Insulin-like Growth Research Articles

Akt1 deficiency does not affect fiber type composition or mitochondrial protein expression in skeletal muscle of male mice.

Insulin-like growth factor-1-induced activation of ATP citrate lyase (ACLY) improves muscle mitochondrial function through an Akt-dependent mechanism. In this study, we examined whether Akt1 deficiency alters skeletal muscle fiber type and mitochondrial function by regulating ACLY-dependent signaling in male Akt1 knockout (KO) mice (12-16 weeks old). Akt1 KO mice exhibited decreased body weight and muscle wet weight, with reduced cross-sectional areas of slow- and fast-type muscle fibers. Loss of Akt1 did not affect the phosphorylation status of ACLY in skeletal muscle. The skeletal muscle fiber type and expression of mitochondrial oxidative phosphorylation complex proteins were unchanged in Akt1 KO mice compared with the wild-type control. These observations indicate that Akt1 is important for the regulation of skeletal muscle fiber size, whereas the regulation of muscle fiber type and muscle mitochondrial content occurs independently of Akt1 activity.

Circulating Adipocytokines and Insulin Like-Growth Factors and Their Modulation in Obesity-Associated Endometrial Cancer

The rising global incidence of uterine cancer is linked to the escalating prevalence of obesity. Obesity results in alterations in adipocytokines and IGFs, driving cancer progression via inflammation, increased cell proliferation, and apoptosis inhibition, although the precise mechanisms are still unclear. This study examined a set of six markers, namely, adiponectin, leptin, IL6, TNFα, IGF1, and IGF2 and compared them between fifty age-matched endometrial cancer patients (study group) and non-cancer patients with benign gynaecological conditions (control group). We also assessed the relationship of these markers with obesity and explored the correlation between these markers and various tumour characteristics. In the cancer population, these markers were also assessed 24 h and 6 months post-surgery. Remarkably, low adiponectin levels were associated with a 35.8% increase in endometrial cancer risk. Interestingly, compared to control subjects where IGF levels decreased after menopause, post-menopausal women in the study group showed elevated IGF1 and IGF2 levels, suggesting a potential influence of endometrial cancer on the IGF system, particularly after menopause. Lastly, it is noteworthy that a discernible inverse relationship trend was observed in the levels of adipocytokines and IGFs 6 months post-surgery. This indicates that treatment for endometrial cancer may have a differential impact on adipocytokines and IGFs, potentially holding clinical significance that merits further investigation.

Impact of differing eccentric-concentric phase durations on muscle damage and anabolic hormones

BACKGROUND: Resistance exercises are widely used to enhance muscle hypertrophy. Hypertrophy occurs with effect of mechanical loading, metabolic stress, and muscle damage. The time under tension in eccentric, isometric, and concentric phases of resistance exercises can alter muscle damage and anabolic hormone responses. OBJECTIVES: The aim of the study was to reveal the effect of the time spent in the concentric and eccentric phases of the movement on muscle damage and anabolic hormone response during resistance exercise. METHODS: Ten male subjects participated in the study. A, B, C tempo protocols were created by changing the time under tension to be 1 or 2 seconds in the eccentric and concentric phases of bench press and squat movements. In all protocols, isometric phases were 0 sec. The metronome was used to apply tempos. Blood samples were taken before each protocol, after administration, and in the 24th, 48th and 72nd hours after exercise; and serum insulin, testosterone, Insuline-like Growth Factor-1 (IGF-1), Creatine Kinase (CK) and Lactate Dehydrogenase (LDH) levels were evaluated. RESULTS: Time-wise changes in CK were statistically different for all protocols (p< 0.05). CK levels in the 24th hour of the protocol C and the 48th hour of the protocol B were significantly higher than those in the other protocols (p< 0.05). IGF-1 and testosterone levels were significantly higher in the protocol B in the post-test, compared to the other protocols (p< 0.05). Insulin levels in the 24t⁢h hour were significantly higher in the protocol B compared to those in others (p< 0.05). Time-wise changes in LDH parameters were not statistically significant in any hours (p> 0.05). CONCLUSIONS: Extending time under tension in the eccentric phase of a bout of resistance exercise appears to affect the anabolic hormone response and muscle damage. In this way, increased metabolic response and mechanical stress can induce muscle mass gain.

