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ObjectiveTo observe the effects of Hedysari Radix polysaccharide on the apoptosis of gastric sinus smooth muscle cells and explore the underlying mechanism via the insulin-like growth factor-1 （IGF-1）/phosphatidylinositol 3-kinase （PI3K）/serine-threonine kinase （Akt） pathway in the rat model of diabetic gastroparesis （DGP）. MethodSixty-two Wistar male rats were randomized into a blank group （n=12） and a modelling group （n=50）. The rat model of DGP was established by small-dose multiple intraperitoneal injections of streptozotocin combined with an irregular high-fat and high-sugar diet for 4 weeks. The modeled rats were randomized into model group， mosapride citrate （1.35 mg·kg-1）， and high-， medium-， and low-dose （200， 100， and 50 mg·kg-1， respectively） Hedysari Radix polysaccharide groups. The rats were administrated with corresponding drugs by gavage， and those in the blank and model groups with equal volumes of pure water by gavage once a day for 8 consecutive weeks. The random blood glucose and body mass were measured every 2 weeks， and gastric emptying rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of smooth muscle in gastric antrum， and terminal deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to detect the apoptosis of smooth muscle cells in the gastric antrum. The expression of IGF-1， phosphorylated （p）-PI3K， and p-Akt in the smooth muscle of gastric sinus tissue was detected by immunohistochemistry. Western blot was employed to determine the protein levels of IGF-1， p-PI3K/PI3K， p-Akt/Akt， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the smooth muscle of the gastric antrum. ResultCompared with the blank group， the model group showed elevated random blood glucose at all time points （P<0.01）， decreased body mass and gastric emptying rate （P<0.01）， increased apoptotic index of smooth muscle cells in the gastric antrum （P<0.01）， down-regulated protein levels of IGF-1， p-PI3K/PI3K， p-Akt/Akt， and Bcl-2， and up-regulated protein level of Bax （P<0.01）. Compared with the model group， the 8 weeks of drug administration lowered the random blood glucose， increased the body mass and gastric emptying rate （P<0.05， P<0.01）， decreased the apoptotic index of smooth muscle cells in the gastric antrum （P<0.05， P<0.01）， up-regulated the protein levels of IGF-1， p-PI3K/PI3K， p-Akt/Akt， and Bcl-2， and down-regulated the protein level of Bax （P<0.05， P<0.01）. Compared with the mosapride citrate group，the administration of low-dose Hedysari Radix polysaccharide for 6 and 8 weeks lowered the random blood glucose and decreased the body mass （P<0.05， P<0.01），low and medium-dose Hedysari Radix polysaccharide decreased the gastric emptying rate and the apoptotic index of smooth muscle cells in the astragaloside low-dose group decreased （P<0.05）. The protein levels of IGF-1，p-PI3K/PI3K，p-Akt/Akt and Bcl-2（low dose）were down-regulated and the protein level of Bax was up-regulated by low doses of Hedysari Radix polysaccharide （P<0.05， P<0.01）. Compared with high-dose Hedysari Radix polysaccharide， low-dose Hedysari Radix polysaccharide elevated random blood glucose and reduced body mass after 6 and 8 weeks of administration （P<0.05， P<0.01）， and the low and medium doses decreased the gastric emptying rate， increased the apoptotic index of smooth muscle cells in the gastric antrum （P<0.05， P<0.01）， down-regulated the protein levels of IGF-1， p-PI3K/PI3K， p-Akt/Akt， and Bcl-2， and up-regulated the protein level of Bax （P<0.05， P<0.01）. Compared with the medium-dose group，the low-dose group of Hedysari Radix polysaccharide had lower body mass，lower gastric emptying rate in rats，higher apoptotic index of smooth muscle cells in gastric sinus tissue after 6 and 8 weeks of administration （P<0.05， P<0.01）， and lower protein expression of IGF-1，p-PI3K/PI3K，p-Akt/Akt. ConclusionHedysari Radix polysaccharide protects the smooth muscle cells in gastric antrum against apoptotic injury and promotes gastric motility by activating the IGF-1/PI3K/Akt signaling pathway， as manifested by the up-regulated expression of IGF-1， p-PI3K， p-Akt， and Bcl-2 and down-regulated expression of Bax.
