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
Background:Administration of progesterone(P4)to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy,likely due to P4-induced up-regulation of key genes in uterine ...Background:Administration of progesterone(P4)to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy,likely due to P4-induced up-regulation of key genes in uterine epithelia responsible for secretion and transport of components of histotroph into the uterine lumen.This study determined if acceleration of blastocyst development induced by exogenous P4 during the pre-implantation period affects fetal-placental development on day 125 of pregnancy.Suffolk ewes(n=35)were mated to fertile rams and assigned randomly to receive daily intramuscular injections of either corn oil vehicle(CO,n=18)or 25 mg progesterone in CO(P4,n=17)for the first 8 days of pregnancy.All ewes were hysterectomized on day 125 of pregnancy and:1)fetal and placental weights and measurements were recorded;2)endometrial and placental tissues were analyzed for the expression of candidate mRNAs involved in nutrient transport and arginine metabolism;and 3)maternal plasma,fetal plasma,allantoic fluid,and amniotic fluid were analyzed for amino acids,agmatine,polyamines,glucose,and fructose.Results:Treatment of ewes with exogenous P4 did not alter fetal or placental growth,but increased amounts of aspartate and arginine in allantoic fluid and amniotic fluid,respectively.Ewes that received exogenous P4 had greater expression of mRNAs for SLC7A1,SLC7A2,SLC2A1,AGMAT,and ODC1 in endometria,as well as SLC1A4,SLC2A5,SLC2A8 and ODC1 in placentomes.In addition,AZIN2 protein was immunolocalized to uterine luminal and glandular epithelia in P4-treated ewes,whereas AZIN2 localized only to uterine luminal epithelia in CO-treated ewes.Conclusions:This study revealed that exogenous P4 administered in early pregnancy influenced expression of selected genes for nutrient transporters and the expression of a protein involved in polyamine synthesis on day 125 of pregnancy,suggesting a‘programming’effect of P4 on gene expression that affected the composition of nutrients in fetal-placental fluids.展开更多
There is currently no standard pharmacological treatment for spinal cord injury. Here, we suggest that progesterone, a steroid hormone, may be a promising therapeutical candidate as it is already for traumatic brain i...There is currently no standard pharmacological treatment for spinal cord injury. Here, we suggest that progesterone, a steroid hormone, may be a promising therapeutical candidate as it is already for traumatic brain injury, where it has reached phase II clinical trials. We rely on previous works showing anti-inflammatory, neuroprotective and promyelinating roles for progesterone after spinal cord injury and in our recent paper, in which we demonstrate that progesterone diminishes lesion, preserves white matter integrity and improves locomotor recovery in a clinically relevant model of spinal cord lesion.展开更多
Background:Administration of exogenous progesterone(P4)to ewes during the pre-implantation period advances conceptus development and implantation.This study determined effects of exogenous P4 on transport of select nu...Background:Administration of exogenous progesterone(P4)to ewes during the pre-implantation period advances conceptus development and implantation.This study determined effects of exogenous P4 on transport of select nutrients and pathways that enhance conceptus development.Pregnant ewes(n=38)were treated with either 25 mg P4 in 1 mL corn oil(P4,n=18)or 1mL corn oil alone(CO,n=20)from day 1.5 through day 8 of pregnancy and hysterectomized on either day 9 or day 12 of pregnancy.Endometrial expression of genes encoding enzymes for synthesis of polyamines,transporters of glucose,arginine,and glycine,as well as progestamedins was determined by RT-qPCR.Results:On day 12 of pregnancy,conceptuses from P4-treated ewes had elongated while those from CO-treated ewes were spherical.The mRNA expression of AZIN2,an arginine decarboxylase,was lower in endometria of P4-treated than CO-treated ewes on day 9 of pregnancy.Expression of FGF10,a progestamedin,was greater in endometria of CO and P4-treated ewes on day 12 of gestation in addition to P4-treated ewes necropsied on day 9 of gestation.Treatment with P4 down-regulated endometrial expression of amino acid transporter SLC1A4 on day 12 of pregnancy.Conclusions:Results indicated that administration of exogenous P4 during the pre-implantation period advanced the expression of FGF10,which may accelerate proliferation of trophectoderm cells,but also was correlated with decreased expression of glycine and serine transporters and polyamine synthesis enzyme AZIN2.Further research with increased sample sizes may determine how differential expression affects endometrial functions and potentially embryonic loss.展开更多