Disorders Causing Secondary Hypertension in Patients Less Than 45 Years of Age

Objective: To determine the frequency of disorders causing secondary hypertension in patients less than 45 years of age.
 Study Design: Cross-sectional study.
 Place and Duration of Study: Department of Pathology and Medicine, Combined Military Hospital (CMH), Risalpur, Pakistan, along with Armed Forces Institute of Pathology (AFIP)and Pak Emirates Military Hospital (PEMH) Rawalpindi, Pakistan from Apr 2017 to Apr 2019.
 Methodology: A total of 50 patients, less than 45 years of age, newly diagnosed with hypertension (systolic blood pres-sure>140 mm Hg or diastolic BP>90 mm Hg) and reported to CMH Risalpur for the workup of HTN were included. Analysis of serum cholesterol, triglycerides, urea, creatinine, sodium, potassium, calcium, thyroid stimulating hormone, plasma glucose random, urine analysis and renal ultrasonography were carried out. In addition, serum cortisol, 24 hours urinary free cortisol, dexamethasone suppression test, growth hormone level, insulin-like growth factor-1,24 hours urinary vanillylmandelic acid, serum aldosterone and renin levels, Doppler renal ultrasonography, renal arteriogram, CT abdomen, MRI pituitary and MR/CT angiography were carried out.
 Results: A total of 50 patients comprised of 82% males and 18% females with a mean age of 36.1±6.2years. Primary hypertension was in observed in 31(62%) cases. Secondary causes of HTN in 19(38%) cases, were obstructive sleep apnea (4, 8%), primary hyperaldosteronism (3,6%), renal parenchymal hypertension (3,6%), renal artery stenosis (1,2%), Cushing's syndrome (2,4%), hyperthyroidism (2,4%), hypothyroidism (2,4%), pheochromocytoma (1,2%) and coarctation of aorta (1,2%) cases.
 Conclusion: Obstructive sleep apnea primary hyper-aldosteronism and renal parenchymal diseases were the commonest.........

Effects of physical distancing by COVID-19 pandemic on diet quality, neurological and immunological markers, and fecal microbiota of Brazilian older women.

Physical distancing was used to prevent transmission of COVID-19, however there are concerns that this may promote harmful impacts on health, such as reduced levels of physical practice and changes in food intake and gut microbiota composition. This study evaluated the impacts of 6 months physical distancing on Brazilian older women upon body mass index (BMI), strength, physical activity level (IPAQ), eating habits, neurological markers (brain-derived neurotrophic factor-BDNF and cortisol), cytokines (IL-2, IL-5, IL-6, IL-10, interferon-IFN-γ, tumor necrosis factor-TNF-α), aging-associated markers (vascular endothelial growth factor-VEGF, insulin-like growth factor-IGF-1, klotho and thymic stromal lymphopoietin-TSLP), besides specific groups of fecal microbiota. Fifteen women, over 60 years old, residents of São Paulo state (Brazil), were evaluated in March and in September 2020. The older adult women, with a mean age 66 ± 6.2 years presented significantly increased BMI and high effect size for non-protective foods consumption, reduced light physical activity and strength 6 months following the physical distancing. Furthermore, the serum concentration of IFN-γ, IGF-1, and IFN-γ/IL-5 were significantly higher, while lower concentration of IL-2 and IL-5 were observed 6 months after the physical distancing. Significant increase was noted only to Blautia spp. abundance after 6 months of physical distancing. Several correlations were observed at both before and after physical distancing, however, interestingly, many of them were lost or inverted 6 months following, while new ones emerged. Taken together, these results showed that lifestyle changes and stress conditions addressed by physical distancing from the COVID-19 pandemic impacted the health of older women included in the present study. Therefore, future follow-up studies are essential to propose interventions in order to restore the health conditions observed before the pandemic period, and thus to maintain the quality of life of older adults in different socioeconomic contexts.

