Characterization of sexual size dimorphism in mandarin fish and association with igfbp-5a/b regulation.

Mandarin fish (Siniperca chuatsi) is an important cultured fish in East Asia that shows sexual size dimorphism (SSD), with females growing faster than males when reaching marketable size. However, the regulatory mechanism of SSD is not clear. To characterize SSD of mandarin fish and its association with gh/igf1/igfbp-5 expression, gonadal developmental atlas of the females and the males were described, and growth parameters and serum levels of E2 and T, as well as the relative expression levels of gh, igf1, and igfbp-5a/b mRNAs, were determined. The results showed that the logistic growth equation of body mass and total length of female and male were W(♀) = 667.57/(1 + e^(4.19 - 1.24*t)), W(♂) = 582.71/(1 + e^(4.07 - 1.27*t)), L(♀) = 31.47/(1 + e^1.95 - 1.08*t)), L(♂) = 26.20/(1 + e^(2.56 - 1.5*t)). The month of inflection points for body mass for females and males were 3.37 mph and 3.20 mph, respectively, when the body mass were 333.79 g and 291.36 g. The month of inflection points for total length growth were 1.80 mph and 1.70 mph, respectively, when the total length were 18.52 cm and 16.28 cm. At 1.5-2.0 mph, SSD was not clearly demonstrated. At 3.0 mph, the body mass of the females was significantly higher than that of the males (P < 0.05), Serum E2, brain gh, and liver igf1 expression of the females was significantly higher than that of the males (P < 0.05); T content of the males was significantly higher than that of the females (P < 0.05). At 4.0 months of age, the body mass of the females was highly significantly higher than that of the males (P < 0.01), Serum E2, brain gh, and liver igf1 expression of the females was highly significantly higher than that of the males (P < 0.05); T content of the males was significantly higher than that of the females (P < 0.05). With the continuous development of gonads, muscle and liver igfbp-5a and -5b expression generally tend to increase in females and males, while igfbp-5a showed a gradual increasing trend, and igfbp-5b expression showed a trend of decreasing and then increasing. Male igfbp-5a/b expression was significantly higher than female at the age of 3.0-4.0 months (P < 0.05). This work verified that the females had faster growth rate since 3.0 mph compared to the males, which may be related to higher E2 levels in females leading to higher igf1 level, through inhibition of igfbp-5a/b expression.

The effect of SGLT2i on the GH/IGF1 axis in newly diagnosed male T2D patients - a prospective, randomized case-control study.

PURPOSE: To investigate the effect of SGLT2i on the GH/IGF1 axis in male patients with newly diagnosed type 2 diabetes (T2D). METHODS: Sixty male patients with newly diagnosed T2D were recruited, and randomly assigned to Metformin+SGLT2i group or Metformin group after baseline assessment. All patients received standard lifestyle interventions, and blood indices were obtained before and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment with Metformin+SGLT2i, there were noteworthy improvements in patients' FPG (Fasting plasma glucose), HBA1c, HOMA-IR, HOMA-ß, TyG (Triglyceride-glucose) index and UACR (P < 0.05). Both IGF1 (P = 0.01) and the IGF1/IGFBP3 ratio (P < 0.01) considerably increased, while GH and IGFBP3 did not show significant changes. When comparing Metformin+SGLT2i group to Metformin group, SGLT2i significantly improved HOMA-IR [P = 0.04], and elevated IGF1/IGFBP3 ratio [P = 0.04], SGLT2i showed a tendency of increasing IGF1 (P = 0.10), but this was not statistically meaningful. There was no effect on GH and IGFBP3. Correlation analysis showed that blood IGF1 was negatively correlated with FPG, HBA1c, HOMA-IR, TyG index and positively correlated with IGFBP3. Regression analysis indicated that FPG and testosterone had a negative effect on blood IGF1 level, while HOMA-IR had no obvious effect. CONCLUSION: In male patients with newly diagnosed T2D, SGLT2i can increase IGF1/IGFBP3 ratio, alleviate insulin resistance, but has no significant effect on GH and IGF1 levels. Additionally, our study showed that Metformin+SGLT2i treatment resulted in an increase in blood IGF1 levels and improved insulin resistance, suggesting a potentially beneficial role of IGF1 in newly diagnosed T2D.

