BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells(BMSCs)has been suggested to be an important cause of decreased osteogenic differentiation.A pharmacological increase in autophagy of ...BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells(BMSCs)has been suggested to be an important cause of decreased osteogenic differentiation.A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate osteoporosis.AIM To explore the effects of sinomenine(SIN)on the osteogenic differentiation of BMSCs and the underlying mechanisms.METHODS For in vitro experiments,BMSCs were extracted from sham-treated mice and ovariectomized mice,and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concen-trations of SIN and the autophagy inhibitor 3-methyladenine.In vivo,the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse femur.RESULTS SIN reduced the levels of AKT and mammalian target of the rapamycin(mTOR)phosphorylation in the phosphatidylinositol 3-kinase(PI3K)/AKT/mTOR signaling pathway,inhibited mTOR activity,and increased autophagy ability of BMSCs,thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in vivo.CONCLUSION The Chinese medicine SIN has potential for the treatment of various types of osteoporosis,bone homeostasis disorders,and autophagy-related diseases.展开更多
Lipid metabolism disorders commonly occur during menopause.Estrogen deficiency has been shown to lead to excessive energy intake and abnormal lipid metabolism in ovariectomized rats,resulting in obesity.Probiotics exh...Lipid metabolism disorders commonly occur during menopause.Estrogen deficiency has been shown to lead to excessive energy intake and abnormal lipid metabolism in ovariectomized rats,resulting in obesity.Probiotics exhibit anti-obesity properties,and their underlying mechanism has been widely reported.In this study,we demonstrated the metabolic benefits of Lactobacillus plantarum CCFM1180 in suppressing appetite,controlling body weight,correcting obesity-induced abnormalities,enhancing liver lipid metabolism,and protecting liver function in estrogen-deficient rats.The mechanisms associated with the anti-obesity and anti-dyslipidemia effects of CCFM1180 on estrogen-deficient rats were clarified.The results showed that CCFM1180 dramatically reduced food intake by activating the expression of estrogen receptor alpha(ERα)and increasing the level of leptin in abdominal adipose tissue.These changes,combined with the increased butyrate concentration and recovered bile acid structure,helped enhance lipid metabolism.Additionally,CCFM1180 treatment was found to be safer than exogenous estrogen supplementation.Thus,L.plantarum CCFM1180 could be considered a new therapeutic strategy for preventing and alleviating menopausal lipid abnormalities.展开更多
Objective To study whether effect of aspirin plus low-dose diethylstilbestrol is more effective and safer than high diethylstilbestrol dose alone on prevention of ovariectomy-induced osteopenia and dyslipidemia. Metho...Objective To study whether effect of aspirin plus low-dose diethylstilbestrol is more effective and safer than high diethylstilbestrol dose alone on prevention of ovariectomy-induced osteopenia and dyslipidemia. Methods Thirty-eight 4-month-old female SD rats were divided into baseline （BAS） group （n=6）, sham operation group （n=8） and ovariectomy （OVX） group （n=24）. The OVX group was further divided into vehicle treatment group （n=8）, diethylstilbestrol （30 ug/kg.d） treatment group （OVX＋D30 group, n=8）, and aspirin （9 mg/kg.d） plus diethylstilbestrol （10 ug/kg.d） treatment group （OVX＋A-D10 group, n=8）. Their left tibiae were collected for the bone histomorphometric analysis in undecalcified sections. Left femurs were collected for the bone mineral density measurement. Results The body weight and serum cholesterol were increased, while uterine weight and cancellous bone mass were decreased in OVX rats compared with the SHAM group. Cancellous bone mass was significantly increased, while body weight and bone resorption parameters were decreased in both A-D10 and D30 treatment group compared with OVX group. The rats treated with A-D10 showed significantly increased in bone formation parameters and decreased in serum triglyceride compared with the D30-treated rats. Conclusion Aspirin plus low-dose diethylstilbestrol can effectively prevent osteopenia by reducing bone resorption, and is thus a better treatment modality for preventing dyslipidemia than high-dose diethylstilbestrol alone.展开更多
