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This study aimed to explore the protective mechanism of Banxia Xiexin Tang (BXXXT) on liver cell damage caused by high glucose (H-G) and to clarify its molecular regulatory pathways. First, the main components in BXXXT-containing serum were analyzed by high-performance liquid chromatography (HPLC) to provide basic data for subsequent experiments. Subsequently, the effect of BXXXT on high glucose (H-G)-induced hepatocyte activity was evaluated through screening of the optimal concentration of drug-containing serum. Experimental results showed that BXXXT significantly reduced the loss of cell activity caused by high glucose. Further research focuses on the regulatory effect of BXXXT on high glucose-induced hepatocyte apoptosis, especially its effect on the PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α) pathway. Experimental results showed that BXXXT reduced high-glucose-induced hepatocyte apoptosis and exerted its protective effect by upregulating the activity of the PGC-1α pathway. BXXXT significantly increased the expression level of IGFBP1 (insulin-like growth factor-binding proteins) in hepatocytes under a high-glucose environment. It cleared mitochondrial ROS (reactive oxygen species) by enhancing SOD2 (superoxide dismutase) enzyme activity and maintained the survival of hepatocytes under a high-glucose environment. Finally, the regulation of PGC-1α by BXXXT is indeed involved in the regulation of IGFBP1 expression in hepatocytes and its downstream SOD2 effector signaling. Taken together, this study provides an in-depth explanation of the protective mechanism of BXXXT on hepatocytes in a high-glucose environment, focusing on regulating the expression of the PGC-1α pathway and IGFBP1, and reducing cell damage by scavenging ROS. This provides an experimental basis for further exploring the potential of BXXXT in the treatment of diabetes-related liver injury. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04060-0.
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BACKGROUND: The immune status is closely linked to cancer progression, metastasis, and prognosis. Lipid metabolism, crucial for reshaping immune status, plays a key role in regulating the advancement of lung adenocarcinoma (LUAD) and deserves further investigation. METHODS: This study classifies LUAD patients into different immune subtypes based on lipid metabolism-related genes and compares the clinical characteristics among these subtypes. Single-multi COX analysis screens out key genes related to prognosis, and a risk feature and prognostic model are constructed. Cell cloning, scratch, transwell, western blotting and flow cytometry cell cycle analysis to detect the function of key genes. A subcutaneous tumor animal model is used to investigate the in vivo function and molecular mechanisms of key genes. RESULTS: LUAD patients are classified into three immune subtypes, among which C3 subtype has lower immune status and higher frequency of gene mutations, and show lower immunoreactivity in immunotherapy. COX analysis identified a prognostic model for four lipid metabolism factors (IGFBP1, NR0B2, PPARA, and POMC). IGFBP1, a core gene in this model, is highly expressed in the C3 subtype. Functionally, knocking down IGFBP1 significantly inhibits tumor cell cloning, scratch, and migration abilities, and downregulates the expression of cell cycle and EMT-related proteins. Knocking down IGFBP1 significantly inhibits tumor burden (P < 0.05). Mechanistically, knocking down IGFBP1 inhibits the activation of PPARα to regulate tumor cell growth. CONCLUSIONS: This study found that lipid metabolism genes are closely related to LUAD, and IGFBP1 may be a key gene in regulating tumor growth and development.
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Non-alcoholic fatty liver disease (NAFLD) affects approximately a quarter of the population and, to date, there is no approved drug therapy for this condition. Individuals with type 2 diabetes mellitus (T2DM) are at a significantly elevated risk of developing NAFLD, underscoring the urgency of identifying effective NAFLD treatments for T2DM patients. Salvianolic acid A (SAA) is a naturally occurring phenolic acid that is an important component of the water-soluble constituents isolated from the roots of Salvia miltiorrhiza Bunge. SAA has been demonstrated to possess anti-inflammatory and antioxidant stress properties. Nevertheless, its potential in ameliorating diabetes-associated NAFLD has not yet been fully elucidated. In this study, diabetic ApoE-/- mice were employed to establish a NAFLD model via a Western diet. Following this, they were treated with different doses of SAA (10 mg/kg, 20 mg/kg) via gavage. The study demonstrated a marked improvement in liver injury, lipid accumulation, inflammation, and the pro-fibrotic phenotype after the administration of SAA. Additionally, RNA-seq analysis indicated that the primary pathway by which SAA alleviates diabetes-induced NAFLD involves the cascade pathways of lipid metabolism. Furthermore, SAA was found to be effective in the inhibition of lipid accumulation, mitochondrial dysfunction and ferroptosis. A functional enrichment analysis of RNA-seq data revealed that SAA treatment modulates the AMPK pathway and IGFBP-1. Further experimental results demonstrated that SAA is capable of inhibiting lipid accumulation through the activation of the AMPK pathway and IGFBP-1.