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Thyroid-associated ophthalmopathy(TAO)is an autoimmune disease associated with thyroid dysfunction that can significantly impact quality of life, result in visual impairment and facial disfigurement. Traditional treatments are often unsatisfactory. Studies have shown that teprotumumab, a human monoclonal antibody that can inhibit insulin-like growth factor 1 receptor(IGF-1R), has become an emerging targeted drug for TAO. Although the drug has proven to be effective and relatively safe in the treatment of TAO, adverse reactions are worthy of attention of ophthalmologists with the continuous promotion of clinical application, including hearing impairment, hyperglycemia, diarrhea, muscle spasms, infusion reactions, cognitive decline, thyroid suppression, alopecia, nausea and fatigue. Teprotumumab was generally well tolerated, with most adverse events being mild or moderate in severity. This paper aims to review the adverse reactions and precautions of teprotumumab in the treatment of TAO.
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@#Type 2 diabetes mellitus(T2DM)was a chronic,non-communicable disease with a combination of multiple genetic and environmental factors,of which the main characteristics included insufficient insulin secretion and insulin resistance.Insulin-like growth factor 2 mRNA binding protein 2(IGF2BP2/IMP2),an important insulin secretion-related protein in human body,is mainly expressed in tissues and cells such as pancreas,fat and intestine.It has been confirmed that IGF2BP2 can down-regulate the expression of IGF2 and the function damage of the related islet β cell is an important cause of T2DM and vascular complications.Therefore,IGF2BP2 gene can be used as an important predictor for diabetes mellitus risk.This paper reviews the correlation between IGF2BP2 gene and T2DM.
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ObjectiveTo investigate the inhibitory effects and mechanism of the compound Phyllanthus urinaria Ⅱ （CPU Ⅱ）on the growth of transplanted hepatocellular carcinoma Hep3B2.1-7 （Short for Hep3R） cells in nude mice. MethodAfter the establishment of a xenograft model of hepatocellular carcinoma Hep3B cells in mice， the model mice were randomly divided into a model group， a high-dose CPU Ⅱ group （57.5 g·kg-1）， a low-dose CPU Ⅱ group （28.75 g·kg-1）， and a 5-fluorouracil （5-FU） group （0.025 g·kg-1）， with eight mice in each group. The mice in the high- and low-dose CPU Ⅱ groups were treated with drugs by gavage， once per day， and those in the model group were treated with the same volume of normal saline. The mice in the 5-FU group were treated by 5-FU by intraperitoneal injection， once every other day. After 28 days of administration， mice were sacrificed， and transplanted tumors were collected. Immunohistochemistry （IHC） was used to detect the expression of proliferating cell nuclear antigen （PCNA） of tumor tissues. Terminal-deoxynucleotidyl transferase-mediated nick end labeling （TUNEL） was used to detect cell apoptosis of tumor tissues. The mRNA expression of miR-122 and insulin-like growth factor 1 receptor （IGF-1R） in tumor tissues was detected by Real-time quantitative PCR （Real-time PCR）. The protein expression of CCAAT/enhancer-binding protein α （C/EBPα）， hepatocyte nuclear factor-4α （HNF-4α）， and IGF-1R in tumor tissues was detected by Western blot. ResultThe tumor suppression rates of the high- and low-dose CPU Ⅱ groups and the 5-FU group were 74.90%， 63.62%， and 64.15%， respectively. Compared with the model group， the CPU Ⅱ groups and the 5-FU group showed reduced weight （P<0.01） and volume of tumors （P<0.01）， decreased PCNA positive cells， shallow staining， increased apoptosis cells of transplanted tumor tissues （P<0.05， P<0.01）， increased expression of mRNA expression of miR-122 （P<0.01）， down-regulated mRNA expression of IGF-1R （P<0.01）， and up-regulated protein expression of C/EBPα and HNF-4α in nude mouse transplanted tumor tissues （P<0.01）. The expression of IGF-1R protein in the high-dose CPU Ⅱ group was down-regulated （P<0.05）. Compared with the low-dose CPU Ⅱ group， the high-dose CPU Ⅱ group showed increased apoptotic cells （P<0.01）， up-regulated mRNA expression of miR-122 （P<0.01）， and increased expression of C/EBPα and HNF-4α proteins （P<0.01）. ConclusionCPU Ⅱ has an obvious inhibitory effect on the growth of transplanted hepatocellular carcinoma Hep3B cells in nude mice. The mechanism of action is related to enhancing the expression of transcription factors HNF-4α and C/EBPα， thereby promoting the expression of miR-122 and inhibiting the expression of its target gene IGF-1R.
