Search

Reference ranges are invaluable in laboratory medicine, as these are indispensable tools for the interpretation of laboratory test results. When assessing measurements on a single analyte, univariate reference intervals are required. In many cases, however, measurements on several analytes are needed by medical practitioners to diagnose more complicated conditions such as kidney function or liver function. For such cases, it is recommended to use multivariate reference regions, which account for the cross-correlations among the analytes. Traditionally, multivariate reference regions (MRRs) have been constructed as ellipsoidal regions. The disadvantage of such regions is that they are unable to detect component-wise outlying measurements. Because of this, rectangular reference regions have recently been put forward in the literature. In this study, we develop methodologies to compute rectangular MRRs that incorporate covariate information, which are often necessary in evaluating laboratory test results. We construct the reference region using tolerance-based criteria so that the resulting region possesses the multiple use property. Results show that the proposed regions yield coverage probabilities that are accurate and are robust to the sample size. Finally, we apply the proposed procedures to a real-life example on the computation of an MRR for three components of the insulin-like growth factor system. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor 1 (IGF-1), primarily synthesized in the liver, was initially discovered due to its capacity to replicate the metabolic effects of insulin. Subsequently, it emerged as a key regulator of the actions of growth hormone (GH), managing critical processes like cell proliferation, differentiation, and apoptosis. Notably, IGF-1 displays a longer half-life compared to GH, making it less susceptible to factors that may affect GH concentrations. Consequently, the measurement of IGF-1 proves to be more specific and sensitive when diagnosing conditions such as acromegaly or GH deficiency. The recognition of the existence of IGFBPs and their potential to interfere with IGF-1 immunoassays urged the implementation of various techniques to moderate this issue and provide accurate IGF-1 results. Additionally, in response to the limitations associated with IGF-1 immunoassays and the occurrence of discordant IGF-1 results, modern mass spectrometric methods were developed to facilitate the quantification of IGF-1 levels. Taking advantage of their ability to minimize the interference caused by IGF-1 variants, mass spectrometric methods offer the capacity to deliver robust, reliable, and accurate IGF-1 results, relying on the precision of mass measurements. This also enables the potential detection of pathogenic mutations through protein sequence analysis. However, despite the analytical challenges, the discordance in IGF-1 reference intervals can be attributed to a multitude of factors, potentially leading to distinct interpretations of results. The establishment of reference intervals for each assay is a demanding task, and it requires nationwide multicenter collaboration among laboratorians, clinicians, and assay manufacturers to achieve this common goal in a cost-effective and resource-efficient manner. In this comprehensive review, we examine the challenges associated with the standardization of IGF-1 measurement methods, the minimization of pre-analytical factors, and the harmonization of reference intervals. Particular emphasis will be placed on the development of IGF-1 measurement techniques using "top-down" or "bottom-up" mass spectrometric methods. [ABSTRACT FROM AUTHOR]

Altered methylation patterns of insulin-like growth factor (IGF)-axis genes in small for gestational age (SGA) have been reported in different populations. In the present study, we analyzed the methylation status of IGF-axis genes in the placenta of appropriate for gestational age (AGA) and SGA neonates of South Indian women. Placental samples were collected from AGA (n = 40) and SAG (n = 40) neonates. The methylation of IGF-axis genes promoter was analyzed using MS-PCR. IGF2, H19, IGF1, and IGFR1 genes promoter methylation was 2.5, 1.5, 5, and 7.5% lower in SGA compared to AGA, respectively. Co-methylation of IGF-axis genes promoter was 40% and 20% in AGA and SGA, respectively. IGF-axis gene promoter methylation significantly (p < 0.05) influenced the levels of IGFBP3 protein, birth weight, mitotic index, gestational weeks, and IGFR1 and IGFR2 gene expression. IGF-axis genes methylation was lower in SGA than in AGA, and the methylation significantly influenced the IGF-axis components. [ABSTRACT FROM AUTHOR]

Insulin-like growth factors 2 (IGF2) is an insulin-like growth factor that plays a major role in animal growth, cell proliferation and differentiation, as well as reproduction. IGF2 is well-known to be a candidate gene of growth and reproductive traits in many agricultural animals. Our previous study revealed that the G63A (Chr2: G26541617A) mutation within IGF2 exon 1 showed a significant association with egg numbers (E180d) of Sanhua goose population (p < 0.05). However, little work focus on the correlation between the IGF2 mutations and goose growth traits. In this study, qPCR indicated that the IGF2 mRNA highly expressed in leg muscle, liver, ovary and pituitary gland. Meanwhile, association analysis showed that the G63A mutation was significantly associated with the body weight of first-hatched Zhedong-White geese (BW0, p < 0.05), and strongly significantly associated with the BW2, BW4, BW6, BW8 and BW10 (p < 0.01). The GG homozygous had the lowest BW (from 4 weeks to 10 weeks) than those of AA and AG genotypes (p < 0.01), and the allele A was also positively correlated with the BW of the Zhedong-White goose population. Therefore, the G63A mutation in IGF2 may be an important genetic marker for goose breeding. [ABSTRACT FROM AUTHOR]

Growth is an important trait in aquaculture and the major genes that regulate it are Insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs). In this study, the full-length coding sequences of IGF2 and IGFBP6 genes in the Indian catfish Clarias magur were cloned and characterized. The full-length cDNA sequences of IGF2 and IGFBP6 were 885 bp (ORF 642 bp) and 928 bp (ORF 600 bp), encoding 213 and 199 amino acids, respectively. Bioinformatics analyses revealed that the magur IGF2 and IGFBP6 proteins are hydrophilic and secretory in nature. Sequence alignment with other teleosts and mammalian orthologues shows conservation of the functional domains. Gene expression analysis in 6 individuals each of high (298 ± 5.0 g) and low (210 ± 6.0 g) growth performing families showed significantly (p < 0.05) higher expression (2.5–3 fold) of IGF2, and lower expression (∼2.5 fold) of IGFBP6 in liver and muscle of fast-growing fish. This study suggests that IGF2 could be playing a major role in the growth regulation of magur. These genes and their expression patterns could be developed into growth-associated markers for magur and other catfishes. [ABSTRACT FROM AUTHOR]

The relationship between intake of dietary supplements and biomarkers such as insulin and insulin-like growth factor has not been well explored. The primary aim of this cross-sectional study was to investigate the associations between supplement intake and biological and lifestyle factors. We hypothesized that dietary supplement intake was associated with healthier lifestyle behaviors. College students attending a Southeast university were recruited between January 2018 and April 2019. Blood samples were collected to measure insulin, insulin-like growth factor 1 (IGF-1) and alanine aminotransferase (ALT). Statistical tests employed were linear regression and analysis of variance. Ninety-eight participants completed the study and 91% reported taking at least one supplement, while 5.1% reported taking 9+ supplements once per week. There were no differences in levels of insulin, IGF-1 and ALT by levels of dietary supplement intake. Although there were no differences in HEI-2015 score among the groups, those who consumed five or more supplements met a higher percentage of the recommended intake for fruits, performed aerobic exercise for longer duration, and had lower body fat percentage compared to participants who consumed two or less supplements at least once per week. These findings are consistent with previous studies and suggest that dietary supplement intake is highly prevalent in college students, and it may be related to healthy lifestyle behaviors. Future studies should employ mixed methodology to examine reasons by which college students consume dietary supplements and to assess perceived and direct health benefits associated with consumption. [ABSTRACT FROM AUTHOR]

Animal welfare can be viewed as the result of integrating repeated affective evaluations of success in coping with environmental challenges, i.e., subjective challenge adequacy. The present work summarizes why established physiological and behavioral welfare parameters are inadequate to assess challenge adequacy. Behavioral tests based on the mood-congruent judgment effect and physiologic parameters based on components of the somatotropic axis are proposed as an alternative. Here, the judgment bias measures an animal's subjective confidence to cope successfully with a challenge, which is in turn modulated by the animal's previous experience. The somatotropic axis incorporates the insulin-like growth factor (IGF) and its binding proteins (IGFBP), which are involved in the regulation of metabolism and growth. First results indicate that in particular IGF-1 and IGFBP-3 react with higher latency and higher inertness to short-term stressful events than established physiological stress parameters. Before these indicators can be utilized for overall welfare assessment, further validation studies are necessary that provide more insights into how repeatable the measurements are under different conditions and which other factors may confound the measures. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor 2 (IGF2) belongs to the member of the insulin-like growth factors family, which plays key roles in animal growth, differentiation and proliferation, as well as reproduction and the regulation of ovarian follicle development. However, little is known about the goose IGF2 gene. In this study, a 1879 bp fragment that covered the complete coding region (CDS) of goose IGF2 cDNA was identified for the first time. The cDNA consists of an open reading frame of 574 nucleotides with the capacity to encode a prepro-IGF-II protein of 187 amino acids, which comprises a signal peptide (24 residues), IGF-II peptide (67 residues), and C-terminal peptide (96 residues), and is closely related to that of chicken. qPCR indicates that the goose IGF2 mRNA is differentially expressed in all examined tissues of fertilized eggs (28 days) and laying Zhedong White geese (270 days). Two novel single nucleotide polymorphisms (SNPs) were detected in exon 1 (G63A, Chr2: G26541617A) and intron 1 (G38A, Chr2: G26541479A) regions, and the synonymous mutation G63A showed a significant association with egg numbers (E180d) of Sanhua goose population (p < 0.05). All the information derived from this study could be valuable and facilitate further studies on the functions of goose IGF2 gene. [ABSTRACT FROM AUTHOR]

