[Objective]The paper was to study the effects of estradiol(E_(2))and progesterone(P4)on the expression of interleukin-1β(IL-1β)mRNA in lipopolysaccharide(LPS)-induced acute salpingitis in ovariectomized mice,and pre...[Objective]The paper was to study the effects of estradiol(E_(2))and progesterone(P4)on the expression of interleukin-1β(IL-1β)mRNA in lipopolysaccharide(LPS)-induced acute salpingitis in ovariectomized mice,and preliminarily explore the anti-inflammatory mechanism associated with estrogen and progesterone.[Method]Healthy female KM mice were randomly assigned to several groups:the sham operation group(LPS+SHAM),the ovarian removal group(LPS+OVX),the ovarian removal+estradiol group(LPS+OVX+E_(2)),the ovarian removal+progesterone group(LPS+OVX+P4),the LPS group and the control group(control).HE staining was conducted to assess the pathological changes in the fallopian tubes of each group.Additionally,the expression levels of IL-1βmRNA in the fallopian tubes of the mice were quantified using RT-qPCR.[Result]The histopathological changes in the fallopian tubes were examined.Estrogen and progesterone demonstrated a significant capacity to mitigate salpingitis induced by LPS.In comparison to the control group,the expression of IL-1βmRNA in the LPS group,LPS+SHAM group,and LPS+OVX+E_(2)group was significantly down-regulated(P<0.05).Furthermore,the expression of IL-1βmRNA in the LPS+OVX+P4 group exhibited an extremely significant down-regulation(P<0.01).When compared to the LPS+OVX group,the expression of IL-1βmRNA in the LPS+OVX+E_(2)group was significantly down-regulated(P<0.05),while the expression in the LPS+OVX+P4 group was extremely significantly down-regulated(P<0.01).[Conclusion]Estrogen and progesterone have the capacity to inhibit the expression of IL-1βmRNA in the inflammatory tissue of the fallopian tubes in mice,consequently diminishing the inflammatory response induced by LPS.展开更多
Objective This study aims to explore the correlation between traditional Chinese medicine(TCM)syndromes and the expression status of estrogen receptor(ER)and progesterone receptor(PR)in breast cancer patients before a...Objective This study aims to explore the correlation between traditional Chinese medicine(TCM)syndromes and the expression status of estrogen receptor(ER)and progesterone receptor(PR)in breast cancer patients before and after adjuvant chemotherapy.Methods A total of 222 breast cancer patients with consistent ER and PR expression scheduled to undergo adjuvant chemotherapy were classified according to TCM syndrome differentiation before and after chemotherapy.The data were analyzed using chi-square tests and binary logistic regression with SPSS 26.0 software,and compared with ER/PR expression results.Results(i)In the ER-positive/PR-positive group,compared with prechemotherapy,syndromes of spleen qi deficiency,spleen deficiency with dampness-phlegm,and spleen–kidney deficiency significantly increased during mid-chemotherapy and after chemotherapy.Compared with mid-chemotherapy,spleen yang deficiency syndrome significantly increased after chemotherapy,with statistical significance(p<0.05).(ii)In the ER-negative/PR-negative group,compared with prechemotherapy,syndromes of spleen qi deficiency and spleen deficiency with dampness-phlegm significantly increased during mid-chemotherapy,while spleen qi deficiency,spleen yang deficiency,and spleen–kidney deficiency significantly increased after chemotherapy.Compared with mid-chemotherapy,spleen–kidney deficiency and spleen yang deficiency syndromes significantly increased after chemotherapy,with statistical significance(p<0.05).(iii)The distribution of spleen qi deficiency syndrome during mid-chemotherapy and after chemotherapy was significantly higher in the ER-positive/PR-positive group than in the ER-negative/PR-negative group,with statistical significance(p<0.05).(iv)ER and PR were not independent influencing factors for the various syndrome types before and after adjuvant chemotherapy(p>0.05).Conclusion After chemotherapy initiation,syndromes of spleen qi deficiency,spleen yang deficiency,and spleen–kidney deficiency significantly increased in both ER-positive/PR-positive and ER-negative/PR-negative groups.The distribution of spleen qi deficiency during mid-chemotherapy and after chemotherapy was significantly higher in the ER-positive/PR-positive group than in the ER-negative/PR-negative group.ER and PR were not independent influencing factors for the syndrome types before and after adjuvant chemotherapy.展开更多
Alzheimer’s disease(AD)is a neurological disorder characterized primarily by a progressive decline in cognitive and behavioral functions.The pathogenesis of AD has not been fully elucidated till now.The progesterone ...Alzheimer’s disease(AD)is a neurological disorder characterized primarily by a progressive decline in cognitive and behavioral functions.The pathogenesis of AD has not been fully elucidated till now.The progesterone receptor(PR)family has recently attracted increasing attention and has become the focus of potential links to factors such as the pathogenesis and pathological changes of AD due to its role in the central nervous system.This article summarizes the progress of research progress on the PR family in AD,including its role in pathophysiology,molecular mechanisms,and potential therapeutic strategies.展开更多