CircCEP85 upregulates IGF1 expression to promote breast cancer progression via sponging miR-1193

BackgroundIncreasing evidence has suggested that circular RNAs (circRNAs) play critical roles in breast cancer (BC) progression. However, the expression level and potential functional role of circRNA centrosomal protein 85 (circCEP85) in BC remains largely unknown. Here, we aimed to explore the role of circCEP85 in BC.MethodsThe levels of circCEP85, insuline-like growth factor I (IGF1) mRNA and microRNA-1193 (miR-1193) were examined by quantitative real-time polymerase chain reaction. The protein level was measured by Western blot. Cell proliferation, migration, apoptosis, angiogenesis and stemness were assessed by cell counting kit-8, 5-ethynyl-2’-deoxyuridine assay, transwell assay, flow cytometry, tube formation and sphere formation assays. Xenograft mouse models were conducted to evaluate the effect of circCEP85 in BC in vivo. Moreover, dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays were preformed to confirm the interaction between miR-1193 and circCEP85 or IGF1.ResultsCircCEP85 was upregulated in BC tissues and cells. Silencing of circCEP85 inhibited proliferation, invasion, angiogenesis and stemness, but promoted apoptosis in BC cells in vitro. In addition, circCEP85 silencing inhibited tumor growth in vivo. Mechanistically, circCEP85 elevated IGF1 expression via sponging miR-1193 to promote breast cancer progression.ConclusionThe circCEP85-miR-1193-IGF1 axis regulated BC progression via the competitive endogenous RNA (ceRNA) mechanism. CircCEP85 might be a prognostic biomarker and therapeutic target for BC.

Abstract 222: Exposure to dim light at night disrupts the nocturnal melatonin signal in male nude rats bearing tissue-isolated castration-sensitive VCaP human prostate cancer: Impact on tumor circadian dynamics of the Warburg effect, lipid signaling and proliferation

Abstract Over 248,000 men in the U.S. alone this year will be diagnosed with prostate cancer, and over 33,300 will die from the disease. The World Health Organization, in the case of breast cancer, has classified night-shift work involving light at night (LAN)-induced circadian disruption to be a probable carcinogen (Class 2A). Exposure to LAN suppresses nighttime pineal melatonin (MLT) production that influences normal and neoplastic tissue metabolism, physiology, and proliferation. Previously, we showed in rodent and human tumors in vivo that MLT inhibits linoleic acid (LA)-uptake and conversion to 13-hydroxyoctadecadienoic acid (13-HODE), a lipoxygenase product that enhances epidermal growth factor and insulin-like growth factor-I-induced mitogenesis. Recently, we developed a tissue-isolated, castration-sensitive VCaP human prostate cancer xenograft model to test the hypothesis that suppression of the nocturnal MLT signal due to exposure to dim LAN (dLAN) accelerates tumor LA-uptake and metabolism, aerobic glycolysis (Warburg Effect), and proliferative activity. Male nude rats (Crl:NIHFoxn1rnu; n=6/group) bearing castration-sensitive VCaP human prostate cancer xenografts were maintained on either a control L(300 lux)D(0 lux),12:12 or experimental LD,12:12dLAN (300 lux light phase followed by dLAN 0.2 lux dark phase intensity) light/dark cycle. Results revealed (Mean ± S.D.) plasma MLT levels in controls peaked in the mid-dark phase (183.4 ± 12.8 pg/mL) and were lowest (2.2 ± 0.4 pg/mL) in the mid-light phase, and low (< 10 pg/mL) throughout the 24-hr period in dLAN rats. Tumors in rats exposed to dLAN exhibited a significantly shorter latency to onset and a two-fold faster growth rate than controls. Harvested control group tumors revealed elevated cAMP levels, LA uptake, 13-HODE production, the Warburg effect, and [3H]thymidine incorporation into DNA, as well as elevated patterns of expression of signaling pathways phospho-ERK1/2, -AKT, -STAT3, -glycogen synthase kinase-3β (GSK3β), and -NF-κβ, and full-length androgen receptor and aldo-keto reductase (AKR1C3), during the light phase and markedly suppressed during the dark phase. In the dLAN group, these measures were markedly elevated throughout the 24-hr period. This is the first evidence in vivo, that dLAN-induced disruption of integrated circadian rhythms of signaling, metabolism, and proliferation results in accelerated growth of castration-sensitive human prostate cancer xenografts. Thus, lighting design strategies to minimize human exposure to LAN that preserve the integrity of the circadian MLT signal may offer a novel approach to suppress the growth progression of human castration-sensitive prostate cancer in our increasingly 24-hour society. Citation Format: Erin M. Dauchy, Robert T. Dauchy, Steven M. Hill, Yan Dong, Victoria P. Belancio, Shulin Xiang, George C. Brainard, John P. Hanifin, David E. Blask. Exposure to dim light at night disrupts the nocturnal melatonin signal in male nude rats bearing tissue-isolated castration-sensitive VCaP human prostate cancer: Impact on tumor circadian dynamics of the Warburg effect, lipid signaling and proliferation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 222.