The Genetic Landscape of Children Born Small for Gestational Age with Persistent Short Stature.

INTRODUCTION: Among children born small for gestational age, 10-15% fail to catch up and remain short (SGA-SS). The underlying mechanisms are mostly unknown. We aimed to decipher genetic aetiologies of SGA-SS within a large single-centre cohort. METHODS: Out of 820 patients treated with growth hormone (GH), 256 were classified as SGA-SS (birth length and/or birth weight <-2 SD for gestational age and life-minimum height <-2.5 SD). Those with the DNA triplet available (child and both parents) were included in the study (176/256). Targeted testing (karyotype/FISH/MLPA/specific Sanger sequencing) was performed if a specific genetic disorder was clinically suggestive. All remaining patients underwent MS-MLPA to identify Silver-Russell syndrome, and those with unknown genetic aetiology were subsequently examined using whole-exome sequencing or targeted panel of 398 growth-related genes. Genetic variants were classified using ACMG guidelines. RESULTS: The genetic aetiology was elucidated in 74/176 (42%) children. Of these, 12/74 (16%) had pathogenic or likely pathogenic (P/LP) gene variants affecting pituitary development (LHX4, OTX2, PROKR2, PTCH1, POU1F1), the GH-IGF-1 or IGF-2 axis (GHSR, IGFALS, IGF1R, STAT3, HMGA2), 2/74 (3%) the thyroid axis (TRHR, THRA), 17/74 (23%) the cartilaginous matrix (ACAN, various collagens, FLNB, MATN3), and 7/74 (9%) the paracrine chondrocyte regulation (FGFR3, FGFR2, NPR2). In 12/74 (16%), we revealed P/LP affecting fundamental intracellular/intranuclear processes (CDC42, KMT2D, LMNA, NSD1, PTPN11, SRCAP, SON, SOS1, SOX9, TLK2). SHOX deficiency was found in 7/74 (9%), Silver-Russell syndrome in 12/74 (16%) (11p15, UPD7), and miscellaneous chromosomal aberrations in 5/74 (7%) children. CONCLUSIONS: The high diagnostic yield sheds a new light on the genetic landscape of SGA-SS, with a central role for the growth plate with substantial contributions from the GH-IGF-1 and thyroid axes and intracellular regulation and signalling.

Response to growth hormone therapy in ring chromosome 15: Review and evidence from a new case on possible beneficial effect in neurodevelopment.

Type 1 Insulin-like Growth Factor Receptor(IGF1R) plays a fundamental role in normal growth and development. Its disruption is usually characterized by severe intrauterine and postnatal growth retardation, microcephaly and neurodevelopmental delay.The efficacy of recombinant human growth hormone treatment remains a challenge for children with IGF1 resistance and pathogenic mutations of IGF1R, with limited data in patients carrying the most severe form of IGF1R defect, the ring chromosome 15. SUBJECT AND METHOD: We tested a high dose of rhGH in a new patient with ring chromosome 15, as confirmed by karyotype and CGH array. We performed a systematic review, and all published r(15) syndrome cases treated by growth hormone(GH) up to April 2023 were searched, and their response to GH therapy was recorded and summarized. RESULTS: Twelve patients with ring chromosome 15 received GH therapy according to a literature review. We expand the spectrum by the 13th case treated by GH, and we report an impressive improvement in intellectual performance and progressive catch-up growth after 5 and 20 months of follow-up. By introducing our new case in the analysis, the sex ratio was 3:10, and GH therapy was started at the age of 5.5 (3/9.4) (years) for an age of diagnosis of 4.75 (1.3/9.5) (years). The height before GH therapy was -5.1(-5.9/-4.1) SDS. The median duration of treatment was 1.7(0.9/2) (years), with a median height gain of 1(0.3/1.8) SDS and an improvement in growth velocity of 4.1(2.8/5.3) (cm/year). CONCLUSION: GH seems to be effective for r(15) syndrome patients with short stature.

Effects of morphological traits on body weight and analysis of growth-related genes of Parabramis pekinensis at different ages.