Understanding basic reproductive physiology is crucial for the management of both captive and free-ranging wolf. In the present study, we determined hormonal changes during pregnancy and the estrous cycle in captive f...Understanding basic reproductive physiology is crucial for the management of both captive and free-ranging wolf. In the present study, we determined hormonal changes during pregnancy and the estrous cycle in captive female wolf by measuring fecal steroids collected during the breeding season with high performance liquid chromatography （HPLC）. These biochemical analyses were validated using chemical devivatization and mass spectrometry, and interpreted along with the behavioral data. All four females undergoing estrus cycles were copulated with their partners and delivered pups successfully. We found that estradiol concen-trations were significantly higher during the estrus cycle than other stages （p0.01） and progesterone was also significantly increased throughout the pregnancy （p0.01）. These hormonal fluctuations demonstrated pregnancy-specific changes in the fecal progesterone and estradiol con-centrations. Patterns of fecal estradiol and progesterone concentrations during estrous cycles were similar to those reported for other canids.展开更多
Objective:To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.Methods:After pregnancy,50 SPF female SD rats were se...Objective:To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.Methods:After pregnancy,50 SPF female SD rats were selected and divided into control group,model group,progesterone group,Zishen Yutai pill group,and progesterone plus Zishen Yutai pill group(combination group),with 10 rats in each group.The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days.Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days.Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin,continuous for 10 days.Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days,and other treatments were the same as previous two groups.Abortion model were established then and live births,numbers of abortion and average rate of abortion were compared between the five groups.Peripheral blood was collected to detect the estradiol(E2) and progestational hormone(P),and obtain ratio of Th1/Th2 cytokines(IL-2,INF-γ,IL-4,IL-10).Results:Significant more live births of rats were found in the control group compared with other four groups(P<0.05).The numbers of live births of the rats in abortion model group were significantly less than that of progesterone group,Zishen Yutai pill group and joint group(P<0.05).The numbers of live births of rats in joint group were significant more than that of progesterone group and Zishen Yutai pill group.The serum E2 level of P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were significant higher than that of abortion model group(P<0.05).Serum levels of E2 and P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were not significant different(P>0.05) but these levels in the control group and Zishen Yutai pill group were significant lower than that of progesterone group and joint group(P<0.05).The maternal-fetal interface IL-4/IL-2,IL-10 / IL-2 of model group were balanced deviating to Th1,while the IL-4/IL-2,IL-10/IL-2 of progesterone group,Zishen Yutai pill group and joint group were balanced deviating to Th2,and joint group' deviation was better than progesterone group and Zishen Yutai pill group(P<0.05).Conclusions:Zishen Yutai pill combined with progesterone has a significant control effect for threatened abortion,which can obviously increase contents of maternal serums E2 and P,and regulate the Thl/Th2 balance with a remarkable effect.展开更多
AIM: To study the dose-dependent of progesterone (P) effect and the interaction between the oxytocin (OT) and P on gastrointestinal motility. METHODS: In order to monitor the gastric emptying and intestinal transit, t...AIM: To study the dose-dependent of progesterone (P) effect and the interaction between the oxytocin (OT) and P on gastrointestinal motility. METHODS: In order to monitor the gastric emptying and intestinal transit, the SD male rats were intubated via a catheter with normal saline (3 ml/kg) containing Na(2)(51)CrO(4) (0.5 microCi/ml) and 10% charcoal. OT was dissolved into normal saline and P was dissolved into 75% alcohol. RESULTS: Low does of P (1 mg/kg, i.p.) enhanced the gastric emptying (75+/-3%, P【0.05) and high dose of P (5 mg/kg, i.p.) inhibit it (42+/-11.2%, P【0.01). P (1 mg/kg) increased the intestinal transit (4.2+/-0.3, P【0.05) while the higher dose (10-20 mg/kg) had no effect. OT (0.8 mg/kg, i.p.) inhibited the gastric emptying (23.5+/-9.8%, P【0.01). The inhibitory effects of P(20 mg/kg) (32+/-9.7%, P【0.05) and OT (0.8 mg/kg) on gastric emptying enhanced each other when the two chemicals were administrated simultaneously (17+/-9.4%, P【0.01). CONCLUSION: Low dose of P increased GI motility while high dose of P decreased it. During the later period of pregnancy, elevated plasma level of OT may also participate in the gastrointestinal inhibition.展开更多