Objective: To determine effects of variations of heart girth, volume trait on embryo quality grade, and to explore the relationship between heart girth and circulating progesterone and correlations of circulating prog...Objective: To determine effects of variations of heart girth, volume trait on embryo quality grade, and to explore the relationship between heart girth and circulating progesterone and correlations of circulating progesterone with embryo quality grade in superstimulated donor Holstein cows. Methods: Nineteen cows were subjected to a standard superstimulation protocol using follicle stimulating hormone. Blood samples were collected before superovulation, at insemination and at collection of embryos for progesterone analysis. Embryo quality grades were compared between high and low heart girth donors. Moreover, Pearson's correlations were determined between heart girth, progesterone and embryo quality. Results: Variation of heart girth was not associated with significant differences in embryo quality grade between high and low heart girth donor cows (P>0.05). However, we observed a significantly higher percentage of the third-grade embryo (24.09%) in low heart girth donors compared to 9.64% in high heart girth donors. Moreover, the percentage of the transferable embryo was numerically higher and that of the degenerated embryo was numerically lower in low heart girth cows. Donor cows with low response to superovulation (total structures ≤ 3) expressed numerically higher mean heart girth, compared to donors with high (total structures>15) and medium (total structures = 4-15) superovulation. Heart girth and body weight of donor cows were moderately correlated (r=0.45, P<0.05), but none was correlated with circulating progesterone at different sampling times except for a moderate correlation between body weight and progesterone at embryo collection (r=0.54, P=0.02). Circulating progesterone before superovulation was moderately correlated to the second-grade embryo (r=0.46, P<0.05) and to the third grade (r=0.52, P<0.05) embryo. Conclusions: Volume traits heart girth may influence the response of Holstein cows to superovulation;however, future studies with a higher number of cows are warranted to clarify significant influences.展开更多
We previously investigated the progesterone metabolite 5β-dihydroprogesterone (5βDHP) in relation to human parturition at term, demonstrating that peripheral venous concentrations decrease in association with the on...We previously investigated the progesterone metabolite 5β-dihydroprogesterone (5βDHP) in relation to human parturition at term, demonstrating that peripheral venous concentrations decrease in association with the onset of spontaneous labour. In this study our aim was to determine if 5βDHP concentrations were lower in women presenting in spontaneous preterm labour than in controls matched for gestational age. Blood samples were obtained from women presenting in spontaneous preterm labour (n = 20). The diagnosis was made on the presence of regular contractions and cervical effacement and dilatation of at least 3 cms. All women in the preterm labour group delivered before 37 weeks gestation. Blood samples were then obtained from controls, closely matched for gestational age with uncomplicated pregnancies. The preterm labour group was further stratified by cause into three groups, chorioamnionitis (n = 5), abruption (n = 4) and idiopathic (n = 11). Following organic solvent extraction, steroids were separated by HPLC and 5βDHP quantified by radioimmunoassay. Women in the idiopathic preterm labour group were found to have significantly lower circulating concentrations of 5βDHP than controls展开更多
Direct photochemical degradations of progesterone (PR) and testosterone (TR), two naturally produced hormones, have been conducted in non-buffered aqueous solution (pH ranging between 5.5 and 6.0). The irradiation exp...Direct photochemical degradations of progesterone (PR) and testosterone (TR), two naturally produced hormones, have been conducted in non-buffered aqueous solution (pH ranging between 5.5 and 6.0). The irradiation experiments were carried out in a batch reactor upon monochromatic (254 nm) and polychromatic (λ > 290 nm) at 25°C. GLC/MS and LC/UV-DAD/MS analyses were performed to investigate phototransformation products after a solid phase extraction (SPE) step for analytes concentration. For each compound several by-products have been identified and are the same ones under both irradiation conditions. Because of the presence of the same chromophore (α, β-unsaturated group) absorbing UV radiations in both hormones, the majority of chromatographic peaks correspond to by-products formed according to identical mechanisms involving isomerization, enolization, oxidation and hydration to lead to the generation of lumiketone, cyclopentenone, spiro-hydration, oxidation and hydroxylation photoproducts.展开更多
