Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using re...Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using retrograde tracing of retinorecipient areas. This is an invasive technique, and its use is precluded in higher mammals such as monkeys. In the past decade, several RGC markers have been described. Here, we reviewed and analyzed the specificity of nine markers used to identify all or most RGCs, i.e., pan-RGC markers, in rats, mice, and macaques. The best markers in the three species in terms of specificity, proportion of RGCs labeled, and indicators of viability were BRN3A, expressed by vision-forming RGCs, and RBPMS, expressed by vision-and non-vision-forming RGCs. NEUN, often used to identify RGCs, was expressed by non-RGCs in the ganglion cell layer, and therefore was not RGC-specific. γ-SYN, TUJ1, and NF-L labeled the RGC axons, which impaired the detection of their somas in the central retina but would be good for studying RGC morphology. In rats, TUJ1 and NF-L were also expressed by non-RGCs. BM88, ERRβ,and PGP9.5 are rarely used as markers, but they identified most RGCs in the rats and macaques and ERRβ in mice. However, PGP9.5 was also expressed by non-RGCs in rats and macaques and BM88 and ERRβ were not suitable markers of viability.展开更多
Postmenopausal women with Alzheimer’s disease exhibit dramatically reduced sensitivity to estrogen replacement therapy,which is though to be related to an estrogen receptor(ER)α/ERβratio imbalance arising from a si...Postmenopausal women with Alzheimer’s disease exhibit dramatically reduced sensitivity to estrogen replacement therapy,which is though to be related to an estrogen receptor(ER)α/ERβratio imbalance arising from a significantly decreased level of ERs of the brain.The aim of our study was to investigate whether valproic acid(VPA)can enhance the beneficial effects of estrogen on cognitive function through restoration of ERαand ERβexpression in the brain.We removed the ovaries of female APP/PS1 mice to simulate the low estrogen levels present in postmenopausal women and then administered VPA(30 mg/kg,intraperitoneal injection,once daily),17β-estradiol(E2)(2.4μg,intraperitoneal injection,once daily),liquiritigenin(LG)(50μg/kg,intragastric infusion,once daily),VPA+E2,or VPA+LG for 4 successive weeks.Compared with treatment with a single drug,treatment with VPA+E2 or VPA+LG significantly increased the level of glycogen synthase kinase 3β,increased the expression of estrogen receptorα,reduced the expression of small ubiquitin-like modifiers,and increased the level of estrogen receptorβ.This resulted in enhanced sensitivity to estrogen therapy,reduced amyloidβaggregation,reduced abnormal phosphorylation of the tau protein,reduced neuronal loss,increased dendritic spine and postsynaptic density,and significantly alleviated memory loss and learning impairment in Alzheimer’s disease.This study was approved by the Chongqing Medical University Animal Protection and Ethics Committee,China on March 6,2013.展开更多
AIM:To investigate the involvement of pericyte-Müller glia interaction in retinal damage repair and assess the influence of suppressing the platelet-derived growth factor receptorβ(PDGFRβ)signaling pathway in r...AIM:To investigate the involvement of pericyte-Müller glia interaction in retinal damage repair and assess the influence of suppressing the platelet-derived growth factor receptorβ(PDGFRβ)signaling pathway in retinal pericytes on photoreceptor loss and Müller glial response.METHODS:Sprague-Dawley rats were exposed to intense light to induce retinal injury.Neutralizing antibody against PDGFRβwere deployed to block the signaling pathway in retinal pericytes through intravitreal injection.Retinal histology and Müller glial reaction were assessed following light injury.In vitro,normal and PDGFRβ-blocked retinal pericytes were cocultured with Müller cell line(rMC-1)to examine morphological and protein expression changes upon supplementation with light-injured supernatants of homogenized retinas(SHRs).RESULTS:PDGFRβblockage 24h prior to intense light exposure resulted in a significant exacerbation of photoreceptor loss.The upregulation of GFAP and p-STAT3,observed after intense light exposure,was significantly inhibited in the PDGFRβblockage