Effect of sericin on diabetic hippocampal growth hormone/insulin-like growth factor 1 axis

Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats.

Ginsenoside Rg3 Promotes the Survival and Migration of Trophoblast Cells in a Rat Model of Gestational Hypertension by Regulating miR-100a/Insulin Growth Factor-2 Axis

Objective:Preeclampsia(PE)is a common complication during pregnancy.miR-100a is expressed in the placenta and regulates the survival and development of placental cells.Insulin growth factor-2(IGF-2)may serve as its downstream target.This study investigated the protective mechanisms of ginsenoside Rg3 against PE in rat model.Materials and Methods:LPS-induced rat PE models were suitable for intravenous administration of the highly expressed miR-100a ginsenoside Rg3 lentiviral vector.Human trophoblasts were cultured in vitro for JEG-3,and PE cell models were constructed.In vivo effects on tumor growth and apoptosis were observed.Ginsenoside Rg3 was treated with different concentrations of shRNA,miR-100a analogs,inhibitors,or IGF-2.Autophagy and the expression of autophagy-related proteins were examined.Trophoblast activity and migration were determined using Cell Counting Kit-8 and Transwell assays.Both drugs strongly inhibited trophoblasts under normal conditions with some synergy between them.Double-luciferase return assay confirmed the binding affinity of miR-100a for IGF-2.Results:In response to Rg3,autophagy and the expression of autophagy-related proteins LC3-I/II,Beclin1,and SQSTM1 were reduced in PE rat placental trophoblasts.Rg3 inhibited autophagy in JEG-3 cells and promoted JEG-3 survival and migration in a concentration-dependent manner.miR-100a upregulated PE expression.These results suggested that autophagy was a vital signaling system.Rg3 intervention inhibited miR-100a expression and miR-100a downregulated IGF-2 expression in placental tissues and promoted autophagy,thereby inhibiting JEG-3cell survival and migration.In rats,Rg3 inhibited PE development by regulating the activity of the miR-100a-IGF-2 signaling axis.Conclusion:Ginsenoside Rg3 positively regulates the miR-100a-IGF-2 axis and protects PE rats by inhibiting trophoblastic autophagy and promoting trophoblastic cell survival and migration.

C23 ameliorates carbon tetrachloride-induced liver fibrosis in mice

BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few reports on its role in liver fibrosis and the underlying mechanism is unknown.AIM To explore whether C23 plays a significant role in carbon tetrachloride(CCl4)-induced liver fibrosis.METHODS CCl4 was injected for 6 weeks to induce liver fibrosis and C23 was used beginning in the second week.Masson and Sirius red staining were used to examine changes in fiber levels.Inflammatory factors in the liver were detected and changes inα-smooth muscle actin(α-SMA)and collagen I expression were detected via immu-nohistochemical staining to evaluate the activation of hematopoietic stellate cells(HSCs).Western blotting was used to detect the activation status of the trans-forming growth factor-beta(TGF-β)/Smad3 axis after C23 treatment.RESULTS CCl4 successfully induced liver fibrosis in mice,while tumor necrosis factor-alpha(TNF-α),IL(interleukin)-1β,and IL-6 levels increased significantly and the IL-10 level decreased significantly.Interestingly,C23 inhibited this process.On the other hand,C23 significantly inhibited the activation of HSCs induced by CCl4,which inhibited the expression ofα-SMA and the synthesis of collagen I.In terms of mechanism,C23 can block Smad3 phosphorylation significantly and inhibits INTRODUCTION At present there is no specific and effective drug for treating liver fibrosis caused by acute or chronic injury.Although preclinical research has made breakthroughs,their suitability as clinical treatments is still unknown.The activation of hepatic stellate cells(HSCs)caused by chronic inflammation is a key process in the development of liver fibrosis and activated HSCs expressα-smooth muscle actin(α-SMA)and transdifferentiate into myofibroblasts with proliferation,migration and secretion abilities,synthesizing the extracellular matrix to deposit in the hepatocyte space and subse-quently forming liver fibrosis[1].Although therapeutic strategies have improved due to past few efforts there is no ideal treatment for hepatic fibrosis[2].Extracellular cold inducible RNA binding protein(CIRP)has been shown to play a role in various acute and chronic inflammatory diseases by promoting tissue inflammation and apoptosis and inducing fibrosis through its receptor Toll-like receptor 4(TLR4)[3].C23 is a recognized competitive inhibitor of CIRP that can competitively bind to CIRP receptors and reduce tissue damage in inflammatory diseases[4].C23 has been shown to significantly reduce serum tumor necrosis factor-alpha(TNF-α),IL(interleukin)-6 and IL-1βlevels.In addition,it can reduce tissue TLR4,TNF-α,IL-6 and IL-1βlevels and inhibit the colocalization of CIRP and TLR4,which plays a significant role in systemic inflammation[5].Re-search has shown that CIRP induces the inflammatory phenotype of lung fibroblasts in a TLR4-dependent manner[6].On the other hand,CIRP is associated with markers of fibrosis andα-SMA is significantly positively correlated with CIRP.Cirp-/-mice exhibit attenuated expression ofα-SMA and collagen(COL1A1 and COL3A1),decreased hydroxyproline content,decreased histological fibrosis scores,and improved pulmonary hypertension[7].C23 inhibited the release of TNF-α,the degradation of IκB and the nuclear translocation of NF-κB in CIRP-stimulated macrophages in a dose-dependent manner and C23 treatment significantly increased the serum levels of lactic dehydrogenase,alanine ami-notransferase,IL-6,TNF-αand IL-1βin septic CLP mice[8].Based on previous research we hypothesized that C23 might alleviate liver fibrosis by inhibiting acute and chronic inflammation.As a selective hepatotoxic chemical carbon tetrachloride(CCl4).can induce inflammation and activate HSCs,promoting liver fibrosis.This study reveals the role and mechanism of C23 in CCl4-induced liver fibrosis in mice.at room temperature for 30 minutes.The gray value of each group was calculated after chemiluminescence.