IGF2 is an insulin-like growth factor that plays an important role in the development of animal embryos. In order to determine whether IGF2 gene is associated with important economic characteristics of donkeys, we investigated the association between single nucleotide polymorphisms (SNPs) of IGF2 gene and body size traits of Chinese Dezhou donkeys and analyzed the expression level of IGF2 gene in different tissues of juvenile and adult Dezhou donkeys. In this study, two SNPs (g.281766 G > A and g.291322 C > T) were detected in IGF2 gene, both of which were in Hardy-Weinberg equilibrium (P > 0.05) and were moderately polymorphic (0.25 < PIC < 0.50). Association analysis showed that the two SNP loci were significantly correlated with body length and rump height (p < 0.05) of female Dezhou donkeys. Quantitative results showed that the expression of IGF2 gene was higher in heart, liver, spleen, lung, kidney, stomach and muscle tissues of juvenile donkeys than that of adult donkeys. Together, IGF2 can be considered as a candidate gene for growth and development of female Dezhou donkey, and its polymorphism can be used as a molecular marker for the Dezhou donkey breeding. [ABSTRACT FROM AUTHOR]

Reference intervals are among the most widely used medical decision-making tools and are invaluable in the interpretation of laboratory results of patients. Moreover, when multiple biochemical analytes are measured on each patient, a multivariate reference region (MRR) is needed. Such regions are more desirable than separate univariate reference intervals since the latter disregard the cross-correlations among variables. Traditionally, assuming multivariate normality, MRRs have been constructed as ellipsoidal regions, which cannot detect componentwise extreme values. Consequently, MRRs are rarely used in actual practice. In order to address the above drawback of ellipsoidal reference regions, we propose a procedure to construct rectangular MRRs under multivariate normality. The rectangular MRR is computed using a prediction region criterion. However, since the population correlations are unknown, a parametric bootstrap approach is employed for computing the required prediction factor. Also addressed in this study is the computation of mixed reference intervals, which include both two-sided and one-sided prediction limits, simultaneously. Numerical results show that the parametric bootstrap procedure is quite accurate, with estimated coverage probabilities very close to the nominal level. Moreover, the expected volumes of the proposed rectangular regions are substantially smaller than the expected volumes obtained from Bonferroni simultaneous prediction intervals. We also explore the computation of covariate-dependent MRRs in a multivariate regression setting. Finally, we discuss real-life applications of the proposed methods, including the computation of reference ranges for the assessment of kidney function and for components of the insulin-like growth factor system in adults. [ABSTRACT FROM AUTHOR]

to verify the effects of aerobic exercise training in circulating BDNF, VEGF165 and IGF-1 plasma levels and cognitive function in Alzheimer's Disease (AD) patients. 34 AD patients participated in the study, divided in two groups: Control Group (CG; n = 16) and Training Group (TG; n = 18 – Moderate aerobic training on the treadmill, three times a week, for 12 weeks). BDNF, VEGF165, and IGF-1 plasma levels were considered as a primary outcome. Secondary outcomes included cognitive functions and aerobic fitness. After 12 weeks, maintenance of executive functioning in the TG was found, yet no significant changes on circulating neurotrophins levels were identified. For aerobic fitness, there was an increment in TG group. Twelve weeks of aerobic training were neither effective in improving cognitive functioning significantly, nor influential on circulating neurotrophins levels in AD patients. [ABSTRACT FROM AUTHOR]

In this systematic review and meta-analysis of clinical controlled trials (CCTs) we aimed to investigate the efficacy of KDs as an adjuvant therapy on cardiometabolic outcomes in patient with cancer compared to conventional non-ketogenic diets. Only CCTs involving cancer patients that were assigned to either a KD or a standard diet control group were selected. Two reviewers independently extracted the data, and a meta-analysis was performed using a random effects model to estimate weighted mean differences (WMDs) and confidence intervals (CIs) in body composition, metabolite, lipid profile, liver and kidney function parameters and quality of life. This meta-analysis showed a significant reduction in body weight (WMD= −2.99 kg; 95% CI: −4.67, −1.31; and P < 0.001), BMI (WMD= −1.08 kg/m2; 95% CI: −1.81, −0.34; P ≤ 0.002) and fat mass (WMD= −1.48 kg; 95% CI: −2.56, −0.40; and P = 0.007) by a KD. KDs significantly decreased glucose (WMD= −5.22 mg/dl; 95% CI: −9.0, −1.44; and P = 0.007), IGF-1 (WMD= −17.52 ng/ml; 95% CI: −20.24, −14.8; and P ˂0.001) and triglyceride (WMD= −24.46 mg/dl; 95% CI: −43.96, −4.95; and P = 0.014) levels. Furthermore, KDs induced ketosis by increasing β-hydroxybutyrate (WMD= 0.56 mmol/l; 95% CI: 0.37, 0.75; and P < 0.001). There were non-significant pooled effects of KDs on improving insulin, C-reactive protein and cholesterol levels and kidney and liver function. Emotional functioning was even increased significantly in the KD compared to the SD groups. In summary we found that KDs result in a greater reduction in glucose, IGF-1, triglycerides, body weight, BMI, and fat mass in cancer patients compared to traditional non-ketogenic diets and improved emotional functioning. The quality of evidence in the meta-analysis was moderate according to the Nutrigrade assessment. [ABSTRACT FROM AUTHOR]

In proliferating cells and tissues a number of checkpoints (G1/S and G2/M) preceding cell division (M-phase) require the signal provided by growth factors present in serum. IGFs (I and II) have been demonstrated to constitute key intrinsic components of the peptidic active fraction of mammalian serum. In vivo genetic ablation studies have shown that the cellular signal triggered by the IGFs through their cellular receptors represents a non-replaceable requirement for cell growth and cell cycle progression. Retroactive and current evaluation of published literature sheds light on the intracellular circuitry activated by these factors providing us with a better picture of the pleiotropic mechanistic actions by which IGFs regulate both cell size and mitogenesis under developmental growth as well as in malignant proliferation. The present work aims to summarize the cumulative knowledge learned from the IGF ligands/receptors and their intracellular signaling transducers towards control of cell size and cell-cycle with particular focus to their actionable circuits in human cancer. Furthermore, we bring novel perspectives on key functional discriminants of the IGF growth-mitogenic pathway allowing re-evaluation on some of its signal components based upon established evidences. [ABSTRACT FROM AUTHOR]

Objective Gene expression in placenta differs between vaginal and cesarean deliveries, but the influence of the duration of labor on placental gene expression is incompletely known. Our aim was to investigate associations between duration of labor and expression of some genes involved in growth or inflammation in human placental tissue. Methods Placenta samples (n = 126) were collected after an uncomplicated, singleton pregnancy and term vaginal delivery at Örebro University Hospital, Sweden. Duration of labor was recorded by the midwife in the delivery room. The expression of the following genes was analyzed by RT-qPCR: tumor necrosis factor (TNF), interleukin-6 (IL6), C-X-C motif chemokine ligand 8, toll-like receptor (TLR) 2, TLR4, insulin receptor, insulin-like growth factor (IGF) 1, IGF2, leptin, hepatocyte growth factor (HGF) and HGF receptor (MET). Multivariable linear regression models were used for the evaluation of associations with labor duration adjusting for potential confounding factors. The Benjamini-Hoschberg method was used to correct for multiple testing. Results The expression of TNF, IL6, IGF1 and IGF2 was inversely associated with the duration of the pushing phase of labor (B coefficients (95% confidence interval) = −0.150 (−0.277 to −0.023), −0.159 (−0.289 to −0.029), −0.099 (−0.176 to −0.021), and −0.081 (−0.145 to −0.017), respectively). Conclusions Longer duration of pushing is associated with downregulation of the expression of genes in placenta from vaginal deliveries. Future research on gene expression in labored placenta should take into account associations with labor duration and especially the pushing phase. Potential impact of these associations on the mother, the fetus and the new-born infant should also be explored. [ABSTRACT FROM AUTHOR]

