IGF-I Research Articles

The expression level of mir-21-3p in platelet-rich plasma: A potential effective factor and predictive biomarker in recurrent implantation failure.

Recurrent implantation failure (RIF) is the most important complication associated with in vitro fertilization (IVF). Despite the good quality of the transferred embryo, the success rate is rather disappointing. Therefore, predictive biomarkers for implantation are critical to making decisions about transferring high-quality embryos or cryopreserving them for cycles with a higher chance of implantation. Recently, intrauterine infusion of autologous platelet-rich plasma (PRP) has been proposed to increase the endometrial receptivity in RIF patients. PRP is rich in both growth factors and microRNAs (miRNAs). We investigated the possible association of mir-21-3p, mir-21-5p, mir-494-3p, mir-145-5p, and insulin-like growth factor-I (IGF-I) levels in PRP and platelet-poor plasma (PPP) samples with the pregnancy outcomes in RIF patients. The miRNA expression level and IGF-I concentration were assessed using real-time PCR and chemiluminescence methods respectively. Mir-21-3p was upregulated in PRP samples of the pregnant group in comparison to the nonpregnant group. There was no difference in the expression of mir-21-3p in PPP samples of these groups. The concentration of IGF-I was higher in PRP and PPP samples of the nonpregnant in comparison to the pregnant group. Receiver-operating characteristic curve analysis showed that mir-21-3p can be a valuable biomarker for the prediction of pregnancy chance in RIF patients treated with PRP.

Altered Circulating Leptin, hGH, and IGF-I in Prediabetes and Screening-Diagnosed T2DM Unrelated to Metabolic Syndrome in Women Post Gestational Diabetes.

Recently, we proposed two pathophysiologic subtypes of type 2 diabetes mellitus (T2DM), one related and one unrelated to metabolic syndrome. To begin to understand the pathophysiology of the subtype unrelated to metabolic syndrome, we now measured selected hormones and signaling molecules in affected individuals. In this cross-sectional analysis, we examined 138 women out of the monocenter, post gestational diabetes study PPSDiab. Of these women, 73 had prediabetes or screening-diagnosed T2DM, 40 related to metabolic syndrome and 33 unrelated. The remaining 65 women were normoglycemic controls. Our analysis included medical history, anthropometrics, oral glucose tolerance testing, laboratory chemistry, and cardiopulmonary exercise testing. In addition, plasma proinsulin/insulin ratio, growth hormone (hGH) nadir during oral glucose tolerance testing, Insulin-like Growth Factor I (IGF-I), Leptin, Resistin, Adiponectin, Fetuin-a, FGF21, and myostatin were measured. Compared to controls, women with prediabetes or screening-diagnosed T2DM unrelated to metabolic syndrome depicted higher plasma Leptin [10.47(6.6-14.57) vs. 5.52(3.15-10.02); p<0.0001] and IGF-I [193.01(171.00-213.30) vs. 167.97(138.77-200.64); p=0.0008], as well as a lower hGH nadir [0.07(0.05-0.15) vs. 0.14(0.08-0.22; p<0.0001]. These differences were independent of body adiposity. Women with prediabetes or T2DM related to metabolic syndrome, in comparison to controls, displayed elevated Leptin, Fetuin-a, and FGF21, as well as reduced Adiponectin and hGH nadir. Based on our study, altered Leptin and hGH/IGF-I signaling could potentially contribute to the pathophysiology of prediabetes and T2DM unrelated to metabolic syndrome. Further mechanistic investigations of these signaling pathways in the context of lean T2DM are necessary to test causal relationships.

