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Abstract Objective: Analyze sex hormone's influence during Chagas disease. Methods: Male and female BALB/c mice were divided into six groups, four experimental (sham, orchiectomized, orchiectomized and supplemented with estradiol, orchiectomized supplemented with testosterone, oophorectomized, oophorectomized and supplemented with estradiol, and oophorectomized and supplemented with testosterone), and two control (healthy and intraperitoneally with T. cruzi strain NINOA infected). Clinical data were recorded daily, parasitemia was evaluated using a Neubauer chamber during the infection, and heart histopathological analysis was performed using the paraffin embedding technique. To analyze parasitemia curves and the area under the parametric curves, two-way ANOVA test was performed to correlate groups' data. P-values < 0.05 were considered statistically significant. Results: Higher mortality rates, cardiomegaly, hepatomegaly, ascites, edema, higher parasitemia levels, more amastigote nests, and more severe inflammatory infiltrate were found in higher testosterone concentration mice, whereas in higher estradiol concentration groups, paresia, prostration, edema, and necrosis were found. Conclusions: Our results showed that testosterone increased infection severity, whereas estradiol had the opposite effect. This research improves the understanding of sex hormones´ infuence upon this infection to contribute with the handling of Chagas´ disease.
Resumen Objetivo: Analizar la influencia de las hormonas durante la enfermedad de Chagas. Métodos: Se separaron grupos de ratones macho y hembras BALB/c, todos infectados con T. cruzi (cepa NINOA), 4 grupos experimentales de machos (Sham, orquidectamizados, orquidectimezados y suplementados con estradiol, orquidectamizaos y suplementados con testosterona). 4 grupos experimentales de hembras (oforectomizadas, oforectomizadas y suplementadas con estradiol, oforectomizadas y suplementadas con testosterona y sham), and y dos grupos control para cada sexo (sin infección e infectados intraperitonealmente con T. cruzi (cepa NINOA). Los datos clínicos fueron registrados diariamente, la parasitemia fue evaluada durante toda la infección utilizando una cámara de Neubauer y el análisis histopatológico del corazón fue realizada con la técnica de inclusión en parafina. Para el análisis de las curvas de parasitemia y el área bajo la curva, se realizó una prueba de ANOVA de dos vías, p < 0.05 fueron considerados estadísticamente diferentes. Resultados: Las mayores tasas de mortalidad, cardiomegalia, hepatomegalia y mayor infiltrado inflamatorio, se encontró en los ratones con una mayor concentración de testosterona. En contraste los ratones con mayor concentración de estradiol presentaron paresia, postración edema y necrosis. Conclusiones: Nuestros resultados ponen en manifiesto que la testosterona incrementa la severidad del curso de la enfermedad de Chagas, mientras que el estradiol tuvo el efecto opuesto. Este trabajo mejora el entendimiento del rol que juegan las hormonas sexuales en esta infección para contribuir en un mejor manejo de la enfermedad de Chagas.
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Abstract Introduction Anxiety, mood- and stress-related behaviors are regulated by sex hormones in pregnant and non-pregnant women. Very scarce information exists about the role of sex steroids in pregnant women displaying high levels of anxiety. Objective To determine sex hormones serum levels in pregnant women exhibiting high levels of anxiety symptoms. Method The Hamilton Anxiety Rating Scale (HARS/ HAM-A) was used to assess the intensity of anxiety symptoms in third-trimester pregnant women. Two groups were included in the study, pregnant women exhibiting severe anxiety (ANX; HARS scores ≥ 25; n = 101) and healthy control subjects (CTRL; n = 40) displaying lower scores for anxiety (HARS scores ≤ 7). Estradiol (E2), progesterone (P4), and testosterone (T) serum levels were measured using a standard chemiluminescent immunoassay. Bivariate and partial correlations were performed to detect significant associations between groups, clinical measures, biochemical data, and HARS scores. Results The anxiety group (ANX) showed an increase in E2 and T serum levels (p < .001) compared to CTRL. Conversely, significantly lower P4 levels were found in the symptomatic group (p < .001) as compared to the CTRL hormone values. The P4:E2 index was significantly reduced in pregnant women with high levels of anxiety (p < .001). Negative correlations between anxiety (HARS) scores, P4 serum levels (p = .02), and P4:E2 ratio (p = .04) were found in the symptomatic group. Conversely, T serum levels displayed a positive association (p = .001) with high levels of anxiety symptoms in the same group, after adjusting our data by clinical confounders. Discussion and conclusion Serum levels of sex-steroid hormones are altered in pregnant women exhibiting severe anxiety.