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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 role of a disintegrin and metalloprotease 12 (ADAM12) gene in chondrocyte injury in patients with Kashin-Beck disease (KBD) and its impact on genes related to insulin-like growth factor binding protein (IGFBP).Methods:Articular cartilage samples were obtained from 5 patients with KBD and 5 control subjects admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University. Chondrocytes were extracted and cultured in vitro. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to detect the expression levels of ADAM12 mRNA and protein in chondrocytes of patients with KBD and control subjects, respectively. Subsequently, ADAM12 gene overexpression was performed using lentivirus in chondrocytes of patients with KBD. MTT assay was used to detect changes in cell viability after ADAM12 gene overexpression, and qRT-PCR was used to detect the mRNA expression levels of chondrocyte differentiation related genes SRY-box transcription factor 9 (SOX9) and type Ⅱ collagen (COLⅡ), apoptosis-related gene B-cell lymphoma/leukaemia-2-associated X protein (BAX), and anabolic related genes IGFBP3 and IGFBP5. Results:The expression levels of ADAM12 mRNA and protein in chondrocytes of patients with KBD (0.57 ± 0.05, 0.81 ± 0.07) were significantly lower than those of control subjects (1.00 ± 0.00, 1.00 ± 0.00), and the differences were statistically significant ( t = - 24.50, - 3.61, P < 0.05). The results of MTT assay showed that the cell viability of chondrocytes in ADAM12 overexpression group (1.09 ± 0.05) was higher than that in empty vector control group (1.00 ± 0.08), and the difference was statistically significant ( t = 4.12, P = 0.031). The results of qRT-PCR showed that compared with empty vector control group, the mRNA expression levels of IGFBP3 (2.35 ± 0.79 vs 0.96 ± 0.25), IGFBP5 (2.13 ± 0.30 vs 0.98 ± 0.34), SOX9 (2.92 ± 0.51 vs 0.94 ± 0.36) and COLⅡ (6.45 ± 2.81 vs 0.87 ± 0.19) in ADAM12 overexpression group were significantly increased, and the differences were statistically significant ( t = 3.19, 5.16, 6.27, 4.10, P < 0.05); while the expression level of BAX mRNA (0.31 ± 0.06 vs 1.02 ± 0.22) was significantly decreased, and the difference was statistically significant ( t = - 11.16, P < 0.001). Conclusion:The ADAM12 gene may have a role in inhibiting apoptosis and promoting differentiation in chondrocyte injury in patients with KBD, and its overexpression can increase expression of IGFBP3 and IGFBP5.
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The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is an essential component of the hypothalamic-pituitary growth hormone axis and plays a crucial role in childhood growth and development. Disruptions and abnormalities in the GH/IGF-1 signaling pathway and its pathways typically manifest as short stature in children. Children with short stature often undergo GH stimulation testing and IGF-1 level measurements to differentiate growth hormone deficiency (GHD) from other causes of growth delay. This article aims to analyze and elucidate the values of GH stimulation testing and IGF-1 measurement, providing reference for the diagnosis of GHD in children.
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Niño , Humanos , Hormona del Crecimiento/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Péptidos Similares a la Insulina , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Hormona de Crecimiento Humana/metabolismo , Enanismo Hipofisario/diagnósticoRESUMEN
OBJECTIVES@#To investigate the changes in the serum levels of Klotho, fibroblast growth factor 23 (FGF23), and insulin-like growth factor-1 (IGF-1) in children with idiopathic short stature (ISS) before and after recombinant human growth hormone (rhGH) treatment, as well as the correlation of Klotho and FGF23 with the growth hormone (GH)/IGF-1 growth axis in these children.@*METHODS@#A prospective study was conducted on 33 children who were diagnosed with ISS in the Department of Pediatrics, Hebei Provincial People's Hospital, from March 10, 2021 to December 1, 2022 (ISS group). Twenty-nine healthy children, matched for age and sex, who attended the Department of Child Healthcare during the same period, were enrolled as the healthy control group. The children in the ISS group were treated with rhGH, and the serum levels of Klotho, FGF23, and IGF-1 were measured before treatment and after 3, 6, and 9 months of treatment. A correlation analysis was conducted on these indexes.@*RESULTS@#There were no significant differences in the serum levels of IGF-1, Klotho, and FGF23 between the ISS and healthy control groups (P>0.05). The serum levels of Klotho, FGF23, and IGF-1 increased significantly in the ISS group after 3, 6, and 9 months of rhGH treatment (P<0.05). In the ISS group, Klotho and FGF23 levels were positively correlated with the phosphate level before treatment (P<0.05). Before treatment and after 3, 6, and 9 months of rhGH treatment, the Klotho level was positively correlated with the IGF-1 level (P<0.05), the FGF23 level was positively correlated with the IGF-1 level (P<0.05), and the Klotho level was positively correlated with the FGF23 level (P<0.05), while Klotho and FGF23 levels were not correlated with the height standard deviation of point (P>0.05).@*CONCLUSIONS@#The rhGH treatment can upregulate the levels of Klotho, FGF23, and IGF-1 and realize the catch-up growth in children with ISS. Klotho and FGF23 may not directly promote the linear growth of children with ISS, but may have indirect effects through the pathways such as IGF-1 and phosphate metabolism. The consistent changes in Klotho, FGF23 and IGF-1 levels show that there is a synergistic relationship among them in regulating the linear growth of ISS children.
