- Growth patterns, metabolic indicators and osteoarticular status in the Lusitano horse: A longitudinal study. [Journal Article]
- PlosPLoS One 2019; 14(7):e0219900
- Development of a healthy musculoskeletal system is of high concern for horse breeders and users. A longitudinal field study was performed in order to: (i) evaluate growth patterns and long-term chang…
Development of a healthy musculoskeletal system is of high concern for horse breeders and users. A longitudinal field study was performed in order to: (i) evaluate growth patterns and long-term changes on bone quality, bone metabolism, growth factors and metabolic variables in the Lusitano horse; and (ii) retrospectively assess whether these changes were related with radiographic findings regarding osteochondrosis-like lesions (OC) at the onset of training. Thirty-four Lusitano foals born and raised at four stud-farms, were periodically weighed (BW), and measured (withers height-WH) from birth to 36 months of age. On the same days, blood samples were collected for determination of osteocalcin, bone alkaline phosphatase, insulin-like growth factor I (IGF-I), leptin, insulin, glucose, parathyroid hormone (PTH), calcium, phosphorus and magnesium plasma concentrations, and quantitative ultrasound measurements were performed on the right third metacarpal bone (McIII). At the end of the study horses underwent radiographic examination of the four fetlocks, hocks and stifles. According to their radiographic status (OC negative vs. OC positive), Richards growth function was adjusted to BW and WH data. Instantaneous BW and WH growth rates (BW IADG and WH IADG) were calculated for each foal, from the resolution of the first derivative of growth models for seven age-classes. The presence of radiographic findings compatible with OC at the onset of training was associated with changes in BW and WH growth rates. Positive horses presented higher BW IADG from six to 18 months of age and lower WH IADG before 45 days of age (P<0.001). Speed of sound measurements (SOS), bone markers, growth factors and other metabolic variables change markedly with age (P<0.01). OC positive horses tended to have lower SOS values at the lateral region of McIII, lower IGF-I, and higher insulin and PTH concentrations (P<0.1). This study provides indirect evidence that monitoring foals' growth during the first year of life may be of assistance in managing the occurrence of OC. Further studies with a higher number of animals and a controlled feed intake should be pursued.
- Circulating IGF-1 promotes prostate adenocarcinoma via FOXO3A/BIM signaling in a double-transgenic mouse model. [Journal Article]
- OOncogene 2019 Jul 16
- High circulating insulin-like growth factor-1 (IGF-1) levels increase the risk of prostate cancer. However, whether circulating IGF-1 levels directly aggravate prostate cancer remains elusive. In thi…
High circulating insulin-like growth factor-1 (IGF-1) levels increase the risk of prostate cancer. However, whether circulating IGF-1 levels directly aggravate prostate cancer remains elusive. In this study, we crossed a transgenic prostate adenocarcinoma mouse model, Hi-Myc mice, with a liver-specific IGF-1 transgenic mouse model (HIT) to increase their circulating IGF-1 levels to investigate the impact of the elevated circulating IGF-1 on prostate cancer development in vivo. The Hi-Myc/HIT mice had increased incidence and invasiveness of prostate cancer. IGF-1 elevation led to the accumulation of FOXO3A in the cytosol of prostate tumor cells and downregulation of its target gene Bim, which resulted in the apoptosis inhibition and prostate cancer overgrowth. The differential expressions of IGF-1R, FOXO3A, and BIM in the benign versus malignant prostate tissues supported a negative association between the FOXO3A/BIM axis and IGF-1R expression in human prostate adenocarcinoma. Our findings suggest that targeting the IGF-1/FOXO3A/BIM signaling axis could be an attractive strategy for prostate cancer prevention or treatment.
- Effect of Hyperbaric Oxygen Therapy on Fatty Acid Composition and Insulin-like Growth Factor Binding Protein 1 in Adult Insulin-Dependent Diabetes Mellitus Patients: A Pilot Study. [Journal Article]
- CJCan J Diabetes 2019 May 08
- CONCLUSIONS: Our results indicate that HBOT exerts beneficial effects in IDDM patients by improving the lipid profile and altering FA composition.
- Overexpressed IGFBP5 promotes cell proliferation and inhibits apoptosis of nucleus pulposus derived from rats with disc degeneration through inactivating the ERK/MAPK axis. [Journal Article]
- JCJ Cell Biochem 2019 Jul 16
- It is previously suggested that insulin-like growth factor binding proteins (IGFBPs) potentially share an association with disc degeneration (DD) that causes back pain. This study aimed at exploring …
It is previously suggested that insulin-like growth factor binding proteins (IGFBPs) potentially share an association with disc degeneration (DD) that causes back pain. This study aimed at exploring the functional relevance of IGFBP5 in DD by establishing a rat model of DD. The nucleus pulposus (NP) cells were transduced with IGFBP5-shRNA or IGFBP5 overexpression to determine the cellular processes (proliferation, apoptosis, as well as colony formation). The protein levels of apoptosis-related proteins were evaluated. Furthermore, NP cells were treated with the extracellular signal-regulated kinases/mitogen-activated protein kinase (ERK/MAPK) pathway inhibitor (PD98059) followed by measurement of ERK protein level and ERK phosphorylation content. The NP cells showed suppressed proliferation and colony formation ability, yet promoted apoptosis after transfection with IGFBP5-shRNA. It was found that silencing of IGFBP5 could lead to the ERK/MAPK axis activation, as indicated by an elevated ERK protein level and ERK phosphorylation content. However, overexpression of IGFBP5 could reverse all the reaction induced by silenced IGFBP5. These key findings demonstrate that overexpressed IGFBP5 inactivates the ERK/MAPK axis to stimulate the proliferation and inhibit apoptosis of NP cells in a rat model of DD.