Renal ischemia–reperfusion injury (IRI) is a common prerequisite of acute renal injury (AKI) that involves the entire system and induces critical illness. The C domain of insulin-like growth factor-1 (IGF-1C) plays an important role in promoting angiogenesis and enhancing the inflammatory response. However, given the shortcomings of its short half-life and poor stability, the application of IGF-1C is restricted. In the present study, IGF-1C nanoparticles (NP-IGF-1C) were constructed by combining 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide (polye thyleneglycol)](DSPE-PEG-MAL) and IGF-1C through a Michael addition reaction to evaluate the effects of NP-IGF-1C on preventing IRI. In vitro studies have shown that NP-IGF-1C is not cytotoxic and protects cells from oxidative damage. The renal enrichment and biocompatibility of NP-IGF-1C were determined in vivo by connecting fluorescent molecules to NP-IGF-1C for in vivo imaging and pathological staining of important organs. After IRI, renal function decreased, and inflammatory cell infiltration, oxidative stress and apoptosis increased. As expected, NP-IGF-1C reversed these changes, indicating that NP-IGF-1C played a protective role in the process of IRI, which may be mediated by its antioxidant, anti-inflammatory and antiapoptotic activities. [ABSTRACT FROM AUTHOR]

Serum creatinine (SCr) is unreliable in detecting acute changes in kidney function. Early recognition of contrast-induced acute kidney injury (CI-AKI) can provide better opportunities for preventive interventions. Therefore, the purpose of this study is to examine the value of the combined detection of urinary neutrophil gelatinase-associated lipocalin (NGAL), insulin-like growth factor binding protein-7 (IGFBP-7), and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the early diagnosis of children with CI-AKI. A prospective, single-center clinical trial was performed and included 172 children aged 0–18 years. The dynamic changes of urinary NGAL, IGFBP-7, and TIMP-2 levels in children with intravascular injection of contrast medium were investigated to determine whether they can diagnose CI-AKI early. CI-AKI occurred in 20 of 137 enrolled patients, and the incidence was 14.59%. In the CI-AKI group, urinary levels of NGAL, IGFBP-7, TIMP-2, and [IGFBP-7]*[TIMP-2] were significantly increased 2 h after angiography and remained at high levels at 6 h. Using a cutoff value of 36.274 ng/mL, the specificity was 70.0%, and the sensitivity was 68.4% for the prediction of CI-AKI, which was excellent for urinary NGAL. When both urinary IGFBP-7 and TIMP-2 were used together, urinary [IGFBP-7]*[TIMP-2] at 0.417(ng/mL)2/1000 was regarded as the cutoff value. The specificity was 80.0%, and the sensitivity was 81.2%. NGAL, IGFBP-7, and TIMP-2 concentrations in the urine of children after receiving injections of contrast medium increased faster than SCr and had good clinical value for the early diagnosis of CI-AKI in children. The combination of IGFBP-7 and TIMP-2 was better than either analyte alone. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor binding protein-3 (IGFBP3) has been reported to be related to the risk of some cancers. Here we focussed on serum IGFBP3 as a possible biomarker of diagnosis and prognosis for oesophageal squamous carcinoma (ESCC). Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum IGFBP3 level in the training cohort including 136 ESCC patients and 119 normal controls and the validation cohort with 55 ESCC patients and 42 normal controls. The receiver operating characteristics curve (ROC) was used to assess the diagnosis value. Cox proportional hazards model was applied to select factors for survival nomogram construction. Serum IGFBP3 levels were significantly lower in early-stage ESCC or ESCC patients than those in normal controls (p <.05). The specificity and sensitivity of serum IGFBP3 for the diagnosis of ESCC were 95.80% and 50.00%, respectively, with the area under the ROC curve (AUC) of 0.788 in the training cohort. Similar results were observed in the validation cohort (88.10%, 38.18%, and 0.710). Importantly, serum IGFBP3 could also differentiate early-stage ESCC from controls (95.80%, 52.54%, 0.777 and 88.10%, 36.36%, 0.695 in training and validation cohorts, respectively). Furthermore, Cox multivariate analysis revealed that serum IGFBP3 was an independent prognostic risk factor (HR = 2.599, p =.002). Lower serum IGFBP3 level was correlated with reduced overall survival (p <.05). Nomogram based on serum IGFBP3, TNM stage, and tumour size improved the prognostic prediction of ESCC with a concordance index of 0.715. We demonstrated that serum IGFBP3 was a potential biomarker of diagnosis and prognosis for ESCC. Meanwhile, the nomogram might help predict the prognosis of ESCC. Serum IGFBP3 showed early diagnostic value in oesophageal squamous cell carcinoma with independent cohort validation. Moreover, serum IGFBP3 was identified as an independent prognostic risk factor, which was used to construct a nomogram with improved prognosis ability in oesophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to examine if people with protein C deficiency, which is a natural anticoagulant and also an endogenous acyl ghrelin peptidase, have elevated circulating levels of acyl ghrelin. The clinical trial was conducted in a university hospital setting. People with protein C deficiency were identified and invited to participate by a specialized coagulation outpatient clinic. People with protein C deficiency were examined and compared to age, sex, and body mass index matched healthy controls with regards to acyl ghrelin, unacylated ghrelin, growth hormone (GH) and insulin-like growth-factor I (IGF-I) in a cross-sectional case-control study. Systemic levels of acyl ghrelin, desacyl ghrelin, acyl-to-desacyl ghrelin ratio, GH and IGF-I were similar in people with protein C deficiency and healthy controls. Despite a significant reduction of protein C in people with protein C deficiency, there was no difference in acyl ghrelin or the secondary end points unacylated ghrelin, GH, or IGF-I in people with protein C deficiency. [ABSTRACT FROM AUTHOR]

Determine if an abnormal preliminary neuroendocrine disorder (NED) blood test screen is associated with mild TBI (mTBI) history or post-concussiveclinical features. Observational Among 1,520 participants with military combatexposure, we measured randomly timed serum levels of insulin-likegrowth factor-1, thyroid stimulating hormone (TSH), and total testosterone as a preliminary NED screen. Using multivariable models, we analyzed relation of screen results in mTBI group membership and post-concussiveclinical features (fatigue, depression, cognitive symptoms, executive function, processing speed). None of the mTBI positive groups, including repetitive (≥3 mTBI) and blast-related,differed from the non-TBIcontrols on rates of abnormal lab screen or rates of growth hormone deficiency (GHD), hypothyroidism or male hypogonadism in treatment records. Lab screen findings were also not associated with any clinical feature. This study shows no evidence that remote mTBI(s) or implicated post-concussiveclinical features are linked to GHD, hypothyroidism or male hypogonadism. Large case-controlstudies incorporating more definitive neuroendocrine disorder NED testing (TSH plus thyroxine, early morning testosterone, LH, FSH, prolactin and GH provocative testing) are needed to determine whether mTBI(s) alone elevate one's risk for chronic NED and how best to select patients for comprehensive testing. [ABSTRACT FROM AUTHOR]

Biotin is increasingly used as dietary supplement. As many immunoassays rely on a binding between biotin and streptavidin, intake of biotin may interfere with laboratory tests, leading to spurious test results. We examined the extent to which levels of aldosterone, renin, insulin-like growth factor 1 (IGF-1), growth hormone (GH) and bone alkaline phosphatase (BAP) were affected by biotin. In an experimental study performed at Aarhus University Hospital, Denmark, patient samples (plasma or serum) were pooled and spiked with biotin in increasing concentrations (0, 20, 50, 100 and 500 ng/mL). All biomarkers were analyzed using Immunodiagnostic Systems (IDS-iSYS) Multi-Discipline Automated System assays. The average bias (%) was calculated, as the difference in concentrations between the sample without biotin (reference) and the samples with increasing concentrations of biotin. Both aldosterone and renin assays showed substantial biotin interference in a dose-dependent manner, with biases up to +3484% for aldosterone and -98% for renin in the highest concentrations of biotin (100-500 ng/mL). IGF-1, GH and BAP results were generally less affected by added biotin and significant bias (>10%) was observed only when the biotin concentration was 100 ng/mL (IGF-1 and GH) or 500 ng/mL (BAP). In conclusion, biotin interfered with the IDS-iSYS immunoassays, particularly for aldosterone and renin. The assays for GH, IGF-1 and BAP were less sensitive and only with high concentrations of biotin. [ABSTRACT FROM AUTHOR]

