In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growt...In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.展开更多
OBJECTIVE CYP2D is one of the most abundant subfamily of CYPs in the brain,especially in the cerebellum.Brain CYP2D is responsible for the metabolism of endogenous neurotransmitters such as tyramine and serotonin.Our ...OBJECTIVE CYP2D is one of the most abundant subfamily of CYPs in the brain,especially in the cerebellum.Brain CYP2D is responsible for the metabolism of endogenous neurotransmitters such as tyramine and serotonin.Our previous studies have shown brain CYP2D can be regulated by exogenous and endogenous substances with tissue-specificity.The purpose of this study is to examine the effects of cerebral CYP2D on the mice behavior and the regulatory mechanism of brain CYP2D by growth hormone.METHODS Mice received the stereotaxic injection with CYP2D inhibitor quinine in deep cerebellar nuclei of cerebellum.The animals were tested with rotarod apparatus,balance beam,water maze,elevated plus maze and open field.The changes in CYP2D22,PPARαand PPARγ in brain regions and liver were assayed in male growth hormone receptor knockout mice,SH-SY5 Y cells and HepG2 cells.RESULTS The inhibition of cerebellum CYP2D significantly affected the spatial learning and exploring ability of mice.Compared with WT mice,CYP2D expression was lower in brain regions from GHR(-/-)male mice;however,hepatic CYP2D level was similar.Pulsatile GH decreased PPARα m RNA level,and increased m RNA levels of CYP2D6 and PPARα in SH-SY5 Y cells.In HepG2 cells,pulsatile GH resulted in decreases in PPARα and PPARγ m RNA levels,but not CYP2D6.PPARα inhibitor induced CYP2D6 m RNA and protein by 1.32-fold and 1.43-fold in SH-SY5 Y cells.PPARγ inhibitor decreased CYP2D6 m RNA and protein by 74.76% and 40.93%.PPARα agonist decreased the level of CYP2D22 m RNA in liver and cerebellum,while PPARγ agonist rosiglitazone resulted in diametrically increases.The luciferase assay showed that PPARγ actived the CYP2D6 gene promoter while PPARα inhibited its function.Pulsatile GH declined the binding of PPARα with CYP2D6 promoter by 40%,promoted the binding of PPARγ with CYP2D6 promoter by approximate60%.The levels of brain and liver PPARα expression in male GHR(-/-)mice is obviously higher than those in WT mice.The level of PPARγ in male GHR(-/-)mice was decreased in the frontal cortex and hippocampus,while remained stable in the cerebellum and striatum;meanwhile,PPARγ was increased in the liver.CONCLUSION Brain CYP2D may be involved in learning and memory functions of central system.Masculine GH secretion altered the PPARs expression and the binding of PPARs to CYP2D promoter,leading to the elevated brain CYP2D in a tissue-specific manner.Growth hormone may specifically alter the metabolic and synthetic of important endogenous substances in the central nervous system(such as serotonin) through the specific regulation of brain CYP2D expression.展开更多
Single nucleotide polymorphisms(SNPs) of the growth hormone(GH) gene were investigated in six pig breeds,consisting of four mini-pig breeds(Wuzhishan,Bama,Xiang and Tibet pig),and two others(Dahlan and Landrace pig).T...Single nucleotide polymorphisms(SNPs) of the growth hormone(GH) gene were investigated in six pig breeds,consisting of four mini-pig breeds(Wuzhishan,Bama,Xiang and Tibet pig),and two others(Dahlan and Landrace pig).Three pairs of primers for promoter regions of the GH gene were designed on the basis of the pig genomic sequence and SNPs were detected by the PCR-SSCP method.The results indicated three mutations in the 5’-flanking region.The analysis results showed that the frequencies of allele A and D in four mini-pig breeds were higher than that in other breeds at a locus within the 5’-flanking region(P【0.05).These results suggest that differences in body size may be associated with these SNPs of 5’-flanking region and amino acid mutation of the signal peptide of GH in these pig breeds.展开更多