group.Fur ther upregulation of cytokines monocyte chemoattractant protein 1(MCP-1)and interleukin-1β(IL-1β)was also observed following PDGFRβinhibition.In the in vitro coculture system,the addition of light-injured SHRs induced pericyte deformation and upregulation of proliferating cell nuclear antigen(PCNA)expression,while Müller cells exhibited neuron-like morphology and expressed Nestin.However,PDGFRβblockage in retinal pericytes abolished these cellular responses to light-induced damage,consistent with the in vivo PDGFRβblockage findings.CONCLUSION:Pericyte-Müller glia interaction plays a potential role in the endogenous repair process of retinal injury.Impairment of this interaction exacerbates photoreceptor degeneration in light-induced retinal injury.展开更多
Estrogen is imperative to mammalian reproductivity,metabolism,and aging.However,the hormone activating estrogen receptor(ERs)αcan cause major safety concerns due to the enrichment of ERαin female tissues and certain...Estrogen is imperative to mammalian reproductivity,metabolism,and aging.However,the hormone activating estrogen receptor(ERs)αcan cause major safety concerns due to the enrichment of ERαin female tissues and certain malignancies.In contrast,ERβis more broadly expressed in metabolic tissues and the skin.Thus,it is desirable to generate selective ERβagonist conjugates for maximizing the therapeutic effects of ERs while minimizing the risks of ERαactivation.Here,we report the design and production of small molecule conjugates containing selective non-steroid ERβagonists Gtx878 or genistein.Treatment of aged mice with our synthesized conjugates improved aging-associated declines in insulin sensitivity,visceral adipose integrity,skeletal muscle function,and skin health,with validation in vitro.We further uncovered the benefits of ERβconjugates in the skin using two inducible skin injury mouse models,showing increased skin basal cell proliferation,epidermal thickness,and wound healing.Therefore,our ERβ-selective agonist conjugates offer novel therapeutic potential to improve aging-associated conditions and aid in rejuvenating skin health.展开更多
Endometriosis refers to as an estrogen-dependent disease.Estrogen receptorβ(ERB),the main estrogen receptor subtype which is encoded by the estrogen receptor 2(ESR2)gene,can mediate the action of estrogen in endometr...Endometriosis refers to as an estrogen-dependent disease.Estrogen receptorβ(ERB),the main estrogen receptor subtype which is encoded by the estrogen receptor 2(ESR2)gene,can mediate the action of estrogen in endometriosis.Although selective estrogen receptor modulators can target the ERβ,they are not specific due to the wide distribution of ERβ.Recently,long noncoding RNAs have been implicated in endometriosis.Therefore,we aim to explore and validate the downstream regulatory mechanism of ERβ,and to investigate the potential role of long intergenic noncoding RNA 1018(LINC01018)as a nonhormonal treatment for endometriosis.Our study demonstrates that the expression levels of ESR2 and LINCo1018 are increased in ectopic endometrial tissues and reveals a significant positive correlation between the ESR2 and LINCo1018 expression.Mechanistically,ERβdirectly binds to an estrogen response element located in the LINCO1018 promoter region and activates LINC01018 transcription.Functionally,ERβcan regulate the CDC25C/CDK1/CyclinB1 pathway and promote ectopic endometrial stromal cell proliferation via LINC01018 in vitro.Consistent with these findings,the knockdown of LINC01018 inhibits endometriotic lesion proliferation in vivo.In summary,our study demonstrates that the ERβ/LINC01018/CDC25C/CDK1/CyclinB1 signaling axis regulates endometriosis progression.展开更多