Glioma is the most common intrinsic tumor in central nervous system and is characterized by their diffuse infiltration of the brain tissue. Insulin-like Growth Factor Binding Protein-6 (IGFBP6) was associated with the insulin-like growth factor binding and insulin-like growth factor II binding processes in many cancers. Herein, we aimed to investigate the biological functions and clinical features of IGFBP6 in gliomas. Totally, we collected 325 RNA sequencing data from CGGA dataset as training cohort, and 969 RNA sequencing data from TCGA dataset as validation cohort. The clinical and molecular characteristics analysis and gene ontology analysis of IGFBP6 were performed. All analyses and graphs were produced based on R language. We found that IGFBP6 expression was significantly upregulated in GBM patients and downregulated in IDH mutant patients. Receiver Operating Characteristic (ROC) analysis revealed that IGFBP6 could be used as a biomarker to predict TCGA mesenchymal subtype. GO analysis revealed that IGFBP6 was correlated with immunological functions and inflammation activities. Meanwhile, higher expression of IGFBP6 suggested significant relationship with worse prognosis in glioma patients. Our findings improved the understanding of IGFBP6 in glioma, and IGFBP6 might be a potential therapeutic target for glioma patients in future clinical trials. [ABSTRACT FROM AUTHOR]

Zinc (Zn), an important microelement in ruminant diet, plays a critical role in various enzymes, hormones and functional proteins involved in nutrient metabolism. The present study was conducted to assess the effect of zinc hydroxychloride (Zn5(OH)8Cl2·H2O [ZnOHCl] and zinc sulphate (ZnSO4) on nutrient utilisation, mineral metabolism and biomarkers pertaining to growth performance in pre-ruminant crossbred calves. Twenty-four crossbred calves [body weight (BW); 31.03 ± 4.30 kg; age 10 d] were randomly allocated to four treatment groups (n = 6), i.e. no supplementation of Zn (0 mg/kg dry matter [DM]), 80 mg/kg DM Zn as ZnSO4(ZnS-80), 40 mg/kg DM Zn as ZnOHCl (ZnH-40) and 80 mg/kg DM Zn as ZnOHCl (ZnH-80) for 90 d experimental period. Results showed that dietary Zn supplementation improved (p < 0.05) feed intake, BW, average daily gain, heart girth, body length, plasma growth hormone, insulin-like growth factor and thyroxin concentration; however, nutrient digestibility remained unaffected among the groups. Addition of Zn increased (p < 0.05) Zn retention and plasma Zn concentration without affecting retention and plasma concentration of other minerals. Retention of Zn was the highest in ZnH-80 group followed by ZnH-40, ZnS-80 and lowest in control group. Overall results of the present study indicate that regardless of sources and levels, Zn supplementation increased growth performance, plasma Zn concentration and hormones levels in pre-ruminant crossbred calves. However, supplementation of hydroxy Zn at 40 mg/kg DM had similar effect as produced by ZnSO4 or ZnOHCl at a supplementation level of 80 mg/kg DM. Therefore, from the present study it can be concluded that ZnOHCl can be used as a Zn source for pre-ruminant calves at a lower dose compared to ZnSO4. [ABSTRACT FROM AUTHOR]

This research is focussed to quantify IGF1 by electroanalytical analysis on InterDigitated electrode surface and characterized by the microscopic observations. For the detection, antibody and aptamer were used to analyze the level of IGF1. The sandwich pattern (aptamer-IGF1-antibody) was designed on the chemically modified IDE surface and reached the limit of detection to 10 fM with 100 folds enhancement in the sensitivity. Different control experiments (absence of IGF1, binding with IGF2 and with non-complementary aptamer) were failed to show the current changes, discriminated the specific detection. A good detection strategy is to complement the currently following imaging systems for AAA. [ABSTRACT FROM AUTHOR]

The incidence of skin cancer has raised in the last few years. One of the important growth factors found in the skin layers is insulin-like growth factor (IGF)-1. It is directly linked with many cancers in different organs. Therefore, we aimed to explore the therapeutic effects of blocking IGF-1 receptor (IGF-R1) pathway by PQ401 in skin cancer as well as studying its effect on tumor invasion markers. We experimentally induced skin cancer in mice by the application of 7,12-dimethylbenz (a) anthracene. Skin samples were removed for determination of gen and protein expression of IGF-1, IGF-R1, glypican-3, MMP9, syndecan-1 and fascin-1 by Western blot and PCR. Moreover, skin sections were stained with hematoxylin/eosin and Mallory. Treatment with PQ401 blocked the expression of IGF-R1 in the skin, which is associated with reduction in the skin cancer-induced tumors and scratches. In addition, PQ401 ameliorated skin cancer induced formation of epidermal atypia and hyperplasia. PQ401 reduced both gene and protein expression of the tumor invasion markers, MMP9, syndecan-1 and fascin-1, without affecting gene and protein expression of glypican-3 and IGF-1 in skin cancer group. Blocking IGF-R1 has therapeutic effects against experimental skin cancer induced in mice. In addition, blocking IGF = R1 attenuated skin cancer-induced activation of tumor invasion markers. IGF-1/IGF-R1is highly expressed in different cancers as skin cancer. Blocking IGF-R1 production ameliorated skin cancer. Blocking IGF-R1 attenuated skin cancer-induced activation of tumor invasion markers. [ABSTRACT FROM AUTHOR]

Hyaluronic acid (HA) is found in connective tissue and participates in wound healing. We investigated the efficacy of a HA gel (2% hyaluronic acid; 1% antioxidants, coenzyme Q10 and vitamin E; and 5% benzocaine) on healing of palatal wounds in rats. We established two groups of rats: a control group treated with vehicle and an HA group treated with HA gel. The control group was divided into five subgroups and the HA group was divided into four subgroups according to the day on which animals were sacrificed. Wounds were created by elevating 5 mm diameter full thickness flaps. Healed and unhealed wound areas were measured using photographs. Transforming growth factor (TGF)-β, insulin-like growth factor (IGF), and collagen I and III expressions were determined using immunohistochemistry. The number of fibroblasts increased and inflammatory cells decreased from day 0 to 21 in both groups. The HA group exhibited more fibroblasts by day 7 compared to controls; (TGF)-β and IGF levels were similar between HA and control groups. HA groups exhibited fewer inflammatory cells than controls on days 3 and 7. We found significant differences in TGF-β and IGF levels among HA groups between days 3 and 21, and among control groups between days 0 and 21. Collagen I and III levels were greater for the day 3 HA group compared to controls. We observed improved wound healing in HA treated rats within 7 days. [ABSTRACT FROM AUTHOR]

Members of the IGF gene family participate in cell differentiation and proliferation during pregnancy. We used 35 cats assigned to experimental groups (G) based on pregnancy stages: G1, pre-implantation; G2, implantation; G3, early pregnancy; G4, mid-pregnancy; G5, nonpregnant. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry were used to analyze the expression of the IGF gene family. During pregnancy, expression of IGF-1 gene was significantly greater at implantation sites in the G1 and G2 groups than at placentation sites in G3 and G4 groups. IGF-2 expression was greater in the G2, G3 and G4 groups than in G1. Expression of the IGF-1R gene was significantly greater at placental sites in G3 than in G1 and G4. IGF-2R genes were expressed in all groups. Insulin-like growth factor binding proteins (IGFBPs) were expressed at intensities that depended on the stage of pregnancy; they were detected in different cell types and at different sites in the uterus. We found that members of the IGF gene family were expressed differentially in the endometrium during pregnancy. Our findings suggest that the IGF family may be a regulatory factor for pregnancy in cats. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease. An increased expression of somatostatin receptor subtype 2 in patients with IPF was identified and lung fibroblasts expressed somatostatin receptors in vitro. In addition, somatostatin analogue inhibits the expression of transforming growth factor-β, insulin-like growth factor (IGF) −1, platelet-derived growth factor, and basic fibroblast growth factor. Therefore, we examined the effects of somatostatin analogue on bleomycin-induced pulmonary fibrosis in mice. In a similar model, it has been reported that administration of high-dose somatostatin analogs suppressed acute inflammation and subsequent pulmonary fibrosis. However, it was clarified that the same effect can be obtained even at the dose used in clinical practice. C57BL/6 mice received a single tracheal instillation of bleomycin. After randomly allocated, mice were treated with subcutaneous injection of either normal saline or somatostatin analogue. Somatostatin analogue reduced the number of neutrophils and lymphocytes in bronchoalveolar lavage (BAL) and IGF-1 level in serum and BAL fluid and attenuated weight loss. The hydroxyproline content of the lung homogenates in somatostatin analogue treatment group was significantly lower than in that of normal saline treatment group. These results suggest that somatostatin analogue may attenuate pulmonary fibrosis after bleomycin treatment at the dose used in clinical practice. [ABSTRACT FROM AUTHOR]