Parabramis pekinensis was treated as research object in order to investigate the correlation between morphological traits and body weight. We measured 9 morphological indexes including total length (X1), body length (X2), body height (X3), head length (X4), snout length (X5), eye diameter (X6), eye distance (X7), caudal stalk length (X8) and caudal stalk height (X9). The principal morphological traits affecting body weight were screened out and the regression equation was established. The regression equation of Y1 (age 1 group) shape character (X) and weight (Y) was Y = - 169.183 + 32.544 × 3 + 10.263 × 4 + 15.655 × 7. The regression equation of Y2 (age 2 group) shape character (X) and weight (Y) was Y = - 694.082 + 7.725 × 1 + 72.822 × 3 + 77.023 × 6, the regression equation of Y3 (age 3 group) shape character (X) and weight (Y) was Y = - 1161.512 + 26.062 × 1 + 22.319 × 2- 107.218 × 5 + 83.901 × 7. Gene expression was consistent with these conclusions. TOR signaling pathway expression raised in Y1 then width increased. And GH-IGF-1 signaling pathway expression raised in Y2 then the length increased. In conclusion, the paper could prove that P. pekinensis showed a growth trend, which was increasing width first and length later. In some sense, the study not only enriched the basic biological data of P. pekinensis, but also provided waiting morphological traits for selective breeding of P. pekinensis artificial breeding in future.

Short stature related to Growth Hormone Insensitivity (GHI) in childhood.

Linear growth during childhood is the result of the synergic contribution of different factors. The best growth determinant system during each period of life is represented by the growth hormone-insulin-like growth factor axis (GH-IGF), even if several other factors are involved in normal growth. Within the broad spectrum of growth disorders, an increased importance has been placed on growth hormone insensitivity (GHI). GHI was reported for the first time by Laron as a syndrome characterized by short stature due to GH receptor (GHR) mutation. To date, it is recognized that GHI represents a wide diagnostic category, including a broad spectrum of defects. The peculiar characteristic of GHI is the low IGF-1 levels associated with normal or elevated GH levels and the lack of IGF-1 response after GH administration. Recombinant IGF-1 preparations may be used in the treatment of these patients.

Lead acetate induces cartilage defects and bone loss in zebrafish embryos by disrupting the GH/IGF-1 axis.

Skeletal system toxicity due to lead exposure has attracted extensive attention in recent years, but few studies focus on the skeletal toxicity of lead in the early life stages of zebrafish. The endocrine system, especially the GH/IGF-1 axis, plays an important role in bone development and bone health of zebrafish in the early life. In the present study, we investigated whether lead acetate (PbAc) affected the GH/IGF-1 axis, thereby causing skeletal toxicity in zebrafish embryos. Zebrafish embryos were exposed to lead PbAc between 2 and 120 h post fertilization (hpf). At 120 hpf, we measured developmental indices, such as survival, deformity, heart rate, and body length, and assessed skeletal development by Alcian Blue and Alizarin Red staining and the expression levels of bone-related genes. The levels of GH and IGF-1 and the expression levels of GH/IGF-1 axis-related genes were also detected. Our data showed that the LC50 of PbAc for 120 h was 41 mg/L. Compared with the control group (0 mg/L PbAc), after PbAc exposure, the deformity rate increased, the heart rate decreased, and the body length was shortened at various time periods, in the 20-mg/L group at 120 hpf, the deformity rate increased by 50 fold, the heart rate decreased by 34%, and the body length shortened by 17%. PbAc altered cartilage structures and exacerbated bone loss in zebrafish embryos; in addition, PbAc exposure down-regulated the expression of chondrocyte (sox9a, sox9b), osteoblast (bmp2, runx2) and bone mineralization-related genes (sparc, bglap), and up-regulated the expression of osteoclast marker genes (rankl, mcsf). The GH level increased and the IGF-1 level declined significantly. The GH/IGF-1 axis related genes (ghra, ghrb, igf1ra, igf1rb, igf2r, igfbp2a, igfbp3, igfbp5b) were all decreased. These results suggested that PbAc inhibited the differentiation and maturation of osteoblasts and cartilage matrix, promoted the formation of osteoclasts, and ultimately induced cartilage defects and bone loss by disrupting the GH/IGF-1 axis.

New Perspectives In The Objective Evaluation Of Animal Welfare, With Focus On The Domestic Pig.

