Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth. The effects of hUCB-MSCs on hair growth were investigated in vivo, and hUCB-MSCs advanced anagen onset and hair follicle neogeneration. We found that hUCB-MSCs co-culture increased the viability and up-regulated hair induction-related proteins of human dermal papilla cells (hDPCs) in vitro. A growth factor antibody array revealed that secretory factors from hUCB-MSCs are related to hair growth. Insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were increased in co-culture medium. Finally, we found that IGFBP-1, through the co-localization of an IGF-1 and IGFBP-1, had positive effects on cell viability; VEGF secretion; expression of alkaline phosphatase (ALP), CD133, and β-catenin; and formation of hDPCs 3D spheroids. Taken together, these data suggest that hUCB-MSCs promote hair growth via a paracrine mechanism.
Alkaline Phosphatase ; Alopecia ; Cell Survival ; Coculture Techniques ; Fetal Blood* ; Hair Follicle ; Hair* ; Humans* ; In Vitro Techniques ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor I ; Intercellular Signaling Peptides and Proteins* ; Mesenchymal Stromal Cells ; Regeneration ; Stem Cells* ; Umbilical Cord* ; Vascular Endothelial Growth Factor A

OBJECTIVETo investigate the efficacy and safety of different doses of recombinant human growth hormone (rhGH) in the treatment of short stature in children born small for gestational age (SGA).

METHODSA total of 37 children with short stature born SGA were enrolled, and based on the dose of rhGH treatment, they were divided into low-dose rhGH group (0.1-0.15 IU/kg daily) and high-dose rhGH group (0.16-0.2 IU/kg daily). The changes in height standard deviation score (ΔHtSDS), height velocity (HV), serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), and fasting blood glucose at 3, 6, 9, 12, and 24 months after treatment were compared between the two groups.

RESULTSΔHtSDS and HV both increased after the treatment with high- and low-dose rhGH, but ΔHtSDS and HV in the high-dose rhGH group were significantly higher than in the low-dose rhGH group 9, 12 and 24 months after treatment (P<0.05). Both high- and low-dose rhGH treatment increased serum levels of IGF-1 and IGFBP-3. Serum levels of IGF-1 and IGFBP-3 were positively correlated with HtSDS in both groups. One child each in the high- and low-dose rhGH groups experienced transient slight increase in fasting blood glucose (6.1 mmol/L). There were no cases of abnormal thyroid function.

CONCLUSIONSrhGH has good efficacy in the treatment of short stature in children born SGA, with few adverse events, and high-dose rhGH has some advantages over low-dose rhGH.

Body Height ; Child ; Child, Preschool ; Female ; Growth Disorders ; blood ; drug therapy ; Human Growth Hormone ; therapeutic use ; Humans ; Infant, Small for Gestational Age ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Recombinant Proteins ; therapeutic use

Cows with different Insulin-like Growth Factor-I (IGF-I) concentrations showed comparable expression levels of hepatic growth hormone receptor (GHR). Suppressor of cytokine signaling 2 (SOCS2), could be responsible for additional inhibition of the GHR signal cascade. The aims were to monitor cows with high or low antepartal IGF-I concentrations (IGF-I(high) or IGF-I(low)), evaluate the interrelationships of endocrine endpoints, and measure hepatic SOCS2 expression. Dairy cows (n = 20) were selected (240 to 254 days after artificial insemination (AI)). Blood samples were drawn daily (day -17 until calving) and IGF-I, GH, insulin, thyroid hormones, estradiol, and progesterone concentrations were measured. Liver biopsies were taken (day 264 +/- 1 after AI and postpartum) to measure mRNA expression (IGF-I, IGFBP-2, IGFBP-3, IGFBP-4, acid labile subunit (ALS), SOCS2, deiodinase1, GHR1A). IGF-I concentrations in the two groups were different (p < 0.0001). However, GH concentrations and GHR1A mRNA expression were comparable (p > 0.05). Thyroxine levels and ALS expression were higher in the IGF-I(high) cows compared to IGF-I(low) cows. Estradiol concentration tended to be greater in the IGF-I(low) group (p = 0.06). It was hypothesized that low IGF-I levels are associated with enhanced SOCS2 expression although this could not be decisively confirmed by the present study.
Animals ; Cattle ; Estradiol/blood ; Female ; Growth Hormone/blood ; Insulin/blood ; Insulin-Like Growth Factor Binding Protein 2/analysis ; Insulin-Like Growth Factor Binding Protein 3/analysis ; Insulin-Like Growth Factor Binding Protein 4/analysis ; Insulin-Like Growth Factor I/*analysis/physiology ; Liver/chemistry ; Pregnancy/metabolism/physiology ; Pregnancy, Animal/*metabolism/physiology ; Progesterone/blood ; Suppressor of Cytokine Signaling Proteins/analysis ; Thyroid Hormones/blood