This study was aimed to examine the effect of ovariectomy on visceral fat, serum adi- ponectin levels and lipid profile. Forty-five female Sprague DawIey rats were divided into three groups （n=15 each）： ovariectomi...This study was aimed to examine the effect of ovariectomy on visceral fat, serum adi- ponectin levels and lipid profile. Forty-five female Sprague DawIey rats were divided into three groups （n=15 each）： ovariectomized group （OVX）, ovariectomized plus estrogen-treated group （OVX＋E2）, and sham-operated group （SHAM）. Body weight, abdominal adipose tissues, serum adiponectin and lipid profile were measured and compared among the groups after three-month feeding post-surgery. Signifi- cant increases in body weight and visceral fat were found in ovariectomized rats when compared with sham-operated ones and significant increases were also observed in serum adiponectin, triglyceride and very low density lipoprotein cholesterol levels in ovariectomized rats. Body weight, visceral fat and se- rum adiponectin levels were profoundly reduced in OVX＋E2 group as compared with OVX group. It was concluded that ovarian hormone deficiency induced by ovariectomy leads to significant increases in body weight and visceral fat, along with increased serum adiponectin, triglyceride and very low density lipoprotein cholesterol levels in rats. Attenuation in these changes can be achieved by estrogen supple- mentation.展开更多
AIM:To compare natural orifice transluminal endoscopic surgery (NOTES) vs standard laparoscopic ovariectomy in mini pigs with respect to technical aspects,complications and parameters of systemic inflammatory response...AIM:To compare natural orifice transluminal endoscopic surgery (NOTES) vs standard laparoscopic ovariectomy in mini pigs with respect to technical aspects,complications and parameters of systemic inflammatory response.METHODS:This was a randomized,experimental,survival study.Ten female mini pigs underwent NOTES transgastric ovariectomy (NOTES group) and ten female mini pigs underwent laparoscopic ovariectomy (LAP group).A "percutaneous endoscopic gastrostomy" approach with guidewire and sphincterotome was used for gastrotomy creation.The ovary was resected using standard biopsy forceps and a snare.The access site was closed using a "KING" closure with a single endoloop and several clips.In the laparoscopic group,a three-port laparoscopy and an ovariectomy were performed with the use of standard laparoscopic devices.C-reactive protein (CRP),white blood count and interleukin (IL)-6 plasma levels were used as indicators of systemic inflammatory response.All animals were euthanized 28 d after surgery.RESULTS:All animals survived without complications.The mean procedure time was 41.3 min ± 17.6 min (NOTES group) and 25.7 min ± 5.25 min (LAP group,P < 0.02).Postmortem examinations demonstrated that 50% and 70% of animals were free of any complications in the NOTES and LAP groups,respectively.The remaining animals developed minor complications (adhesions) in a comparable frequency between the two groups.In the NOTES group,one animal developed a small intramural gastric abscess close to the gastrotomy site.A minor serous exudate that was present in 50% and 40% of the animals in the NOTES and laparoscopy groups,respectively,was not considered a complication.In both groups CRP levels increased significantly on the 2nd and 7th postoperative days (POD) and returned to normal after 28 d.On POD 2,an increase of CRP level was significantly higher in the NOTES group compared to the LAP group.Values of IL-6 did not differ from baseline values in either of the groups postoperatively.Interestingly,the platelet count decreased significantly on POD 2,but returned close to baseline values on POD 7 and PODs 28-30.CONCLUSION:Both NOTES and laparoscopic ovariectomies had a similar frequency of minor complications.However,the NOTES technique produced an increased systemic inflammatory response on POD 2.展开更多
Growth hormone (GH) and estrogen are essential stimulators of mammary cell proliferation and mammary development as mammals near puberty. Mammary ductal growth requires modifications of the extracellular matrix (ECM) ...Growth hormone (GH) and estrogen are essential stimulators of mammary cell proliferation and mammary development as mammals near puberty. Mammary ductal growth requires modifications of the extracellular matrix (ECM) for this tissue expansion to occur. Our purpose was to evaluate the effects of exogenous GH and ovariectomy (known to impact estrogen production) on gene expression of selected ECM proteins in the mammary parenchyma (PAR) and mammary fat pad (MFP) of prepubertal calves. Our hypothesis was that both GH and ovariectomy would alter the mRNA expression of multiple mammary ECM proteins. However, treatment with GH significantly reduced the expression of only fibronectin in PAR. However, the mRNA expression of all of the ECM proteins tested was numerically lower in PAR from GH treated calves. In contrast, staged ovariectomy decreased expression of fibronectin and heat shock protein 90 but increased expression of epimorphin in mammary PAR. In the MFP expression of Rac-1 and fascin were increased. These findings suggest that effects of exogenous GH on mammary gland composition are only marginally dependent on alterations in ECM proteins but the more pronounced effects of ovariectomy (reduced PAR mass and altered myoepithelial ontogeny) are more likely linked to changes in expression of ECM proteins.展开更多
基金Supported by National Natural Science Foundation of China,No.82072425.