Relationship of serum adiponectin and IGF-I concentrations with progesterone and their effect on pregnancy rates in cows

The aims of this study were to determine serum adiponectin and insulin-like growth factor-I (IGF-I) concentrations in early and late luteal phases following artificial insemination, to evaluate their relationship with progesterone concentrations, and to detect their effects on the pregnancy rate. We used 45 Holstein cows aged 3–4 years who had given birth at least once and who did not have any problem in the genital system as observed on rectal palpation/ultrasonography examination. Presynch–ovsynch synchronization protocol was applied on cows. Blood samples were collected to determine the concentrations of progesterone, adiponectin, and IGF-I on days 5 and 18 following artificial insemination. Pregnancy examination using real-time ultrasonography was performed on day 30 following artificial insemination. Fifteen (33.33%) of the 45 cows were determined as pregnant. The pregnancy rates were increased with increasing progesterone concentration on day 5 following artificial insemination, and the pregnancy rates were the highest (53.84%) among the cows with progesterone concentration of &gt;2.00 ng/mL. Adiponectin and IGF-I concentrations were determined as 26.69±11.84 vs 24.14±9.19 and 17.52±4.19 vs 17.42±2.92, on days 5 and 18 after artificial insemination, respectively (P&gt;0.05). Negative correlation was observed between adiponectin and progesterone concentrations (P&lt;0.05), whereas positive correlation was observed between IGF-I and progesterone on day 5 following artificial insemination (P&lt;0.05). Progesterone and IGF-I concentrations in pregnant cows were higher than in nonpregnant cows on days 5 and 18 following artificial insemination (P&lt;0.05). In conclusion, the progesterone and IGF-I concentrations in early and late luteal phase following artificial insemination had a positive effect on the pregnancy rate. However, although early adiponectin concentration affected progesterone concentrations, it did not affect the pregnancy rate.

Merging bioresponsive release of insulin-like growth factor I with 3D printable thermogelling hydrogels.

3D printing of biomaterials enables spatial control of drug incorporation during automated manufacturing. This study links bioresponsive release of the anabolic biologic, insulin-like growth factor-I (IGF-I) in response to matrix metalloproteinases (MMP) to 3D printing using the block copolymer of poly(2-methyl-2-oxazoline) and thermoresponsive poly(2-n-propyl-2-oxazine) (POx-b-POzi). For that, a chemo-enzymatic synthesis was deployed, ligating IGF-I enzymatically to a protease sensitive linker (PSL), which was conjugated to a POx-b-POzi copolymer. The product was blended with the plain thermogelling POx-b-POzi hydrogel. MMP exposure of the resulting hydrogel triggered bioactive IGF-I release. The bioresponsive IGF-I containing POx-b-POzi hydrogel system was further detailed for shape control and localized incorporation of IGF-I via extrusion 3D printing for future applications in biomedicine and biofabrication.

High association of a novel variant in the adiponectin gene with the litter size in Awassi ewes

Flock productivity is affected by reproductive traits controlled by many factors such as ovulation rate, hormones, and genetics. Many genes are associated with fertility and other features related to it such as melatonin receptor 1A ( MNTR1A ) gene, inhibin βA ( INHBA) gene, insulin-like growth factor-I ( IGF-1 ) gene, and prolactin gene, and many other new candidates, adiponectin gene ( ADIPOQ ) is one of them, which are associated with reproduction and fertility. This study aimed to evaluate the genetic variation of the ADIPOQ gene concerning the litter size of Awassi ewes. Genomic DNA isolated from 114 Awassi ewes produced single lambs and 84 Awassi ewes produced twin lambs. By polymerase chain reaction (PCR), we amplified all three exons (368 bp, 448 bp, and 363 bp) of the ADIPOQ gene (exons 1, 2, and 3). Three genotypes were found in the 368 bp amplicons, the CC, CA, and AA genotypes. Novel mutation c.198473337C > A was discovered in the CA genotype through a sequencing reaction. This single nucleotide polymorphism (SNP) showed a highly significant ( P ≤ 0.01) association with litter size, in that the sheep with this SNP had a larger litter size than those without it. The ewes with the AA genotype had 1.97 lambs more than those with the CC and CA genotypes. Using logistic regression, the c.198473337C > A SNP was confirmed to be responsible for increasing the litter size. In conclusion, the c.198473337C > A SNP appears to have an interesting and positive impact on reproductive traits (especially litter size) in Awassi sheep. In light of these data, the genetic variant of the ADIPOQ gene could be used for developing marker-assisted selection programs to improve litter size in Awassi sheep.