Intravitreal bevacizumab (Avastin) is an irreversible vascular endothelial growth factor (VEGF) inhibitor used to treat severe retinopathy of prematurity (ROP) in extremely low gestational age neonates (ELGANs). ELGANs who are at the highest risk for developing severe ROP often experience brief intermittent hypoxia (IH) episodes which may cause oxidative damage. We tested the hypothesis that intravitreal Avastin leaks into the systemic circulation during exposure to IH and has adverse effects on biomarkers of pulmonary microvascular maturation, thus leading to pulmonary hemorrhage and long-term pulmonary sequelae. Neonatal rats at postnatal day (PN) 0 (birth) were exposed to either: 1) hyperoxia (50% O2) or 2) neonatal IH (50% O2 with brief episodes of 12% O2) from PN0 to PN14. Room air (RA) littermates served as controls. At PN14, the time of eye opening in rats, a single dose of Avastin (0.125 mg in 5 µL) was injected into the vitreous cavity of the left eyes. A control group received equivalent volume saline. At PN23 and PN45, blood gases, lung-to-body weight ratios, histology, immunofluorescence, and lung biomarkers of angiogenesis were examined. At PN23, Avastin increased lung VEGF, nitric oxide derivatives (NOx), and hypoxia-inducible factor (HIF)1a in the hyperoxia-exposed groups, but decreased soluble VEGFR-1 (sVEGFR-1). At PN45, lungs from animals exposed to neonatal IH and treated with Avastin were severely hemorrhagic with morphologic changes in lung architecture consistent with chronic lung disease. This was associated with higher VEGF and NOx levels, and lower insulin-like growth factor (IGF)-I and sVEGFR-1. These findings prove our hypothesis that intravitreal Avastin penetrates the blood–ocular barrier in IH and alters lung biomarkers of angiogenesis. Avastin targeting of VEGF could affect normal lung development which may be exaggerated under pathologic conditions such as IH, ultimately leading to vascular permeability, vessel rupture, and pulmonary hemorrhage. [ABSTRACT FROM AUTHOR]

The insulin-like growth factor binding-protein 7 (IGFBP7) has binding affinities to IGFs and is able to either positively or negatively regulate the IGFs signaling pathway. It also plays a crucial role in cell growth, differentiation and development in an IGF-independent manner. Herein, we investigated the specific regulation of the gene encoding for IGFBP7during the differentiation process of the adipocyte cells of the Yan Yellow Cattle by interfering with or by overexpressing the IGFBP7 gene. As a result, we found that the mRNA expression levels of IGFBP7 were significantly increased during the formation of progenitor cells. In addition, the expression levels of the lipoprotein lipase (LPL) and transcription factors (PPARγ, C/EBPα) were also significantly increased. IGFBP7 gene overexpression and RNA interfering promoted and inhibited respectively the lipid accumulation and triglyceride production in mature adipocytes, and the expression of the LPL and transcription factors (PPARγ, C/EBPα). The changes in the protein expression levels of IGFBP7 and adipogenic factors were in accord with the changes observed in the mRNA levels. In conclusion, our results indicate that IGFBP7 plays an important regulatory role in the differentiation of preadipocyte cells. [ABSTRACT FROM AUTHOR]

Beside the pulmonary vasoconstriction observed in pulmonary arterial hypertension (PAH), severe proliferative and antiapoptotic cellular phenotypes result in vascular remodelling. Many recent findings indicate similarities between PAH and tumour pathology. For instance, insulin-like growth factor (IGF)-1 signalling, which is known to promote tumour development, is implicated in PAH. Higher circulating IGF binding protein (IGFBP)-1 levels are associated with worse survival in PAH. The present study aimed to investigate the relationship between plasma levels of various tumour-related biomarkers and PAH. Methods: IGFBP-1, -2 and -7, along with other tumour-related biomarkers, were measured in plasma from 48 treatment-naïve PAH patients and 16 healthy controls, using proximity extension assays. Among the PAH patients, 33 were also studied at an early treatment follow-up. Results: Plasma IGFBP-1 (p <.003), IGFBP-2 (p <.001), IGFBP-7 (p <.008), vimentin (p <.001), carbonic anhydrase 9 (p <.001), S100A11 (p <.001), human epididymis protein 4 (p <.001) and folate receptor-α (p <.004) were elevated in PAH, compared to controls. IGFBP-1 exhibited the most interesting correlations to clinical parameters and was selected for further analyses. IGFBP-1 correlated specifically to N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (r = 0.44, p <.002), mean right atrial pressure (r = 0.41, p <.004), venous oxygen saturation (r = –0.43, p <.003), cardiac index (r = –0.32, p <.03) and 6-minute walking distance (r = –0.29, p <.05). Plasma IGFBP-1 also correlated to risk scores based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) PAH guidelines (r = 0.43, p <.003) and the REVEAL model (r = 0.46, p <.001). PAH patients with supra-median baseline IGFBP-1 levels showed a trend for worse overall survival than those with infra-median levels (p =.087). IGFBP-1 was unaltered between baseline and an early treatment follow-up. However, IGFBP-1 changes, between baseline and follow-up, correlated to changes in NT-proBNP (r = 0.48, p <.006). Conclusion: Plasma IGFBP-1 levels at PAH diagnosis show moderate association to NT-proBNP and hemodynamics as well as with ESC/ERS and REVEAL risk scores. [ABSTRACT FROM AUTHOR]

Retinal pigment epithelium and photoreceptor cells are a microenvironment where 90 different peptides are synthesized for transduction, visual cycle, intracellular electron transport chain, and removal of metabolic wastes. Depending on the inheritance pattern, either mutant proteins accumulate inside the cells or the energy cycle is disrupted. Disruption of homeostasis causes the cells to switch to the dormant phase; if the improper conditions last longer, then apoptosis eventually develops resulting in a loss of visual function. In neural tissues, growth factors such as neural growth factor, brain-derived neurotrophic factor, ciliary neurotrophic factor, and insulin-like growth factor are regulatory peptides for intracellular energy cycle and intracellular digestion. In this study, it has been shown histopathologically that autologous growth factors can prevent apoptosis and prevent loss of outer retinal thickness in the retinal degeneration model created with sodium iodate. [ABSTRACT FROM AUTHOR]

The species-specific differences and mechanisms of action of bee pollen on reproduction have not been well studied. We compared the effects of bee pollen extracts from different plants on ovarian cell functions. We compared the effects of pollens from black alder, dandelion, maize, rapeseed, and willow at 0, 0.01, 0.1, 1, 10, or 100 µg/mL on cultured porcine ovarian granulosa cells. Cell viability was assessed with a Trypan blue test, the cell proliferation marker (PCNA), and an apoptosis marker (BAX) were assessed by immunocytochemistry. Insulin-like growth factor (IGF-I) release was measured by an enzyme-linked immunosorbent assay. Addition of any bee pollen reduced cell viability, promoted accumulation of both proliferation and apoptosis markers, and promoted IGF-I release. The ability of various pollens to suppress cell viability ranked as follows: rapeseed > dandelion > alder > maize > willow. The biological activity of bee pollens regarding their stimulatory action on ovarian cell proliferation ranked as follows: dandelion > willow > maize > alder > rapeseed. Cell apoptosis was promoted by pollens as follows: range > dandelion > alder > rapeseed > willow > maize. The ability of the pollens to stimulate IGF-I output are as follows: willow > dandelion > rapeseed > maize > alder. Bee pollen can promote ovarian cell proliferation by promoting IGF-I release, but it induces the dominance of apoptosis over proliferation and the reduction in ovarian cell viability in a species-specific manner. This is the first demonstration of adverse effects of bee pollen on ovarian cell viability and of its direct stimulatory influence on proliferation, apoptosis, and IGF-I release. The biological potency of bee pollen is dependent on the plant species. [ABSTRACT FROM AUTHOR]