Objective Traumatic brain injury （TBI） is one of the leading causes of morbidity and mortality in young people. Inflammatory cytokines play an important part in the pathophysiology of TBI. Recent studies demonstrate...Objective Traumatic brain injury （TBI） is one of the leading causes of morbidity and mortality in young people. Inflammatory cytokines play an important part in the pathophysiology of TBI. Recent studies demonstrate that progesterone significantly reduces cerebral edema and enhances functional recovery from TBI and stroke in several animal models. This study was designed to investigate the inhibitory effect of progesterone on inflammatory response after traumatic brain injury. Methods Progesterone was injected intraperitoneally using rats as a model of traumatic brain injury, and Western blot technique was applied to detect the expression of three inflammation-related factors： nuclear factor kappa B p65 （NFκB p65）, glial fibrillary acidic protein （GFAP）, and tumor necrosis factor-α （TNF-α）. The water content of injured brain was also examined. A neurological severity score was recorded to evaluate the effect of progesterone on neurodeficit recovery. Results NFκB p65, GFAP, and TNF-α were increased in all injured animals. In rats treated with progesterone, the expression level of NFκB p65 and TNF-α were reduced significantly in comparison with vehicle-treated rats. However, progesterone did not alter the expression of GFAP in the injured rats. Progesterone also reduced the water content of injured brain and the lesion volume. In addition, progesterone-treated injured rats showed significant improvements in the Neurological Severity Score test, compared with vehicle-treated ones. Conclusions Progesterone inhibits the inflammatory response after experimental traumatic brain injury and mitigates the severity of brain damage.展开更多
AIM To investigate the clinicopathological significance of progesterone receptor membrane component 1(PGRMC1) and PGRMC2 in hepatocellular carcinoma(HCC). METHODS We performed immunohistochemical staining to evaluate ...AIM To investigate the clinicopathological significance of progesterone receptor membrane component 1(PGRMC1) and PGRMC2 in hepatocellular carcinoma(HCC). METHODS We performed immunohistochemical staining to evaluate the estrogen receptor(ER), progesterone receptor(PR), PGRMC1, and PGRMC2 in a clinical cohort consisting of 89 paired HCC and non-tumor liver samples. We also analyzed HCC data(n = 373) from The Cancer Genome Atlas(TCGA). We correlated the expression status of PGRMC1 and PGRMC2 with clinicopathological indicators and the clinical outcomes of the HCC patients. We knocked down or overexpressed PGRMC1 in HCC cell lines to evaluate its biological significance in HCC cell proliferation, differentiation, migration, and invasion. RESULTS We found that few HCC cases expressed ER(5.6%) and PR(4.5%). In contrast, most HCC cases expressed PGRMC1(89.9%) and PGRMC2(100%). PGRMC1 and PGRMC2 exhibited significantly lower expression in tumor tissue than in non-tumor tissue(P < 0.001). Lower PGRMC1 expression in HCC was significantly associated with higher serum alpha-fetoprotein expression(P = 0.004), poorer tumor differentiation(P = 0.045) and liver capsule penetration(P = 0.038). Low PGRMC1 expression was an independent predictor for worse disease-free survival(P = 0.002, HR = 2.384,CI: 1.377-4.128) in our cases, as well as in the TCGA cohort(P < 0.001, HR = 2.857, CI: 1.781-4.584). The expression of PGRMC2 did not relate to patient outcome. PGRMC1 knockdown promoted a poorly differentiated phenotype and proliferation of HCC cells in vitro, while PGRMC1 overexpression caused the opposite effects.CONCLUSION PGRMC1 is a non-classical hormonal receptor that negatively regulates hepatocarcinogenesis. PGRMC1 down-regulation is associated with progression of HCC and is a poor prognostic indicator.展开更多
In this study, human umbilical cord mesenchymal stem cells from full-term neonates born by vagina delivery were cultured in medium containing 150 mg/mL of brain tissue extracts from Sprague-Dawley rats （to mimic the ...In this study, human umbilical cord mesenchymal stem cells from full-term neonates born by vagina delivery were cultured in medium containing 150 mg/mL of brain tissue extracts from Sprague-Dawley rats （to mimic the brain microenvironment）. Immunocytochemical analysis demonstrated that the cells differentiated into neuron-like cells. To evaluate the effects of progesterone as a neurosteroid on the neuronal differentiation of human umbilical cord mesenchymal stem cells, we cultured the cells in medium containing progesterone （0.1, 1, 10 pM） in addition to brain tissue extracts. Reverse transcription-PCR and flow cytometric analysis of neuron specific enolase-positive cells revealed that the percentages of these cells increased significantly following progesterone treatment, with the optimal progesterone concentration for neuron-like differentiation being 1 tJM. These results suggest that progesterone can enhance the neuronal differentiation of human umbilical cord mesenchymal stem cells in culture medium containing brain tissue extracts to mimic the brain microenvironment.展开更多
There are currently no federally approved neuroprotective agents to treat traumatic brain injury. Progesterone, a hydrophobic steroid hormone, has been shown in recent studies to exhibit neu-roprotective effects in co...There are currently no federally approved neuroprotective agents to treat traumatic brain injury. Progesterone, a hydrophobic steroid hormone, has been shown in recent studies to exhibit neu-roprotective effects in controlled cortical impact rat models. Akt is a protein kinase known to play a role in cell signaling pathways that reduce edema, inlfammation, apoptosis, and promote cell growth in the brain. This study aims to determine if progesterone modulates the phosphor-ylation of Aktvia its threonine 308 phosphorylation site. Phosphorylation at the threonine 308 site is one of several sites responsible for activating Akt and enabling the protein kinase to carry out its neuroprotective effects. To assess the effects of progesterone on Akt phosphorylation, C57BL/6 mice were treated with progesterone （8 mg/kg） at 1 （intraperitonally）, 6, 24, and 48 hours （subcutaneously） post closed-skull traumatic brain injury. The hippocampus was harvest-ed at 72 hours post injury and prepared for western blot analysis. Traumatic brain injury caused a signiifcant decrease in Akt phosphorylation compared to sham operation. However, mice treat-ed with progesterone following traumatic brain injury had an increase in phosphorylation of Akt compared to traumatic brain injury vehicle. Our ifndings suggest that progesterone is a viable treatment option for activating neuroprotective pathways after traumatic brain injury.展开更多