OBJECTIVE GubenyiliuⅡ(GYⅡ),a traditional Chinese medicine(TCM)formula used in our hospital,has shown beneficial effects in cancer patients.In this study,we investigated the molecular mechanisms underlying the benefi...OBJECTIVE GubenyiliuⅡ(GYⅡ),a traditional Chinese medicine(TCM)formula used in our hospital,has shown beneficial effects in cancer patients.In this study,we investigated the molecular mechanisms underlying the beneficial effects of GYⅡon murine breast cancer models.METHODS Inhibition of tumor growth and metastasis was evaluated by assessment of tumor weight and analysis of bioluminescent signal after a homograft inoculation.Viability of cultured breast cancer cells was determined using MTT assay andreal-time cell analysis(RTCA).Cell migratory ability was evaluated by Transwell?assay and wound healing assay.Subsequently,the potential anti-tumor and anti-metastatic mechanism was investigated by Western blotting and Immunohistochemistry.RESULTS GYⅡshowed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model.And GYⅡsuppressed theproliferation of 4T1 and MCF-7 cells in a dose-dependent manner.A better inhibitory effect on 4T1 cells proliferation and migration was found in sub-fractions(SF)of GYⅡ.Moreover,heparanase expression and degree of angiogenesis were reduced in tumor tissues.Western blotting analysis showed decreased expression of heparanase and growth factors in the cells treated with GYⅡand its sub-fractions(SF2 and SF3),there by a reduction in phosphorylation of ERK and AKT.CONCLUSION GYⅡexerts anti-tumor growth and anti-metastatic effects on murine breast cancer model.Sub-fractions 2 and 3 exhibits higher potency of the anti-tumor activity that is,at least partly,associated with decreased heparanase and growth factor sexpression,which subsequently sup-pressed activation of ERK and AKT pathways.展开更多
基金This work was supported by the Special Project of Performance Incentive and Guidance for Scientific Research Institutions of Chongqing,China (jxyn2022-5)。
文摘In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.
基金supported by National Natural Science Foundation of China(81673503 and 30973582)
文摘OBJECTIVE CYP2D is one of the most abundant subfamily of CYPs in the brain,especially in the cerebellum.Brain CYP2D is responsible for the metabolism of endogenous neurotransmitters such as tyramine and serotonin.Our previous studies have shown brain CYP2D can be regulated by exogenous and endogenous substances with tissue-specificity.The purpose of this study is to examine the effects of cerebral CYP2D on the mice behavior and the regulatory mechanism of brain CYP2D by growth hormone.METHODS Mice received the stereotaxic injection with CYP2D inhibitor quinine in deep cerebellar nuclei of cerebellum.The animals were tested with rotarod apparatus,balance beam,water maze,elevated plus maze and open field.The changes in CYP2D22,PPARαand PPARγ in brain regions and liver were assayed in male growth hormone receptor knockout mice,SH-SY5 Y cells and HepG2 cells.RESULTS The inhibition of cerebellum CYP2D significantly affected the spatial learning and exploring ability of mice.Compared with WT mice,CYP2D expression was lower in brain regions from GHR(-/-)male mice;however,hepatic CYP2D level was similar.Pulsatile GH decreased PPARα m RNA level,and increased m RNA levels of CYP2D6 and PPARα in SH-SY5 Y cells.In HepG2 cells,pulsatile GH resulted in decreases in PPARα and PPARγ m RNA levels,but not CYP2D6.PPARα inhibitor induced CYP2D6 m RNA and protein by 1.32-fold and 1.43-fold in SH-SY5 Y cells.PPARγ inhibitor decreased CYP2D6 m RNA and protein by 74.76% and 40.93%.PPARα agonist decreased the level of CYP2D22 m RNA in liver and cerebellum,while PPARγ agonist rosiglitazone resulted in diametrically increases.The luciferase assay showed that PPARγ actived the CYP2D6 gene promoter while PPARα inhibited its function.Pulsatile GH declined the binding of PPARα with CYP2D6 promoter by 40%,promoted the binding of PPARγ with CYP2D6 promoter by approximate60%.The levels of brain and liver PPARα expression in male GHR(-/-)mice is obviously higher than those in WT mice.The level of PPARγ in male GHR(-/-)mice was decreased in the frontal cortex and hippocampus,while remained stable in the cerebellum and striatum;meanwhile,PPARγ was increased in the liver.CONCLUSION Brain CYP2D may be involved in learning and memory functions of central system.Masculine GH secretion altered the PPARs expression and the binding of PPARs to CYP2D promoter,leading to the elevated brain CYP2D in a tissue-specific manner.Growth hormone may specifically alter the metabolic and synthetic of important endogenous substances in the central nervous system(such as serotonin) through the specific regulation of brain CYP2D expression.