Subject(s)
AMP-Activated Protein Kinases , Caffeic Acids , Insulin-Like Growth Factor Binding Protein 1 , Lactates , Non-alcoholic Fatty Liver Disease , Signal Transduction , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Animals , Mice , Lactates/pharmacology , Lactates/therapeutic use , Lactates/chemistry , AMP-Activated Protein Kinases/metabolism , Caffeic Acids/pharmacology , Caffeic Acids/chemistry , Caffeic Acids/therapeutic use , Insulin-Like Growth Factor Binding Protein 1/metabolism , Insulin-Like Growth Factor Binding Protein 1/genetics , Male , Signal Transduction/drug effects , Mice, Inbred C57BL , Liver/drug effects , Liver/metabolism , Liver/pathology , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Lipid Metabolism/drug effects , Mice, KnockoutABSTRACT
BACKGROUND: Stomach cancer is a leading cause of cancer-related deaths globally due to its high grade and poor response to treatment. Understanding the molecular network driving the rapid progression of stomach cancer is crucial for improving patient outcomes. METHODS: This study aimed to investigate the role of unfolded protein response (UPR) related genes in stomach cancer and their potential as prognostic biomarkers. RNA expression data and clinical follow-up information were obtained from the TCGA and GEO databases. An unsupervised clustering algorithm was used to identify UPR genomic subtypes in stomach cancer. Functional enrichment analysis, immune landscape analysis, and chemotherapy benefit prediction were conducted for each subtype. A prognostic model based on UPR-related genes was developed and validated using LASSO-Cox regression, and a multivariate nomogram was created. Key gene expression analyses in pan-cancer and in vitro experiments were performed to further investigate the role of the identified genes in cancer progression. RESULTS: A total of 375 stomach cancer patients were included in this study. Analysis of 113 UPR-related genes revealed their close functional correlation and significant enrichment in protein modification, transport, and RNA degradation pathways. Unsupervised clustering identified two molecular subtypes with significant differences in prognosis and gene expression profiles. Immune landscape analysis showed that UPR may influence the composition of the tumor immune microenvironment. Chemotherapy sensitivity analysis indicated that patients in the C2 molecular subtype were more responsive to chemotherapy compared to those in the C1 molecular subtype. A prognostic signature consisting of seven UPR-related genes was constructed and validated, and an independent prognostic nomogram was developed. The gene IGFBP1, which had the highest weight coefficient in the prognostic signature, was found to promote the malignant phenotype of stomach cancer cells, suggesting its potential as a therapeutic target. CONCLUSIONS: The study developed a UPR-related gene classifier and risk signature for predicting survival in stomach cancer, identifying IGFBP1 as a key factor promoting the disease's malignancy and a potential therapeutic target. IGFBP1's role in enhancing cancer cell adaptation to endoplasmic reticulum stress suggests its importance in stomach cancer prognosis and treatment.
Subject(s)
Biomarkers, Tumor , Stomach Neoplasms , Tumor Microenvironment , Unfolded Protein Response , Stomach Neoplasms/genetics , Stomach Neoplasms/immunology , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Humans , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Unfolded Protein Response/genetics , Unfolded Protein Response/immunology , Prognosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic , Female , Male , Nomograms , Transcriptome , Gene Expression Profiling , Middle AgedABSTRACT
Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25-30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled "the obesity paradox". Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5-25), overweight (25-30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3-6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30-4.14) and obese (OR 2.25, 95% CI 1.08-4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.