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Niño , Humanos , Hormona de Crecimiento Humana/farmacología , Factor I del Crecimiento Similar a la Insulina/farmacología , Factor-23 de Crecimiento de Fibroblastos , Estudios Prospectivos , Trastornos del Crecimiento , Fosfatos/farmacología , EstaturaRESUMEN
OBJECTIVES@#To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions.@*METHODS@#A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups.@*RESULTS@#After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05).@*CONCLUSIONS@#In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.
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Niño , Femenino , Humanos , Embarazo , Estatura , Hormona de Crecimiento Humana/uso terapéutico , Hiperplasia , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina , Estudios Prospectivos , Hipófisis/patología , Proteínas Recombinantes/uso terapéuticoRESUMEN
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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ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg-1·d-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg-1·d-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.
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Abstract Objective: To determine the prevalence of vitamin A deficiency (VAD) and serum concentrations of retinol, correlating them with IGF-1 concentrations in preschoolers with DS. Methods: Cross-sectional study was conducted on 47 children with DS aged 24 to 72 months, in Ribeirão Preto, Brazil. VAD was determined by the relative dose-response (RDR) test. Retinol serum concentration ≤ 0.70 μmol/L and IGF-1 serum concentration below the 3rd percentile for sex and age were considered to represent deficiency. C-reactive protein (CRP) was determined at the beginning of the study. Weight, height, and information about fever and/or diarrhea were obtained at the beginning of the study. Results: VAD prevalence was 25.5% (12/47), and 74.5% (35/47) of the children had deficient retinol before the intervention. CRP was not associated with VAD. Mean IGF-1 were 103.5 ng/mL (SD = 913) for the group with VAD and 116.3 ng/mL (SD = 54.9) for the group with no VAD (p-value = 0.85); 8.5% (4/47) of the children showed deficient IGF-1, but without VAD. No association was observed between VAD and IGF-1 deficiency. A moderate positive correlation was observed between pre-intervention retinol and IGF-1 (ρ = 0.37; p-value = 0.01). Conclusion: a high prevalence of VAD and deficient retinol was observed and there was a positive correlation between serum retinol and IGF-1.
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Humanos , Preescolar , Niño , Deficiencia de Vitamina A/epidemiología , Factor I del Crecimiento Similar a la Insulina/análisis , Síndrome de Down , Vitamina A , Brasil/epidemiología , Prevalencia , Estudios TransversalesRESUMEN
Introdução: a hiperplasia adenotonsilar (HAT) é uma das causas mais comuns da Síndrome do Respirador Oral (SRO) devido à obstrução de via aérea superior em crianças e adolescentes. Tal afecção pode causar alterações ortodônticas, miofuncionais orofaciais, posturais, cardiopulmonares, antropométricas e polissonográficas. O diagnóstico precoce e indicação de Adenotonsilectomia (A&T) é essencial para reversão dessas consequências deletérias da SRO e restauração do bem estar biopsicossocial da criança.Objetivo: avaliar o estado nutricional, patência nasal, distúrbios do sono e fator de crescimento semelhante à insulina tipo 1 (IGF-1) em crianças de dois a doze anos de idade com SRO devido HAT grave e comparar com a reavaliação após seis meses de pós-cirúrgico das crianças operadas e com as demais que permanecem com obstrução da via aérea e aguardam a cirurgia na fila de espera do Sistema Único de Saúde. Métodos: trinta pacientes com SRO por HAT grave e indicação de A&T foram submetidos à avaliação antropométrica, polissonográfica, dosagem do IGF-1, rinomanométrica, teste alérgico cutâneo, questionário de padrão alimentar e prática de atividade física antes da A&T. Dez pacientes repetiram essa avaliação seis meses após o procedimento cirúrgico (grupo intervenção). Vinte pacientes aguardam a cirurgia na fila de espera do SUS e tiveram seus dados antropométricos e de IGF-1 reavaliados após seis meses com obstrução da via aérea (grupo controle). Resultados: trinta crianças realizaram a fase pré-operatória do