Efficient transdermal delivery of functional protein cargoes by a hydrophobic peptide MTD 1067

The skin has a protective barrier against the external environment, making the transdermal delivery of active macromolecules very difficult. Cell-penetrating peptides (CPPs) have been accepted as useful delivery tools owing to their high transduction efficiency and low cytotoxicity. In this study, we evaluated the hydrophobic peptide, macromolecule transduction domain 1067 (MTD 1067) as a CPP for the transdermal delivery of protein cargoes of various sizes, including growth hormone-releasing hexapeptide-6 (GHRP-6), a truncated form of insulin-like growth factor-I (des(1-3)IGF-I), and platelet-derived growth factor BB (PDGF-BB). The MTD 1067-conjugated GHRP-6 (MTD-GHRP-6) was chemically synthesized, whereas the MTD 1067-conjugated des(1-3)IGF-I and PDGF-BB proteins (MTD-des(1-3)IGF-I and MTD-PDGF-BB) were generated as recombinant proteins. All the MTD 1067-conjugated cargoes exhibited biological activities identical or improved when compared to those of the original cargoes. The analysis of confocal microscopy images showed that MTD-GHRP-6, MTD-des(1-3)IGF-I, and MTD-PDGF-BB were detected at 4.4-, 18.8-, and 32.9-times higher levels in the dermis, respectively, compared to the control group without MTD. Furthermore, the MTD 1067-conjugated cargoes did not show cytotoxicity. Altogether, our data demonstrate the potential of MTD 1067 conjugation in developing functional macromolecules for cosmetics and drugs with enhanced transdermal permeability.

Effect of the Tea Tree Oil on Growth Performance, Meat Quality, Serum Biochemical Indices, and Antioxidant Capacity in Finishing Pigs.

The increased use of antibiotics continues to pose a threat to public health because of the increasing concern of antibiotic residue. Tea tree oil (TTO) is an extract of the Australian plant Melaleuca alternifolia with anti-inflammatory and antioxidant properties. However, there is little information on TTO supplementation in the diet of finishing pigs. Hence, the present study aimed to investigate the effect of TTO supplemented diets on the growth performance, meat quality, serum biochemical indices, and antioxidant capacity of the finishing pigs. Our results showed that TTO supplementation increased (P < 0.05) the mRNA expression of insulin-like growth factors -I (IGFs-I), growth acceleration hormone (GH), and heart fatty acid-binding protein (H-FABP), while the mRNA expression of myostatin gene (MSTN), and calpain-1 (CAST) decreased by the TTO supplementation, compared with the control group. In addition, TTO supplementation increased (P < 0.05) serum alkaline phosphatase (ALP), immunoglobulin G (IgG), and IgM levels but decreased (P < 0.05) serum aspartate transaminase (AST) concentration, relative to the control group. In addition, we found that the live weight and intramuscular fat enhanced (P < 0.05) significantly, and muscle pH 24 min value, cooking loss, and shear force decreased (P < 0.05) dramatically in the TTO group. The TTO supplementation increased (P < 0.05) C18:2n6t concentration and decreased (P < 0.05) C12:0 and C16:0 concentration, relative to the control group. Dietary supplementation with TTO decreased (P < 0.05) malondialdehyde (MDA) and increased (P < 0.05) glutathione peroxidase (GSH-Px) activity in serum. These results indicated that TTO supplementation could improve immunity and antioxidant, carcass traits, the nutritional value of pork, and the antioxidant capacity of finishing pigs. Therefore, TTO has potential positive effects as a feed additive in the pig industry.

Insulin and insulin-like growth factor-I receptors in astrocytes exert different effects on behavior and Alzheimer´s-like pathology.