Effects of forskolin on progesterone and plasminogen activator production in pseudopregnant ratcorpora lutea was investigated using isolated in vitro perfused ovaries.Progesterone andplasminogen activator production w...Effects of forskolin on progesterone and plasminogen activator production in pseudopregnant ratcorpora lutea was investigated using isolated in vitro perfused ovaries.Progesterone andplasminogen activator production were measured on day 1,8 and 18 of hCG-inducedpseudopregnancy.The results indicated:different concentrations of forskolin(100,200,400 and800 μg)administered to ovaries on the 8th day of pseudopregnancy caused elevation of progesteronesecretion in a dose-dependent manner.After 8 hours of perfusion,PA contents increasedsignificantly in ovaries treated with forskolin.With exogenous PA-urokinase(800 U)added to theperfusion solution,progesterone secretion increased significantly as compared to control group andremained on high level throughout the perfusion period.Though exerting no apparent effects in lowdosage(5 mM),AMCHA,a PA inhibitor,administered in higher dosage(10 and 15 mM)led tomarked reduction in PA activity and progesterone secretion as compared to control group.Thusforskolin causes significant elevation of level of progesterone secretion and PA activity inpseudopregnant rat ovary perfused in vitro.And PA seems to regulate progesterone secretion in theperfused rat corpora luteum.展开更多
[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: Progesterone (P4) is the optimal agent for luteal support in assisted reproductive technologies. Despite the availability of various formulations, the impacts of P4 treatment administered through different ...Objective: Progesterone (P4) is the optimal agent for luteal support in assisted reproductive technologies. Despite the availability of various formulations, the impacts of P4 treatment administered through different routes on offspring growth remain unevaluated. This study aimed to investigate and compare the effects of P4 administration through three different routes in pregnant rats during the teratogenesis-sensitive period on fertility outcomes and the behavior, plasma P4 and pregnenolone levels, and alterations in gut microbiota in the filial generation (F1) of offspring.Methods: Female rats that mated successfully were randomly classified into four groups: Group 1, the normal control group;Group 2, the IG group, in which utrogestan was administeredvia intragastric gavage;Group 3, the IM group, in which P4 was administeredvia intramuscular injection;and Group 4, the VAGIN group, in which P4 sustained-release vaginal gel was administered through the vagina. Except for the control group, P4 was administered in other groups through their respective routes for 13 consecutive days daily during the teratogenic-sensitive gestation period (days 6–18). The fertility outcomes of the maternal rats were observed, and open-field and three-chamber social preference tests were conducted to assess anxiety and social behavior, along with an exhaustive swimming experiment to evaluate the motor endurance of the offspring. Plasma P4 and pregnenolone levels in the offspring were measured, and fecal samples were assessed using gut microbiota sequencing and subsequent bioinformatics analysis.Results: No significant alterations in fertility outcomes were observed through three P4 administration routes-intragastric gavage, intramuscular injection, and vaginal administration-in rats. However, in behavioral experiments in offspring, a significant increase was observed in swimming time in the IG group than in the control group (P = 0.013). Furthermore, the offspring in the IG group exhibited a marked decrease in non-social behaviors compared with the control group (P = 0.030). No significant behavioral changes were observed in the F1 offspring in the open-field test. Additionally, the offspring in the IG group exhibited a significant elevation in plasma pregnenolone levels compared with the control group (P = 0.019) 30 days after birth. No notable differences in the α-diversity of gut microbiota were observed among the groups. However, significant differences in β-diversity were observed in both the IG and IM groups compared with the control group, indicating that P4 treatmentvia the two routes exhibited a significant impact on the gut microbiota composition of F1 offspring. Distinct differences were observed in the gut microbiota of the offspring among the three P4 treatment groups, with 22, 28, and 33 differential bacterial taxa identified in the IG, IM, and VAGIN groups, respectively, using linear discriminant effect size analysis, whereasOlivella appeared exclusively in the control group rather than in the P4 treatment groups.Conclusion: Oral administration of P4 to maternal rats during the teratogenesis-sensitive period enhanced motor endurance and plasma pregnenolone levels and altered the composition of the gut microbiota in the offspring. Our findings demonstrated different effects on offspring growth when P4 is administered orally, intramuscularly, or vaginally.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