AIM:To investigate the effects of estradiol (E2) and progesterone on the unstimulated and oxidative stressstimulated production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, and macrophage chemotactic...AIM:To investigate the effects of estradiol (E2) and progesterone on the unstimulated and oxidative stressstimulated production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, and macrophage chemotactic protein (MCP)-1 by peripheral blood mononuclear cells (PBMCs) from patients with chronic hepatitis C and healthy controls. METHODS:The PBMCs were separated from agematched 72 males and 71 females with and without chronic hepatitis C, who were divided into two groups based on a mean menopausal age of 50 years. Oxidative stress was induced by hydrogen peroxide in the cells incubated in serum-free media. Cytokines in the culture supernatant were measured by an enzyme-linked immunosorbent assay. RESULTS:The highest levels of the spontaneous production of TNF-α, IL-1β, IL-8, and MCP-1 by the unstimulated PBMCs were in the older male patients with chronic hepatitis C and the lowest levels were in the premenopausal female healthy controls. E2 inhibited the cytokine production by the unstimulated PBMCs from the older male and post-menopausal female patients, which was further stimulated by progesterone. The exposure to hydrogen peroxide in the PBMCs from the younger male and pre-menopausal female healthy subjects induced the production of cytokines. The change rates of the hydrogen peroxide-stimulated cytokine production were suppressed by E2 and enhanced by progesterone. CONCLUSION:These findings suggest that E2 may play a favorable role in the course of persistent liver injury by preventing the accumulation of monocytes-macrophages and by inhibiting proinflammatory cytokine production, whereas progesterone may counteract the favorable E2 effects.展开更多
Progesterone is an efficient candidate for treating stroke and traumatic brain damage.The current study was designed to investigate the effects of pro gesterone on glucose transporter proteins(GLUT1 and GLUT3)during h...Progesterone is an efficient candidate for treating stroke and traumatic brain damage.The current study was designed to investigate the effects of pro gesterone on glucose transporter proteins(GLUT1 and GLUT3)during hypoxicischemic injury in a neo natal rat model.We demonstrated strong staining for GLUT1 in the walls of blood vessels and GLUT3 im munoreactivity in hippocampal neurons after hypoxia ischemia.Hypoxiaischemia elevated GLUT1 and GLUT3 at both the mRNA and protein levels in the hippocampus,and pretreatment with progesterone(8 mg/kg)further enhanced their accumulation until 24 h after hypoxicischemic injury.These results showed that progesterone treatment induced the accumula tion of both GLUT1 and GLUT3 transporters,and an energycompensation mechanism may be involved in the neuroprotective effect of progesterone during hy poxicischemic injury after cerebral ischemic attacks.展开更多
Distribution and accumulation of Nd, and its effect on secretion of progesterone in mice were studied using radioisotope tracer ((()^(147)Nd)) technique. Following single intraperitoneal administration of neodymium tr...Distribution and accumulation of Nd, and its effect on secretion of progesterone in mice were studied using radioisotope tracer ((()^(147)Nd)) technique. Following single intraperitoneal administration of neodymium traced with (()^(147)Nd) at a dose of 200 mg·kg^(-1), uneven distribution of the radioactive Nd occurred in various tissues and organs. Much amount of (()^(147)Nd) accumulates in the bone, and the residue increases with the lapse of time. Some amount of radioactivity was also detected in eyes, blood and brain, but the accumulation decreased with the time due to excretion and re-distribution in mice. In comparison with controls, concentration of progesterone is found to be significantly lower in the serum of administered mice, indicating a significantly inhibitory effect of Nd on secretion of progesterone.展开更多
Progesterone has nongenomic effects on inducible nitric oxide synthase(iNOS),which is mediated by mitogen activated protein kinase(MAPK)pathways.This effect is supposed to have some potential association with asymptom...Progesterone has nongenomic effects on inducible nitric oxide synthase(iNOS),which is mediated by mitogen activated protein kinase(MAPK)pathways.This effect is supposed to have some potential association with asymptomatic gonococcal infections in women by immunological depression.In this study,polymorphonuclear leukocytes(PMNs)challenged by gonococci were used to study the nongenomic effects of progesterone.The activation of iNOS was assessed by measuring [3H] L-arginine converses to [3H] L-citrulline,and t...展开更多
基金Supported by Health Science and Technology Programme Project of Inner Mongolia Autonomous Region Health and Health Commission(202201194)General Program of Inner Mongolia Medical University(YKD2023MS032)+2 种基金Innovation and Entrepreneurship Training Program for College Students of Inner Mongolia Medical University(202210132059)Natural Science Foundation of Inner Mongolia Autonomous Region(2022LHMS03001)Talent Introduction Project of Inner Mongolia Autonomous Region in 2020.