Subject(s)
Body Mass Index , Inflammation , Insulin Resistance , Insulin-Like Growth Factor Binding Protein 1 , Humans , Female , Male , Aged , Insulin-Like Growth Factor Binding Protein 1/blood , Insulin-Like Growth Factor Binding Protein 1/metabolism , Inflammation/metabolism , Inflammation/blood , Middle Aged , Obesity/metabolism , Obesity/complications , Obesity/blood , Stroke/metabolism , C-Reactive Protein/metabolism , Biomarkers/blood , Overweight/metabolism , Overweight/blood , Insulin-Like PeptidesABSTRACT
Cystitis is a common disease closely associated with urinary tract infections, and the specific mechanisms underlying its occurrence and development remain largely unknown. In this study, we discovered that IGFBP1 suppresses the occurrence and development of cystitis by stabilizing the expression of Umod through m6A modification, inhibiting the NF-κB and ERK signaling pathways. Initially, we obtained a bladder cystitis-related transcriptome dataset from the GEO database and identified the characteristic genes Umod and IGFBP1. Further exploration revealed that IGFBP1 in primary cells of cystitis can stabilize the expression of Umod through m6A modification. Overexpression of both IGFBP1 and Umod significantly inhibited cell apoptosis and the NF-κB and ERK signaling pathways, ultimately suppressing the production of pro-inflammatory factors. Finally, using a rat model of cystitis, we demonstrated that overexpression of IGFBP1 stabilizes the expression of Umod, inhibits the NF-κB and ERK signaling pathways, reduces the production of pro-inflammatory factors, and thus prevents the occurrence and development of cystitis. Our study elucidates the crucial role of IGFBP1 and Umod in cystitis and reveals the molecular mechanisms that inhibit the occurrence and development of cystitis. This research holds promise for offering new insights into the treatment of cystitis in the future.
Subject(s)
Cystitis , Insulin-Like Growth Factor Binding Protein 1 , MAP Kinase Signaling System , NF-kappa B , Rats, Sprague-Dawley , Animals , Female , Humans , Rats , Apoptosis , Cystitis/metabolism , Disease Models, Animal , Insulin-Like Growth Factor Binding Protein 1/metabolism , Insulin-Like Growth Factor Binding Protein 1/genetics , NF-kappa B/metabolism , Urinary Bladder/pathology , Urinary Bladder/metabolismABSTRACT
BACKGROUND: Abnormal stromal-epithelial cell communication is a pathogenic mechanism in endometriosis, and metformin can modulate it. Insulin-like growth factor binding protein-1 (IGFBP1) plays a role in endometriosis, but the exact mechanism is unknown. IGFBP1 is reportedly a downstream target of metformin in some diseases. We aimed to investigate the role of IGFBP1 in endometriosis development, whether it is associated with abnormal communication, and whether metformin affects IGFBP1 expression. METHODS: Patients who underwent surgical treatment for endometriosis or other diseases were enrolled. Ten patients with ovarian-type endometriosis and eight patients each who underwent surgical treatment for other lesions with or without endometriosis were selected, and their tissues taken for cell proliferation, western blotting, polymerase chain reaction, and knockdown experiments. RESULTS: Ectopic and eutopic stromal cells (EcSCs and EuSCs) lost their ability to inhibit epithelial cell proliferation, and IGFBP1 expression was downregulated in both groups of stromal cells compared to that in normal stromal cells (NSCs; 1.09 vs. 0.25, p = .0002 1.09 vs. 0.57, p = .0029). In an EcSC IGFBP1 overexpression model, the ability of EcSCs to inhibit epithelial cell proliferation was enhanced (EdU positivity decreased from 38% to 25%, p = .0001). Furthermore, adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation was downregulated in EcSCs and EuSCs compared to that in NSCs (0.99 vs. 0.42, p = .0006/0.99 vs. 0.57, p = 0.0032). Treatment of EcSCs with metformin increased AMPK phosphorylation (0.47 vs. 1.04, p = .0107) while upregulating IGFBP1 expression (0.69 vs. 1.01, p = .0164), whereas pre-treatment with an AMPK phosphorylation inhibitor abrogated metformin-induced IGFBP1 upregulation. CONCLUSIONS: IGFBP1 mediates aberrant stromal-epithelial communication in endometriosis. Metformin can upregulate IGFBP1 expression in EcSCs by activating AMPK, and upregulated IGFBP1 enhances the inhibition of epithelial cell proliferation. IGFBP1 is expected to be a therapeutic target for endometriosis.