Effects of dietary genistein on GH/IGF-I axis of Nile tilapia Oreochromis niloticus

There is considerable concern that isoflavones,such as genistein in fish feed composed of soybean protein,affects somatic growth in fish.Our previous works demonstrated that 30 and 300 μg/g dietary genistein had no significant effect on growth performance in Nile tilapia(Oreochromis niloticus),but the higher level of genistein(3 000 μg/g) significantly depressed growth.This study was conducted to further examine the effects of dietary genistein on the endocrine disruption on growth hormone/insulin-like growth factor-I(GH/IGF-I) axis in Nile tilapia(O.niloticus).Juvenile fish were fed by hand twice daily to satiation with one of four isonitrogenous and isoenergetic diets,each containing either 0,30,300 or3 000 μg/g genistein.Following an 8-week feeding period,plasma GH and IGF-I levels were investigated by radioimmunoassay and gene expression levels of gh,ghrelin,gnrhs,ghr,npy,npyrs,pacap,ghrs,igf-I,igf-Ir,and igfbp3 were examined by real-time PCR.The results show that no significant change in plasma GH and IGF-I levels in fish fed with diets containing 30 μg/gand 300 μg/g genistein.mRNA expression of genes along the GH/IGF-I axis remained unaffected,except for igf-Ir,which was stimulated by the 300 μg/g genistein diet.While in fish fed the 3 000 μg/g genistein diet,the plasma GH and IGF-I levels decreased,and mRNA expression of gh,ghr2,npyr1,igf-I,and igf-Ir were also significantly depressed.In contrast,npy and igfbp3 mRNA expression were enhanced.This study provides convincing evidence for growth impediment by genistein by disturbing the GH/IGF-I axis in Nile tilapia O.niloticus.