文摘[Objective]The paper was to study the effects of estradiol(E_(2))and progesterone(P4)on the expression of interleukin-1β(IL-1β)mRNA in lipopolysaccharide(LPS)-induced acute salpingitis in ovariectomized mice,and preliminarily explore the anti-inflammatory mechanism associated with estrogen and progesterone.[Method]Healthy female KM mice were randomly assigned to several groups:the sham operation group(LPS+SHAM),the ovarian removal group(LPS+OVX),the ovarian removal+estradiol group(LPS+OVX+E_(2)),the ovarian removal+progesterone group(LPS+OVX+P4),the LPS group and the control group(control).HE staining was conducted to assess the pathological changes in the fallopian tubes of each group.Additionally,the expression levels of IL-1βmRNA in the fallopian tubes of the mice were quantified using RT-qPCR.[Result]The histopathological changes in the fallopian tubes were examined.Estrogen and progesterone demonstrated a significant capacity to mitigate salpingitis induced by LPS.In comparison to the control group,the expression of IL-1βmRNA in the LPS group,LPS+SHAM group,and LPS+OVX+E_(2)group was significantly down-regulated(P<0.05).Furthermore,the expression of IL-1βmRNA in the LPS+OVX+P4 group exhibited an extremely significant down-regulation(P<0.01).When compared to the LPS+OVX group,the expression of IL-1βmRNA in the LPS+OVX+E_(2)group was significantly down-regulated(P<0.05),while the expression in the LPS+OVX+P4 group was extremely significantly down-regulated(P<0.01).[Conclusion]Estrogen and progesterone have the capacity to inhibit the expression of IL-1βmRNA in the inflammatory tissue of the fallopian tubes in mice,consequently diminishing the inflammatory response induced by LPS.
基金supported by the 2022 Traditional Chinese Medicine Scientific Research Special Project of Henan Province,China(2022ZY1048)2023 Traditional Chinese Medicine Scientific Research Special Project of Henan Province,China(2023YZ2043)General Program of Natural Science Foundation of Henan Province,China(232300421183).
文摘Objective This study aims to explore the correlation between traditional Chinese medicine(TCM)syndromes and the expression status of estrogen receptor(ER)and progesterone receptor(PR)in breast cancer patients before and after adjuvant chemotherapy.Methods A total of 222 breast cancer patients with consistent ER and PR expression scheduled to undergo adjuvant chemotherapy were classified according to TCM syndrome differentiation before and after chemotherapy.The data were analyzed using chi-square tests and binary logistic regression with SPSS 26.0 software,and compared with ER/PR expression results.Results(i)In the ER-positive/PR-positive group,compared with prechemotherapy,syndromes of spleen qi deficiency,spleen deficiency with dampness-phlegm,and spleen–kidney deficiency significantly increased during mid-chemotherapy and after chemotherapy.Compared with mid-chemotherapy,spleen yang deficiency syndrome significantly increased after chemotherapy,with statistical significance(p<0.05).(ii)In the ER-negative/PR-negative group,compared with prechemotherapy,syndromes of spleen qi deficiency and spleen deficiency with dampness-phlegm significantly increased during mid-chemotherapy,while spleen qi deficiency,spleen yang deficiency,and spleen–kidney deficiency significantly increased after chemotherapy.Compared with mid-chemotherapy,spleen–kidney deficiency and spleen yang deficiency syndromes significantly increased after chemotherapy,with statistical significance(p<0.05).(iii)The distribution of spleen qi deficiency syndrome during mid-chemotherapy and after chemotherapy was significantly higher in the ER-positive/PR-positive group than in the ER-negative/PR-negative group,with statistical significance(p<0.05).(iv)ER and PR were not independent influencing factors for the various syndrome types before and after adjuvant chemotherapy(p>0.05).Conclusion After chemotherapy initiation,syndromes of spleen qi deficiency,spleen yang deficiency,and spleen–kidney deficiency significantly increased in both ER-positive/PR-positive and ER-negative/PR-negative groups.The distribution of spleen qi deficiency during mid-chemotherapy and after chemotherapy was significantly higher in the ER-positive/PR-positive group than in the ER-negative/PR-negative group.ER and PR were not independent influencing factors for the syndrome types before and after adjuvant chemotherapy.