Objectives:Folates are B vitamins that are essential for several molecular,cellular,and biological processes,including nucleotide synthesis,methylation,and methionine cycling.The physiological impacts of these process...Objectives:Folates are B vitamins that are essential for several molecular,cellular,and biological processes,including nucleotide synthesis,methylation,and methionine cycling.The physiological impacts of these processes on health also extend to cell proliferation,folate deficiency anemia,and reduction of the risk of birth defects during pregnancy.The primary objective of this study was to characterize the binding affinities of different folate forms,folic acid(FA),5-methyltetrahydrofolate(5MTHF),and folinic acid,to the folate receptorsαandβ,and to the bovine milk folate binding protein.These three dietary forms of folate are found in enriched grains(FA),various fruits and leafy vegetables(folinic acid),and red blood cells(5MTHF).Methods:The half maximal inhibitory concentration values and binding curves of each of these folates for each receptor were determined.Results:Our results indicated that FA had the highest affinity for all folate receptors,followed by 5MTHF,and lastly,by folinic acid,examined by several orders of magnitudes.Conclusion:These data are expected to provide new insights into the therapeutic applications of the different forms of folate in a variety of diseases.展开更多
Objective:This study aimed to investigate the differentiation of human adipose-derived stem cells(hASCs)into endometrial epithelial cells(EECs)under certain induction conditions and to a further step provide a promisi...Objective:This study aimed to investigate the differentiation of human adipose-derived stem cells(hASCs)into endometrial epithelial cells(EECs)under certain induction conditions and to a further step provide a promising approach for ASCs in clinical practice to the treatment of severe intrauterine adhesion.Methods:Four groups of hASCs were separately cultured as follows:in Group 1,hASCs were cultured in a control medium(5%fetal bovine serum[FBS]+α-minimum Eagle’s medium[α-MEM]);in Group 2,hASCs were cultured in an induction medium(5%FBS+α-MEM+[1×10-7 mol/L 17β-estradiol]+10 ng/mL transforming growth factorβ1[TGF-β1]+10 ng/mL epidermal growth factor[EGF]+10 ng/mL platelet-derived growth factor BB[PDGF-BB]);in Group 3,hASCs and human endometrium cells(hEMCs)were cocultured in the control medium;and in Group 4,hASCs and hEMCs were cocultured in the induction medium.Results:When cocultured with hEMCs,the morphology of hASCs became similar with EECs,and the addition of factors such as EGF,TGFβ,PDGF-BB,and 17β-estradiol promoted differentiation.This study,for the first time,demonstrated estrogen receptor(ER)αand ERβexpression in hASCs and preliminarily explored changes in ERα,ERβ,β-catenin,and H19 mRNA expression during hASC differentiation.Furthermore,we concluded that H19 mRNA expression was negatively correlated with differentiation,which is seemingly related to the estrogen signaling pathway.Conclusions:hASCs revealed the potential for differentiating to EECs when cocultured with hEMCs.展开更多
Objective:To study the relationship between peroxisome proliferator-activated receptorβ(PPARβ) expression in rectus abdominis as well as abdominal subcutaneous fat of patients with gestational diabetes mellitus (GDM...Objective:To study the relationship between peroxisome proliferator-activated receptorβ(PPARβ) expression in rectus abdominis as well as abdominal subcutaneous fat of patients with gestational diabetes mellitus (GDM) and glucolipid metabolism.Methods:The pregnant women who received routine antenatal care and planned to receive selective caesarean section in Obstetrics Department of our hospital between May 2012 and March 2016 were retrospectively analyzed, and 74 healthy pregnant women and 58 pregnant women with GDM were screened and included in the control group and gestational diabetes mellitus group (GDM group) respectively. Rectus abdominis and abdominal subcutaneous fat were collected during Cesarean section to determine the expression of PPARβ was measured;peripheral blood was collected at middle-late pregnancy to determine the content of blood glucose metabolism and lipid metabolism indexes as well as adipocytokines.Results:PARβ mRNA expression and protein expression in rectus abdominis and abdominal subcutaneous fat of GDM group were significantly lower than those of control group (P<0.05);homeostasis model assessment insulin secretion index (HOMA-β), homeostasis model assessment insulin resistance (HOMA-IR) and OGTT glucose curve (AUCG) levels as well as serum low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), cholesterol (TC), Leptin, Resistin and Chemerin content of GDM group were significantly higher than those of control group (P<0.05) while early insulin secretion index (ΔI30/ΔG30) and insulin sensitive index composite (ISIcomp) levels as well as serum high-density lipoprotein cholesterol (HDL-C), Omentin-1 and Omentin-1 and adiponectin (ADPN) content were significantly lower than those of control group (P<0.05);PARβ mRNA expression and protein expression were negatively correlated with HOMA-β, HOMA IR, area under the AUCG, LDL-C, TG, TC, Leptin, Resistin and Chemerin, and positively correlated withΔI30/ΔG30, ISIcomp, HDL-C, and ADPN.Conclusions:PPARβ expression significantl展开更多
