of NIS in lactating breast cells.