Objective: To explore the effect of traditional Chinese medicine (TCM) on abnormalmaternal-fetal immune and endocrine in 24cases of threatened abortion (TA) and 68 cases of recurrent spontaneous abortion (RSA).Methods...Objective: To explore the effect of traditional Chinese medicine (TCM) on abnormalmaternal-fetal immune and endocrine in 24cases of threatened abortion (TA) and 68 cases of recurrent spontaneous abortion (RSA).Methods: The levels of blocking effect (BE),antiidiotype antibody (AIA), cytotoxin antibody (CTA), β-human chorionic gonadotropin(β-hCG), progesterone (P), estradiol (E2)were measured in all 92 patients. Results: Incidence rates of the lack of BE, AIA and CTAin 92 cases were 60. 87%, 57. 61 % and 72.83% respectively. The lower levels of BE,AIA and CTA were elevated significantly (P< 0. 05 ～0. 01 ), and the serial levels β- hCG, P and E2 were markedly increasing (P< 0. 01 ) in all successful pregnant patients.The rate of the successful pregnancy of 92 cases was 89. 13 % (to TA 91. 67%, to RSA 88.24 % respectively). Conclusions: It suggeststhat the lack of blocking antibody (BA) andendocrine hormone deficiency may result inspontaneous abortion during early pregnancy.The therapeutic mechanism of those herbs intreating spontaneous abortion was associatedwith the growing levels of BA and hormone byregulating the maternal-fetal immunity and endocrine.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： To study the clinical effects of Prescription Zhuyun-Ⅲ （助孕3号方, ZYⅢ） on early pregnant women diagnosed as threatened abortion, and its mechanism in immunity and endocrine by determining serum Th1- a...Objective： To study the clinical effects of Prescription Zhuyun-Ⅲ （助孕3号方, ZYⅢ） on early pregnant women diagnosed as threatened abortion, and its mechanism in immunity and endocrine by determining serum Th1- and Th2-type cytokines, progesterone, and β-human chorionic gonadotropin （β-HCG）. Methods： The treatment group comprised 30 early pregnant women diagnosed as threatened abortion of deficiency syndrome of Pi （脾）, Shen （肾）, or both. The control group consisted of 20 normal early pregnant women of similar gestational age. Patients in the treatment group were administered with ZYⅢ for 4 weeks. Peripheral blood samples were collected pre- and post-treatment from both the treatment and the control groups. Serum Thl-type cytokine [interleukin-2 （IL-2）] and Th2-type cytokine [interleukin-10 （IL-10）] were determined by flow cytometry, and serum progesterone and 13-HCG were determined by ELISA. Results： （1） The treatment was effective in 26 and ineffective in 4 patients of the treatment group. Therefore, the cure percentage was 86.67%. （2） In the treatment group before the treatment, IL-2 was significantly higher, IL-10 tended to be less, and the Th1/Th2 balance shifted toward Thl compared with those in the control group. （3） After the treatment, IL-2 was decreased, IL-10 was increased, and IL-2/IL-10 was decreased. Both progesterone and β-HCG were increased. Changes of progesterone were positively correlated with changes of IL-10, whereas changes of β-HCG were negatively correlated with changes of IL-2. Conclusions： Our study suggests that ZYⅢ has an evident function of protecting the fetus, and one of its mechanisms is inhibiting the secretion of Thl cytokines, promoting the secretion of Th2 cytokines, and recovering the pathological shift of the Th1/Th2 balance. The other possible mechanism is increasing serum progesterone and β-HCG concentrations. Moreover, there are some correlations between the above two effects.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
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
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This research was supported by Agriculture and Food Research Initiative Competitive Grant no.2016-67015-24958 from the USDA National Institute of Food and AgricultureThis research was supported by Agriculture and Food Research Initiative Competitive Grant no.2016-67015-24958 from the USDA National Institute of Food and Agriculture.