Background Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction, pulmonary inflammation and airway remodeling. Current standard therapies for asthma provide symptomatic control, ...Background Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction, pulmonary inflammation and airway remodeling. Current standard therapies for asthma provide symptomatic control, but fail to target the underlying disease pathology. Furthermore, no therapeutic agent is effective in preventing airway remodeling. A substantial amount of evidence suggests that statins have anti-inflammatory properties and immunomodulatory activity. In this study, we investigated the effect of rosuvastatin on airway inflammation and its inhibitory mechanism in mucus hypersecretion in a murine model of chronic asthma. Methods BALB/c mice were sensitized and challenged by ovalbumin to induce asthma. The recruitment of inflammatory cells into bronchoalveolar lavage fluid （BALF） and the lung tissues were measured by Diff-Quik staining and hematoxylin and eosin （H＆E） staining. ELISA was used for measuring the levels of IL-4, IL-5, IL-13 and TNF-a in BALE Periodic acid-Schiff （PAS） staining was used for mucus secretion. Gamma-aminobutyric acid type A receptor （GABAAR） β2 expression was measured by means of immunohistochemistry, reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting. Results Rosuvastatin reduced the number of total inflammatory cells, lymphocytes, macrophages, neutrophils, and eosinophils recruited into BALF, the levels of IL-4, IL-5, IL-13 and TNF-a in BALF, along with the histological mucus index （HMI） and GABAAR 132 expression. Changes occurred in a dose-dependent manner. Conclusions Based on its ability to reduce the inflammatory response and mucus hypersecretion by regulating GABAAR activity in a murine model of chronic asthma, rosuvastatin may be a useful therapeutic agent for treatment of asthma.展开更多
基金supported by the Spanish Ministry of Economy and Competitiveness(PID2019-106498GB-I0)Instituto de Salud Carlos III,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”(PI19/00071)+2 种基金Fundación Séneca,Agencia de Ciencia y Tecnología Región de Murcia(19881/GERM/15)Spanish Ministry of Science and Innovation(PID 2019-106498 GB-I00)Intramural Research Program of the National Eye Institute,National Institutes of Health(NIH/NEI RO1 EY029087)。
文摘Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using retrograde tracing of retinorecipient areas. This is an invasive technique, and its use is precluded in higher mammals such as monkeys. In the past decade, several RGC markers have been described. Here, we reviewed and analyzed the specificity of nine markers used to identify all or most RGCs, i.e., pan-RGC markers, in rats, mice, and macaques. The best markers in the three species in terms of specificity, proportion of RGCs labeled, and indicators of viability were BRN3A, expressed by vision-forming RGCs, and RBPMS, expressed by vision-and non-vision-forming RGCs. NEUN, often used to identify RGCs, was expressed by non-RGCs in the ganglion cell layer, and therefore was not RGC-specific. γ-SYN, TUJ1, and NF-L labeled the RGC axons, which impaired the detection of their somas in the central retina but would be good for studying RGC morphology. In rats, TUJ1 and NF-L were also expressed by non-RGCs. BM88, ERRβ,and PGP9.5 are rarely used as markers, but they identified most RGCs in the rats and macaques and ERRβ in mice. However, PGP9.5 was also expressed by non-RGCs in rats and macaques and BM88 and ERRβ were not suitable markers of viability.
基金This study was supported by the National Natural Science Foundation of China,Nos.81671257,81371221,31600825(all to GQH).