文摘BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells(BMSCs)has been suggested to be an important cause of decreased osteogenic differentiation.A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate osteoporosis.AIM To explore the effects of sinomenine(SIN)on the osteogenic differentiation of BMSCs and the underlying mechanisms.METHODS For in vitro experiments,BMSCs were extracted from sham-treated mice and ovariectomized mice,and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concen-trations of SIN and the autophagy inhibitor 3-methyladenine.In vivo,the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse femur.RESULTS SIN reduced the levels of AKT and mammalian target of the rapamycin(mTOR)phosphorylation in the phosphatidylinositol 3-kinase(PI3K)/AKT/mTOR signaling pathway,inhibited mTOR activity,and increased autophagy ability of BMSCs,thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in vivo.CONCLUSION The Chinese medicine SIN has potential for the treatment of various types of osteoporosis,bone homeostasis disorders,and autophagy-related diseases.
基金funded by the National Natural Science Foundation of China(31972052,32021005,31820103010)the Fundamental Research Funds for the Central Universities(JUSRP22006,JUSRP51501)the Program of Collaborative Innovation Centre of Food Safety and Quality Control in Jiangsu Province。
文摘Lipid metabolism disorders commonly occur during menopause.Estrogen deficiency has been shown to lead to excessive energy intake and abnormal lipid metabolism in ovariectomized rats,resulting in obesity.Probiotics exhibit anti-obesity properties,and their underlying mechanism has been widely reported.In this study,we demonstrated the metabolic benefits of Lactobacillus plantarum CCFM1180 in suppressing appetite,controlling body weight,correcting obesity-induced abnormalities,enhancing liver lipid metabolism,and protecting liver function in estrogen-deficient rats.The mechanisms associated with the anti-obesity and anti-dyslipidemia effects of CCFM1180 on estrogen-deficient rats were clarified.The results showed that CCFM1180 dramatically reduced food intake by activating the expression of estrogen receptor alpha(ERα)and increasing the level of leptin in abdominal adipose tissue.These changes,combined with the increased butyrate concentration and recovered bile acid structure,helped enhance lipid metabolism.Additionally,CCFM1180 treatment was found to be safer than exogenous estrogen supplementation.Thus,L.plantarum CCFM1180 could be considered a new therapeutic strategy for preventing and alleviating menopausal lipid abnormalities.
基金supported by grants from the National Science Foundation of China (No:30973574)Science and Technology Planning Project of Guangdong Province (No:2010B060500014)Science & Technology Innovation Fund of Guangdong Medical College (STIF201104)
文摘Objective To study whether effect of aspirin plus low-dose diethylstilbestrol is more effective and safer than high diethylstilbestrol dose alone on prevention of ovariectomy-induced osteopenia and dyslipidemia. Methods Thirty-eight 4-month-old female SD rats were divided into baseline （BAS） group （n=6）, sham operation group （n=8） and ovariectomy （OVX） group （n=24）. The OVX group was further divided into vehicle treatment group （n=8）, diethylstilbestrol （30 ug/kg.d） treatment group （OVX＋D30 group, n=8）, and aspirin （9 mg/kg.d） plus diethylstilbestrol （10 ug/kg.d） treatment group （OVX＋A-D10 group, n=8）. Their left tibiae were collected for the bone histomorphometric analysis in undecalcified sections. Left femurs were collected for the bone mineral density measurement. Results The body weight and serum cholesterol were increased, while uterine weight and cancellous bone mass were decreased in OVX rats compared with the SHAM group. Cancellous bone mass was significantly increased, while body weight and bone resorption parameters were decreased in both A-D10 and D30 treatment group compared with OVX group. The rats treated with A-D10 showed significantly increased in bone formation parameters and decreased in serum triglyceride compared with the D30-treated rats. Conclusion Aspirin plus low-dose diethylstilbestrol can effectively prevent osteopenia by reducing bone resorption, and is thus a better treatment modality for preventing dyslipidemia than high-dose diethylstilbestrol alone.