Insulin-like growth factor binding protein 1 (IGFBP1) is a protein that regulates cell growth and proliferation and is expressed at abnormal levels in patients with endometriosis. In some cases, metformin has been shown to modulate the expression of this protein. Here, we investigated the role of IGFBP1 in endometriosis development, whether it is associated with abnormal communication, and whether metformin affects IGFBP1 expression in endometrial cells. We found that downregulation of IGFBP1 in endometriosis diminished the ability of stromal cells to inhibit the proliferation of epithelial cells through inhibition of the protein kinase B and extracellular regulated protein kinase pathways. In addition, metformin upregulated IGFBP1 expression by activating adenosine 5'-monophosphate-activated protein kinase, suggesting that IGFBP1 may be one of the potential targets for drug therapy for endometriosis.
Subject(s)
Endometriosis , Metformin , Female , Humans , Insulin-Like Peptides , AMP-Activated Protein Kinases , Cell Proliferation , Epithelial Cells , Metformin/pharmacologyABSTRACT
Reproduction is a high energy consuming process, so long-term malnutrition can significantly inhibit gonadal development. However, little is known about the molecular mechanism by which fasting inhibits reproduction. Our present study found that fasting could dramatically induce insulin-like growth factor binding protein 1 (IGFBP1) expression in the liver, hypothalamus, pituitary and ovaries of grass carp. In addition, IGFBP1a in the hypothalamus-pituitary-gonad axis could inhibit the development of gonads. These results indicated that fasting may participate in the regulation of fish gonadal development through the mediation of IGFBP1a. Further studies found that IGFBP1a could markedly inhibit gonadotropin-releasing hormone 3 expressions in hypothalamus cells. At the pituitary level, IGFBP1a could significantly reduce the gonadotropin hormones (LH and FSH) expression by blocking the action of pituitary insulin-like growth factor 1. Interestingly, IGFBP1a could also directly inhibit the expression of lhr, fshr, and sex steroid hormone synthase genes (cyp11a, cyp17a, and cyp19a1) in the ovary. These results indicated that IGFBP1a should be a nutrient deficient response factor that could inhibit fish reproduction through the hypothalamus-pituitary-ovary axis.
Subject(s)
Carps , Ovary , Animals , Female , Ovary/metabolism , Pituitary Gland/metabolism , Hypothalamus/metabolism , Gonadotropin-Releasing Hormone/metabolism , ReproductionABSTRACT
Circulating cytokines could be optimal biomarkers for prognostication and management decisions in colorectal cancer (CRC). Chemorefractory CRC patients with available plasma samples were included in this study. In the discovery cohort (n = 85), 182 circulating cytokines were tested with a semi-quantitative multiplex assay, and prognostic cytokines were analyzed in the validation cohort (n = 111) by ELISA. Overall survival (OS) was the primary outcome measure, with the false discovery rate (FDR) method (significance level of <0.01) being used to correct for multiple comparisons. Four cytokines were associated with OS in the discovery cohort: insulin-like growth factor-binding protein 1 (IGFBP-1) (HR 2.1 [95%CI: 1.58-2.79], FDR < 0.001), insulin-like growth factor-binding protein 2 (IGFBP-2) (HR 1.65 [95%CI: 1.28-2.13], FDR = 0.006), serum amyloid A (SAA) (HR 1.84 [95%CI: 1.39-2.43], FDR < 0.001), and angiotensin II (HR 1.65 [95%CI: 1.29-2.1], FDR = 0.006). Of these, IGFBP-1 (HR 2.70 [95%CI: 1.56-4.76], FDR = 0.007) and IGFBP-2 (HR 3.33 [95%CI: 1.64-6.67], FDR = 0.008) were confirmed to be independently associated with OS in the validation cohort. Patients with high concentrations of IGFBP-1 and/or IGFBP-2 had a median OS of 3.0 months as compared with 6.9 months for those with low concentrations of both cytokines (HR 2.44 [95%CI: 1.52-4.0], FDR = 0.002) Validation of circulating IGFBP-1 and IGFBP-2 as independent prognostic biomarkers for chemorefractory CRC in larger, independent series is warranted.