文摘Postmenopausal women with Alzheimer’s disease exhibit dramatically reduced sensitivity to estrogen replacement therapy,which is though to be related to an estrogen receptor(ER)α/ERβratio imbalance arising from a significantly decreased level of ERs of the brain.The aim of our study was to investigate whether valproic acid(VPA)can enhance the beneficial effects of estrogen on cognitive function through restoration of ERαand ERβexpression in the brain.We removed the ovaries of female APP/PS1 mice to simulate the low estrogen levels present in postmenopausal women and then administered VPA(30 mg/kg,intraperitoneal injection,once daily),17β-estradiol(E2)(2.4μg,intraperitoneal injection,once daily),liquiritigenin(LG)(50μg/kg,intragastric infusion,once daily),VPA+E2,or VPA+LG for 4 successive weeks.Compared with treatment with a single drug,treatment with VPA+E2 or VPA+LG significantly increased the level of glycogen synthase kinase 3β,increased the expression of estrogen receptorα,reduced the expression of small ubiquitin-like modifiers,and increased the level of estrogen receptorβ.This resulted in enhanced sensitivity to estrogen therapy,reduced amyloidβaggregation,reduced abnormal phosphorylation of the tau protein,reduced neuronal loss,increased dendritic spine and postsynaptic density,and significantly alleviated memory loss and learning impairment in Alzheimer’s disease.This study was approved by the Chongqing Medical University Animal Protection and Ethics Committee,China on March 6,2013.
基金Supported by National Natural Science Foundation of China(No.81900862)。
文摘AIM:To investigate the involvement of pericyte-Müller glia interaction in retinal damage repair and assess the influence of suppressing the platelet-derived growth factor receptorβ(PDGFRβ)signaling pathway in retinal pericytes on photoreceptor loss and Müller glial response.METHODS:Sprague-Dawley rats were exposed to intense light to induce retinal injury.Neutralizing antibody against PDGFRβwere deployed to block the signaling pathway in retinal pericytes through intravitreal injection.Retinal histology and Müller glial reaction were assessed following light injury.In vitro,normal and PDGFRβ-blocked retinal pericytes were cocultured with Müller cell line(rMC-1)to examine morphological and protein expression changes upon supplementation with light-injured supernatants of homogenized retinas(SHRs).RESULTS:PDGFRβblockage 24h prior to intense light exposure resulted in a significant exacerbation of photoreceptor loss.The upregulation of GFAP and p-STAT3,observed after intense light exposure,was significantly inhibited in the PDGFRβblockage group.Fur ther upregulation of cytokines monocyte chemoattractant protein 1(MCP-1)and interleukin-1β(IL-1β)was also observed following PDGFRβinhibition.In the in vitro coculture system,the addition of light-injured SHRs induced pericyte deformation and upregulation of proliferating cell nuclear antigen(PCNA)expression,while Müller cells exhibited neuron-like morphology and expressed Nestin.However,PDGFRβblockage in retinal pericytes abolished these cellular responses to light-induced damage,consistent with the in vivo PDGFRβblockage findings.CONCLUSION:Pericyte-Müller glia interaction plays a potential role in the endogenous repair process of retinal injury.Impairment of this interaction exacerbates photoreceptor degeneration in light-induced retinal injury.
基金This work was supported by the Columbia University startup packages(Li Qiang and Jianwen Que)and the University of Tennessee College of Pharmacy Drug Discovery Center(Wei Li).
文摘Estrogen is imperative to mammalian reproductivity,metabolism,and aging.However,the hormone activating estrogen receptor(ERs)αcan cause major safety concerns due to the enrichment of ERαin female tissues and certain malignancies.In contrast,ERβis more broadly expressed in metabolic tissues and the skin.Thus,it is desirable to generate selective ERβagonist conjugates for maximizing the therapeutic effects of ERs while minimizing the risks of ERαactivation.Here,we report the design and production of small molecule conjugates containing selective non-steroid ERβagonists Gtx878 or genistein.Treatment of aged mice with our synthesized conjugates improved aging-associated declines in insulin sensitivity,visceral adipose integrity,skeletal muscle function,and skin health,with validation in vitro.We further uncovered the benefits of ERβconjugates in the skin using two inducible skin injury mouse models,showing increased skin basal cell proliferation,epidermal thickness,and wound healing.Therefore,our ERβ-selective agonist conjugates offer novel therapeutic potential to improve aging-associated conditions and aid in rejuvenating skin health.