Insulin-like growth factor-1 (IGF-1) as predictor of cardiovascular mortality in heart failure patients: data from the T.O.S.CA. registry

IntroductionData from the “Trattamento Ormonale nello Scompenso CArdiaco” (T.O.S.CA) registry showed that heart failure (HF) represents a complex clinical syndrome with different hormonal alterations. Renal failure represents a frequent complication in HF. We evaluated the relationship between renal function and insuline-like growth factor-1 (IGF-1) deficiency and its impact on cardiovascular mortality (CVM) in patients enrolled in the T.O.S.CA. registry.MethodsAt the enrolment, all subjects underwent chemistry examinations, including circulating hormones and cardiovascular functional tests. COX regression analysis was used to evaluate factors related to CVM during the follow-up period in all populations, in high-risk patients and in the young-adult population. Also, we evaluate the effects of renal function on the CVM.Results337 patients (41 deceased) were analyzed. CVM was related to severe renal dysfunction (HR stages IV–V = 4.86), high-risk conditions (HR 2.25), serum IGF-1 (HR 0.42), and HF etiology (HR 5.85 and HR 1.63 for valvular and ischemic etiology, respectively). In high-risk patients, CVM was related to IGF-1 levels, severe renal dysfunction and valvular etiology, whereas in young patients CMV was related to the high-risk pattern and serum IGF-1 levels.ConclusionsOur study showed the clinical and prognostic utility of the IGF-1 assay in patients with HF.

Pharmacokinetics and neurotropic effects of cyclo-L-prolylglycine and its modified analogues

The review presents the results of studies on the pharmacokinetics, metabolism, and bioavailability of new neurotropic dipeptide cyclo-Lprolilglycine (CPG) and their pharmacological activity. It was shown that the pharmacologically active metabolite of the nootropic drug noopept cyclo-Lprolilglycine (CPG) is an endogenous dipeptide, it is a fragment of the terminal Tripeptide of the insulin-like nerve growth factor IGF-1. Much attention is paid both in Russia and abroad to the development of modified CPG analogues with improved pharmacokinetic properties, enzymatically more stable, better penetrating the BBB, and highly effective when used in micromolar doses. CPG shows neuroprotective activity in ischemic-hypoxic and other brain injuries, in addition, it has a complex of other pharmacological effects and therefore CPG can be considered not only as a potential drug, but also as a basic structure for the development of new neurotropic drugs – analogs of CPG with improved pharmacokinetic properties, greater enzymatic resistance and higher bioavailability for the central nervous system.

Нарушение секреции соматотропного гормона у женщин с синдромом поликистозных яичников в сравнении с больными с неактивными аденомами гипофиза