文摘Background:Administration of progesterone(P4)to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy,likely due to P4-induced up-regulation of key genes in uterine epithelia responsible for secretion and transport of components of histotroph into the uterine lumen.This study determined if acceleration of blastocyst development induced by exogenous P4 during the pre-implantation period affects fetal-placental development on day 125 of pregnancy.Suffolk ewes(n=35)were mated to fertile rams and assigned randomly to receive daily intramuscular injections of either corn oil vehicle(CO,n=18)or 25 mg progesterone in CO(P4,n=17)for the first 8 days of pregnancy.All ewes were hysterectomized on day 125 of pregnancy and:1)fetal and placental weights and measurements were recorded;2)endometrial and placental tissues were analyzed for the expression of candidate mRNAs involved in nutrient transport and arginine metabolism;and 3)maternal plasma,fetal plasma,allantoic fluid,and amniotic fluid were analyzed for amino acids,agmatine,polyamines,glucose,and fructose.Results:Treatment of ewes with exogenous P4 did not alter fetal or placental growth,but increased amounts of aspartate and arginine in allantoic fluid and amniotic fluid,respectively.Ewes that received exogenous P4 had greater expression of mRNAs for SLC7A1,SLC7A2,SLC2A1,AGMAT,and ODC1 in endometria,as well as SLC1A4,SLC2A5,SLC2A8 and ODC1 in placentomes.In addition,AZIN2 protein was immunolocalized to uterine luminal and glandular epithelia in P4-treated ewes,whereas AZIN2 localized only to uterine luminal epithelia in CO-treated ewes.Conclusions:This study revealed that exogenous P4 administered in early pregnancy influenced expression of selected genes for nutrient transporters and the expression of a protein involved in polyamine synthesis on day 125 of pregnancy,suggesting a‘programming’effect of P4 on gene expression that affected the composition of nutrients in fetal-placental fluids.
文摘There is currently no standard pharmacological treatment for spinal cord injury. Here, we suggest that progesterone, a steroid hormone, may be a promising therapeutical candidate as it is already for traumatic brain injury, where it has reached phase II clinical trials. We rely on previous works showing anti-inflammatory, neuroprotective and promyelinating roles for progesterone after spinal cord injury and in our recent paper, in which we demonstrate that progesterone diminishes lesion, preserves white matter integrity and improves locomotor recovery in a clinically relevant model of spinal cord lesion.