Dear Editor, We report our work on the association of two important biomarkers (serum Insulin-like growth factor -1(IGF-1) and human growth hormone (HGH) with adverse outcomes in kidney transplant recipients with confirmed SARS-CoV-2 infections. Higher HGH in patients who did not survive SARS-CoV-2 may support previously published findings of HGH resistance in ARDS [[3]]. HGH was higher in those patients recovering from (SARS-CoV-2) than in the non-survivors in Group 2 (patients with cardiac dysfunction) after getting infection (P value 0.19) (Table 2). [Extracted from the article]

The objective of this study was to evaluate the effects of in ovo injection with glycerol (GLY) and insulin-like growth factor (IGF-I) on hatchability, biochemical parameters, intestinal morphometry, performance, and carcass characteristics of broiler chickens. A total of 400 fertilised eggs were distributed into five experimental groups. The treatments were arranged as non-injected (control), saline solution injected (0.9% NaCl solution), GLY solution injected (10 nmol/ml), IGF-I solution injected (100 ng/ml), and GLY + IGF-I solution injected. At 17.5 d of incubation, 0.5 ml of each solution was injected into the amniotic fluid of each egg of the injected groups. The injection of different solutions did not influence the hatchability and incubation time of the eggs. Compared to intact eggs, IGF-I and IGF-I+ GLY increased (p < 0.01) the blood IGF-I at hatching. Higher hepatic glycogen was observed (p < 0.05) with GLY or IGF-I. The tested substances decreased (p = 0.02) the fructose 1,6-biphosfate phosphatase activity but did not affect glycaemia. No difference in performance was observed in the first week. Higher feed intake and weight gain with lower feed conversion ratio was obtained (p < 0.05) with IGF-I at 14 d. At 21 d, higher weight gain was obtained (p = 0.05) with IGF-I, GLY, IGF-I, and GLY + IGF-I, resulting (p < 0.01) in birds with greater weight gain at 35 and 42 d of age. GLY provided higher villus height in the ileum at hatching and at 7 d of age. The tested solutions increased the relative weight of the liver at hatching. At 42 d of age, no carcass characteristics were influenced. It is concluded that GLY and IGF-I, together or separately, can be used in the in ovo feeding to improve the post-hatch performance of broilers, without affecting hatchability and carcass composition. [ABSTRACT FROM AUTHOR]

Introduction: Acute kidney injury following cardiac surgery is a dreaded complication contributing to early mortality. Diagnosing AKI using serum creatinine usually results in a delay. To combat this, certain kidney damage specific biomarkers were investigated to identify if they can serve as early predictors of cardiac surgery-associated AKI (CSA-AKI). This study systematically reviews three such biomarkers; NGAL, tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP7) to identify if they can serve as early predictors of CSA-AKI. Methods: Systematic search was carried out on literature reporting the diagnostic ability of the three biomarkers from databases in accordance with PRISMA guidelines. Results: We found 43 articles reporting urinary-NGAL levels (n = 34 in adults, n = 9 in children) and 10 studies reporting TIMP-2 and IGFBP7 levels among adults. Interestingly, NGAL showed high diagnostic value in predicting AKI in children (seven among nine studies with AUROC > 0.8). The cell cycle arrest biomarkers, namely TIMP-2 and IGFBP7, showed high diagnostic value in predicting AKI in adults (five among ten studies with AUROC > 0.8). Conclusion: In predicting CSA-AKI; the diagnostic value of NGAL is high in the paediatric population while the diagnostic value of TIMP-2 and IGFBP7 is high in adults. [ABSTRACT FROM AUTHOR]

Preclinical, clinical, and population studies have provided robust evidence for an important role for the insulin-like growth factor (IGF) system in the development of prostate cancer. An overview of the IGF system is provided. The evidence implicating the IGF system in the development of prostate cancer is summarized. The compelling evidence culminated in a number of clinical trials of agents targeting the system; the reasons for the failure of these trials are discussed. Clinical trials of agents targeting the IGF system in prostate cancer were terminated due to limited objective clinical responses and are unlikely to be resumed unless a convincing predictive biomarker is identified that would enable the selection of likely responders. The aging population and increased screening will lead to greater diagnosis of prostate cancer. Although the vast majority will be indolent disease, the epidemics of obesity and diabetes will increase the proportion that progress to clinical disease. The increased population of worried men will result in more trials aimed to reduce the risk of disease progression; actual clinical endpoints will be challenging and the IGFs remain the best intermediate biomarkers to indicate a response that could alter the course of disease. [ABSTRACT FROM AUTHOR]

The present study was conducted to analyze the mRNA expression of the BMP/SMAD signaling and steroidogenesis associated genes in the granulosa cells (GCs) of newly developed Booroola homozygous carrier GMM (FecBBB) and non-carrier GMM (FecB++) ewes through qRT-PCR. Results showed that the expression of BMP2 (P < 0.05) and BMP6 (P < 0.01) was significantly higher in the GCs of the homozygous carrier GMM (FecBBB) than the non-carrier GMM (FecB++) ewes, while the expression of BMP4 was significantly higher (P < 0.001) in the GCs of non-carrier GMM (FecB++) than the homozygous carrier GMM (FecBBB). In comparison, the expression of TGFβR1, BMPR1A, BMPR1B, and BMPRII was not significantly different between GCs of the homozygous carrier GMM (FecBBB) and non-carrier GMM (FecB++) ewes. Similarly, the expression of SMAD1, SMAD2, SMAD3, SMAD4, and SMAD5 was not significantly different between GCs of homozygous carrier GMM (FecBBB) and non-carrier GMM (FecB++). Further, expression of the INHIBIN, P4R, CYP11A1, and 3βHSD1 genes were not significantly different among the GCs of homozygous carrier GMM (FecBBB) and non-carrier GMM (FecB++), while the expression of StAR was significantly higher (P < 0.01) in the GCs of homozygous carrier GMM (FecBBB) than that of GCs of non-carrier GMM (FecB++) ewes. It is concluded that the FecB mutation significantly up-regulates the expression of BMP2, BMP6, and StAR genes and down-regulate the expression of BMP2 in granulosa cells of newly developed GMM ewes. BMP: Bone morphogenetic protein; TGFβ: Transforming growth factor-beta; SMAD: Fusion of Caenorhabditis elegans Sma genes and the Drosophila Mad, Mothers against decapentaplegic; GCs: Granulosa cells; GMM: Garole x Malpura x Malpura; FecB: Booroola fecundity; BMPR: Bone morphogenetic protein receptor; CYP11A1: Cytochrome P450 family 11 subfamily A member 1; StAR (Steroidogenic acute regulatory protein); 3βHSD1: 3 Beta-hydroxysteroid dehydrogenase; IGF: Insulin-like growth factor; ActR2: Activin receptor 2; ACVR1: Activin A receptor, type I; ACVR2: Activin A receptor, type II; ACVRL1: Activin A receptor like type 1; ACVR1B: Activin A receptor type 1B; ACVR1C: Activin A receptor type 1C; RFLP-PCR: Restriction fragment length polymorphism-polymerase chain reaction; qRT-PCR: Quantitative real-time PCR; ANOVA: Analysis of variance; P4R: Progesterone receptor: AMH: Anti mullerian hormone; RT-PCR: Reverse transcriptase-polymerase chain reaction; ER: Estrogen receptor; FSHR: Follicle stimulating hormone receptor. [ABSTRACT FROM AUTHOR]

Mexico ranks 2nd in adult obesity and 4th in milk intake worldwide. Low levels of IGF-1 have been related to obesity and can be reverted by milk intake. The rs6214 polymorphism has been associated with an increase in the expression of IGF-1. Therefore, the aim of the study was to evaluate the association between both, rs6214 polymorphism and milk intake, and obesity. We analysed 99 adult volunteers, with and without a history of milk intake, for the presence of this polymorphism through qPCR and body composition by electro-bioimpedance. Univariate logistic regression analyses showed that TT genotype is inversely associated with obesity and body fat mass. Besides, milk intake is also related to low obesity, body fat mass and visceral fat, and high percentage of lean mass. Multivariate logistic regression analyses confirm the univariate relationships, showing a clear inverted association between TT genotype, milk intake and obesity. [ABSTRACT FROM AUTHOR]