Цель исследования — изучить нарушение секреции гормона роста у женщин с синдромом поликистозных яичников (СПКЯ) в сравнении с больными с неактивными аденомами гипофиза (НАГ). Под амбулаторным наблюдением в период с сентября 2015 по март 2016 года было обследовано 15 взрослых пациенток фертильного возраста с СПКЯ и 15 — с НАГ. Средний возраст больных составил 25,5 и 28,9 года соответственно. Давность заболевания колебалась в пределах от 7 месяцев до 9 лет. Было установлено, что в обеих группах наблюдались нейроэндокринные нарушения, свойственные каждой из патологий. Так, в первой группе пациенток с СПКЯ наиболее часто встречались такие нарушения, как ожирение, стрии, акантоз, акне, гиперандрогения, гиперполименорея, а во второй — вторичная аменорея, гиперпролактинемия, пангипопитуитаризм. В обеих группах наблюдалась ановуляция, а также снижение секреции соматотропного гормона (СТГ), инсулиноподобного фактора роста‑1 (ИФР‑1). Кроме того, в группе пациенток с НАГ были выявлены наиболее достоверно сниженные базальные уровни тропных гормонов гипофиза — СТГ, лютеинизирующего гормона (ЛГ), фолликулостимулирующего гормона (ФСГ) на фоне гиперпролактинемии и нормальных значений ИФР‑1, в то время как у пациенток с СПКЯ отмечалось снижение СТГ, ЛГ, ФСГ на фоне гиперандрогении и снижения ИФР‑1. Таким образом, установлено, что в группе больных с СПКЯ было выявлено наиболее достоверное снижение базальных уровней ИФР‑1, в то время как дефицит СТГ встречался реже. У пациенток с НАГ имел место пангипопитуитаризм, а именно — сочетанный дефицит СТГ, ЛГ, ФСГ, тиреотропного гормона, в то время как дефицит ИФР‑1 встречался реже. Выявленные в нашем исследовании нарушения секреции СТГ и ИФР‑1 подтверждают данные литературы о том, что у пациенток с СПКЯ имеет место снижение уровней СТГ и ИФР‑1 на фоне гиперинсулинемии и гиперандрогении.

Blocking hsa_circ_0074027 suppressed non-small cell lung cancer chemoresistance via the miR-379-5p/IGF1 axis

ABSTRACT Cancer cell chemoresistance is the primary reason behind cancer treatment failure. Previous reports suggest that circular RNA (circRNA) hsa_circ_0074027 (HC0074027) is a crucial modulator of non-small cell lung cancer (NSCLC) disease progression. Herein, we delineated the underlying mechanism of HC0074027-regulated chemoresistance in NSCLC. We employed quantitative real-time polymerase chain reaction (qRT-PCR) or Elisa in the detection of HC0074027, micoRNA-379-5p (miR-379-5p), and insuline-like growth factor I (IGF1) expressions. Cell survival was evaluated via the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Direct associations among HC0074027, miR-379-5p, and IGF1 were examined via dual-luciferase reporter (DLR) and RNA immunoprecipitation (RIP) assays. Lastly, HC0074027 was incorporated into nude mice to examine its biological activity in vivo. Based on our analysis, HC0074027 levels strongly correlated with NSCLC chemoresistance to docetaxel (DTX), cisplatin (DDP), and paclitaxel (PTX). Alternately, HC0074027 silencing enhanced chemosensitivity in vitro. In vivo, HC0074027 downregulation suppressed tumor expansion and increased cancer cell sensitivity to chemotherapy. We also revealed that HC0074027 physically interacts with miR-379-5p to exert its biological function in vitro. Moreover, IGF1 is a functionally crucial target of miR-379-5p in modulating NSCLC chemoresistance in vitro. Finally, we demonstrated that HC0074027 can indirectly modulate IGF1 levels via sequestering miR-379-5p. We demonstrated that HC0074027 promotes NSCLC chemoresistance via sequestering miR-379-5p activity, and modulating IGF1 expression. Our work highlights the significance of HC0074027 in NSCLC chemoresistance and suggests HC0074027 to be an excellent candidate for targeted NSCLC therapy.

Effects of different small-sided games on blood lactate and GH/IGF-1 axis responses in young soccer players

Soccer and its intense workouts cause lactate accumulation and extensive metabolic changes. This study, therefore, aimed to compare the percentage of maximum heart rate (%HRmax), blood lactate, growth hormone (GH), and insulin-like growth factor‑1 (IGF-1) responses across different formats of small-sided games (SSG) in young soccer players. Twenty-four soccer players (mean age: 17.1 ± 1.12 years, weight 67.28 ± 1.65 kg and body mass index 20.8 ± 1.18 kg/m2) were randomly divided into three equal groups, including control, 2 vs. 2 (8 periods of 2 min separated by 1 min of passive recovery, with a pitch of 20 m × 25 m) and 4 vs. 4 (4 periods of 4 min separated by 2 min of passive recovery, with a pitch of 28 m × 35 m). Blood samples were taken immediately before and after small-sided games. The results showed that the heart rate increased significantly in young soccer players at different minutes of SSG (p ≤ 0.05). The comparison of these two SSG did not show any significant differences on lactate and somatotropic hormone concentrations (p > 0.05), although each alone significantly increased lactate, GH and IGF‑1 levels compared to control group (p < 0.05). Hence, it can be concluded that due to the sufficient intensity of these two modes of SSG, the cellular relationship between the GH/IGF‑1 axis and lactate helps improve the physiological capacity of young soccer players. However, further studies were needed to consider more accurate effects of these variables (lactate, GH and IGF-1) with two SSG modalities (2 vs. 2 and 4 vs. 4).