Diabetes and cancer: Epidemiological and biological links

The incidence of diabetes and cancer has increased significantly in recent years.Furthermore,there are many common risk factors for both diabetes and cancer,such as obesity,sedentary lifestyle,smoking,and ageing.A large body of epidemiological evidence has indicated that diabetes is considered as an independent risk factor for increased rates of heterogeneous types of cancer occurrence and death.The incidence and mortality of various types of cancer,such as pancreas,liver,colorectal,breast,endometrial,and bladder cancers,have a modest growth in diabetics.However,diabetes may work as a protective factor for prostate cancer.Although the underlying biological mechanisms have not been totally understood,studies have validated that insulin/insulin-like growth factor(IGF)axis(including insulin resistance,hyperinsulinemia,and IGF),hyperglycemia,inflammatory cytokines,and sex hormones provide good circumstances for cancer cell proliferation and metastasis.Insulin/IGF axis activates several metabolic and mitogenic signaling pathways;hyperglycemia provides energy for cancer cell growth;inflammatory cytokines influence cancer cell apoptosis.Thus,these three factors affect all types of cancer,while sex hormones only play important roles in breast cancer,endometrial cancer,and prostate cancer.This minireview consolidates and discusses the epidemiological and biological links between diabetes and various types of cancer.

ASSOCIATION ANALYSIS OF POLYMORPHISMS IN SIX GENES WITHIN THE GH/IGF-1 AXIS IN PATIENTS WITH IDIOPATHIC SHORT STATURE IN THE CHINESE HAN POPULATION

Objective To investigate relationships of polymorphisms in six genes （ GHR, IGF-1, IGF-1R, IGFBP-3, JAK2, and STAT5b） in the growth hormone （GH）/insulin-like growth factor-1 （IGF-1） axis with idiopathic short stature （ISS） in the Chinese Han population. Methods A case- control study was carried out on a cohort of 198 ISS patients and 306 healthy controls. A total of 106 tagging single nucleotide polymorphisms （tagSNPs） from the six genes were selected from the HapMap （haplotype map of the human genome ） Han Chinese in the Beijing subset. Results of genotyping conducted by high- throughput lllumina GoldenGateTM Assay were analyzed by statistical software. Results Both individual tagSNPs and haplotypes showed an association with 1SS in the Han Chinese population （ P 〈 O. 05 ）. For each single test, both allele and genotype were tested. By allele frequency analysis, six positive SNP sites （ rsNo. 1, rsNo. 2, rsNo. 3, rsNo. 4, rsNo. 5, and rsNo. 6） of 3 genes （ JAK2, 1GF-1R, and GHR） were found having associations with ISS. By genotype frequency analysis, there were significant differences between the patient and control groups in the following SNP sites： 4 sites in JAK2 gene （ rsNo. 1, rsNo. 2, rsNo. 3, and rsNo. 4） and 1 site in GHR gene （ rsNo. 6）. The risk which affected ISS was found related to the JAK2 gene in 4 sites （ increase in rsNo. 1 and decrease in rsNo. 2, rsNo. 3, and rsNo. 4 ） and to the GHR gene in 1 site （decrease in rsNo. 6）. They were four haplotypes in gene of IGF-1R as ＂TGC＂, ＂CGCT＂, ＂TA＂, and ＂ CA＂, one haplotype in IGFBP-3 as ＂TA＂, and one haplotype in JAK2 as ＂CTG＂, which revealed high significance for risks of affecting ISS. At last, multivariate logistic regression analysis of specific site rsNo. 6 of the GHR gene revealed that the serum IGF-1 was related to genotypes AA and AC, with genotype CC as the reference （ P =0. 015）. Conclusion Genetic variances in six genes within the GH/IGF-1 axis may be important etiological factors for ISS in the Chinese Han population.

Unusual Spherulitic Morphology of Poly(propylene fumarate)

Spherulites are the most common crystalline morphology and thus the visual expression of crystal structures for polymers.The diversified patterns have provided intuitive morphology probes for various crystallization behaviors,while the correlations between them are still needed to be enriched.In this work,the complicated spherulitic morphology of poly(propylene fumarate)(PPF),which is sensitive to crystallization temperature,is investigated.PPF melt,respectively,crystallizes into rough spherulites,regularly banded spherulites,and spherulites containing both two kinds of morphology at low,high,and mediate temperatures.By systematically assaying,it is clear that the growth axis along the radial direction changes from a-axis to b-axis as the crystallization temperature increases,which leads to the formation of unique crystallization-temperature-dependent spherulites.Based on detailed characterization of Fourier transform infrared spectroscopy,the packing state of the specific hydrogen bonds of"C=C-H…O=C-C=C"in PPF crystal lattices is determined,and furthermore,the mechanism for temperature-dependent selection of growth axes for PPF spherulites in melt is reasonably speculated.