文摘Alzheimer’s disease(AD)is a neurological disorder characterized primarily by a progressive decline in cognitive and behavioral functions.The pathogenesis of AD has not been fully elucidated till now.The progesterone receptor(PR)family has recently attracted increasing attention and has become the focus of potential links to factors such as the pathogenesis and pathological changes of AD due to its role in the central nervous system.This article summarizes the progress of research progress on the PR family in AD,including its role in pathophysiology,molecular mechanisms,and potential therapeutic strategies.
基金This research was supported by Program for New Century Excellent Talents (NCET-07-0507)Shandong Province Natural Science Foundation (Z2008D01)+1 种基金Project of Science and Technology Development Plan in Shandong Province (2007GG2009011)Shandong Province Science Fund for Distinguished Young Scholars(2005BS02005, 2008BS09011)
文摘Understanding basic reproductive physiology is crucial for the management of both captive and free-ranging wolf. In the present study, we determined hormonal changes during pregnancy and the estrous cycle in captive female wolf by measuring fecal steroids collected during the breeding season with high performance liquid chromatography （HPLC）. These biochemical analyses were validated using chemical devivatization and mass spectrometry, and interpreted along with the behavioral data. All four females undergoing estrus cycles were copulated with their partners and delivered pups successfully. We found that estradiol concen-trations were significantly higher during the estrus cycle than other stages （p0.01） and progesterone was also significantly increased throughout the pregnancy （p0.01）. These hormonal fluctuations demonstrated pregnancy-specific changes in the fecal progesterone and estradiol con-centrations. Patterns of fecal estradiol and progesterone concentrations during estrous cycles were similar to those reported for other canids.
基金supported by Natural Sciences Fund of Zhejiang Province(grant number:LY14H040011)Subject of Zhejiang Provincial Administration of traditional Chinese Medicine(grant number:2013ZB058)
文摘Objective:To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.Methods:After pregnancy,50 SPF female SD rats were selected and divided into control group,model group,progesterone group,Zishen Yutai pill group,and progesterone plus Zishen Yutai pill group(combination group),with 10 rats in each group.The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days.Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days.Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin,continuous for 10 days.Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days,and other treatments were the same as previous two groups.Abortion model were established then and live births,numbers of abortion and average rate of abortion were compared between the five groups.Peripheral blood was collected to detect the estradiol(E2) and progestational hormone(P),and obtain ratio of Th1/Th2 cytokines(IL-2,INF-γ,IL-4,IL-10).Results:Significant more live births of rats were found in the control group compared with other four groups(P<0.05).The numbers of live births of the rats in abortion model group were significantly less than that of progesterone group,Zishen Yutai pill group and joint group(P<0.05).The numbers of live births of rats in joint group were significant more than that of progesterone group and Zishen Yutai pill group.The serum E2 level of P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were significant higher than that of abortion model group(P<0.05).Serum levels of E2 and P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were not significant different(P>0.05) but these levels in the control group and Zishen Yutai pill group were significant lower than that of progesterone group and joint group(P<0.05).The maternal-fetal interface IL-4/IL-2,IL-10 / IL-2 of model group were balanced deviating to Th1,while the IL-4/IL-2,IL-10/IL-2 of progesterone group,Zishen Yutai pill group and joint group were balanced deviating to Th2,and joint group' deviation was better than progesterone group and Zishen Yutai pill group(P<0.05).Conclusions:Zishen Yutai pill combined with progesterone has a significant control effect for threatened abortion,which can obviously increase contents of maternal serums E2 and P,and regulate the Thl/Th2 balance with a remarkable effect.
基金Chinese Developing Funds (provided by Taiwan)Scientific Initiating Grants of Shandong University
文摘AIM: To study the dose-dependent of progesterone (P) effect and the interaction between the oxytocin (OT) and P on gastrointestinal motility. METHODS: In order to monitor the gastric emptying and intestinal transit, the SD male rats were intubated via a catheter with normal saline (3 ml/kg) containing Na(2)(51)CrO(4) (0.5 microCi/ml) and 10% charcoal. OT was dissolved into normal saline and P was dissolved into 75% alcohol. RESULTS: Low does of P (1 mg/kg, i.p.) enhanced the gastric emptying (75+/-3%, P【0.05) and high dose of P (5 mg/kg, i.p.) inhibit it (42+/-11.2%, P【0.01). P (1 mg/kg) increased the intestinal transit (4.2+/-0.3, P【0.05) while the higher dose (10-20 mg/kg) had no effect. OT (0.8 mg/kg, i.p.) inhibited the gastric emptying (23.5+/-9.8%, P【0.01). The inhibitory effects of P(20 mg/kg) (32+/-9.7%, P【0.05) and OT (0.8 mg/kg) on gastric emptying enhanced each other when the two chemicals were administrated simultaneously (17+/-9.4%, P【0.01). CONCLUSION: Low dose of P increased GI motility while high dose of P decreased it. During the later period of pregnancy, elevated plasma level of OT may also participate in the gastrointestinal inhibition.