estudo. A idade média foi de 5,6 anos (±2,17). Dezessete (56,7%) eram do sexo masculino e treze (43,3%) do sexo feminino. O teste cutâneo foi positivo em dezesseis indivíduos (53,3%) As médias dos escores Z de estatura por idade foi de -0,95 (±1,09); peso por idade de 0,17 (±1,42); índice de massa corporal (IMC) por idade de 0,31 (±1,36). A média do fluxo nasal inspiratório total (FNIT) foi de 444,63 ml/s (±161,02) e da patência nasal de 72,9% (±24,76). A média do índice de Apneia e Hipopneia (IAH) do sono foi de 4,95 ev/h (±4,07); da saturação mínima de oxihemoglobina no sono (Nadir de O2) de 78,93% (±6,00); da percentagem de sono com saturação menor que 90% (T90) de 4,16% (±5,48); da porcentagem do sono com ondas lentas (sono N3) de 37,62% (±9,61). A média do escore Z de IGF-1 foi de 0,72 (±1,30). O grupo intervenção e grupo controle não apresentaram alterações dos dados antropométricos com significância estatística. Houve diminuição do IGF-1 após a cirurgia sendo a média do escore Z de IGF-1 pré-operatório de 1,33 (±1,74) e pós-cirúrgico de -0,07 (±0,85); p=0,03. No grupo controle a variação do IGF-1 não foi significativa. O grupo intervenção não apresentou alteração com significância estatística do FNIT e da patência nasal. Nas dez crianças operadas foi constatada uma melhora da média do IAH de 5,25 ev/h (±4,29) para 1,99 ev/h (±1,16) e do T90 de 6,27% (±7,46) para 0,64% (±0,55) com p<0,05. Já o sono N3 e o Nadir de O2 não apresentaram alterações significativas. Não houve mudança qualitativa no padrão alimentar e na prática de atividade física nos dois períodos avaliados na vigência da pandemia de COVID19. Conclusão: Após A&T houve diminuição do IGF-1; p=0,03, melhora do IAH; p=0,03 e do T90; p=0,04. A cirurgia não modificou o estado nutricional com significância estatística nas dez crianças após 6 meses de pós-operatório. No pós-cirúrgico, não houve diferença estatística do FNIT e da patência nasal, assim como nessa amostra também não ocorreram alterações significativas do sono N3 e do Nadir de O2. O padrão alimentar e a prática de atividade física foram semelhantes qualitativamente no pré e no pós-operatório. Vinte crianças no grupo controle não tiveram alterações significativas dos dados antropométricos e do IGF-1 com seis meses de espera pela cirurgia e permanência da obstrução da via aérea. Não houve diferença estatística dos dados antropométricos e do IGF-1 entre o grupo controle e o grupo intervenção.
Introduction: adenotonsillar hyperplasia (ATH) is one of the most common causes of Mouth Breathing Syndrome (MBS) due to upper airway obstruction in children and adolescents. This condition can cause orthodontic, orofacial myofunctional, postural, cardiopulmonary, anthropometric and polysomnographic changes. Early diagnosis and indication of Adenotonsillectomy (T&A) is essential to revert these deleterious consequences of MBS and restore the child's biopsychosocial well-being. Objective: to evaluate the nutritional status, nasal patency, sleep disorders and insulin-like growth factor 1 (IGF-1) in children aged two to twelve years old with MBS due to severe ATH and compare with reassessment after six months post-surgical care of operated children and others who remain with airway obstruction and are waiting for surgery on the Unified Health System (UHS) waiting list. Methods: Thirty patients with MBS due to severe ATH and indication for T&A were submitted to anthropometric, polysomnographic, IGF-1 dosage, rhinomanometric, allergic skin test, dietary pattern questionnaire and physical activity practice before T&A. Ten patients repeated this evaluation six months after the surgical procedure (intervention group). Twenty patients were waiting for surgery on the UHS waiting list and had their anthropometric and IGF-1 data reassessed after six months with airway obstruction (control group). Results: Thirty children underwent the preoperative phase of the study. The mean age was 5.6 years (±2.17). Seventeen (56.7%) were male and thirteen (43.3%) were female. The skin test was positive in sixteen individuals (53.3%) The average Z-scores for height for age were -0.95 (±1.09); weight for age 0.17 (±1.42); body mass index (BMI) for age of 0.31 (±1.36). The mean total inspiratory nasal flow (TINF) was 444.63 ml/s (±161.02) and nasal patency was 72.9% (±24.76). The average sleep apnea and hypopnea index (AHI) was 4.95 ev/h (±4.07); minimum oxyhemoglobin