Resumen Introducción La ansiedad, el estado de ánimo y el estrés están regulados por diversos esteroides sexuales. Existe poca información sobre el papel que juegan estos esteroides en mujeres embarazadas con niveles elevados de ansiedad. Objetivo Determinar los niveles séricos de hormonas sexuales en mujeres embarazadas con altos índices de síntomas de ansiedad con respecto a mujeres gestantes sanas. Método Determinación de la intensidad de síntomas ansiosos empleando la escala de Hamilton de Ansiedad (HAM-A) en 141 mujeres embarazadas en el tercer trimestre de gestación. Cuantificación de los niveles séricos de estradiol (E2), progesterona (P4) y testosterona (T) por inmunoensayo estándar. Aplicación de las correlaciones de Pearson para detectar asociaciones entre parámetros clínicos y valores hormonales entre los grupos de estudio. Resultados Las mujeres con ansiedad severa (ANX; n = 101; HAM-A ≥ 25) mostraron niveles séricos más altos de E2 y T (p < .001), así como niveles más bajos de P4 (p < .001) en relación con el grupo control (CTRL, n = 40, HAM-A < 7). Se detectó una disminución significativa en el índice P4:E2 en el grupo de ANX (p < .001) y se observaron correlaciones negativas y positivas entre los puntajes elevados de ansiedad con los niveles circulantes de P4 (p = .02), en la taza P4:E2 (p = .04) y en los niveles séricos de T (p = .001) respectivamente, al ajustar nuestros datos con variables confusoras. Discusión y conclusión Los niveles circulantes de los esteroides sexuales se encontraron alterados en mujeres con ansiedad severa.
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Objective:To analyze the clinical value of ultrasound monitoring of endometrial thickness in assessing pregnancy rate improvement after estrogen administration following a missed abortion.Methods:A retrospective study was conducted on 86 patients who underwent surgical abortion at Cixi Maternal and Child Health Hospital from January 2022 to June 2023. Based on the treatment received, the patients were divided into two groups: a control group and an observation group, with 43 patients in each group. The control group received only routine postoperative care without any medication, while the observation group received estrogen treatment after surgery. The clinical efficacy, endometrial thickness, intrauterine adhesion and re-pregnancy rate were compared between the two groups.Results:In the observation group, there was significant difference in endometrial thickness in terms of intergroup, group-by-time interaction, and time effect ( Fintergroup =129.49, Finteraction =14.25, Ftime =146.64, all P < 0.001). Intrauterine adhesions were less severe in the observation group compared with the control group ( χ2 = 4.34, P < 0.05). The clinical effective rate was significantly higher in the observation group than in the control group [88.37% (38/43) vs. 69.76% (30/43), Z = 2.35, P = 0.019]. Additionally, the rate of re-pregnancy was significantly higher in the observation group than in the control group [46.54% (20/43) vs. 13.95% (6/43), χ2 = 10.81, P < 0.05]. Conclusion:Patients who have retained abortion can benefit from ultrasound examination to assess endometrial thickness after estrogen administration. This approach significantly enhances endometrial thickness, promotes menstrual recovery, and reduces intrauterine adhesions. It also improves the rate of re-pregnancy and is highly valuable in clinical settings.
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Diabetic nephropathy is one of the most common and harmful microvascular complications of diabetes. In recent years, it has become a leading cause of end-stage renal disease due to its high incidence rate, challenging control, and poor prognosis. Studies have revealed that patients with diabetic nephropathy often exhibit imbalanced levels of sex hormones such as testosterone, dehydroepiandrosterone, estradiol, sex hormone binding globulin, and gonadotropin. Conversely, the imbalance of sex hormones can also influence the progression of diabetic nephropathy. Therefore, clarifying the potential relationship and interaction between sex hormones and diabetic nephropathy is essential for effective prevention and treatment of diabetic nephropathy. This warrants further research and consideration.