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The Insulin-like growth factor 2 (IGF-2) has been recently proven to alleviate depressive-like behaviors in both rats and mice models. However, its potential role as a peripheral biomarker has not been evaluated in depression. To do this, we measured plasma IGF-2 and other members of the IGF family such as Binding Proteins (IGFBP-1, IGFBP-3, IGFBP-5 and IGFBP-7) in a depressed group of patients (n = 51) and in a healthy control group (n = 48). In some of these patients (n = 15), we measured these proteins after a period (19 ± 6 days) of treatment with antidepressants. The Hamilton Depressive Rating Scale (HDRS) and the Self-Assessment Anhedonia Scale (SAAS) were used to measure depression severity and anhedonia, respectively. The general cognition state was assessed by the Mini-Mental State Examination (MMSE) test and memory with the Free and Cued Selective Reminding Test (FCSRT). The levels of both IGF-2 and IGFBP-7 were found to be significantly increased in the depressed group; however, only IGF-2 remained significantly elevated after correction by age and sex. On the other hand, the levels of IGF-2, IGFBP-3 and IGFBP-5 were significantly decreased after treatment, whereas only IGFBP-7 was significantly increased. Therefore, peripheral changes in the IGF family and their response to antidepressants might represent alterations at the brain level in depression.
Subject(s)
Depressive Disorder, Major , Insulin-Like Growth Factor II , Humans , Rats , Animals , Mice , Insulin-Like Growth Factor II/metabolism , Insulin-Like Growth Factor Binding Protein 3 , Insulin-Like Growth Factor Binding Protein 5 , Depressive Disorder, Major/drug therapy , Insulin-Like Growth Factor I/metabolism , Anhedonia , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Insulin-Like Growth Factor Binding Protein 2ABSTRACT
Effective therapies for hepatocellular carcinoma (HCC) are urgently needed, as it is a type of cancer resistant to chemotherapy. Recent evidence showed that PF-429242, a membrane-bound transcription factor site-1 protease (MBTPS1) inhibitor, exhibited anticancer activities against glioblastomas, renal cell carcinoma, and pancreatic cancer. However, its anticancer activity against HCC has yet to be investigated. In this study, we found that PF-429242 induced autophagy-dependent cell death in HCC cells. RNA-sequencing analysis indicated that the primary effect of PF-429242 was inhibition of the sterol regulatory element-binding protein (SREBP) signaling pathway. However, overexpression of SREBP proteins did not efficiently rescue PF-429242-induced autophagy and cell death. Mechanistically, PF-429242 induced forkhead box protein O1 (FOXO1)-dependent autophagic cell death. Additionally, PF-429242 caused FOXO1-independent upregulation of insulin-like growth factor-binding protein 1 (IGFBP1), ultimately leading to autophagy-independent cell death. The in vivo anticancer activity of PF-429242 against HCC cells was demonstrated in a tumor xenograft mouse model. Therefore, PF-429242 is a potential anticancer agent to treat HCC by triggering FOXO1-dependent autophagic cell death and IGFBP1-mediated anti-survival signaling in parallel.
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OBJECTIVE: To determine the molecular differences between iMCD-thrombocytopenia, anasarca, fevers, reticulin myelofibrosis, organomegaly (TAFRO), and iMCD-not otherwise specified (NOS). METHODS: CD4-positive T cells were isolated from two iMCD-TAFRO and two iMCD-NOS patients for RNA sequencing comparison. Serum proteins of two iMCD-TAFRO and four iMCD-NOS patients were comprehensively analyzed to identify pathogenesis-associated proteins. IGFBP-1 protein, extracted from serum analysis, was compared to healthy controls, iMCD, systemic lupus erythematosus, and rheumatoid arthritis patients. RESULTS: RNA sequencing of CD4-positive T cells revealed enhanced mTOR-related signaling in iMCD-TAFRO compared to iMCD-NOS. Comprehensive serum analysis found IGFBP-1 linked to iMCD pathogenesis, significantly higher in iMCD-TAFRO. This protein may be elevated in patients with iMCD caused by an enhanced mTOR pathway. CONCLUSION: The mTOR pathway is suggested to be activated in iMCD-TAFRO compared to iMCD-NOS, which may elevate the protein IGFBP-1. This protein may be a biomarker to distinguish iMCD-TAFRO from iMCD-NOS.