Abstract 17449: Predictive Value of Growth Hormone Levels in Cardiogenic Shock Patients

Introduction: Despite improved supportive care, cardiogenic shock still has a significantly high mortality. Among many factors, multiple changes in the neuroendocrine system, are responsible for the high morbidity and mortality. Reduced circulating level of insuline-like growth factor and an elevated level of growth hormone are the reported characteristic findings early in the course of sepsis and. The role of insuline-like growth factor and growth hormone levels in patients with cardiogenic shock has not been described. Methods: The aim of this study was to evaluate the changes of growth hormone/ insuline-like growth factor 1 axis in patients with cardiogenic shock. Results: When admitted, the average GH value of the patient collective was 2.86 μg / l ± 0.78. The values of the majority of the patients (31/41 = 75.6%) were within the normal range. There we no differences among survivors and non-survivors over the 96h observational period. We did not observe differences between either elder and younger patients or female and male CS patients. On admission IGF-1 levels were 76.23 ± 5.67 μg/l (normal range 70– 270 μg/l) at the lower end of the normal range. Over the next 48-72 hours, the value dropped to 66.8 μg/l. However, the drop was not significant (p = 0.14). Non-survivors showed a more rapid decline compared to survivors which stayed within the normal range.Considering the subgroup analysis, it emerges that the average IGF-1 value of male patients remains above 70 μg/l and thus within the normal range, while the IGF-1 level of the female patients during the course which was up to 55.3 μg/l decreases in the course. Clearly female CS patients showed a steeper decline compared to the male patients. Further younger CS patients showed higher levels compared to patients above 70 years. Conclusion: There were no significant changes of growth hormone levels over time and we observed a decrease of insuline-like growth factor 1 in cardiogenic shock patients. In addition, in non-survivors we detected even lower levels of growth hormone and lower levels of insuline-like growth factor 1. We think that both growth hormone and insuline-like growth factor 1 may have l prognostic value to serve as a marker in cardiogenic shock.

Relationship between of Insuline Like growth Factor-2 Gene and Growth Traits in Crosses of Indonesian Local Chicken

Kedu chicken is known as a laying hen, while Sentul and Kampung chicken are known as dual-purpose type chickens. The crossing of Sentul, Kedu and Kampung chicken were produced SKKedu and KeduSK chickens. One of gene that control growth is IGF-2 (Insuline-like Growth Factor 2). This study aims to analyze the diversity of IGF-2 genes and analyze association of genes with growth in SKKedu and KeduSK chickens. The samples used were 23 KeduSK chicken DNA and 17 SKKedu chicken DNA 12 weeks old. Growth measurements consist of body weight, body weight gain, feed consumption and feed conversion ratio. DNA extracted from the blood samples were analysed by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). The diversity of IGF-2 genes was analysed with X2 test. The results showed of IGF-2 gene in SKKedu and KeduSK chickens (CC, TC, dan TT). IGF-2 gene was polymorphic and was in a Hardy-Weinberg equilibrium state. The growth traits of SKKedu and KeduSK chickens based on differences in genotype on IGF-2 genes are almost the same,there were no differences in the growth traits. There was no correlation between IGF-2 genotype of SKKedu and KeduSK chicken with growth traits.

Pediatric adrenocortical tumor - review and management update.