- Genistein improves the reproductive performance and bone status of breeder hens during the late egg-laying period. [Journal Article]
- PSPoult Sci 2019 Jul 15
- Genistein (GEN), a type of soy isoflavones, is similar to estrogen structurally and functionally. The effects of dietary gen on the reproductive performance and bone status of breeder hens were inves…
Genistein (GEN), a type of soy isoflavones, is similar to estrogen structurally and functionally. The effects of dietary gen on the reproductive performance and bone status of breeder hens were investigated. A total pf 720 laying broiler breeder (LBB) hens were randomly allocated into 3 groups with supplemental dietary GEN doses (0, 40, 400 mg/kg). Each treatment has 8 replicates of 30 birds. The results indicated that supplemental GEN significantly improved the egg production and eggshell strength of LBB hens. Dietary GEN was deposited into the egg yolk, which decreased malonaldehyde in the follicle and egg yolk. The levels of vitellogenin (VTG), progesterone, and follicle-stimulating hormone in the serum of GEN-treated groups were elevated compared with the control group. Furthermore, GEN treatment downregulated the mRNA expression of insulin-like growth factor binding protein in the fallopian tube, whereas 40 mg/kg GEN treatment upregulated estrogen receptor α expression. Both the mRNA expression of VTG-II in the liver and mRNA expression of amphiregulin in the fallopian tube were upregulated after 40 and 400 mg/kg GEN treatment. In the 400 mg/kg GEN-treated group, the levels of calcitonin and alkaline phosphatase in the serum were increased compared with the control group, which was consistent with the increased levels of calcium and phosphorus in the tibia. Supplemental GEN (400 mg/kg) improved the tibia strength of LBB hens, whereas 40 mg/kg GEN had better effects on laying performance. In summary, dietary GEN could improve the egg production and quality, as well as the bone status of LBB hens during the late egg-laying period.
- Differential Uptake of NAGLU-IGF2 and Unmodified NAGLU in Cellular Models of Sanfilippo Syndrome Type B. [Journal Article]
- MTMol Ther Methods Clin Dev 2019 Sep 13; 14:56-63
- Sanfilippo syndrome type B, or mucopolysaccharidosis IIIB (MPS IIIB), is a rare autosomal recessive lysosomal storage disease caused by a deficiency of α-N-acetylglucosaminidase (NAGLU). Deficiency i…
Sanfilippo syndrome type B, or mucopolysaccharidosis IIIB (MPS IIIB), is a rare autosomal recessive lysosomal storage disease caused by a deficiency of α-N-acetylglucosaminidase (NAGLU). Deficiency in NAGLU disrupts the lysosomal turnover of heparan sulfate (HS), which results in the abnormal accumulation of partially degraded HS in cells and tissues. BMN 250 (NAGLU-insulin-like growth factor 2 [IGF2]) is a recombinant fusion protein developed as an investigational enzyme replacement therapy for MPS IIIB. The IGF2 peptide on BMN 250 promotes enhanced targeting of the enzyme to lysosomes through its interaction with the mannose 6-phosphate receptor. The focus of these studies was to further characterize the ability of NAGLU-IGF2 to clear accumulated HS compared to unmodified NAGLU in primary cellular models of MPS IIIB. Here, we establish distinct primary cell models of MPS IIIB with HS accumulation. These cellular models revealed distinct NAGLU uptake characteristics that depend on the duration of exposure. We found that with sustained exposure, NAGLU uptake and HS clearance occurred independent of known lysosomal targeting signals. In contrast, under conditions of limited exposure duration, NAGLU-IGF2 was taken up more rapidly than the unmodified NAGLU into MPS IIIB primary fibroblasts, astrocytes, and cortical neurons, where it efficiently degraded accumulated HS. These studies illustrate the importance of using physiologically relevant conditions in the evaluation of enzyme replacement therapies in cellular models.