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Objective @#To study the effect of sex-determining region Y-frame protein 3 (SOX3) on proliferation and estradiol secretion in human ovarian granulosa cells (KGN cell line) . @*Methods@#The gene sequence of human SOX3 (NM_005634. 3) was searched in Gene-Bank , an NCBI database , and the target gene SOX3 was amplified by PCR , which was cloned into lentiviral vector pLV-EF1a-GFP-2A-Puro to obtain the overexpression lentiviral re- combinant plasmid pLV-EF1a-GFP-2A-Puro- SOX3 ; the correctly sequenced overexpressed lentiviral recombinant plasmid as well as packaging plasmids ( pGag/Pol , pRev , pVSV-G) were co-transfected into human embryonic kidney cell line ( HEK 293T) cells ( pLV-SOX3 group) , and pLV-EF1a-GFP-2A-Puro and packaging plasmids (pGag/Pol , pRev , pVSV- G) were co-transfected into HEK 293T cells (pLV-NC group) , the lentiviral particles of both groups were collected and the titers of the viruses were measured after 48 h of transfection , the lentiviruses of the two groups were infected into KGN cells , and the stably expressed cell lines were obtained after puromycin screening for 2 weeks; real-time fluorescence quantitative PCR (RT-qPCR) and Western blot were used to detect the SOX3 mRNA and protein levels in the two groups; CCK-8 assay was used to detect the proliferative ability of the cells in the two groups; ELISA was used to determine the concentration of estradiol in the two groups .@*Results@#The identification of PCR products and sequencing results showed that the SOX3 gene fragment was amplified successfully , and the enzyme digestion and sequencing results indicated that the construction of overexpression lentiviral recombinant plasmid was completed; green fluorescence could be detected after lentiviral infection of HEK 293T cells , which indicated that lentiviral packaging was successful; the lentivirus was screened by puromycin after lentiviral infection of KGN cells , and the cells were observed to express green fluorescence under the fluorescence microscope; RT- qPCR and Western blot assays both showed that the expression level of SOX3 in the pLV-SOX3 group was significantly higher than that in the pLV-NC group ( P < 0. 05) . CCK-8 assay results showed that the proliferation ability of the cells in the pLV-SOX3 group significantly increased compared with that in the pLV-NC group (P < 0. 01) . ELISA results showed that estradiol concentration was elevated in the pLV-SOX3 group com- pared with the pLV-NC group (P < 0. 05) . @*Conclusion@#Overexpression of the transcription factor SOX3 can pro- mote the proliferation and estradiol secretion of human ovarian granulosa cells KGN .
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OBJECTIVE To observe the efficacy and safety of goserelin combined with estradiol valerate in the treatment of endometriosis （EMs） in patients of childbearing age after laparoscopic surgery. METHODS The clinical data of 144 patients with EMs of childbearing age who underwent laparoscopic surgery in our hospital from January 2020 to December 2022 were collected retrospectively， and those patients were divided into control group （70 cases） and combination group （74 cases） based on different postoperative medication regimens. Control group was given Acetate goserelin sustained-release implant on the 1st to 5th day of their first menstrual cycle after laparoscopic surgery， while combination group was additionally given Estradiol valerate tablets on the basis of control group. The short-term and long-term efficacy of 2 groups were observed； preoperative and postoperative pain scores， ovarian reserve function， and the incidence of adverse reactions were all recorded in 2 groups. RESULTS There was no statistically significant difference in short-term total effective rate， 1-year postoperative recurrence rate and the incidence of decreased libido， vaginal dryness， gastrointestinal reactions， rash， or arrhythmia between two groups （P＞0.05）. The natural pregnancy rate of combination group was significantly higher than control group at 1 year after surgery， while the incidence E-mail：wanghuiling0518@126.com of early miscarriage， hot flashes and sweating， emotional fluctuations， insomnia and fatigue， joint muscle pain， dizziness and headache were significantly lower than control group （P＜0.05）. However， at 6 months after surgery， pain scores and the levels of anti-Müllerian hormone， follicle stimulating hormone， luteinizing hormone， estradiol of both groups were significantly lower than before surgery in the same group， while the number of antral follicle count was significantly higher than before surgery in the same group； the levels of anti-Müllerian hormone， luteinizing hormone， estradiol， and the number of antral follicles in the combination group were significantly higher than control group， while pain score and follicle stimulating hormone level were significantly lower than control group （P＜0.05）. CONCLUSIONS The combination of goserelin and estradiol valerate after laparoscopic surgery has a significant therapeutic effect and good safety in the treatment of EMs of childbearing age.