The aim of the current study was to evaluate the dietary supplementations of a yeast nucleotide (NT) in doses of 0.0, 0.5, 1.5 and 2.5 g NT/kg diet on growth, hemato-biochemical parameters and expressions of some growth-related genes in Nile tilapia, Oreochromis niloticus. After 60 days, highest growth performance, feed utilization, and protein efficiency ratio were recorded in fish fed 2.5 g NT/kg diet. The haemato-biochemical parameters showed the highest significant values in NT-fed fish compared with the control one. Significant increases in values of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), Alkaline Phosphatase (ALP), urea, and creatinine were observed in fish supplemented with 2.5 g NT/kg diet. Stimulatory effects on lipase, amylase, and growth hormone were observed in higher NT-supplemented fish groups. The highest whole body protein and fat contents were recorded in fish fed 0.5 and 2.5 g NT/kg diet, respectively. Ghrelin and insulin-like growth factor gene expressions showed significant up-regulation in the fish supplemented with 1.5 and 2.5 g NT/kg diet, successively. The results recommended the administration of dietary NT at percentages of 1.5– 2.5 g NT/kg diet had beneficial effects on Nile tilapia. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of chronic growth hormone deficiency (GHD) and its association with other hormonal deficiencies was determined in middle-aged patients post-stroke with and without consideration of body mass index (BMI). Methods: Clinical records were reviewed to determine pituitary function at least 3 months post-stroke. Patients with a history of endocrine anomalies were excluded. GHD was determined by utilizing standard peak GH cutoffs following the glucagon stimulation test. A secondary analysis was conducted with stricter BMI-adjusted cutoffs. The accuracy of IGF-1 in predicting GHD was also examined. Results: GHD was diagnosed in 54% of patients (≥5.0 μg/L), with 32% falling into the severe (≤3 μg/L) category. Patients with GHD had lower levels of FSH, T3, LH, and SHBG. Analyzes of BMI-adjusted GH levels, revealed that 14% of patients were GHD. These patients had higher prolactin. IGF-1 values were not predictive of GHD. Latency to be admitted to post-acute rehabilitation was greater in patients with GHD. Conclusions: Evidence suggests patients with stroke may be at risk for developing GHD. GHD was associated with decreased levels of other hormones. Co-morbidities for stroke and neuroendocrine dysfunction overlap and may have implications for recovery following stroke. [ABSTRACT FROM AUTHOR]

HOXA10 is an important regulator of embryo adhesion. Reduced expression may contribute to embryo implantation failure. The expression of Nur77 and HOXA10 has been shown to be reduced in the endometrium of patients with recurrent implantation failure. In this study, we found that Nur77 was directly bound to the HOXA10 promoter and promoted HOXA10 protein expression in a dose-dependent manner in Ishikawa cells. Furthermore, the promoting effect of Nur77 on embryo adhesion was significantly blocked when endogenous HOXA10 expression was knocked down in Ishikawa cells. Moreover, the Nur77 agonist 6-MP was also confirmed to promote embryo adhesion. This study is the first to show that Nur77 promotes embryo adhesion by transcriptionally regulating HOXA10 expression. Nur77 and 6-MP may provide a basis to develop a new treatment for patients who suffer from embryo adhesion dysfunction. Abbreviations: HB-EGF: heparin-binding epidermal growth factor-like growth factor; HOXA10: homeobox A10; NGFI-B: nerve growth factor-induced gene B; RIF: recurrent implantation failure; RPL: recurrent pregnancy loss; 6-MP: 6-mercaptopurine; IGFBP-1: insulin-like growth factor binding protein-1; LIF: leukemia inhibitory factor; IL-1β: Interleukin - 1β; CRISPR/Cas9: Clustered Regularly Interspaced Short Palindromic Repeats; AF-1: activation function-1 domain; HIF-1α: hypoxia-inducible factor 1α; CREB: cAMP response element binding [ABSTRACT FROM AUTHOR]

Background: The aim of the current study was to determine if 4 weeks of consumption of Bang® Pre-Workout Master Blaster® (BMB; Vital Pharmaceuticals Inc., Weston, FL) combined with resistance training resulted in greater increases in muscle mass and maximal strength compared with resistance training combined with placebo (PLA). Additionally, we aimed to determine if BMB ingestion combined with resistance training preferentially altered resting skeletal muscle expression of microRNAs (miRs) or resting serum insulin-like growth factor (IGF-1). Methods: Sixteen recreationally-active men completed the study. The study employed a block-randomized, double-blind, placebo-controlled, parallel design. Participants completed two testing sessions separated by 4 weeks of resistance exercise combined with daily supplementation of BMB or PLA. At each testing session, hemodynamics, body composition, and muscle and blood samples were obtained followed by strength assessments of the lower- and upper-body via measurement of squat and bench press one-repetition maximum (1-RM), respectively. A separate general linear model was utilized for analysis of each variable to determine the effect of each supplement (between-factor) over time (within-factor) using an a priori probability level of ≤0.05. Results: No significant effects were observed for dietary intake, hemodynamics, fat mass, body fat percentage, or serum IGF-1. A greater increase in total body mass (3.19 kg, 95% CI, 1.98 kg, 4.40 kg vs. 0.44 kg, 95% CI, − 0.50 kg, 1.39 kg) and lean body mass (3.15 kg, 95% CI, 1.80 kg, 4.49 kg vs. 0.89 kg, 95% CI, − 0.14 kg, 1.93 kg) was observed for the BMB group compared with PLA (p < 0.01). A significant increase over time was observed for miR-23a (p = 0.02) and miR-23b (p = 0.05) expression. A greater increase in squat 1-RM was observed for the BMB group (23.86 kg, 95% CI, 16.75 kg, 30.97 kg) compared with the PLA group (14.20 kg, 95% CI, 7.04 kg, 21.37 kg, p = 0.04). Conclusions: BMB supplementation combined with resistance exercise training for 4 weeks resulted in superior adaptations in maximal strength and LBM compared with resistance training with a placebo. No adverse resting hemodynamic or clinical blood safety markers were observed as a result of BMB supplementation. The superior outcomes associated with BMB supplementation could not be explained by resting serum IGF-1 or the skeletal muscle miRs measured, although resting miR-23a and miR-23b expression both increased as a result of resistance training. [ABSTRACT FROM AUTHOR]

Growth failure (GF) is a frequent problem after pediatric allogeneic hematopoietic stem cell transplantation (HSCT). Growth hormone deficiency (GHD) occurs in 20 to 85%, but published data on the efficacy of growth hormone treatment (GHT) are conflicting. Currently, there are no recommendations on screening for and treatment of GHD after HSCT. We aimed to describe the management of endocrine follow-up (FU)and details of GHT within European Society for Blood and Marrow Transplantation (EBMT) centers. In a retrospective questionnaire study, all EBMT centers performing pediatric HSCT were invited. Results were evaluated in correlation with the structure of endocrine aftercare (HSCT-clinicians and endocrinologists). The majority of centers (80%) reported endocrine FU by an endocrinologist – either within the HSCT-center or in a separate endocrine clinic. Fifty-four percent reported FU outside of the HSCT-center. As diagnostic tests the insulin-like growth factor IGF-I and insulin-like growth factor binding protein IGFBP3, insulin tolerance test and arginine stimulation test were most frequently used. Sixty-four percent of centers performed GHT and endocrinologists were more likely to prescribe GH (74%) compared to HSCT-clinicians (33%). The most frequent indication for GHT was GHD in 60%, with a distinct different approach of endocrinologists in comparison with HSCT-clinicians. Our study reveals substantial variation in practice and emphasizes the need for endocrine aftercare performed by dedicated endocrinologists in close collaboration with the HSCT-center. Our results indicate that the management of GHT depends on the structure of endocrine aftercare, which is important for the future development and distribution of studies and guidelines. [ABSTRACT FROM AUTHOR]

Large bone defects have always been a big challenge. The use of bone marrow mononuclear cells (BMCs) combined with an osteoconductive scaffold has been proved a good alternative for the treatment of large bone defects. Another autologous source for tissue engineering is platelet rich fibrin (PRF). PRF is a blood concentrate system obtained through a one-step centrifugation. The generated 3D matrix of the PRF clot serves as a reservoir of growth factors. Those growth factors might support the regenerative response of BMC, and therefore the effect of PRF, centrifuged with either high medium (208 g) or low (60 g) relative centrifugation force (RCF) on BMCs was evaluated in vitro in the present study. The two PRF matrices obtained were initially characterized and compared to human serum. Significantly increased concentrations of insulin-like growth factor (IGF), soluble intercellular adhesion molecule-1 (sICAM1) and transforming growth factor (TGF)-β were found in PRF compared to human serum whereas VEGF concentration was not significantly altered. A dose-response study revealed no further activation of BMC's metabolic activity, if concentration of both PRF matrices exceeded 10% (v/v). Effect of both PRF preparations [10%] on BMC was analyzed after 2, 7, and 14 days in comparison to human serum [10%]. Metabolic activity of BMC increased significantly in all groups on day 14. Furthermore, gene expression of matrix metalloproteinases (MMP)-2, −7, and −9 was significantly stimulated in BMC cultivated with the respective PRF matrices compared to human serum. Apoptotic activity of BMC incubated with PRF was not altered compared to BMC cultivated with serum. In conclusion, PRF could be used as a growth factor delivery system of autologous or allogeneic source with the capability of stimulating cells such as BMC. [ABSTRACT FROM AUTHOR]