基金This research was supported by Agriculture and Food Research Initiative Competitive Grant no.2016-67015-24958 from the USDA National Institute of Food and Agriculture。
文摘Background:Administration of exogenous progesterone(P4)to ewes during the pre-implantation period advances conceptus development and implantation.This study determined effects of exogenous P4 on transport of select nutrients and pathways that enhance conceptus development.Pregnant ewes(n=38)were treated with either 25 mg P4 in 1 mL corn oil(P4,n=18)or 1mL corn oil alone(CO,n=20)from day 1.5 through day 8 of pregnancy and hysterectomized on either day 9 or day 12 of pregnancy.Endometrial expression of genes encoding enzymes for synthesis of polyamines,transporters of glucose,arginine,and glycine,as well as progestamedins was determined by RT-qPCR.Results:On day 12 of pregnancy,conceptuses from P4-treated ewes had elongated while those from CO-treated ewes were spherical.The mRNA expression of AZIN2,an arginine decarboxylase,was lower in endometria of P4-treated than CO-treated ewes on day 9 of pregnancy.Expression of FGF10,a progestamedin,was greater in endometria of CO and P4-treated ewes on day 12 of gestation in addition to P4-treated ewes necropsied on day 9 of gestation.Treatment with P4 down-regulated endometrial expression of amino acid transporter SLC1A4 on day 12 of pregnancy.Conclusions:Results indicated that administration of exogenous P4 during the pre-implantation period advanced the expression of FGF10,which may accelerate proliferation of trophectoderm cells,but also was correlated with decreased expression of glycine and serine transporters and polyamine synthesis enzyme AZIN2.Further research with increased sample sizes may determine how differential expression affects endometrial functions and potentially embryonic loss.
文摘Objective: To determine effects of variations of heart girth, volume trait on embryo quality grade, and to explore the relationship between heart girth and circulating progesterone and correlations of circulating progesterone with embryo quality grade in superstimulated donor Holstein cows. Methods: Nineteen cows were subjected to a standard superstimulation protocol using follicle stimulating hormone. Blood samples were collected before superovulation, at insemination and at collection of embryos for progesterone analysis. Embryo quality grades were compared between high and low heart girth donors. Moreover, Pearson's correlations were determined between heart girth, progesterone and embryo quality. Results: Variation of heart girth was not associated with significant differences in embryo quality grade between high and low heart girth donor cows (P>0.05). However, we observed a significantly higher percentage of the third-grade embryo (24.09%) in low heart girth donors compared to 9.64% in high heart girth donors. Moreover, the percentage of the transferable embryo was numerically higher and that of the degenerated embryo was numerically lower in low heart girth cows. Donor cows with low response to superovulation (total structures ≤ 3) expressed numerically higher mean heart girth, compared to donors with high (total structures>15) and medium (total structures = 4-15) superovulation. Heart girth and body weight of donor cows were moderately correlated (r=0.45, P<0.05), but none was correlated with circulating progesterone at different sampling times except for a moderate correlation between body weight and progesterone at embryo collection (r=0.54, P=0.02). Circulating progesterone before superovulation was moderately correlated to the second-grade embryo (r=0.46, P<0.05) and to the third grade (r=0.52, P<0.05) embryo. Conclusions: Volume traits heart girth may influence the response of Holstein cows to superovulation;however, future studies with a higher number of cows are warranted to clarify significant influences.
文摘We previously investigated the progesterone metabolite 5β-dihydroprogesterone (5βDHP) in relation to human parturition at term, demonstrating that peripheral venous concentrations decrease in association with the onset of spontaneous labour. In this study our aim was to determine if 5βDHP concentrations were lower in women presenting in spontaneous preterm labour than in controls matched for gestational age. Blood samples were obtained from women presenting in spontaneous preterm labour (n = 20). The diagnosis was made on the presence of regular contractions and cervical effacement and dilatation of at least 3 cms. All women in the preterm labour group delivered before 37 weeks gestation. Blood samples were then obtained from controls, closely matched for gestational age with uncomplicated pregnancies. The preterm labour group was further stratified by cause into three groups, chorioamnionitis (n = 5), abruption (n = 4) and idiopathic (n = 11). Following organic solvent extraction, steroids were separated by HPLC and 5βDHP quantified by radioimmunoassay. Women in the idiopathic preterm labour group were found to have significantly lower circulating concentrations of 5βDHP than controls
文摘Direct photochemical degradations of progesterone (PR) and testosterone (TR), two naturally produced hormones, have been conducted in non-buffered aqueous solution (pH ranging between 5.5 and 6.0). The irradiation experiments were carried out in a batch reactor upon monochromatic (254 nm) and polychromatic (λ > 290 nm) at 25°C. GLC/MS and LC/UV-DAD/MS analyses were performed to investigate phototransformation products after a solid phase extraction (SPE) step for analytes concentration. For each compound several by-products have been identified and are the same ones under both irradiation conditions. Because of the presence of the same chromophore (α, β-unsaturated group) absorbing UV radiations in both hormones, the majority of chromatographic peaks correspond to by-products formed according to identical mechanisms involving isomerization, enolization, oxidation and hydration to lead to the generation of lumiketone, cyclopentenone, spiro-hydration, oxidation and hydroxylation photoproducts.