Preeclapsia (PE) is a severe disorder that occurs during pregnancy, leading to maternal and fetal morbidity and mortality. PE affects about 3-8% of all pregnancies. In this study, we conducted liquid chromatographymass spectrometry/mass spectrometry (LC-MS/MS) to analyze serum samples depleted of the six most abundant proteins from normal and PE-affected pregnancies to profile serum proteins. A total of 237 proteins were confidently identified with < 1% false discovery rate from the two groups of duplicate analysis. The expression levels of those identified proteins were compared semiquantitatively by spectral counting. To further validate the candidate proteins with a quantitative mass spectrometric method, selective reaction monitoring (SRM) and enzyme linked immune assay (ELISA) of serum samples collected from pregnant women with severe PE (n = 8) or normal pregnant women (n = 5) was conducted. alpha2-HS-glycoprotein (AHSG), retinol binding protein 4 (RBP4) and alpha-1-microglobulin/bikunin (AMBP) and Insulin like growth factor binding protein, acid labile subunit (IGFBP-ALS) were confirmed to be differentially expressed in PE using SRM (P < 0.05). Among these proteins, AHSG was verified by ELISA and showed a statistically significant increase in PE samples when compared to controls.
Adult ; Alpha-Globulins/metabolism ; Amino Acid Sequence ; Biological Markers/blood ; Blood Proteins/*analysis ; Case-Control Studies ; Female ; Humans ; Insulin-Like Growth Factor Binding Proteins/blood ; Molecular Sequence Data ; Pre-Eclampsia/*blood/diagnosis ; Pregnancy ; Proteome/*analysis ; Retinol-Binding Proteins, Plasma/metabolism ; alpha-2-HS-Glycoprotein/metabolism

OBJECTIVETo study serum levels and clinical significance of insulin-like growth factor-1 (IGF-1) and growth factor binding protein 3 (IGFBP-3) in children with acute lymphocytic leukemia (ALL).

METHODSSerum samples were obtained from 36 children with ALL before treatment and 6 months after complete remission. Thirty children with surgical diseases severed as the control group. Serum IGF-1 levels were measured using radioimmunoassay (RIA). Serum IGFBP-3 levels were measured using immunoradioassays (IRMA).

RESULTSSerum levels of IGF-1 and IGFBP-3 in the ALL group were 19±4 ng/mL and 1216±132 ng/mL, respectively before treatment, which were lower than those in the control group (32±3 ng/mL and 2104±191 ng/mL respectively) (P<0.01). Serum levels of IGF-1 and IGFBP-3 in the ALL group increased to 30±3 ng/mL and 1941±164 ng/mL respectively 6 months after complete remission, which were significantly higher than those before treatment (P<0.01) and were similar to the levels of the control group.

CONCLUSIONSSerum levels of IGF-1 and IGFBP-3 are reduced in children with ALL, but increase significantly after complete remission, suggesting that IGF-1 and IGFBP-3 might serve as useful markers for the diagnosis and evaluation of therapeutic effects of childhood ALL.

Adolescent ; Biomarkers, Tumor ; blood ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; diagnosis

OBJECTIVEHuman growth hormone (hGH) is an essential therapeutic drug for the treatment of growth hormone (GH) deficiency (GHD). However, the process of dissolving hGH of the powder form is complicated and potentially hazardous. In the present study, we evaluated the efficacy and safety of preparation in the replacement therapy for children with GH deficiency.