saturation during sleep (O2 Nadir) of 78.93% (±6.00); percentage of sleep with saturation lower than 90% (T90) of 4.16% (±5.48); percentage of sleep with slow waves (N3) of 37.62% (±9.61). The mean IGF-1 Z-score was 0.72 (±1.30). The intervention group and control group did not show statistically significant changes in anthropometric data. There was a decrease in IGF-1 after surgery, with a mean preoperative IGF-1 Z-score of 1.33 (±1.74) and postoperative value of -0.07 (±0.85); p=0.03. In the control group, the IGF-1 variation was not significant. The intervention group did not show statistically significant changes in TINF and nasal patency. In the ten operated children, an improvement in the mean AHI from 5.25 ev/h (±4.29) to 1.99 ev/h (±1.16) and T90 of 6.27% (±7. 46) to 0.64% (±0.55) with p<0.05. On the other hand, N3 sleep and O2 Nadir showed no significant changes. There was no qualitative change in dietary patterns and physical activity in the two periods evaluated during the COVID19 pandemic. Conclusion: After T&A there was a decrease in IGF-1; p=0.03, AHI improvement; p=0.03 and T90 too; p=0.04. The surgery did not change the nutritional status with statistical significance in the ten children after 6 months postoperatively. Post-surgery, there was no statistical difference in TINF and nasal patency, as well as in this sample there were no significant changes in N3 sleep and O2 Nadir either. The dietary pattern and the practice of physical activity were qualitatively similar before and after the operation. Twenty children in the control group did not have significant alterations in anthropometric data and IGF-1 after six months of waiting for the surgery and the remaining airway obstruction. There was no statistical difference in anthropometric and IGF-1 data between the control and intervention groups.
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Tonsilectomía , Adenoidectomía , Insuficiencia de Crecimiento , Respiración por la Boca , Trastornos del Sueño-Vigilia , Niño , Estado Nutricional , Polisomnografía , Tesis Académica , RinomanometríaRESUMEN
Objective:To determine whether or not shock wave therapy promotes the repair of muscle injury by regulating insulin-like growth factor-1 (IGF-1) and/or the phosphorylation of protein kinase B (p-Akt).Methods:Sixty-six adult male Sprague-Dawley rats were randomly divided into a normal group, a model group and a treatment group. A custom-made striker was used to induce blunt contusion in the gastrocnemius muscles of the rats of the model and treatment groups. The normal and model groups were then not given any therapeutic intervention. Twenty-four hours later, the treatment group underwent 500-impulse shockwave treatment at 0.14mJ/mm 2 and 10Hz. That was repeated 4 days later. The injured muscle was sampled on the 1st, 3rd, 5th, and 7th day after modeling. Hematoxylin and eosin staining was applied to observe the arrangement of muscle fibers, and the expressions of myostatin, myogenic differentiation antigen 1 (MYOD1), IGF-1 and p-AKTs473 were detected by immunohistochemistry and western blotting. Results:(1) The staining showed that in the model group the space between the muscle cells was larger than in the normal group. In the treatment group there were more newly-formed mononuclear or multinucleated muscle tubes. The regeneration of skeletal muscle in the treatment group was superior to that in the model group at the same time points. (2) The average myostatin expression of the model group increased significantly compared with the normal group at all the time points, while that of the treatment group had decreased significantly compared with the model group. Moreover, no significant differences were found on the 7th day between the treatment and normal groups. (3) Western blotting showed that the expression of MyoD1 in the model group was significantly higher than that in the normal group on days 1 and 3, and the expression of MyoD1 in the treatment group was significantly higher than in the model group. The expression levels of IGF-1 and P-AKTS473 in the model group were higher than those in the normal group at the same time point, and the expression levels in the treatment group were significantly higher than those in the model group.Conclusion:Extracorporeal shock wave therapy can promote the regeneration and repair of skeletal muscle by regulating IGF-1 and p-AKT levels.