基金the National Natural Science Foundation of China(82271676)for funding support.
文摘Endometriosis refers to as an estrogen-dependent disease.Estrogen receptorβ(ERB),the main estrogen receptor subtype which is encoded by the estrogen receptor 2(ESR2)gene,can mediate the action of estrogen in endometriosis.Although selective estrogen receptor modulators can target the ERβ,they are not specific due to the wide distribution of ERβ.Recently,long noncoding RNAs have been implicated in endometriosis.Therefore,we aim to explore and validate the downstream regulatory mechanism of ERβ,and to investigate the potential role of long intergenic noncoding RNA 1018(LINC01018)as a nonhormonal treatment for endometriosis.Our study demonstrates that the expression levels of ESR2 and LINCo1018 are increased in ectopic endometrial tissues and reveals a significant positive correlation between the ESR2 and LINCo1018 expression.Mechanistically,ERβdirectly binds to an estrogen response element located in the LINCO1018 promoter region and activates LINC01018 transcription.Functionally,ERβcan regulate the CDC25C/CDK1/CyclinB1 pathway and promote ectopic endometrial stromal cell proliferation via LINC01018 in vitro.Consistent with these findings,the knockdown of LINC01018 inhibits endometriotic lesion proliferation in vivo.In summary,our study demonstrates that the ERβ/LINC01018/CDC25C/CDK1/CyclinB1 signaling axis regulates endometriosis progression.
文摘Objectives:Folates are B vitamins that are essential for several molecular,cellular,and biological processes,including nucleotide synthesis,methylation,and methionine cycling.The physiological impacts of these processes on health also extend to cell proliferation,folate deficiency anemia,and reduction of the risk of birth defects during pregnancy.The primary objective of this study was to characterize the binding affinities of different folate forms,folic acid(FA),5-methyltetrahydrofolate(5MTHF),and folinic acid,to the folate receptorsαandβ,and to the bovine milk folate binding protein.These three dietary forms of folate are found in enriched grains(FA),various fruits and leafy vegetables(folinic acid),and red blood cells(5MTHF).Methods:The half maximal inhibitory concentration values and binding curves of each of these folates for each receptor were determined.Results:Our results indicated that FA had the highest affinity for all folate receptors,followed by 5MTHF,and lastly,by folinic acid,examined by several orders of magnitudes.Conclusion:These data are expected to provide new insights into the therapeutic applications of the different forms of folate in a variety of diseases.
基金funded by grants from the National Natural Science Foundation of China(No.81671463)the Key Research and Development Plan of Shaanxi Province(No.2017ZDCXL-SF-02-03)。
文摘Objective:This study aimed to investigate the differentiation of human adipose-derived stem cells(hASCs)into endometrial epithelial cells(EECs)under certain induction conditions and to a further step provide a promising approach for ASCs in clinical practice to the treatment of severe intrauterine adhesion.Methods:Four groups of hASCs were separately cultured as follows:in Group 1,hASCs were cultured in a control medium(5%fetal bovine serum[FBS]+α-minimum Eagle’s medium[α-MEM]);in Group 2,hASCs were cultured in an induction medium(5%FBS+α-MEM+[1×10-7 mol/L 17β-estradiol]+10 ng/mL transforming growth factorβ1[TGF-β1]+10 ng/mL epidermal growth factor[EGF]+10 ng/mL platelet-derived growth factor BB[PDGF-BB]);in Group 3,hASCs and human endometrium cells(hEMCs)were cocultured in the control medium;and in Group 4,hASCs and hEMCs were cocultured in the induction medium.Results:When cocultured with hEMCs,the morphology of hASCs became similar with EECs,and the addition of factors such as EGF,TGFβ,PDGF-BB,and 17β-estradiol promoted differentiation.This study,for the first time,demonstrated estrogen receptor(ER)αand ERβexpression in hASCs and preliminarily explored changes in ERα,ERβ,β-catenin,and H19 mRNA expression during hASC differentiation.Furthermore,we concluded that H19 mRNA expression was negatively correlated with differentiation,which is seemingly related to the estrogen signaling pathway.Conclusions:hASCs revealed the potential for differentiating to EECs when cocultured with hEMCs.