基金supported by grants from the National Natural Science Foundation of China(No.30671765)Scientific Research Foundation for Returned Overseas Chinese Scholars,Ministry of Education of China(No.20101561)
文摘This study was aimed to examine the effect of ovariectomy on visceral fat, serum adi- ponectin levels and lipid profile. Forty-five female Sprague DawIey rats were divided into three groups （n=15 each）： ovariectomized group （OVX）, ovariectomized plus estrogen-treated group （OVX＋E2）, and sham-operated group （SHAM）. Body weight, abdominal adipose tissues, serum adiponectin and lipid profile were measured and compared among the groups after three-month feeding post-surgery. Signifi- cant increases in body weight and visceral fat were found in ovariectomized rats when compared with sham-operated ones and significant increases were also observed in serum adiponectin, triglyceride and very low density lipoprotein cholesterol levels in ovariectomized rats. Body weight, visceral fat and se- rum adiponectin levels were profoundly reduced in OVX＋E2 group as compared with OVX group. It was concluded that ovarian hormone deficiency induced by ovariectomy leads to significant increases in body weight and visceral fat, along with increased serum adiponectin, triglyceride and very low density lipoprotein cholesterol levels in rats. Attenuation in these changes can be achieved by estrogen supple- mentation.
文摘AIM:To compare natural orifice transluminal endoscopic surgery (NOTES) vs standard laparoscopic ovariectomy in mini pigs with respect to technical aspects,complications and parameters of systemic inflammatory response.METHODS:This was a randomized,experimental,survival study.Ten female mini pigs underwent NOTES transgastric ovariectomy (NOTES group) and ten female mini pigs underwent laparoscopic ovariectomy (LAP group).A "percutaneous endoscopic gastrostomy" approach with guidewire and sphincterotome was used for gastrotomy creation.The ovary was resected using standard biopsy forceps and a snare.The access site was closed using a "KING" closure with a single endoloop and several clips.In the laparoscopic group,a three-port laparoscopy and an ovariectomy were performed with the use of standard laparoscopic devices.C-reactive protein (CRP),white blood count and interleukin (IL)-6 plasma levels were used as indicators of systemic inflammatory response.All animals were euthanized 28 d after surgery.RESULTS:All animals survived without complications.The mean procedure time was 41.3 min ± 17.6 min (NOTES group) and 25.7 min ± 5.25 min (LAP group,P < 0.02).Postmortem examinations demonstrated that 50% and 70% of animals were free of any complications in the NOTES and LAP groups,respectively.The remaining animals developed minor complications (adhesions) in a comparable frequency between the two groups.In the NOTES group,one animal developed a small intramural gastric abscess close to the gastrotomy site.A minor serous exudate that was present in 50% and 40% of the animals in the NOTES and laparoscopy groups,respectively,was not considered a complication.In both groups CRP levels increased significantly on the 2nd and 7th postoperative days (POD) and returned to normal after 28 d.On POD 2,an increase of CRP level was significantly higher in the NOTES group compared to the LAP group.Values of IL-6 did not differ from baseline values in either of the groups postoperatively.Interestingly,the platelet count decreased significantly on POD 2,but returned close to baseline values on POD 7 and PODs 28-30.CONCLUSION:Both NOTES and laparoscopic ovariectomies had a similar frequency of minor complications.However,the NOTES technique produced an increased systemic inflammatory response on POD 2.
文摘Growth hormone (GH) and estrogen are essential stimulators of mammary cell proliferation and mammary development as mammals near puberty. Mammary ductal growth requires modifications of the extracellular matrix (ECM) for this tissue expansion to occur. Our purpose was to evaluate the effects of exogenous GH and ovariectomy (known to impact estrogen production) on gene expression of selected ECM proteins in the mammary parenchyma (PAR) and mammary fat pad (MFP) of prepubertal calves. Our hypothesis was that both GH and ovariectomy would alter the mRNA expression of multiple mammary ECM proteins. However, treatment with GH significantly reduced the expression of only fibronectin in PAR. However, the mRNA expression of all of the ECM proteins tested was numerically lower in PAR from GH treated calves. In contrast, staged ovariectomy decreased expression of fibronectin and heat shock protein 90 but increased expression of epimorphin in mammary PAR. In the MFP expression of Rac-1 and fascin were increased. These findings suggest that effects of exogenous GH on mammary gland composition are only marginally dependent on alterations in ECM proteins but the more pronounced effects of ovariectomy (reduced PAR mass and altered myoepithelial ontogeny) are more likely linked to changes in expression of ECM proteins.