METHODSA 12-month randomized, open-label, multicenter trial was conducted in 31 previously untreated children with growth failure secondary to GH deficiency [20 boys and 11 girls, mean age (10.5 +/- 4.1) years]. An recombined human growth hormone (rhGH) solution (Iintropin AQ) was given via subcutaneous injection daily in every evening at a weekly dose of 0.25 mg/kg. The patients were followed up at 3, 6, 9, and 12 months of the treatment, and the course of treatment was 12 months. Body height was measured 3-monthly and height velocity (HV) and mean height standard deviation score (HT SDS) were calculated. Serum Insulin-like growth factor I (IGF-1), Insulin-like growth factor binding protein 3 (IGFBP-3), GH antibodies and safety parameters were assessed at the baseline and at 3-month intervals. Bone age (BA) was assessed at the baseline and the rate of skeletal maturation (DeltaBA/DeltaCA) was calculated after 6 and 12 months of rhGH treatment by a central bone age reader. Moreover, the safety of rhGH solution treatment was assessed.

RESULTSAfter 12 months of liquid rhGH therapy, growth parameters were significantly increased over baseline. (1) The mean (+/- SD) height increment DeltaHT (cm) was 4.0 +/- 1.3, 7.0 +/- 2.0, 10.3 +/- 2.6 and 12.9 +/- 3.3 after 3, 6, 9, and 12 months of treatment, respectively (P < 0.01), which indicated linear growth after treatment. The GV (cm/years) was 2.7 +/- 0.9 before treatment and increased to 16.0 +/- 5.1, 14.1 +/- 4.0, 13.7 +/- 3.5, and 12.9 +/- 3.3 after treatment, suggesting that catch-up growth was significant after treatment as compared to the pre-treatment status (P < 0.01). Accordingly, post-treatment catch-up growth was obvious, significant differences were observed in HT SDS, which was -4.62 +/- 1.46 at the onset of therapy and increased significantly after the treatment to -3.80 +/- 1.53, -3.28 +/- 1.60, -2.86 +/- 1.75 and -2.47 +/- 1.86, respectively (P < 0.01). The height difference between GH deficient children and unimpaired children of the same age and gender gradually decreased after treatment, which was significantly different from that seen before treatment (P < 0.01). (2) The levels of serum IGF-1 and IGFBP-3 were increased comparably for the treatment. IGF-1 level (microg/L) was 41 +/- 64 at baseline and increased to 179 +/- 155, 202 +/- 141, 156 +/- 155 and 159 +/- 167 after 3, 6, 9, 12 months of treatment. IGFBP-3 level (mg/L) was 1540 +/- 1325 at baseline, and increased to 3891 +/- 1815, 4051 +/- 1308, 3408 +/- 1435 and 3533 +/- 1413, respectively, suggesting that with the increases in height, IGF-1, and IGFBP-3 were significantly activated to relatively high levels by the medication and reached peak values between 3 and 6 months of treatment. The levels of IGF-1 and IGFBP-3 were significantly different before and after treatment (P < 0.01). The IGF-1/IGFBP-3 molar ratio significantly increased during GH therapy (0.143 +/- 0.013 pre-therapy up to 0.240 +/- 0.055 post-therapy, P < 0.01). The IGF-1/IGFBP-3 molar ratio tended to stabilize after 3-month GH therapy. (3) The bone age assessment carried out 6 and 12 months after treatment showed that the bone maturity (DeltaBA/DeltaCA) was 1.01 +/- 0.57 and 1.07 +/- 0.75, respectively, suggesting that there was no speed-up development in the bone age. No severe adverse events were observed during the trial and the most frequent accompanying event was mild hypothyroidism.

CONCLUSIONSrhGH solution (Iintropin AQ) is a safe and effective preparation in the replacement therapy for children with GH deficiency.

Child ; China ; Dwarfism, Pituitary ; blood ; drug therapy ; Female ; Growth Disorders ; blood ; drug therapy ; Human Growth Hormone ; deficiency ; therapeutic use ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; metabolism ; Male ; Prospective Studies ; Recombinant Proteins ; therapeutic use

Alanine Transaminase ; blood ; Animals ; Antibodies ; pharmacology ; Apoptosis ; Collagen Type I ; biosynthesis ; DNA-Binding Proteins ; metabolism ; Disease Models, Animal ; Insulin-Like Growth Factor Binding Protein 1 ; immunology ; L-Lactate Dehydrogenase ; blood ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; drug therapy ; immunology ; metabolism ; Male ; Mice ; Protective Agents ; pharmacology ; Thioacetamide ; Transforming Growth Factor beta ; metabolism

AIMTo investigate the relationships of serum testosterone, insulin-like growth factor (IGF)-1 and IGF-binding protein (IGFBP)-3 levels with prostate cancer risk and also with known prognostic parameters of prostate cancer in Korean men who received radical retropubic prostatectomy (RRP) for clinically-localized prostate cancer.