Background: Pleiotropic actions of insulin and insulin-like growth factor I (IGF-I) in the brain are context- and cell-dependent, but whether this holds for their receptors (insulin receptor (IR) and IGF-I receptor (IGF-IR), respectively), is less clear. Methods: We compared mice lacking IR or IGF-IR in glial fibrillary astrocytic protein (GFAP)-expressing astrocytes in a tamoxifen-regulated manner, to clarify their role in this type of glial cells, as the majority of data of their actions in brain have been obtained in neurons. Results: We observed that mice lacking IR in GFAP astrocytes (GFAP IR KO mice) develop mood disturbances and maintained intact cognition, while at the same time show greater pathology when cross-bred with APP/PS1 mice, a model of familial Alzheimer´s disease (AD). Conversely, mice lacking IGF-IR in GFAP astrocytes (GFAP-IGF-IR KO mice) show cognitive disturbances, maintained mood tone, and show control-dependent changes in AD-like pathology. Conclusions: These observations confirm that the role of IR and IGF-IR in the brain is cell-specific and context-dependent.

Neuroendocrine, inflammatory, and extracellular vesicle responses during the Navy Special Warfare Screener Selection Course.

Military operational stress is known to increase adrenal hormones and inflammatory cytokines, while decreasing hormones associated with the anabolic milieu and neuroendocrine system. Less is known about the role of extracellular vesicles (EVs), a form of cell-to-cell communication, in military operational stress and their relationship to circulating hormones. The purpose of this study was to characterize the neuroendocrine, cytokine, and EV response to an intense. 24-h selection course known as the Naval Special Warfare (NSW) Screener and identify associations between EVs and cytokines. Blood samples were collected the morning of and following the NSW Screener in 29 men (18-26 yr). Samples were analyzed for concentrations of cortisol, insulin-like growth factor I (IGF-I), neuropeptide-Y (NPY), brain-derived neurotrophic factor (BDNF), α-klotho, tumor necrosis factor-α (TNFα), and interleukins (IL) -1β, -6, and -10. EVs stained with markers associated with exosomes (CD63), microvesicles (VAMP3), and apoptotic bodies (THSD1) were characterized using imaging flow cytometry and vesicle flow cytometry. The selection event induced significant changes in circulating BDNF (-43.2%), IGF-I (-24.6%), TNFα (+17.7%), and IL-6 (+13.6%) accompanied by increases in intensities of THSD1+ and VAMP3+ EVs (all P < 0.05). Higher concentrations of IL-1β and IL-10 were positively associated with THSD1+ EVs (P < 0.05). Military operational stress altered the EV profile. Surface markers associated with apoptotic bodies were positively correlated with an inflammatory response. Future studies should consider a multiomics assessment of EV cargo to discern canonical pathways that may be mediated by EVs during military stress.

Insulin-like growth factor-I biocompartmentalization across blood, interstitial fluid and muscle, before and after 3 months of chronic resistance exercise.