Adrenocortical tumor (ACT) is a rare disease with an annual worldwide incidence of 0.3-0.38/million children below 15 years old, and Brazilian population presents the highest incidence because of germline mutation in the TP53. Pediatric ACT is associated with virilizing features and hypercortisolism in most cases. Malignancy is defined when local invasion or metastasis is found, and it is associated with a poor prognosis. However, the correct and early diagnosis and treatment may impact on overall and disease-free survival. A complete understanding of the disease and its singularities facilitates the assistance to the pediatric patient with ACT. The new insights about adrenal tumorigenesis have provided a better understanding of this disease. In this scenario, the era of molecular studies is leading to the refinement of the taxonomy, and it is offering the opportunity to discover new biomarkers and pathways of tumorigenesis, beyond the knowing β-catenin, Insulin-like growth factor-II/IGF-IR, and the p53/Rb signaling. The rarity of this disease makes it a real challenge. Here, we present a review focusing on clinical practice. A methodic approach aiming to clarify the diagnosis and a follow-up are suggested to guide physicians in the assistance of pediatrics patients, improving the prognosis.

Irisin prevents dexamethasone-induced atrophy in C2C12 myotubes

Irisin is a myokine secreted mainly from skeletal muscle that is known for having beneficial metabolic effects via enhancement of energy expenditure and insulin sensitivity. Studies show that irisin also acts as an autocrine/paracrine to promote myogenesis and muscle growth. However, the protective role of irisin against muscular wasting remains unclear. We confirmed that irisin secretion was upregulated by electrical pulse stimulation an in vitro exercise mimetic model. Next, we tested if irisin exerted an anti-atrophic effect on cultured C2C12 myotubes treated with dexamethasone (DEX), a representative inducer of muscular atrophy. Treatment of cultured myotubes with DEX reduced myotube size and increased proteasome activity, which were attenuated by irisin. Also, irisin effectively prevented dephosphorylation of forkhead box O (FoxO) 3α and upregulation of muscle-specific ubiquitin ligases in DEX-treated myotubes. The protective effect of irisin on DEX-mediated myotube atrophy was partially regulated by insulin-like growth factor-1-dependent signaling. These results suggested that irisin may prevent glucocorticoid-induced muscle atrophy by inhibiting FoxO-mediated ubiquitin-proteasome overactivity.

Research Note: Metabolic changes and physiological responses of broilers in the final stage of growth exposed to different environmental temperatures

There is no information regarding the influence of heat stress (HS) on host metabolic profile. In this study, we investigated the effects of different environmental temperatures on oxidative status, hormone levels, HS indicators, and plasma metabolites in broilers. A total of 1,680 yellow-feather broilers (28 D old) were randomly allotted to 4 groups with 6 replicates. The broilers (29–57 D old) were maintained in thermostatic rooms (20°C, 25°C, 28°C, and 30°C) for 28 consecutive days. The results showed that the plasma cortisol and adrenocorticotropic hormone levels and creatine kinase and lactate dehydrogenase activities gradually increased when the temperature increased from 20°C to 30°C. However, the insulin-like growth factor-І level decreased gradually. Furthermore, heat shock protein 70 expression significantly increased in the liver and breast muscle (P < 0.01). As the temperature increased, the total anti-oxidant capacity in the plasma and liver gradually decreased, whereas the malondialdehyde level increased. The activity of plasma glutathione peroxidase and total superoxide dismutase in the liver showed a similar increasing trend (P < 0.01). In addition, 15 metabolites were identified at higher (P < 0.05) levels, whereas 2 metabolites were identified at lower (P < 0.05) levels in the 30°C treatment group than those in the 25°C treatment group. Most of these potentially diagnostic biomarkers are involved in carbohydrate, amino acid, lipid, or gut microbiome-derived metabolism, indicating that HS affected the metabolic pathways in broilers. Six candidate metabolites (tartronic acid, l-bethreine, tartaric acid, allose, glutaric acid, and neohesperidin) were selected as biomarkers, as they showed high sensitivity, specificity, and accuracy in diagnosing broilers under HS (P < 0.01). In conclusion, in the final stage of growth, we identified 6 plasma differential metabolites as potential biomarkers of HS-induced metabolic disorders in yellow-feathered broilers. This work offers new insights into the metabolic alterations of broilers exposed to HS and provides a new perspective for further study.