基金supported by National Natural Special Scientific and Techndogical Resources Sharing Platform (No.2005DKA21101)the 11th Five-year Plan of National Science and Technology Support(No.2006BAD73B08)the 15th Key Project"Chinese Experimental Miniature Pig Resources Development and Research Applications"Ministry of Science and Technology(No.2004BA717B- 01)
文摘Single nucleotide polymorphisms(SNPs) of the growth hormone(GH) gene were investigated in six pig breeds,consisting of four mini-pig breeds(Wuzhishan,Bama,Xiang and Tibet pig),and two others(Dahlan and Landrace pig).Three pairs of primers for promoter regions of the GH gene were designed on the basis of the pig genomic sequence and SNPs were detected by the PCR-SSCP method.The results indicated three mutations in the 5’-flanking region.The analysis results showed that the frequencies of allele A and D in four mini-pig breeds were higher than that in other breeds at a locus within the 5’-flanking region(P【0.05).These results suggest that differences in body size may be associated with these SNPs of 5’-flanking region and amino acid mutation of the signal peptide of GH in these pig breeds.
基金The project supported by National Natural Science Foundation of China(81202840,81373815)Specialized Research Fund for the Doctoral Program of Higher Education of China(20131107110014)+1 种基金Beijing Natural Science Foundation(7162084)Swedish Cancer Foundation(150815)
文摘OBJECTIVE GubenyiliuⅡ(GYⅡ),a traditional Chinese medicine(TCM)formula used in our hospital,has shown beneficial effects in cancer patients.In this study,we investigated the molecular mechanisms underlying the beneficial effects of GYⅡon murine breast cancer models.METHODS Inhibition of tumor growth and metastasis was evaluated by assessment of tumor weight and analysis of bioluminescent signal after a homograft inoculation.Viability of cultured breast cancer cells was determined using MTT assay andreal-time cell analysis(RTCA).Cell migratory ability was evaluated by Transwell?assay and wound healing assay.Subsequently,the potential anti-tumor and anti-metastatic mechanism was investigated by Western blotting and Immunohistochemistry.RESULTS GYⅡshowed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model.And GYⅡsuppressed theproliferation of 4T1 and MCF-7 cells in a dose-dependent manner.A better inhibitory effect on 4T1 cells proliferation and migration was found in sub-fractions(SF)of GYⅡ.Moreover,heparanase expression and degree of angiogenesis were reduced in tumor tissues.Western blotting analysis showed decreased expression of heparanase and growth factors in the cells treated with GYⅡand its sub-fractions(SF2 and SF3),there by a reduction in phosphorylation of ERK and AKT.CONCLUSION GYⅡexerts anti-tumor growth and anti-metastatic effects on murine breast cancer model.Sub-fractions 2 and 3 exhibits higher potency of the anti-tumor activity that is,at least partly,associated with decreased heparanase and growth factor sexpression,which subsequently sup-pressed activation of ERK and AKT pathways.