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.

Growth regulation in brook charr Salvelinus fontinalis.

Fish growth can be modulated through genetic selection. However, it is not known whether growth regulatory mechanisms modulated by genetic selection can provide information about phenotypic growth variations among families or populations. Following a five-generation breeding program that selected for the absence of early sexual maturity and increased growth in brook charr we aimed to understand how the genetic selection process modifies the growth regulatory pathway of brook charr at the molecular level. To achieve this, we studied the regulation of growth traits at three different levels: 1) between lines-one under selection, the other not, 2) among-families expressing differences in average growth phenotypes, which we termed family performance, and 3) among individuals within families that expressed extreme growth phenotypes, which we termed slow- and fast-growing. At age 1+, individuals from four of the highest performing and four of the lowest performing families in terms of growth were sampled in both the control and selected lines. The gene expression levels of three reference and ten target genes were analyzed by real-time PCR. Results showed that better growth performance (in terms of weight and length at age) in the selected line was associated with an upregulation in the expression of genes involved in the growth hormone (GH)/insulin growth factor-1 (IGF-1) axis, including the igf-1 receptor in pituitary; the gh-1 receptor and igf-1 in liver; and ghr and igf-1r in white muscle. When looking at gene expression within families, family performance and individual phenotypes were associated with upregulations of the leptin receptor and neuropeptid Y-genes related to appetite regulation-in the slower-growing phenotypes. However, other genes related to appetite (ghrelin, somatostatin) or involved in muscle growth (myosin heavy chain, myogenin) were not differentially expressed. This study highlights how transcriptomics may improve our understanding of the roles of different key endocrine steps that regulate physiological performance. Large variations in growth still exist in the selected line, indicating that the full genetic selection potential has not been reached.

Cysteamine-supplemented diet for cashmere goats: A potential strategy to inhibit rumen biohydrogenation and enhance plasma antioxidant capacity.

Cysteamine (CS), as a feed supplement, can increase the level of growth hormone (GH) in the blood, promote animal growth. However, little attention has been paid to the effects of CS on the rumen microbiome and metabolic profile in cashmere goats. This study aimed to assess the effects of rumen microbiota, metabolites, and plasma antioxidative capacity induced by CS supplementation in cashmere goats. We selected 30 Inner Mongolia white cashmere goat ewes (aged 18 months), and randomly separate the goats into three groups (n = 10 per group) to experiment for 40 days. Oral 0 (control group, CON), 60 (low CS, LCS), or 120 mg/kg BW-1 (high CS, HCS) coated CS hydrochloride every day. Using 16S and internal transcribed spacer (ITS) rRNA gene amplicon sequencing, we identified 12 bacterial and 3 fungal genera with significant changes among the groups, respectively. We found a significant increase in rumen NH3-N and total volatile fatty acid (TVFA) concentrations in the LCS and HCS groups compared with the CON. With untargeted LC-MS/MS metabolomics, we screened 59 rumen differential metabolites. Among the screened metabolites, many unsaturated and saturated fatty acids increased and decreased with CS treatment, respectively. CS supplementation increased the levels of plasma total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), GH, and insulin-like growth factor-1(IGF-1). Spearman correlation analysis revealed that the abundance of U29-B03, Lactococcus, and Brochothrix were positively associated with the levels of δ2-THA, TVFA and antioxidant capacity. In conclusion, CS significantly affected rumen microbiota and fermentation parameters, and ultimately inhibited the biohydrogenation of rumen metabolites, enhanced plasma antioxidant capacity, and regulated some hormones of the GH-IGF-1 axis. This study provides an overall view into the CS application as a strategy to improve health production in cashmere goats.

Association Between the Growth Hormone/Insulin-Like Growth Factor-1 Axis and Muscle Density in Children and Adolescents of Short Stature.