文摘Objective Traumatic brain injury （TBI） is one of the leading causes of morbidity and mortality in young people. Inflammatory cytokines play an important part in the pathophysiology of TBI. Recent studies demonstrate that progesterone significantly reduces cerebral edema and enhances functional recovery from TBI and stroke in several animal models. This study was designed to investigate the inhibitory effect of progesterone on inflammatory response after traumatic brain injury. Methods Progesterone was injected intraperitoneally using rats as a model of traumatic brain injury, and Western blot technique was applied to detect the expression of three inflammation-related factors： nuclear factor kappa B p65 （NFκB p65）, glial fibrillary acidic protein （GFAP）, and tumor necrosis factor-α （TNF-α）. The water content of injured brain was also examined. A neurological severity score was recorded to evaluate the effect of progesterone on neurodeficit recovery. Results NFκB p65, GFAP, and TNF-α were increased in all injured animals. In rats treated with progesterone, the expression level of NFκB p65 and TNF-α were reduced significantly in comparison with vehicle-treated rats. However, progesterone did not alter the expression of GFAP in the injured rats. Progesterone also reduced the water content of injured brain and the lesion volume. In addition, progesterone-treated injured rats showed significant improvements in the Neurological Severity Score test, compared with vehicle-treated ones. Conclusions Progesterone inhibits the inflammatory response after experimental traumatic brain injury and mitigates the severity of brain damage.
基金Supported by the Ministry of Science and Technology,No.NSC102-2320-B-006-011.,No.MOST103-2320-B-006-021-MY2,and No.MOST105-2320-B-006-033 to Tsai HWNational Cheng Kung University Hospital,Taiwan,No.NCKUH-10406002 and No.NCKUH-10509001 to Tsai HW
文摘AIM To investigate the clinicopathological significance of progesterone receptor membrane component 1(PGRMC1) and PGRMC2 in hepatocellular carcinoma(HCC). METHODS We performed immunohistochemical staining to evaluate the estrogen receptor(ER), progesterone receptor(PR), PGRMC1, and PGRMC2 in a clinical cohort consisting of 89 paired HCC and non-tumor liver samples. We also analyzed HCC data(n = 373) from The Cancer Genome Atlas(TCGA). We correlated the expression status of PGRMC1 and PGRMC2 with clinicopathological indicators and the clinical outcomes of the HCC patients. We knocked down or overexpressed PGRMC1 in HCC cell lines to evaluate its biological significance in HCC cell proliferation, differentiation, migration, and invasion. RESULTS We found that few HCC cases expressed ER(5.6%) and PR(4.5%). In contrast, most HCC cases expressed PGRMC1(89.9%) and PGRMC2(100%). PGRMC1 and PGRMC2 exhibited significantly lower expression in tumor tissue than in non-tumor tissue(P < 0.001). Lower PGRMC1 expression in HCC was significantly associated with higher serum alpha-fetoprotein expression(P = 0.004), poorer tumor differentiation(P = 0.045) and liver capsule penetration(P = 0.038). Low PGRMC1 expression was an independent predictor for worse disease-free survival(P = 0.002, HR = 2.384,CI: 1.377-4.128) in our cases, as well as in the TCGA cohort(P < 0.001, HR = 2.857, CI: 1.781-4.584). The expression of PGRMC2 did not relate to patient outcome. PGRMC1 knockdown promoted a poorly differentiated phenotype and proliferation of HCC cells in vitro, while PGRMC1 overexpression caused the opposite effects.CONCLUSION PGRMC1 is a non-classical hormonal receptor that negatively regulates hepatocarcinogenesis. PGRMC1 down-regulation is associated with progression of HCC and is a poor prognostic indicator.
基金supported by the Military Medical Research Program during the 12th Five-Year Plan Period, No.BWS11J002
文摘In this study, human umbilical cord mesenchymal stem cells from full-term neonates born by vagina delivery were cultured in medium containing 150 mg/mL of brain tissue extracts from Sprague-Dawley rats （to mimic the brain microenvironment）. Immunocytochemical analysis demonstrated that the cells differentiated into neuron-like cells. To evaluate the effects of progesterone as a neurosteroid on the neuronal differentiation of human umbilical cord mesenchymal stem cells, we cultured the cells in medium containing progesterone （0.1, 1, 10 pM） in addition to brain tissue extracts. Reverse transcription-PCR and flow cytometric analysis of neuron specific enolase-positive cells revealed that the percentages of these cells increased significantly following progesterone treatment, with the optimal progesterone concentration for neuron-like differentiation being 1 tJM. These results suggest that progesterone can enhance the neuronal differentiation of human umbilical cord mesenchymal stem cells in culture medium containing brain tissue extracts to mimic the brain microenvironment.