文摘Effects of forskolin on progesterone and plasminogen activator production in pseudopregnant ratcorpora lutea was investigated using isolated in vitro perfused ovaries.Progesterone andplasminogen activator production were measured on day 1,8 and 18 of hCG-inducedpseudopregnancy.The results indicated:different concentrations of forskolin(100,200,400 and800 μg)administered to ovaries on the 8th day of pseudopregnancy caused elevation of progesteronesecretion in a dose-dependent manner.After 8 hours of perfusion,PA contents increasedsignificantly in ovaries treated with forskolin.With exogenous PA-urokinase(800 U)added to theperfusion solution,progesterone secretion increased significantly as compared to control group andremained on high level throughout the perfusion period.Though exerting no apparent effects in lowdosage(5 mM),AMCHA,a PA inhibitor,administered in higher dosage(10 and 15 mM)led tomarked reduction in PA activity and progesterone secretion as compared to control group.Thusforskolin causes significant elevation of level of progesterone secretion and PA activity inpseudopregnant rat ovary perfused in vitro.And PA seems to regulate progesterone secretion in theperfused rat corpora luteum.
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.
文摘Objective: Progesterone (P4) is the optimal agent for luteal support in assisted reproductive technologies. Despite the availability of various formulations, the impacts of P4 treatment administered through different routes on offspring growth remain unevaluated. This study aimed to investigate and compare the effects of P4 administration through three different routes in pregnant rats during the teratogenesis-sensitive period on fertility outcomes and the behavior, plasma P4 and pregnenolone levels, and alterations in gut microbiota in the filial generation (F1) of offspring.Methods: Female rats that mated successfully were randomly classified into four groups: Group 1, the normal control group;Group 2, the IG group, in which utrogestan was administeredvia intragastric gavage;Group 3, the IM group, in which P4 was administeredvia intramuscular injection;and Group 4, the VAGIN group, in which P4 sustained-release vaginal gel was administered through the vagina. Except for the control group, P4 was administered in other groups through their respective routes for 13 consecutive days daily during the teratogenic-sensitive gestation period (days 6–18). The fertility outcomes of the maternal rats were observed, and open-field and three-chamber social preference tests were conducted to assess anxiety and social behavior, along with an exhaustive swimming experiment to evaluate the motor endurance of the offspring. Plasma P4 and pregnenolone levels in the offspring were measured, and fecal samples were assessed using gut microbiota sequencing and subsequent bioinformatics analysis.Results: No significant alterations in fertility outcomes were observed through three P4 administration routes-intragastric gavage, intramuscular injection, and vaginal administration-in rats. However, in behavioral experiments in offspring, a significant increase was observed in swimming time in the IG group than in the control group (P = 0.013). Furthermore, the offspring in the IG group exhibited a marked decrease in non-social behaviors compared with the control group (P = 0.030). No significant behavioral changes were observed in the F1 offspring in the open-field test. Additionally, the offspring in the IG group exhibited a significant elevation in plasma pregnenolone levels compared with the control group (P = 0.019) 30 days after birth. No notable differences in the α-diversity of gut microbiota were observed among the groups. However, significant differences in β-diversity were observed in both the IG and IM groups compared with the control group, indicating that P4 treatmentvia the two routes exhibited a significant impact on the gut microbiota composition of F1 offspring. Distinct differences were observed in the gut microbiota of the offspring among the three P4 treatment groups, with 22, 28, and 33 differential bacterial taxa identified in the IG, IM, and VAGIN groups, respectively, using linear discriminant effect size analysis, whereasOlivella appeared exclusively in the control group rather than in the P4 treatment groups.Conclusion: Oral administration of P4 to maternal rats during the teratogenesis-sensitive period enhanced motor endurance and plasma pregnenolone levels and altered the composition of the gut microbiota in the offspring. Our findings demonstrated different effects on offspring growth when P4 is administered orally, intramuscularly, or vaginally.