Objective: To evaluate the association between the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis and muscle density in children and adolescents of short stature. Methods: Participants were children and adolescents of short stature hospitalized in the Affiliated Hospital of Jining Medical University between January 2020 and June 2021. All participants had CT scan images available. We performed an analysis of the images to calculate the muscle density or skeletal muscle attenuation (SMA), skeletal muscle index (SMI), and fat mass index (FMI). Bioelectrical impedance analysis (BIA) was used to ensure that chest CT is a credible way of evaluating body composition. Results: A total of 297 subjects were included with the mean age of 10.00 ± 3.42 years, mean height standard deviation score (SDS) of -2.51 ± 0.53, and mean IGF-1 SDS of -0.60 ± 1.07. The areas of muscle and fat tissues at the fourth thoracic vertebra level in the CT images showed strong correlation with the total weights of the participants (R2  = 0.884 and 0.897, respectively). The peak of GH was negatively associated with FMI (r = - 0.323, P <.01) and IGF-1 SDS was positively associated with SMI (r = 0.303, P <.01). Both the peak GH and IGF-1 SDS were positively associated with SMA (r = 0.244, P <.01 and r = 0.165, P <.05, respectively). Multiple stepwise linear regression analysis demonstrated that the GH peak was the predictor of FMI (ß = - 0.210, P < .01), the IGF-1 SDS was the predictor of SMI (ß = 0.224, P < .01), and both the peak GH and IGF-1 SDS were predictors of SMA (ß = 0.180, P < .01 and ß = 0.222, P < .01). Conclusions: A chest CT scan is a credible method of evaluating body composition in children and adolescents of short stature. In these patients, peak GH and IGF-1 SDS are independent predictors of muscle density and the GF/IGF-1 axis may regulate body composition through complex mechanisms.

OSAHS Growth Impairment and Resolution after Adenotonsillectomy in Children.

Introduction: One of the most important complications of OSAHS in children is growth delay. The aim of this study was to investigate changes in clinical body growth, and laboratory growth in children with OSAHS after adeno-tonsillar surgery. Materials and Methods: In our study, among 102 children suffering from sleep-disordered breathing, 70 met the inclusion criteria because they were affected by OSAHS and adenotonsillar hypertrophy. In total, 96 children affected by adeno-tonsillar hypertrophy (55 males and 41 females) underwent nocturnal cardiorespiratory monitoring with Embletta MPR, monitoring for post-operative 24 hours. Patients underwent blood sampling to evaluate preoperative GH and IGF-1 serum levels, "placement" in Cacciari's growth charts and adenotonsillectomy and saturation monitoring for post-operative 24 hours. According to auxological parameters, 82.86% of the patients were below the fiftieth percentile of BMI Cacciari's growth charts and IGF-1 preoperative serum levels were below the normal range. All patients underwent adenotonsillectomy. Results: All 70 patients recovered from OSAHS according to the results of nocturnal cardiorespiratory monitoring after six months. IGF-1 serum levels significantly increased after three months and one year after. All the auxological parameters showed a significant increase after surgery. We calculated the average annual growth in height of the patients before and after adenotonsillectomy (AT): the growth rate was impaired by OSAHS (5.4±1.3 cm/year), while in the following year post-surgery we found a significant growth speed acceleration (9.9±1.7 cm/year, P=0.001). Conclusions: In conclusion, growth delay in children can be caused by OSAHS, and when it is due to adenotonsillar hypertrophy, adenotonsillectomy is to be considered as the therapy of choice.

Transcriptome analysis revealed hub genes for muscle growth in Indian major carp, Catla catla (Hamilton, 1822).

Catla (Catla catla) is the fastest growing Indian major carp species and forms an important component of the freshwater aquaculture systems in the Indian sub-continent. The molecular mechanisms of growth of the species in response to seasonal water temperature variations hitherto are still unknown. In the current study, high-throughput transcriptome sequencing was used to study the differential gene expression pattern in catla muscle tissues between pre-winter and post-winter fingerling groups and fast-growing table size fish. Transcriptome analysis identified 1677 differentially expressed genes (DEGs) in three different growth stages and 236 common DEGs between fingerling at low temperature and table fish post-winter, including four genes under GH/IGF1 axis and 163 genes under signature for compensatory muscle growth. Molecular pathways for the mapped genes identified 42 KEGG pathways and the critical pathways under Environmental Information Processing identified were PI3K-Akt signaling, AMPK signaling pathway, Calcium signaling pathway and MAPK signaling pathway. In this study, 14 differentially expressed potential regulatory hub genes for growth were identified, for the first time and categorized into three major GO groups: unfolded protein binding, rNA processing and biogenesis and muscle development and differentiation. These regulatory hub genes, except acta1, were found to be upregulated in fast-growing table size and post-winter fingerling groups. The results provided valuable information about the key genes, with potential to be used as biomarkers of growth in breeding programs and contributed to our understanding of the molecular mechanisms and pathways regulating muscle growth, in response to temperature fluctuations and different growth stages in C. catla.