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Objective:To investigate the effect of milk on sebum secretion in golden hamsters, and to explore its possible mechanism of action.Methods:Eighteen golden hamsters were randomly and equally divided into 3 groups: blank control group receiving no intervention, whole-milk group gavaged with whole milk, and skimmed-milk group gavaged with skimmed milk. The gavage feeding was performed at a dose of 2.5 ml twice a day for 4 consecutive weeks. The maximum transverse diameter and maximum longitudinal diameter of bilateral sebaceous gland spots were measured on days 0, 7, 14, 21 and 28 after the start of intervention, and the area of sebaceous gland spots was calculated; at 24 hours after the last gavage, bilateral sebaceous gland spot tissues were resected, and subjected to immunohistochemical study to determine the expression of insulin-like growth factor-1 (IGF-1) /sterol regulatory element-binding protein-1 (SREBP-1) /acetyl-coenzyme A carboxylase (ACC-1) signaling pathway in sebaceous gland spots. Statistical analysis was carried out by using repeated measures analysis of variance, one-way analysis of variance for independent groups, Kruskal-Wallis H test, and least significant difference- t test for multiple comparisons. Results:Repeated measures analysis of variance showed that there was no significant difference in the area of sebaceous gland spots of golden hamsters among the 3 groups ( F= 0.96, P= 0.417) . The IGF-1 expression was significantly higher in the skimmed-milk group (0.39 ± 0.03) than in the blank control group (0.35 ± 0.03, t= 2.62, P= 0.021) and whole-milk group (0.33 ± 0.02, t= 3.82, P= 0.002) ; compared with the blank control group (0.36 ± 0.02) , the skimmed-milk group showed significantly increased SREBP-1 expression (0.42 ± 0.04, t= 2.64, P= 0.021) ; the ACC-1 expression was significantly higher in the skimmed-milk group (0.40 ± 0.03) and whole-milk group (0.40 ± 0.05) than in the blank control group (0.34 ± 0.03; t= 2.39, 2.47, P= 0.031, 0.026, respectively) . Conclusion:Milk may promote sebum secretion in golden hamsters through the IGF-1/SREBP-1/ACC-1 signaling pathway.
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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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Sepsis is an important cause of acute kidney injury (AKI). About 60% of sepsis patients will develop AKI. At present, the standard of clinical diagnosis of AKI is still based on the changes in serum creatinine and urine volume. Because of its lag in time, it may lead to delay in treatment and increase the mortality. To find a new biomarker similar to "troponin" for the diagnosis of AKI, and to achieve the early diagnosis and prevention of AKI, is of great significance to reduce the mortality of AKI. In recent years, it has been found that tissue inhibitors of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) can be used for early diagnosis of sepsis associated-acute kidney injury (SA-AKI). They also have important values in risk stratification, prognosis judgment, intervention and other aspects of SA-AKI. In this paper, the research progress of the application of TIMP-2 and IGFBP7 in SA-AKI is reviewed.
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Objective:To investigate the serum level of insulin-like growth factor binding protein 7 (IGFBP7) in patients with gastric cancer and its diagnostic significance.Methods:A total of 100 gastric cancer patients (gastric cancer group) including 49 patients with early gastric cancer (early gastric cancer group) , who were hospitalized in Sun Yat-sen University Cancer Center from May to December 2019 were selected as the research subjects, and 94 physical examination subjects during the same period were selected as the normal control group. The levels of serum IGFBP7 were detected by enzyme-linked immunosorbent assay. At the same time, the laboratory carcinoembryonic antigen (CEA) test results were collected. The relationships between the level of serum IGFBP7 and the clinicopathological features of gastric cancer patients were analyzed. The diagnostic value was evaluated by receiver operating characteristic (ROC) curve.Results:The level of serum IGFBP7 in the gastric cancer group was (1.595±0.159) ng/ml, and that in the normal control group was (1.850±0.328) ng/ml, with a statistically significant difference ( t=-0.26, P<0.001) , and among them, the level of serum IGFBP7 in the early gastric cancer group was (1.601±0.153) ng/ml, and there was a statistically significant difference compared with the normal control group ( t=-0.26, P<0.001) . The level of serum CEA in the gastric cancer group was 2.230 (2.043) ng/ml, and that in the normal control group was 1.805 (1.020) ng/ml, with a statistically significant difference ( U=0.45, P=0.004) , and among them, the level of serum CEA in the early gastric cancer group was 2.220 (1.780) ng/ml, and there was a statistically significant difference compared with the normal control group ( U=0.53, P=0.002) . There were no significant correlations between IGFBP7 and CEA level ( χ2=0.36, P=0.547) , age ( χ2=0.16, P=0.688) , gender ( χ2=0.97, P=0.326) , depth of invasion ( χ2=0.30, P=0.585) , lymph node metastasis ( χ2=0.17, P=0.684) , distant metastasis ( χ2=0.09, P=0.767) and TNM stage ( χ2=0.38, P=0.537) . ROC curve analysis showed that the area under the curve (AUC) of IGFBP7 for gastric cancer diagnosis was 0.84 (95% CI: 0.78-0.89) , the AUC of CEA for gastric cancer diagnosis was 0.62 (95% CI: 0.54-0.70) , and there was a statistically significant difference ( Z=4.33, P<0.001) . The AUC of IGFBP7 combined with CEA for gastric cancer diagnosis was 0.85 (95% CI: 0.79-0.90) . Compared with CEA alone, there was a statistically significant difference ( Z=4.97, P<0.001) . Compared with IGFBP7 alone, there was no statistically significant difference ( Z=1.41, P=0.159) . The AUC of IGFBP7 in the diagnosis of early gastric cancer was 0.84 (95% CI: 0.78-0.91) , the AUC of CEA in the diagnosis of early gastric cancer was 0.66 (95% CI: 0.56-0.75) , and there was a statistically significant difference ( Z=3.11, P=0.002) . The AUC of IGFBP7 combined with CEA in the diagnosis of early gastric cancer was 0.85 (95% CI: 0.78-0.91) . Compared with CEA alone, there was a statistically significant difference ( Z=3.54, P<0.001) . Compared with IGFBP7 alone, there was no statistically significant difference ( Z=1.19, P=0.232) . Conclusion:The serum IGFBP7 level of gastric cancer patients is lower than that of normal controls. Compared with CEA, serum IGFBP7 has better diagnostic value for gastric cancer.