This investigation examined the influence of 12-week ballistic resistance training programs on the IGF-I system in circulation, interstitial fluid, and skeletal muscle, at rest and in response to acute exercise. Seventeen college-aged subjects (11 women/6 men; 21.7 ± 3.7 yr) completed an acute ballistic exercise bout before and after the training program. Blood samples were collected pre-, mid-, and postexercise and analyzed for serum total IGF-I, free IGF-I, and IGF binding proteins (IGFBPs) 1-4. Dialysate and interstitial free IGF-I were analyzed in vastus lateralis (VL) interstitial fluid collected pre- and postexercise via microdialysis. Pre- and postexercise VL muscle biopsies were analyzed for IGF-I protein expression, IGF-I receptor phosphorylation (p-IGF-IR), and AKT phosphorylation (p-AKT). Following training, basal serum IGF-I, free IGF-I, IGFBP-2, and IGFBP-3 decreased whereas IGFBP-1 and IGFBP-4 increased. Training reduced basal dialysate and interstitial free IGF-I but had no effect on basal skeletal muscle IGF-I, p-IGF-IR, or p-AKT. Acute exercise elicited transient changes in IGF-I system concentrations and downstream anabolic signaling both pre- and posttraining; training did not affect this acute exercise response. Posttraining, acute exercise-induced changes in dialysate/interstitial free IGF-I were strongly correlated with the changes in intramuscular IGF-I expression, p-IGF-IR, and p-AKT. The divergent influence of resistance training on circulating/interstitial and skeletal muscle IGF-I demonstrates the importance of concurrent, multiple biocompartment analysis when examining the IGF-I system. As training elicited muscle hypertrophy, these findings indicate that IGF-I's anabolic effects on skeletal muscle are mediated by local, rather than systemic mechanisms.NEW & NOTEWORTHY In the first investigation to assess resistance training's effects on the IGF-I system in serum, interstitial fluid, and skeletal muscle, training decreased basal circulating and interstitial IGF-I but did not alter basal intramuscular IGF-I protein activity. Posttraining, acute exercise-induced interstitial IGF-I increases were strongly correlated with intramuscular IGF-I expression and signaling. These findings highlight the importance of multibiocompartment measurement when analyzing IGF-I and suggest that IGF-I's role in hypertrophic adaptations is locally mediated.

How insulin-like growth factor I binds to a hybrid insulin receptor type 1 insulin-like growth factor receptor

SummaryMonomers of the insulin receptor and type 1 insulin-like growth factor receptor (IGF-1R) can combine stochastically to form heterodimeric hybrid receptors. These hybrid receptors display ligand binding and signaling properties that differ from those of the homodimeric receptors. Here, we describe the cryoelectron microscopy structure of such a hybrid receptor in complex with insulin-like growth factor I (IGF-I). The structure (ca. 3.7 Å resolution) displays a single IGF-I ligand, bound in a similar fashion to that seen for IGFs in complex with IGF-1R. The IGF-I ligand engages the first leucine-rich-repeat domain and cysteine-rich region of the IGF-1R monomer (rather than those of the insulin receptor monomer), consistent with the determinants for IGF binding residing in the IGF-1R cysteine-rich region. The structure broadens our understanding of this receptor family and assists in delineating the key structural motifs involved in binding their respective ligands.

Combined statistical decision limits based on two GH-2000 scores for the detection of growth hormone misuse.

The growth hormone-2000 biomarker method, based on the measurements of insulin-like growth factor-I and the amino-terminal pro-peptide of type III collagen, has been developed as a powerful technique for the detection of growth hormone misuse by athletes. Insulin-like growth factor-I and amino-terminal pro-peptide of type III collagen are combined in gender-specific formulas to create the growth hormone-2000 score, which is used to determine whether growth hormone has been administered. To comply with World Anti-Doping Agency regulations, each analyte must be measured by two methods. Insulin-like growth factor-I and amino-terminal pro-peptide of type III collagen can be measured by a number of approved methods, each leading to its own growth hormone-2000 score. Single decision limits for each growth hormone-2000 score have been introduced and developed by Bassett, Erotokritou-Mulligan, Holt, Böhning and their co-authors in a series of papers. These have been incorporated into the guidelines of the World Anti-Doping Agency. A joint decision limit was constructed based on the sample correlation between the two growth hormone-2000 scores generated from an available sample to increase the sensitivity of the biomarker method. This paper takes this idea further into a fully developed statistical approach. It constructs combined decision limits when two growth hormone-2000 scores from different assay combinations are used to decide whether an athlete has been misusing growth hormone. The combined decision limits are directly related to tolerance regions and constructed using a Bayesian approach. It is also shown to have highly satisfactory frequentist properties. The new approach meets the required false-positive rate with a pre-specified level of certainty.

Insulin-like growth factor I sensitization rejuvenates sleep patterns in old mice.