Previous studies have shown that insulin-like growth factor (IGF)-1 levels are positively and IGF binding protein (IGFBP)-3 levels negatively associated with risk of certain cancers. Also, dietary factors may influence the IGF system. We aimed to analyze the associations of current, childhood and adolescent milk intake with IGF-1 levels, IGFBP-3 levels and IGF-1:IGFBP-3 molar ratio in adulthood. Multivariable linear regression analyses by sex and race/ethnicity were performed using cross-sectional data from the Third National Health and Nutrition Examination Survey. A total of 5,805 participants were included in the analyses. Adult IGF-1 levels and IGF-1:IGFBP-3 molar ratio had significant inverse associations (P-trend = 0.02) with adolescent milk intake in non-Hispanic white men, but not in men of other race/ethnicities or in women. There were no associations between current or childhood milk intake and IGF-1 levels or IGF-1:IGFBP-3 molar ratio in adulthood. Current milk intake and childhood milk intake had significant positive associations (P-trend = 0.02) with adult IGFBP-3 levels in non-Hispanic white and non-Hispanic black women, respectively, but no associations were observed in Mexican American women or in men. Overall, there were long-term and short-term associations between milk intake and IGF-1 and IGFBP-3 levels, but the associations varied by race/ethnicity and sex. [ABSTRACT FROM AUTHOR]

Calcium and, to a lesser extent, dairy products are consistently modestly inversely associated with colorectal cancer (CRC). Dairy products may contain components other than calcium and fat, such as insulin-like growth factor-1, that may affect CRC risk. In the prospective Iowa Women's Health Study, calcium, dairy product, and vitamin D intakes were assessed using a semiquantitative food frequency questionnaire. To investigate dairy products independent of their calcium components, we estimated residuals from linear regression models of their associations with dietary calcium. Of the 35,221 55–69-year-old cancer-free women at baseline in 1986, 1,731 developed CRC during follow-up through 2012. For those in the highest relative to the lowest intake quintiles, the adjusted hazards ratios and 95% confidence intervals from multivariable Cox proportional hazards regression models for overall and distal CRC were 0.81 (0.67–0.98; Ptrend = 0.004) and 0.59 (0.44–0.80; Ptrend = 0.003), respectively, for total calcium; and 0.79 (0.66–0.94; Ptrend = 0.01) and 0.69 (0.53–0.90; Ptrend = 0.003) for total dairy products, respectively. The various dairy product residuals were not associated with CRC. These results support that, among women, calcium and dairy products may be inversely associated with CRC—perhaps primarily distal CRC—but suggest that the non-calcium, non-fat component of dairy products may not be associated with CRC. [ABSTRACT FROM AUTHOR]

Objectives: Our objectives were: 1) to determine whether maximal aerobic exercise increased serum neurotrophins in chronic stroke and 2) to determine the factors that predict resting and exercise-dependent levels. Methods: We investigated the potential predictors of resting and exercise-dependent serum insulin-like growth factor-1 and brain-derived neurotrophic factor among 35 chronic stroke patients. Predictors from three domains (demographic, disease burden, and cardiometabolic) were entered into 4 separate stepwise linear regression models with outcome variables: resting insulin-like growth factor, resting brain-derived neurotrophic factor, exercise-dependent change in insulin-like growth factor, and exercise-dependent change brain-derived neurotrophic factor. Results: Insulin-like growth factor decreased after exercise (p = 0.001) while brain-derived neurotrophic factor did not change (p = 0.38). Greater lower extremity impairment predicted higher resting brain-derived neurotrophic factor (p = 0.004, r2 = 0.23). Higher fluid intelligence predicted greater brain-derived neurotrophic factor response to exercise (p = 0.01, r2 = 0.18). There were no significant predictors of resting or percent change insulin-like growth factor-1. Discussion: Biomarkers have the potential to characterize an individual's potential for recovery from stroke. Neurotrophins such as insulin-like growth factor-1 and brain-derived neurotrophic factor are thought to be important in neurorehabilitation; however, the factors that modulate these biomarkers are not well understood. Resting brain-derived neurotrophic factor and percent change in brain-derived neurotrophic factor were related to physical and cognitive recovery in chronic stroke, albeit weakly. Insulin-like growth factor-1 was not an informative biomarker among chronic stroke patients. The novel finding that fluid intelligence positively correlated with exercise-induced change in brain-derived neurotrophic factor warrants further research. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effect of growth hormone (GH) therapy on appetite-regulating hormones and to examine the association between these hormones and the response to GH, body composition, and resting energy expenditure (REE). Methods: Nine pre-pubertal children with idiopathic short stature underwent a standard meal test before and 4 months following initiation of GH treatment. Ghrelin, GLP-1, leptin, and insulin levels were measured; area under the curve (AUC) was calculated. Height, weight, body composition, REE, and insulin-like growth factor levels were recorded at baseline and after 4 and 12 months. Results: Following 4 months of GH therapy, food intake increased, with increased height-standard deviation score (SDS), weight-SDS, and REE (p <.05). Significant changes in appetite-regulating hormones included a decrease in postprandial AUC ghrelin levels (p =.045) and fasting GLP-1 (p =.038), and an increase in fasting insulin (p =.043). Ghrelin levels before GH treatment were positively correlated with the changes in weight-SDS (fasting: r =.667, p =.05; AUC: r =.788, p =.012) and REE (fasting: r =.866, p =.005; AUC: r =.847, p =.008) following 4 months of GH therapy. Ghrelin AUC at 4 months was positively correlated with the changes in height-SDS (r =.741, p =.022) and fat-free-mass (r =.890, p =.001) at 12 months of GH treatment. Conclusions: The reduction in ghrelin and GLP-1 following GH treatment suggests a role for GH in appetite regulation. Fasting and meal-AUC ghrelin levels may serve as biomarkers for predicting short-term (4 months) changes in weight and longer term (12 months) changes in height following GH treatment. The mechanisms linking GH with changes in appetite-regulating hormones remain to be elucidated. Abbreviations: SDS: standard deviation score; REE: resting energy expenditure; SMT: standard meal test; AUC: area under the curve; ISS: idiopathic short stature; SGA: small for gestational age; FFM: fat-free-mass; FM: fat mass; EER: estimated energy requirements; DRI: dietary reference intakes; IQR: inter-quartile range [ABSTRACT FROM AUTHOR]

A soy protein-based supplement may optimize bone health, support physical growth, and stimulate bone formation. This study aimed to assess the effect of a daily soy protein supplement (SPS) on nutritional status, bone formation markers, lipid profile, and daily energy and macronutrient intake in children. One hundred seven participants (62 girls), ages 2 to 9, started the study and were randomly assigned to lunch fruit juice with (n = 57, intervention group) or without (n = 50, control group) addition of 45 g (230 Kcal) of a commercial SPS during 12 months; 84 children (51 girls, 33 boys) completed the study (45 and 39 intervention and control, respectively). Nutritional assessment included anthropometry and nutrient intakes; initial and final blood samples were taken; insulin-like growth factor-I (IGF-I), osteocalcin, bone specific alkaline phosphatase (BAP), insulin-like growth factor binding protein-3 (IGFBP-3), cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were analyzed. Statistically significant changes (p <.05) in body mass index and weight for age Z scores were observed between groups while changes in body composition were not. Changes in energy, total protein, and carbohydrate intakes were significantly higher in the intervention group (p <.01). Calorie intake changes were statistically significant between groups (p <.001), and BAP decreased in both groups, with values within normal ranges. Osteocalcin, IGFBP-3, and lipid profile were not different between groups. IGF-I levels and IGF/IGFBP-3 ratio increased significantly in both groups. In conclusion, changes in macronutrient and energy intake and nutritional status in the intervention group compared to control group may ensure harmonious and adequate bone health and development. [ABSTRACT FROM AUTHOR]