The immune proteome of the zebra mussel deciphered by deep proteogenomics

High-throughput sequencing has revolutionised comparative and evolutionary genome biology. It has now become relatively commonplace to generate multiple genomes and/or transcriptomes to characterize the evolution of large taxonomic groups of interest. Nevertheless, such efforts may be unsuited to some research questions or remain beyond the scope of some research groups. Here we show that targeted high-throughput sequencing offers a viable alternative to study genome evolution across a vertebrate family of great scientific interest. Specifically, we exploited sequence capture and Illumina sequencing to characterize the evolution of key components from the insulin-like growth (IGF) signalling axis of salmonid fish at unprecedented phylogenetic resolution. The IGF axis represents a central governor of vertebrate growth and its core components were expanded by whole genome duplication in the salmonid ancestor ~ 95 Ma. Using RNA baits synthesised to genes encoding the complete family of IGF binding proteins (IGFBP) and an IGF hormone (IGF2), we captured, sequenced and assembled orthologous and paralogous exons from species representing all ten salmonid genera. This approach generated 299 novel sequences, most as complete or near-complete protein-coding sequences. Phylogenetic analyses confirmed congruent evolutionary histories for all nineteen recognized salmonid IGFBP family members and identified novel salmonid-specific IGF2 paralogues. Moreover, we reconstructed the evolution of duplicated IGF axis paralogues across a replete salmonid phylogeny, revealing complex historic selection regimes - both ancestral to salmonids and lineage-restricted - that frequently involved asymmetric paralogue divergence under positive and/or relaxed purifying selection. Our findings add to an emerging literature highlighting diverse applications for targeted sequencing in comparative-evolutionary genomics. We also set out a viable approach to obtain large sets of nuclear genes for any member of the salmonid family, which should enable insights into the evolutionary role of whole genome duplication before additional nuclear genome sequences become available.

Mo1385 – Igf-1 (INSULIN LIKE GROWTH FACTOR 1) and Igfbp-2 (Insulin Like Growth Factor Binding Protein 2) Serum Levels As Potential Biomarkers in Differentiation Between Chronic Pancreatitis (CP) and Pancreatic Adenocarcinoma (PDAC) in Reference to Pancreatic Diabetes

Mo1385 – Igf-1 (INSULIN LIKE GROWTH FACTOR 1) and Igfbp-2 (Insulin Like Growth Factor Binding Protein 2) Serum Levels As Potential Biomarkers in Differentiation Between Chronic Pancreatitis (CP) and Pancreatic Adenocarcinoma (PDAC) in Reference to Pancreatic Diabetes

The concentration of insuline-like growth factor in colostrum, milk and plasma of cows

Recently, a significant amount of data has been reported indicating on the link between consumption of dairy products and development of oncological diseases. This could be explained by the presence in milk of various hormones, particularly insulin-like growth factor (IGF). This hormone is a mediator between somatotropin and tissues. In response to the increase of the blood level of growth hormone, hepatocytes begin actively synthesize the IGF, which accelerates the rate of the metabolism, including those of onco-cells. The majority of studies relate to humane medicine, and data on the dependence of IGF milk levels on breed, period of lactation, diet, physiological, and clinical status of an animal are lacking. Taking this into consideration, the purpose of this study was to analyze the concentration of insulin-like factor in colostrum, milk of cows and blood plasma at various stages of lactation. Study was performed on cows of Ukrainian black-and-white dairy breed in their from second to fifth lactation with milk yield 5100–5700 kg per previous lactation. Concentration of IGF was detected in colostrum, milk and plasma of cows, using enzyme immunoassay. Obtained material gives evidence that the highest IGF level is present in colostrum. After that hormone concentration decreases up to 10–14 day of lactation. High level of IGF in colostrum might be associated with necessity to stimulate metabolism of calves in early postnatal period of ontogenesis. Immediately after calving plasma level of IGF decreases. The highest level was observed on 10–14th days of lactation. Taking into consideration physiological function of the given hormone, there is no univocal explanation of the decrease of its plasma level in cows at the beginning of lactation. This could be associated with energy deficit, physiological condition of animals or with developing of lactation dominant and levels of other hormones. Potential of further research lies in investigation of the dependence of the IGF level in the secretion of the mammary gland on productivity, breed, age and diet of animals.