Sleep disturbances are common during aging. Compared to young animals, old mice show altered sleep structure, with changes in both slow and fast electrocorticographic (ECoG) activity and fewer transitions between sleep and wake stages. Insulin-like growth factor I (IGF-I), which is involved in adaptive changes during aging, was previously shown to increase ECoG activity in young mice and monkeys. Furthermore, IGF-I shapes sleep architecture by modulating the activity of mouse orexin neurons in the lateral hypothalamus (LH). We now report that both ECoG activation and excitation of orexin neurons by systemic IGF-I are abrogated in old mice. Moreover, orthodromical responses of LH neurons are facilitated by either systemic or local IGF-I in young mice, but not in old ones. As orexin neurons of old mice show dysregulated IGF-I receptor (IGF-IR) expression, suggesting disturbed IGF-I sensitivity, we treated old mice with AIK3a305, a novel IGF-IR sensitizer, and observed restored responses to IGF-I and rejuvenation of sleep patterns. Thus, disturbed sleep structure in aging mice may be related to impaired IGF-I signaling onto orexin neurons, reflecting a broader loss of IGF-I activity in the aged mouse brain.

INFLUENCE OF INSULIN-LIKE GROWTH FACTOR-I LEVELS ON THE COURSE OF ACUTE MYOCARDIAL INFARCTION: review

Over the last many years, cardiovascular disease has reached epidemic proportions among chronic noncommunicable diseases worldwide. According to the latest tendencies, cardiovascular diseases play the leading role in the formation of current negative health and demographic trends in Ukraine and all over the world: they significantly affect the main health indicators: morbidity, mortality, disability, life expectancy and quality of life. If we take the last 20 years, we can see that the prevalence of CVDs among the Ukrainian population has tripled, and the mortality rate from them has risen by 40%. Review was analysed serum level insulin-like growth factor-I (IGF-I) in patients with acute myocardial infarction and his role in left ventricular remodelling was established. The scientific data regarding the neurohumoral component of acute myocardial infarction pathogenesis have been expanded by increasing levels of the angiogenesis marker IGF-I, which can be explained by his properties as markers of the acute phase of inflammation. An analysis of the relationship between troponin I and IGF-I, a marker of myocardial damage, showed a direct relationship, indicating an increase in troponin I concentration with rising serum IGF-I levels. This indicates that the activity of the angiogenesis marker IGF-I may be associated with the severity and depth of myocardial damage.

The prevalence of IGF-I axis genetic polymorphisms among decathlon athletes

ObjectiveDecathlon is a combined track and field competition, consisting of ten, mainly anaerobic events. Insulin-like growth factor-I (IGF1) axis plays a pivotal role in athletes' structural and functional muscle adaptation to exercise training, and in their competitive performance. Based on the great demand for speed physiological characteristics among decathlon athletes, the aim of this study was to assess the prevalence of IGF genetic polymorphisms among decathletes, to present an optimal genetic profile for enhancing performance. MethodsThe participants included 151 male athletes and 75 male non-athletic controls from Israel and Estonia. Athletes were divided into four groups, according to the field of expertise: (a) 40 sprinters and long jumpers; (b) 40 middle distance runners; (c) 44 Weightlifters; and (d) 27 decathletes. Genomic DNA was extracted from the participants' buccal epithelial cells using standard protocol and then analyzed for IGF1 axis related genetic polymorphism using the allelic discrimination assay. ResultsA significantly higher prevalence of the IGF1 rs35767 TT genotype was found among decathletes compared to the other athletes, as well as a lower prevalence of the IGF1 rs7136446 GG genotype, a higher prevalence of the IGF1R rs1464430 AA genotype, and a higher prevalence of the IGF2 rs680 GG genotype. Moreover, among the decathletes, carriers of the IGF1 rs7136446 GG genotype achieved higher decathlon scores compared to A-allele carriers. ConclusionsThe findings of this study suggest a potential beneficial role for some IGF-axis polymorphisms (mainly the IGF1 1245 TT and the IGF2 GG) among decathletes, both of which are associated with improved speed performance.

Endocannabinoid and Nitric Oxide-Dependent IGF-I-Mediated Synaptic Plasticity at Mice Barrel Cortex.