Subject(s)
Castleman Disease , Insulin-Like Growth Factor Binding Protein 1 , Humans , Insulin-Like Growth Factor Binding Protein 1/metabolism , Signal Transduction , Castleman Disease/pathology , TOR Serine-Threonine Kinases/metabolismABSTRACT
We conducted a prospective double-blind study to compare two vaginal diagnostic methods in singleton pregnancies with threatened preterm labor (TPL) at the University Hospital of Clermont-Ferrand (France) from August 2018 to December 2020. Our main objective was to compare the diagnostic capacity at admission, in terms of positive predictive value (PPV) and negative predictive value (NPV), of Premaquick® (combined detection of IL-6/total IGFBP-1/native IGFBP-1) and QuikCheck fFN™ (fetal fibronectin) for delivery within 7 days in cases of TPL. We included 193 patients. Premaquick® had a sensitivity close to 89%, equivalent to QuikCheck fFN™, but a higher statistical specificity of 49.5% against 38.6% for QuikCheck fFN™. We found no superiority of Premaquick® over QuickCheck fFN™ in terms of PPV (6.6% vs. 7.9%), with NPV being equivalent in predicting childbirth within 7 days in cases of TPL (98.6% vs. 98.9%). Nevertheless, the combination of positive native and total IGFBP-1 and the combination of all three positive markers were associated with a higher PPV. Our results, though non-significant, support this combined multiple-biomarker approach to improve testing in terms of predictive values.
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Objective: The objective of the study is to extract the patient's endometrium at the time of proliferative stage using hydrosalpinx in order to culture the cells and decidualization induction in vitro. Further, the study is also intended at identifying the expression of HOXA10mRNA and related factors and understand the hydrosalpinx's impact upon the working mechanism of endometrial cells. Methods: Once the extraction of the primary cells is over, the cells are cultured and other activities are performed such as the cell identification, CCK8 assay, cell decidua induction and HE staining. The researchers assessed the expression levels of HOXA10, IGFBP1 and avß3 in either proliferation or secretion of the endometrium. This was accomplished using Western blot assay and real-time fluorescence quantitative PCR. Results: The results confirmed that at the time of endometrial proliferation, there was a decline in the expression of HOXA10 as a result of tubal effusion influence. This affected its expression in the secretory stage i.e., corresponding function. Further, a significant decline was observed in the levels of HOXA10mRNA of endometrial cells that were subjected to continuous tubal effusion, post decidualization. It was found that during decidualization, if thetubal effusion is removed, it is possible to restore the expression of HOXA10mRNA to a certain extent, though it is not possible to reach the general endometrial level. So, in terms of clinical aspects, the expression of HOxa10 mRNA by the endometrial cells decreases significantly when blocking the hydrosalpinx. Conclusions: Among hydrosalpinx patients, one of the major mechanisms that damage the endometrium was found to be the abnormal expression of HOXA10 followed by IGFBP1 and avß3, its downstream genes. This further results in the implantation of the embryo as well. Though it is possible to gradually repair the damage after the removal of hydrosalpinx, the recovery is a time-consuming process.
ABSTRACT
Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor-I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p < 0.01), but not in the acute phase after stroke, compared with the controls. Higher acute s-IGFBP-1 was associated with poor functional outcome (mRS score > 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4-8.5 and OR 5.7, 95% CI: 2.5-12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1-3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality.
Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Humans , Ischemic Stroke/complications , Brain Ischemia/complications , Insulin-Like Growth Factor Binding Protein 1 , Risk Factors , Stroke/complicationsABSTRACT
Background: The results regarding the association between insulin-like growth factor binding protein 1 (IGFBP1) expression and cancer risk were controversial. We performed a meta-analysis to provide novel evidence on relationship between IGFBP1 expression and cancer risk. Methods: PubMed, Embase, Cochrane library and Web of science were searched for relevant cohort and case-control studies exploring the relationship between IGFBP1 expression and cancer risk. Odds ratios (ORs) were pooled in this meta-analysis using random model. Subgroup analyses were performed based on ethnicity, tumor types, publication year, study type, Newcastle-Ottawa Scale (NOS) score and sex. Results: A total of 27 studies including 16 cohort and 11 case-control studies were identified by literature search. No significant association was found between IGFBP1 expression and risk of various cancers [0.90, 95% confidence interval (CI): 0.79, 1.03]. The overall results showed that the pooled ORs were 0.71 (95% CI: 0.57, 0.88] for prostate cancer risk and 0.66 (95%CI: 0.44, 0.99) for colorectal cancer (CRC) risk. However, there is no significant association between IGFBP1 expression and risk for ovarian cancer (1.70, 95%CI: 0.41, 6.99), breast cancer (1.02, 95%CI: 0.85, 1.23), endometrial cancer (1.19, 95%CI: 0.64, 2.21), colorectal adenoma (0.93; 95%CI: 0.81, 1.07), lung cancer (0.81, 95%CI: 0.39, 1.68) or multiple myeloma (1.20, 95%CI: 0.98, 1.47). Conclusion: In this study, compared with individuals at low IGFBP1 expression adjusted for age, smoking status, alcohol intake and so on, risk of the prostate cancer and CRC were decreased among individuals of high IGFBP1 expression. There needs further study to confirm this issue.
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INTRODUCTION: Approximately 47% of women with an episode of preterm labor deliver at term; however, their infants are at greater risk of being small for gestational age and for neurodevelopmental disorders. In these cases, a pathologic insult may disrupt the homeostatic responses sustaining pregnancy. We tested the hypothesis of an involvement of components of the insulin-like growth factor (IGF) system. METHODS: This is a cross-sectional study in which maternal plasma concentrations of pregnancy-associated plasma protease (PAPP)-A, PAPP-A2, insulin-like growth factor-binding protein 1 (IGFBP-1), and IGFBP-4 were determined in the following groups of women: (1) no episodes of preterm labor, term delivery (controls, n = 100); (2) episode of preterm labor, term delivery (n = 50); (3) episode of preterm labor, preterm delivery (n = 100); (4) pregnant women at term not in labor (n = 61); and (5) pregnant women at term in labor (n = 61). Pairwise differences in maternal plasma concentrations of PAPP-A, PAPP-A2, IGFBP-1, and IGFBP-4 among study groups were assessed by fitting linear models on log-transformed data and included adjustment for relevant covariates. Significance of the group coefficient in the linear models was assessed via t-scores, with p < 0.05 deemed a significant result. RESULTS: Compared to controls, (1) women with an episode of premature labor, regardless of a preterm or a term delivery, had higher mean plasma concentrations of PAPP-A2 and IGFBP-1 (each p < 0.05); (2) women with an episode of premature labor who delivered at term also had a higher mean concentration of PAPP-A (p < 0.05); and (3) acute histologic chorioamnionitis and spontaneous labor at term were not associated with significant changes in these analytes. CONCLUSION: An episode of preterm labor involves the IGF system, supporting the view that the premature activation of parturition is a pathologic state, even in those women who delivered at term.
Subject(s)
Chorioamnionitis , Obstetric Labor, Premature , Somatomedins , Infant, Newborn , Female , Pregnancy , Humans , Insulin-Like Growth Factor Binding Protein 4/metabolism , Insulin-Like Growth Factor Binding Protein 1/metabolism , Cross-Sectional Studies , Pregnancy-Associated Plasma Protein-A/metabolism , Obstetric Labor, Premature/metabolism , Chorioamnionitis/metabolism , Somatomedins/metabolism , Amniotic Fluid/metabolismABSTRACT
IGFBP1 plays a critical role in the pathogenesis of preeclampsia (PE), but the association between single nucleotide polymorphism (SNP) of IGFBP1 gene and PE susceptibility has not yet been determined. In our study, 229 women with PE and 361 healthy pregnant (non-PE) women were enrolled to investigate its association via TaqMan genotyping assay. In addition, the protein levels of IGFBP1 under different genotypes were explored by ELISA and IHC. We found that IGFBP1 SNP rs1065780A > G was associated with an decreased risk for PE. Women with GG (P = 0.027) or AG (Padj. = 0.023) genotype manifested a significantly lower risk for PE compared to women with AA genotype. In PE group, women carrying G allele exhibited greater fetal birth weight, lower diastolic BP, and lower levels of ALT and AST. The G genotype was found significantly less frequently in the severe preeclampsia (SPE) group than in the non-PE group (GG vs. AA, P = 0.007; G vs. A, P = 0.006). Additionally, women in the PE group who experienced fetal growth restriction (FGR) reflected a lower level of the allele G than did the non-FGR group (P = 0.032); this was not the case for the non-PE group.Rs1065780A>G elevated IGFBP1 protein level in plasma and decidua in PE group. In conclusion Chinese Han women with the SNP IGFBP1 rs1065780 occupied by G exhibited a lower risk of developing PE relative to women with the A genotype and augured for improved pregnancy outcomes through elevation of IGFBP1 protein level.