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.
文摘Objective: To explore the effect of traditional Chinese medicine (TCM) on abnormalmaternal-fetal immune and endocrine in 24cases of threatened abortion (TA) and 68 cases of recurrent spontaneous abortion (RSA).Methods: The levels of blocking effect (BE),antiidiotype antibody (AIA), cytotoxin antibody (CTA), β-human chorionic gonadotropin(β-hCG), progesterone (P), estradiol (E2)were measured in all 92 patients. Results: Incidence rates of the lack of BE, AIA and CTAin 92 cases were 60. 87%, 57. 61 % and 72.83% respectively. The lower levels of BE,AIA and CTA were elevated significantly (P< 0. 05 ～0. 01 ), and the serial levels β- hCG, P and E2 were markedly increasing (P< 0. 01 ) in all successful pregnant patients.The rate of the successful pregnancy of 92 cases was 89. 13 % (to TA 91. 67%, to RSA 88.24 % respectively). Conclusions: It suggeststhat the lack of blocking antibody (BA) andendocrine hormone deficiency may result inspontaneous abortion during early pregnancy.The therapeutic mechanism of those herbs intreating spontaneous abortion was associatedwith the growing levels of BA and hormone byregulating the maternal-fetal immunity and endocrine.
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.
基金Supported by Guangdong Province Key Scientific and Technological Project(No.C30103)
文摘Objective： To study the clinical effects of Prescription Zhuyun-Ⅲ （助孕3号方, ZYⅢ） on early pregnant women diagnosed as threatened abortion, and its mechanism in immunity and endocrine by determining serum Th1- and Th2-type cytokines, progesterone, and β-human chorionic gonadotropin （β-HCG）. Methods： The treatment group comprised 30 early pregnant women diagnosed as threatened abortion of deficiency syndrome of Pi （脾）, Shen （肾）, or both. The control group consisted of 20 normal early pregnant women of similar gestational age. Patients in the treatment group were administered with ZYⅢ for 4 weeks. Peripheral blood samples were collected pre- and post-treatment from both the treatment and the control groups. Serum Thl-type cytokine [interleukin-2 （IL-2）] and Th2-type cytokine [interleukin-10 （IL-10）] were determined by flow cytometry, and serum progesterone and 13-HCG were determined by ELISA. Results： （1） The treatment was effective in 26 and ineffective in 4 patients of the treatment group. Therefore, the cure percentage was 86.67%. （2） In the treatment group before the treatment, IL-2 was significantly higher, IL-10 tended to be less, and the Th1/Th2 balance shifted toward Thl compared with those in the control group. （3） After the treatment, IL-2 was decreased, IL-10 was increased, and IL-2/IL-10 was decreased. Both progesterone and β-HCG were increased. Changes of progesterone were positively correlated with changes of IL-10, whereas changes of β-HCG were negatively correlated with changes of IL-2. Conclusions： Our study suggests that ZYⅢ has an evident function of protecting the fetus, and one of its mechanisms is inhibiting the secretion of Thl cytokines, promoting the secretion of Th2 cytokines, and recovering the pathological shift of the Th1/Th2 balance. The other possible mechanism is increasing serum progesterone and β-HCG concentrations. Moreover, there are some correlations between the above two effects.
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.