Insulin-like growth factor-I (IGF-I) signaling plays a key role in learning and memory. IGF-I increases the spiking and induces synaptic plasticity in the mice barrel cortex (Noriega-Prieto et al., 2021), favoring the induction of the long-term potentiation (LTP) by Spike Timing-Dependent Protocols (STDP) (Noriega-Prieto et al., 2021). Here, we studied whether these IGF-I effects depend on endocannabinoids (eCBs) and nitric oxide (NO). We recorded both excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs) evoked by stimulation of the basal dendrites of layer II/III pyramidal neurons of the Barrel Cortex and analyzed the effect of IGF-I in the presence of a CB1R antagonist, AM251, and inhibitor of the NO synthesis, L-NAME, to prevent the eCBs and the NO-mediated signaling. Interestingly, L-NAME abolished any modulatory effect of the IGF-I-induced excitatory and inhibitory transmission changes, suggesting the essential role of NO. Surprisingly, the inhibition of CB1Rs did not only block the potentiation of EPSCs but reversed to a depression, highlighting the remarkable functions of the eCB system. In conclusion, eCBs and NO play a vital role in deciding the sign of the effects induced by IGF-I in the neocortex, suggesting a neuromodulatory interplay among IGF-I, NO, and eCBs.

Histologic characterization of orbicularis oris muscle with anew acellular dermal matrix grafts in a rabbit model.

Muscular dysplasia is the key factor in influencing surgical outcomes in patients with cleft lip/palate. In this research, we attempted to evaluate a new acellular dermal matrix (ADM) as a substitute for reconstruction of the orbicularis oris muscle with growth factors such as Insulin-Like Growth Factor I (IGF-I), vascular endothelial growth factor (VEGF) in a rabbit model. 30 male New Zealand Rabbits (2-3m, 1700-2000g) were divided into four groups as follows; a group in which the orbicularis oris muscle of the upper lip was implanted with ADM, a group in which the orbicularis oris muscle of the upper lip was implanted with ADM+IGF-I+VEGF, a group in which the upper lip was operated without implantation of an ADM scaffold, and a normal upper lip for comparison. Macroscopic observation, histological evaluation, and immunohistochemistry were employed to evaluate levels of the muscle regeneration, vascularization, and inflammation at 1, 2, 4, 6, and 12weeks after the operation. All wounds healed well without infection, immune rejection and so on. Histological evaluation showed that ADM was totally degraded and replaced by connective tissue. The area in which the ADM scaffold was coated with growth factors show a significant increase in the formation of new myofibers after injury, and the vascularization improved compared to the control group and the normal group. In regard to the degrees of inflammation, there were no notable differences among the groups. In conclusion, Our study indicated that ADM grafts combined with IGF-I and VEGF have potential advantages in alleviating muscular dysplasia in cleft lip treatment.

Essential Amino Acid Intake Is Required for Sustaining Serum Insulin-like Growth Factor-I Levels but Is Not Necessarily Needed for Body Growth.

Essential amino acids (EAAs) are those that cannot be synthesized enough to meet organismal demand; therefore, it is believed that they must be taken from the diet for optimal growth. The growth hormone (GH)/insulin-like growth factor-I (IGF-I) system is also considered significant for growth regulation in mammals. This study aimed to evaluate the relative contributions of protein nutrition and the GH/IGF-I system to body growth regulation. Experiments using rodents and hepatocyte-derived cell lines subjected to EAA deficiency showed that a reduction in the serum EAA concentration hinders Igf1 transcription in the liver in a cell-autonomous manner, thereby decreasing serum IGF-I levels. Remarkably, when the serum IGF-I level of mice on a low-protein diet was restored by the recombinant IGF-I infusion, the body growth was mostly rescued, although the mice were still deficient in EAA intake. Meanwhile, the GH signal activation and subsequent Igf1 transcription were also dramatically diminished by EAA deprivation in the cell culture model. Altogether, we demonstrate that EAAs are not strictly necessary for animal growth as building blocks but are required as IGF-I-tropic cues. The results will bring a paradigm shift regarding the definition of “essential” amino acids.