Subject(s)
Pre-Eclampsia , Pregnancy , Female , Humans , Pre-Eclampsia/genetics , Fetal Growth Retardation/genetics , Polymorphism, Single Nucleotide , Genotype , Blood Pressure , Case-Control Studies , Genetic Predisposition to Disease , Insulin-Like Growth Factor Binding Protein 1/geneticsABSTRACT
BACKGROUND: Diabetes is one of the global health threat. Type 2 Diabetes mellitus (T2DM) is associated with life-threatening complications. This work, aimed to study the association between T2DM and IGFBP-1 gene methylation, gene polymorphism and serum levels of IGFBP-1. METHOD: We included 100 subjects with T2DM and 100 control. DNA methylation of IGFBP-1 was analyzed using pyrosequencing, IGFBP-1 gene polymorphism was analyzed using real time polymerase chain reaction and serum level of IGFBP-1 was measured by ELISA. RESULTS: There was DNA hyper methylation levels of IGFBP1 gene at each of the six CpG sites in T2DM patients than control (P < 0.001). IGFBP-1 gene polymorphism (rs 2854843) CC pattern was significantly associated with DM, P = 0.002. Also, there was decrease in serum IGFBP-1 in patients with T2DM than control group (P < 0.001). CONCLUSION: We concluded that DNA hyper methylation of IGFBP-1 gene and CC polymorphism (rs 2854843) of IGFBP-1 gene are associated with T2DM in Egyptian patients, also, decrease serum level of IGFBP-1. Further cohort study is recommended with large sample size to detect which one, epigenetic changes or polymorphism of IGFBP-1 gene, is the cause of T2DM or even both.
Subject(s)
Diabetes Mellitus, Type 2 , Humans , Cohort Studies , Diabetes Mellitus, Type 2/complications , DNA , Egypt , Epigenesis, Genetic , Insulin-Like Growth Factor Binding Protein 1/genetics , Insulin-Like Growth Factor Binding Protein 1/metabolism , Insulin-Like Growth Factor I/metabolismABSTRACT
The metabolic syndrome is a cluster of overlapping conditions resulting in an increased incidence of type 2 diabetes, cardiovascular disease, and cancer. In the last few decades, prevalence of the metabolic syndrome in the Western world has reached epidemic proportions and this is likely due to alterations in diet and the environment as well as decreased physical activity. This review discusses how the Western diet and lifestyle (Westernization) has played an important etiological role in the pathogenesis of the metabolic syndrome and its consequences by exerting negative effects on activity of the insulin-insulin-like growth factor-I (insulin-IGF-I) system. It is further proposed that interventions that normalize/reduce activity of the insulin-IGF-I system may play a key role in the prevention and treatment of the metabolic syndrome. For successful prevention, limitation, and treatment of the metabolic syndrome, the focus should be primarily on changing our diets and lifestyle in accordance with our genetic make-up, formed in adaptation to Paleolithic diets and lifestyles during a period of several million years of human evolution. Translating this insight into clinical practice, however, requires not only individual changes in our food and lifestyle, starting in pediatric populations at a very young age, but also requires fundamental changes in our current health systems and food industry. Change is needed: primary prevention of the metabolic syndrome should be made a political priority. New strategies and policies should be developed to stimulate and implement behaviors encouraging the sustainable use of healthy diets and lifestyles to prevent the metabolic syndrome before it develops.