METHODSSerum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 were determined in 592 patients who subsequently received prostate biopsy. Results were compared between patients who eventually received RRP for prostate cancer (n=159) and those who were not diagnosed with prostate cancer from biopsy (control group, n=433). Among the prostate cancer only patients, serum hormonal levels obtained were analyzed in relation to serum prostate specific antigen (PSA), pathological T stage and pathological Gleason score.

RESULTSProstate cancer patients and the control group demonstrated no significant differences regarding serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 across the different age groups. Among the cancer only patients, no significant associations were observed for serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 levels with pathological T stage, pathological Gleason score and preoperative PSA.

CONCLUSIONOur data indicate that simple quantifications of serum testosterone and IGF-1 along with IGFBP-3 levels might not provide useful clinical information in the diagnosis of clinically localized prostate cancer in Korean men. Also, our results suggest that serum levels of testosterone, IGF-1 and IGFBP-3 might not be significantly associated with known prognostic factors of clinically localized prostate cancer in Korean men.

Aged ; Biomarkers, Tumor ; blood ; Biopsy, Needle ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins ; blood ; Insulin-Like Growth Factor I ; analysis ; Korea ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms ; blood ; pathology ; Testosterone ; blood

PURPOSE: This study was designed to examine the effects of adiponectin, leptin, insulin, insulin-like growth factor (IGF)-I and IGF binding protein (BP)-3 levels in cord blood on weight, length, and adiposity at birth in healthy term infants. In addition, we evaluated the mechanism to change the hormone levels in appropriate for gestational age (AGA) during the first month. METHODS: We collected cord blood from 200 term neonates (109 males, 91 females) with no perinatal problems, and measured the hormone levels and anthropometric parameters including weight, length, and skin-fold thickness. Term neonates were divided into 3 groups as follows: birth weight appropriate for gestational age (AGA) (n=132), birth weight less for gestational age (SGA) (n=29), and birth weight more for gestational age (LGA) (n=39). Venous blood samples of 15 fullterm healthy neonates were obtained at 3, 7, and 30 d after birth. RESULTS: The adiponectin, insulin, and IGF-I levels were significantly lower in the SGA group than in the AGA and LGA groups. The leptin levels were significantly higher in the LGA group than in the AGA and SGA groups. Cord blood adiponectin, leptin, insulin, IGF-I, and IGFBP-3 levels correlated significantly and positively with birth weight and the sum of the skin-fold thickness. A significant positive correlation was observed between adiponectin, leptin, and IGF-I levels and birth weight. Adiponectin level correlated significantly with that leptin level (r=0.191, P=0.038), but not with insulin, IGF-I and IGFBP-3 levels. IGF-I levels were higher in females than in males. At 7 d after birth, the leptin level decreased along with physiologic weight loss, and then increased. IGF-I, also decreased at 3 d, significantly increased 1 month later. CONCLUSION: We suggest that adiponectin, leptin, insulin, IGF-I, and IGFBP-3 play an important role in regulating fetal growth. Adiponectin may be involved in regulating fetal growth through mechanisms different from those mediated by insulin or IGF-I. High levels of IGF-I in female neonates indicates a gender difference which serves as evidence for in utero sexual dimorphism. It is likely that IGF-I has a more important role than that of hormones in postnatal growth.
Adiponectin ; Adiposity ; Birth Weight ; Carrier Proteins ; Female ; Fetal Blood ; Fetal Development ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Insulin ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Leptin ; Male ; Parturition ; Weight Loss

Animals ; Colorectal Neoplasms ; blood ; etiology ; Humans ; Hyperinsulinism ; blood ; complications ; Insulin ; blood ; Insulin Resistance ; Insulin-Like Growth Factor Binding Proteins ; blood ; Insulin-Like Growth Factor I ; metabolism ; Metabolic Syndrome ; blood ; complications ; Receptor, IGF Type 1 ; blood ; Receptor, Insulin ; blood