Molecular vital signs: wearable technologies for the real-time measurement of molecular markers of health and human performance

Introduction: Warfighters operate in complex and chaotic multi-stressor environments. Soldier interface with the external world on the battlefield impacts health and performance and is reflected through changes in internal physiology. Previous studies of operational stress using either cross-sectional or repeated measures designs have demonstrated substantial alterations in physiology including heightened hypothalamic-pituitary-adrenal axis (HPA) arousal, suppressed function of hypogonadal (HPG) and hypothalamic-pituitary-thyroid (HPT) axes, and increased immune system activation1. Responses of these systems are monitored and measured via biological analytes including, but not limited to, epinephrine, norepinephrine, adrenocorticotrophic hormone, cortisol, insulin-like growth factor-I, testosterone, thyroid hormones, and inflammatory cytokines2. However, interpretation of these results is complicated by pre-analytical factors such as collection timing, sample processing, nutrient intake, and hydration status. Therefore, we propose the implementation of continuous or real-time monitoring of biological fluids (e.g., saliva, blood, sweat) for actionable information regarding hydration, muscle status, inflammation, injury risk, and metabolic health that can be used for individualized recommendations and performance optimization. Application platforms and monitoring technologies for active and passive data collection have evolved to the point where holistic surveillance is becoming feasible. For example, continuous monitoring of hormones related to systemic anabolic/catabolic balance and inflammation can help enhance physical performance and minimize overtraining, respectively3,4. Future directions: Real-time, high-fidelity tracking of biomarkers across multiple biocompartments for the purposes of enhancing health, performance, and career longevity is a next critical step for optimizing soldier readiness, lethality, and survivability in combat. Future technologies will likely enable a wider range and more precise tracking of systemic signalling (e.g., multi-omics), leading to actionable information, at the individual level, for military leaders to use in training and combat. Soldier self-report input, however, will likely remain an important aspect for guiding practices. Real-time tracking may also reorient our perception of what is deemed most physiologically relevant for monitoring soldier performance. References 1Henning PC, Park B-S, Kim J-S. Physiological decrements during sustained military operational stress. Mil Med 2011; 176:991-997. https://doi.org/10.7205/MILMED-D-11-00053 2Lee EC, Fragala MS, Kavouras SA, et al. Biomarkers in sports and exercise: tracking health, performance, and recovery in athletes. J Strength Cond Res 2017; 31:2920-2937. https://doi.org/10.1519/JSC.0000000000002122 3Kraemer WJ, Ratamess NA, Nindl BC. Recovery responses of testosterone, growth hormone, and IGF-1 after resistance exercise. J App Physiol 2017; 122:549-558. https://doi.org/10.1152/japplphysiol.00599.2016 4Smith LL. Cytokine hypothesis of overtraining: a physiological adaptation to excessive stress? Med Sci Sports Exerc 2000; 32:317-331.

Targeting Insulin-Like Growth Factor-I in Management of Neurological Disorders.

The degradation of neurons marks as the pathological reason for onset of most of the neurological diseases although the functional deficiencies and symptoms may vary. Insulin-like growth factor-I (IGF-I) boosts regeneration of both motor and sensory neurons and thus presents as a potential treatment in management of neurological disorders. IGF-I is a pleiotropic agent which stimulates the survival and outgrowth of neurons accompanied by their motility as well as myelination by glial cells. This hormone has been found to possess neuroprotective properties which is in association with its antioxidant and mitochondrial protection activity. Studying and exploring the signaling pathways which mediate pleotropic responses intracellularly have elucidated significant therapeutic approach in treatment and management of neurological disorders by IGF-I. The current review highlights the role of IGF-I in management of major neurological disorders such as depression, Parkinson's disease, and Alzheimer's disease and also covers the mechanisms involved in the process.