Anabolic Deficiencies in Heart Failure: Ready for Prime Time?

"Chronic heart failure (CHF) is a complex syndrome characterized by symptoms and signs supported by different forms of cardiac impairment. The link between multiple hormonal and metabolic derangements and the development of CHF and the beneficial effects seen with hormonal replacement therapy suggest that a reduction of anabolic pathways might contribute to the onset of CHF. Therefore, an imbalance between anabolic and catabolic forces could be responsible for the development of CHF. There are sufficient evidence to support the screening in patients with CHF of hormonal deficiencies and their correction with replacement therapy."

Combined growth hormone and insulin-like growth factor-1 rescues growth retardation in glucocorticoid-treated mdxmice but does not prevent osteopenia.

Short stature and osteoporosis are common in Duchenne muscular dystrophy (DMD) and its pathophysiology may include an abnormality of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, which is further exacerbated by long-term glucocorticoid (GC) treatment. Hence, an agent that has anabolic properties and may improve linear growth would be beneficial in this setting and therefore requires further exploration. A 5-week-old x-linked muscular dystrophy (mdx) mice were used as a model of DMD. They were treated with prednisolone ± GH + IGF-1 for 4 weeks and then compared to control mdx mice to allow the study of both growth and skeletal structure. GC reduced cortical bone area, bone fraction, tissue area and volume and cortical bone volume, as assessed by micro computed tomography (CT) In addition, GC caused somatic and skeletal growth retardation but improved grip strength. The addition of GH + IGF-1 therapy rescued the somatic growth retardation and induced additional improvements in grip strength (16.9% increase, P < 0.05 compared to control). There was no improvement in bone microarchitecture (assessed by micro-CT and static histomorphometry) or biomechanical properties (assessed by three-point bending). Serum bone turnover markers (Serum procollagen 1 intact N-terminal propeptide (P1NP), alpha C-terminal telopeptide (αCTX)) also remained unaffected. Further work is needed to maximise these gains before proceeding to clinical trials in boys with DMD.

Low prevalence of neuropathic-like pain symptoms in long-term controlled acromegaly.

PURPOSE: Pain is a common symptom of acromegaly, impairing health-related quality of life (HR-QoL) significantly despite long-term disease remission. Neuropathic-like pain (NP-like) symptoms are invalidating, with great impact on HR-QoL. Studies characterizing or investigating the etiology of pain in acromegaly are scarce. Therefore, we aimed to assess NP-like symptoms in a cohort of controlled acromegaly patients. METHODS: Forty-four long-term controlled acromegaly patients (aged 62.6 ± 12.6 years; 56.8% female) were included in this cross-sectional study. NP-like symptoms were assessed using the validated painDETECT questionnaire. Patients were divided in three probability-based NP-like symptoms categories based on the total score (range 0-35): unlikely (≤ 12), indeterminate (13-18) and likely (≥ 19). HR-QoL (physical component score (PCS), and mental component score (MCS)), and self-reported pain were assessed using Short Form-36 (SF-36). Potential risk factors were determined using linear regression analyses. RESULTS: Self-reported pain was reported by 35 patients (79.5%). Likely NP-like symptoms were present in 4/44 patients (9.1%), and indeterminate NP-like symptoms in 6/44 patients (13.6%). All patients with likely NP-like symptoms were female. Higher painDETECT scores were negatively associated with HR-QoL (PCS: r = - 0.46, P = 0.003; MCS: r = - 0.37, P = 0.018), and SF-36 pain scores (r = - 0.63, P < 0.0001). Female sex was a risk factor for NP-like symptoms. CONCLUSIONS: Pain was prevalent in controlled acromegaly patients, whereas NP-like symptoms were relatively infrequent, and only observed in females. NP-like symptoms were associated with lower HR-QoL in acromegaly. Since specific analgesic therapy is available, awareness for characterization, increased understanding, and clinical trials regarding neuropathic pain identification and treatment in acromegaly patients are warranted.