文摘Objective:To study the relationship between peroxisome proliferator-activated receptorβ(PPARβ) expression in rectus abdominis as well as abdominal subcutaneous fat of patients with gestational diabetes mellitus (GDM) and glucolipid metabolism.Methods:The pregnant women who received routine antenatal care and planned to receive selective caesarean section in Obstetrics Department of our hospital between May 2012 and March 2016 were retrospectively analyzed, and 74 healthy pregnant women and 58 pregnant women with GDM were screened and included in the control group and gestational diabetes mellitus group (GDM group) respectively. Rectus abdominis and abdominal subcutaneous fat were collected during Cesarean section to determine the expression of PPARβ was measured;peripheral blood was collected at middle-late pregnancy to determine the content of blood glucose metabolism and lipid metabolism indexes as well as adipocytokines.Results:PARβ mRNA expression and protein expression in rectus abdominis and abdominal subcutaneous fat of GDM group were significantly lower than those of control group (P<0.05);homeostasis model assessment insulin secretion index (HOMA-β), homeostasis model assessment insulin resistance (HOMA-IR) and OGTT glucose curve (AUCG) levels as well as serum low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), cholesterol (TC), Leptin, Resistin and Chemerin content of GDM group were significantly higher than those of control group (P<0.05) while early insulin secretion index (ΔI30/ΔG30) and insulin sensitive index composite (ISIcomp) levels as well as serum high-density lipoprotein cholesterol (HDL-C), Omentin-1 and Omentin-1 and adiponectin (ADPN) content were significantly lower than those of control group (P<0.05);PARβ mRNA expression and protein expression were negatively correlated with HOMA-β, HOMA IR, area under the AUCG, LDL-C, TG, TC, Leptin, Resistin and Chemerin, and positively correlated withΔI30/ΔG30, ISIcomp, HDL-C, and ADPN.Conclusions:PPARβ expression significantl
基金This study was partially supported by the National Natural Science Foundation of China （No. 30971303）.
文摘Background Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction, pulmonary inflammation and airway remodeling. Current standard therapies for asthma provide symptomatic control, but fail to target the underlying disease pathology. Furthermore, no therapeutic agent is effective in preventing airway remodeling. A substantial amount of evidence suggests that statins have anti-inflammatory properties and immunomodulatory activity. In this study, we investigated the effect of rosuvastatin on airway inflammation and its inhibitory mechanism in mucus hypersecretion in a murine model of chronic asthma. Methods BALB/c mice were sensitized and challenged by ovalbumin to induce asthma. The recruitment of inflammatory cells into bronchoalveolar lavage fluid （BALF） and the lung tissues were measured by Diff-Quik staining and hematoxylin and eosin （H＆E） staining. ELISA was used for measuring the levels of IL-4, IL-5, IL-13 and TNF-a in BALE Periodic acid-Schiff （PAS） staining was used for mucus secretion. Gamma-aminobutyric acid type A receptor （GABAAR） β2 expression was measured by means of immunohistochemistry, reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting. Results Rosuvastatin reduced the number of total inflammatory cells, lymphocytes, macrophages, neutrophils, and eosinophils recruited into BALF, the levels of IL-4, IL-5, IL-13 and TNF-a in BALF, along with the histological mucus index （HMI） and GABAAR 132 expression. Changes occurred in a dose-dependent manner. Conclusions Based on its ability to reduce the inflammatory response and mucus hypersecretion by regulating GABAAR activity in a murine model of chronic asthma, rosuvastatin may be a useful therapeutic agent for treatment of asthma.