文摘There are currently no federally approved neuroprotective agents to treat traumatic brain injury. Progesterone, a hydrophobic steroid hormone, has been shown in recent studies to exhibit neu-roprotective effects in controlled cortical impact rat models. Akt is a protein kinase known to play a role in cell signaling pathways that reduce edema, inlfammation, apoptosis, and promote cell growth in the brain. This study aims to determine if progesterone modulates the phosphor-ylation of Aktvia its threonine 308 phosphorylation site. Phosphorylation at the threonine 308 site is one of several sites responsible for activating Akt and enabling the protein kinase to carry out its neuroprotective effects. To assess the effects of progesterone on Akt phosphorylation, C57BL/6 mice were treated with progesterone （8 mg/kg） at 1 （intraperitonally）, 6, 24, and 48 hours （subcutaneously） post closed-skull traumatic brain injury. The hippocampus was harvest-ed at 72 hours post injury and prepared for western blot analysis. Traumatic brain injury caused a signiifcant decrease in Akt phosphorylation compared to sham operation. However, mice treat-ed with progesterone following traumatic brain injury had an increase in phosphorylation of Akt compared to traumatic brain injury vehicle. Our ifndings suggest that progesterone is a viable treatment option for activating neuroprotective pathways after traumatic brain injury.
文摘AIM:To investigate the effects of estradiol (E2) and progesterone on the unstimulated and oxidative stressstimulated production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, and macrophage chemotactic protein (MCP)-1 by peripheral blood mononuclear cells (PBMCs) from patients with chronic hepatitis C and healthy controls. METHODS:The PBMCs were separated from agematched 72 males and 71 females with and without chronic hepatitis C, who were divided into two groups based on a mean menopausal age of 50 years. Oxidative stress was induced by hydrogen peroxide in the cells incubated in serum-free media. Cytokines in the culture supernatant were measured by an enzyme-linked immunosorbent assay. RESULTS:The highest levels of the spontaneous production of TNF-α, IL-1β, IL-8, and MCP-1 by the unstimulated PBMCs were in the older male patients with chronic hepatitis C and the lowest levels were in the premenopausal female healthy controls. E2 inhibited the cytokine production by the unstimulated PBMCs from the older male and post-menopausal female patients, which was further stimulated by progesterone. The exposure to hydrogen peroxide in the PBMCs from the younger male and pre-menopausal female healthy subjects induced the production of cytokines. The change rates of the hydrogen peroxide-stimulated cytokine production were suppressed by E2 and enhanced by progesterone. CONCLUSION:These findings suggest that E2 may play a favorable role in the course of persistent liver injury by preventing the accumulation of monocytes-macrophages and by inhibiting proinflammatory cytokine production, whereas progesterone may counteract the favorable E2 effects.
基金supported by the National Natural Science Foundation of China(81100912)the Science Foundation of Xinxiang Medical University,China(CL and ZD 2009-63)the Science and Technology Project of Henan Province,China(092102310098)
文摘Progesterone is an efficient candidate for treating stroke and traumatic brain damage.The current study was designed to investigate the effects of pro gesterone on glucose transporter proteins(GLUT1 and GLUT3)during hypoxicischemic injury in a neo natal rat model.We demonstrated strong staining for GLUT1 in the walls of blood vessels and GLUT3 im munoreactivity in hippocampal neurons after hypoxia ischemia.Hypoxiaischemia elevated GLUT1 and GLUT3 at both the mRNA and protein levels in the hippocampus,and pretreatment with progesterone(8 mg/kg)further enhanced their accumulation until 24 h after hypoxicischemic injury.These results showed that progesterone treatment induced the accumula tion of both GLUT1 and GLUT3 transporters,and an energycompensation mechanism may be involved in the neuroprotective effect of progesterone during hy poxicischemic injury after cerebral ischemic attacks.
文摘Distribution and accumulation of Nd, and its effect on secretion of progesterone in mice were studied using radioisotope tracer ((()^(147)Nd)) technique. Following single intraperitoneal administration of neodymium traced with (()^(147)Nd) at a dose of 200 mg·kg^(-1), uneven distribution of the radioactive Nd occurred in various tissues and organs. Much amount of (()^(147)Nd) accumulates in the bone, and the residue increases with the lapse of time. Some amount of radioactivity was also detected in eyes, blood and brain, but the accumulation decreased with the time due to excretion and re-distribution in mice. In comparison with controls, concentration of progesterone is found to be significantly lower in the serum of administered mice, indicating a significantly inhibitory effect of Nd on secretion of progesterone.
基金supported by the Young Scientists Fund Program of National Natural Science Fund Program from National Natural Sciences Foundation of China(No.30371293)Medical Research Foundation of Guangdong Province of China(No.B2009193)
文摘Progesterone has nongenomic effects on inducible nitric oxide synthase(iNOS),which is mediated by mitogen activated protein kinase(MAPK)pathways.This effect is supposed to have some potential association with asymptomatic gonococcal infections in women by immunological depression.In this study,polymorphonuclear leukocytes(PMNs)challenged by gonococci were used to study the nongenomic effects of progesterone.The activation of iNOS was assessed by measuring [3H] L-arginine converses to [3H] L-citrulline,and t...