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Glucagon⁃like peptide⁃2 (GLP⁃2) is a peptide hormone secreted by L cells in the gut. GLP⁃2 plays an important role in anti⁃inflammation, promoting proliferation and repair, and promoting nutrient absorption through various signaling pathways in the gastrointestinal tract. Long ⁃ acting analogs of GLP ⁃ 2 have been used in the treatment of short bowel syndrome and Crohn’s disease, but using GLP⁃2 also has the risk of promoting tumorigenesis. This article introduces GLP ⁃ 2 and its physiological role in gastrointestinal tract, and expounds the possible mechanism of GLP ⁃ 2 related to tumorigenesis and the tumorigenesis risk of endogenous and exogenous GLP⁃2 therapy.
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Background Diabetes is a major threat to public health across the world. Studies have shown that exposure to p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) is closely related to the occurrence of type 2 diabetes mellitus. However, the relevant molecular mechanism is not clear. Objective To investigate the effects of p,p'-DDE on H19 differentially methylated region (DMR) methylation and insulin secretion of rat insulinoma cells (INS-1 cells). Methods INS-1 cells were cultured with different concentrations (0, 3.125, 6.25, 12.5, 25, 50, and 75 µmol·L−1) of p,p'-DDE for 24 h, and the viability of INS-1 cells was detected by CCK-8 method. INS-1 cells were exposed to 0, 12.5, 25, and 50 µmol·L−1 p,p'-DDE for 24 h in subsequent experiments. The methylation levels of 24 CpG sites in H19 DMR were analyzed by bisulfite genomic sequencing. The expression levels of insulin-like growth factor 2 (IGF2) mRNA were detected by real-time quantitative PCR. The expression levels of IGF2 and insulin-like growth factor-1 receptor (IGF1R) proteins were detected by Western blotting. The insulin secretion function of INS-1 cells was determined by glucose-stimulatedinsulin secretion test (5 and 25 mmol·L−1 glucose, respectively). Results Compared with the control group, the viability of INS-1 cells increased significantly after treatment with 12.5 µmol·L−1 p,p'-DDE; however, it was significantly inhibited after treatment with 50 or 75 µmol·L−1 p,p'-DDE (P<0.01); therefore, 50 µmol·L−1 was chosen as the maximum concentration of exposure for subsequent experiments. The 25 µmol·L−1 p,p'-DDE treatment decreased the methylation levels of CpG18 and CpG22-CpG24 sites in H19 DMR, and the 50 µmol·L−1 p,p'-DDE treatment decreased the methylation levels of CpG10-CpG24 sites (P<0.05 or P<0.05). Multiple concentrations (12.5, 25, and 50 µmol·L−1) of p,p'-DDE down-regulated the mRNA and protein relative expression levels of IGF2 and the protein relative expression levels of IGF1R. The transcription level of IGF2 decreased to 67.8%, 68.6%, and 62.5% of the control group, the protein level of IGF2 decreased to 73.3%, 79.5%, and 80.9% of the control group, and the protein level of IGF1R decreased to 54.8%, 25.6%, and 12.9% of the control group, respectively (P<0.01). In the high glucose context, p,p'-DDE at selected concentrations inhibited the insulin secretion levels to 85.0%, 58.6%, and 49.5% of the control group, respectively (P<0.01). Conclusion p,p'-DDE could down-regulate methylation level of H19 DMR, interfere the IGF2/IGF1R signaling pathway, and inhibit insulin secretion of islet cells.