- Enhancer of zeste 2 polycomb repressive complex 2 subunit promotes sorafenib resistance of hepatocellular carcinoma though insulin-like growth factor 1 receptor. [Journal Article]
- ADAnticancer Drugs 2019; 30(7):e0746
- Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) is the core component of polycomb repressive complex 2 and is overexpressed in several types of solid malignancies. It has been report…
Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) is the core component of polycomb repressive complex 2 and is overexpressed in several types of solid malignancies. It has been reported that EZH2 contributes to sorafenib resistance of hepatocellular carcinoma (HCC). However, its underlying molecular mechanisms remain unknown. In this study, we demonstrated that EZH2 induced sorafenib resistance of HCC cells in vitro. Mechanistically, EZH2 was a potent regulator of insulin-like growth factor 1 receptor (IGF1R) and EZH2-modulated IGF1R expression by directly transcriptionally repressing a set of microRNAs (miRNAs) including miR-101, miR-122, miR-125b, and miR-139. These miRNAs were required for EZH2-mediated sorafenib resistance by promoting IGF1R expression. Surprisingly, IGF1R inhibitors significantly reversed EZH2-induced sorafenib resistance. Collectively, we proposed a novel model for an EZH2 - miRNAs - IGF1R regulatory axis, which might provide insights into how EZH2 contributes to sorafenib resistance in HCC.
- Sevoflurane downregulates insulin-like growth factor-1 to inhibit cell proliferation, invasion and trigger apoptosis in glioma through the PI3K/AKT signaling pathway. [Journal Article]
- ADAnticancer Drugs 2019; 30(7):e0744
- Sevoflurane is a new type of inhalation anesthetic used widely in the clinic. It has the characteristics of rapid induction, rapid recovery, and less irritative to the airway. Studies have shown that…
Sevoflurane is a new type of inhalation anesthetic used widely in the clinic. It has the characteristics of rapid induction, rapid recovery, and less irritative to the airway. Studies have shown that sevoflurane can affect the invasion and migration of a variety of malignant tumors. However, its effects on human glioma cells and related mechanisms are not clear. Cultured U251 and U87 cells were pretreated with sevoflurane. The effect of sevoflurane on proliferation was evaluated by MTT, and cell migration assay, cell apoptosis, and invasion ability were evaluated by wound-healing assay, cell apoptosis, and Transwell assays. Insulin-like growth factor-1 (IGF-1) and PI3K/AKT signaling pathway gene expression in sevoflurane-treated cell lines was measured by western blotting analysis, respectively. 5% sevoflurane significantly inhibited proliferation ability in both U251 and U87 cells. Sevoflurane inhibited glioma cells invasion and migration, and promoted apoptosis. Sevoflurane inhibited IGF-1 and promoted the expression of apoptosis-related proteins in glioma cells. In addition, sevoflurane inhibited the PI3K/AKT signaling pathway in glioma cells. This study clarifies that sevoflurane inhibits proliferation, invasion, and migration, and promotes apoptosis in glioma cells. These effects are regulated by IGF-1, an upstream gene of the PI3K/AKT signaling pathway. These findings may be significant for the selection of anesthetic agents in glioma surgery to improve the prognosis of patients.
- Association between CA repeat polymorphism in IGF1 gene promoter and colorectal cancer risk in a native Chinese population. [Journal Article]
- NNeoplasma 2019 Jul 12; 2019
- Insulin-like growth factor 1 (IGF1) is implicated in normal cell growth. It has been reported that IGF1 has a mitogenic and anti-apoptotic effect on colorectal cancer cells. However, results of studi…
Insulin-like growth factor 1 (IGF1) is implicated in normal cell growth. It has been reported that IGF1 has a mitogenic and anti-apoptotic effect on colorectal cancer cells. However, results of studies on the association between cytosine-adenine (CA) repeat polymorphism in IGF1 gene promoter and colorectal cancer (CRC) risk are inconsistent. We aimed to evaluate the association between CA repeat polymorphism and CRC risk, as well as the relationship with the clinicopathological characteristics of CRC and circulating IGF1 level in a native Chinese population. There were 734 participants who were native Chinese in this case-control study, including 367 CRC cases and 367 age- and sex-matched controls. CA repeat polymorphism was genotyped by PCR and fragment analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated by unconditional logistic regression analysis. Circulating level of IGF1 in cases was significantly higher than that in controls (P = 0.002), particularly in males. Less than 38 CA repeats were associated with decreased CRC risk after adjusting for age and sex (37 versus 38 CA repeats: OR = 0.45; 95%CI = 0.26-0.78), especially in males. (CA)18/19 genotype showed approximately half reduced CRC risk comparing to (CA)19/19 genotype (OR = 0.46; 95%CI = 0.25-0.85). There was a significant association between the sum of CA repeats and degree of differentiation of CRC (P = 0.044). We observed a trend that circulating level of IGF1 in individuals with CA ≤ 38 repeats was lower than that in individuals with CA > 38 repeats with a borderline statistically significance in overall and males. In conclusion, our findings support the possible role of CA repeat polymorphism in CRC risk.
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- Optimizing a serum-free/xeno-free culture medium for culturing and promoting the proliferation of human dental pulp stem cells. [Journal Article]
- SCStem Cell Investig 2019; 6:15
- CONCLUSIONS: The proposed combination of supplements utilized in the proposed culture media successfully increased the proliferation potential of DPSCs in addition to enhancing the stemness properties. Thus, it can be considered a promising and safe substitute to traditional animal derived supplements like fetal bovine serum (FBS).