Adult height and long-term outcomes after rhIGF-1 therapy in two patients with PAPP-A2 deficiency.

PAPP-A2 deficiency is a novel syndrome characterized by short stature due to low IGF bioactivity, skeletal abnormalities and decreased bone mineral density (BMD). Treatment with recombinant human IGF-1 (rhIGF-1) for 1 year demonstrated to increase growth velocity and BMD, without reported adverse effects, but data regarding the long-term efficacy and safety of rhIGF-1 administration in this entity has not yet been reported. Two Spanish siblings with short stature due to a homozygous loss-of-function mutation in the PAPP-A2 gene (p.D643fs25*) were treated with rhIGF-1 twice daily for six years. Growth velocity continued to increase and both patients achieved their target height. Free IGF-1 concentrations increased notably after rhIGF-1 administration, with serum IGFBP-3, IGFBP-5 and ALS levels also being higher during treatment. BMD was progressively normalized and an increase in lean mass was also noted during treatment. No episodes of hypoglycemia or any other adverse effects were documented. An increase in the growth of kidney and spleen length was observed in one of the patients.

Dual Characters of GH-IGF1 Signaling Pathways in Radiotherapy and Post-radiotherapy Repair of Cancers.

Radiotherapy remains one of the most important cancer treatment modalities. In the course of radiotherapy for tumor treatment, the incidental irradiation of adjacent tissues could not be completely avoided. DNA damage is one of the main factors of cell death caused by ionizing radiation, including single-strand (SSBs) and double-strand breaks (DSBs). The growth hormone-Insulin-like growth factor 1 (GH-IGF1) axis plays numerous roles in various systems by promoting cell proliferation and inhibiting apoptosis, supporting its effects in inducing the development of multiple cancers. Meanwhile, the GH-IGF1 signaling involved in DNA damage response (DDR) and DNA damage repair determines the radio-resistance of cancer cells subjected to radiotherapy and repair of adjacent tissues damaged by radiotherapy. In the present review, we firstly summarized the studies on GH-IGF1 signaling in the development of cancers. Then we discussed the adverse effect of GH-IGF1 signaling in radiotherapy to cancer cells and the favorable impact of GH-IGF1 signaling on radiation damage repair to adjacent tissues after irradiation. This review further summarized recent advances on research into the molecular mechanism of GH-IGF1 signaling pathway in these effects, expecting to specify the dual characters of GH-IGF1 signaling pathways in radiotherapy and post-radiotherapy repair of cancers, subsequently providing theoretical basis of their roles in increasing radiation sensitivity during cancer radiotherapy and repairing damage after radiotherapy.

Milk Polar Lipids Supplementation to Obese Rats During Pregnancy and Lactation Benefited Skeletal Outcomes of Male Offspring.

SCOPE: Dietary intervention to obese dams during pregnancy and lactation period provides avenues for improving metabolic profiles of the offspring. In the current study, the effects of polar lipids-enriched milk fat globule membrane (MFGM-PL) supplementation to obese dams during pregnancy and lactation on the skeletal outcomes of male offspring are investigated. METHODS AND RESULTS: MFGM-PL is supplemented to obese rats induced by high-fat diet during pregnancy and lactation at a dose of 400 mg kg-1 body weight. Results show that maternal MFGM-PL supplementation significantly ameliorates the stunted skeletal growth of male offspring at weaning. In adulthood offspring, maternal MFGM-PL supplementation protects against high-fat diet (HFD)-induced bone microstructure degeneration and bone marrow adipocyte accumulation. Further investigation shows that maternal supplementation of MFGM-PL significantly ameliorates insulin resistance and increases the mRNA expression of growth hormone releasing hormone (GHRH) in the hypothalamus of HFD offspring. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis is subsequently enhanced in MFGM-PL + HFD offspring, contributing to the beneficial skeletal outcomes. CONCLUSION: The findings suggest that maternal MFGM-PL supplementation of HFD dam during pregnancy and lactation shows desirable effects on fetal skeletal development, with lasting beneficial programming impacts on skeletal outcomes of offspring.