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BACKGROUND:Exercise is an effective method for preventing and treating osteoporosis,but it is unclear whether its effect on postmenopausal osteoporosis is related to changes in bone autophagy levels. OBJECTIVE:To observe the effects of exercise via cellular autophagy on the morphology and mechanical properties of bone tissue in ovariectomized rats,and to explore the mechanism of exercise on bone mass in ovariectomized rats from the perspective of autophagy. METHODS:A rat model of postmenopausal osteoporosis was established,and a 24-week moderate-intensity exercise was used for intervention.After the experiment,serum estradiol levels were measured by ELISA,and bone mineral density and bone microstructure of the cortical and trabecular bone were detected by micro-CT.The biomechanical indicators of the tibia were tested by a three-point bending test.Autophagosomes were observed by transmission electron microscopy.The expression of LC3 and ATG7 proteins was analyzed by western blot. RESULTS AND CONCLUSION:The serum estradiol level in the ovariectomized group was significantly lower than that of the sham-operation group and ovariectomized+exercise group(P＜0.01).The body mass of rats in each group increased,and the order was the ovariectomized group＞the ovariectomized+exercise group＞the sham-operation group＞the sham-operation+exercise group.The bone mineral density and bone mass of rats in all groups significantly increased(P＜0.01),but the increase in the ovariectomized group was significantly lower than that of the other groups,and the increase in the ovariectomized+exercise group was significantly higher than that of the ovariectomized group.Compared with the sham-operation group,the bone mineral density of the tibial cancellous bone in the sham-operation+exercise group was significantly increased(P＜0.01),while the bone mineral density in the ovariectomized and ovariectomized+exercise groups was significantly decreased(P＜0.01).Compared with the ovariectomized+exercise group,the ovariectomized group showed significantly lower bone volume fraction,number of trabeculae,and bone mineral density of cancellous bone(P＜0.05),extremely significantly lower trabecular thickness(P＜0.01),and significantly higher mean trabecular pattern factor,trabecular separation,and structural model index(P＜0.01).Compared with the ovariectomized group,the LC3-Ⅱ/LC3-I ratio and the relative expression of ATG7 protein significantly increased in the ovariectomized+exercise group(P＜0.05).Compared with the sham-operation and ovariectomized groups,the number of autophagosomes increased in the sham-operation+exercise and ovariectomized+exercise groups,respectively.To conclude,moderate-intensity treadmill exercise can improve the bone microstructure and biomechanical properties of the tibial cancellous bone and increase bone mass in ovariectomized rats by increasing serum estradiol levels and bone autophagy levels.
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BACKGROUND:Osteonecrosis of the femoral head is a common and disabling disease,which is mainly characterized by microcirculation disorders and bone cell metabolism disorders.Luzhongjiangu decoction was developed by Shandong Academy of Chinese Medicine and used in the form of soup in the clinic,which has good efficacy in the treatment of osteonecrosis of the femoral head.However,its mechanism of action has not been clarified. OBJECTIVE:To study the effect mechanism of Luzhongjiangu decoction on intestinal flora in rats with osteonecrosis of the femoral head based on 16S rDNA sequencing technique. METHODS:The model of osteonecrosis of the femoral head was established in Wistar rats by intragastric administration of retinoic acid.The therapeutic effect of Luzhongjiangu decoction was evaluated by serum hormone,bone histopathology and serum hormone levels.16s rDNA sequencing technique was used to detect the intestinal flora of rats in the blank control group,model group and middle-dose Luzhongjiangu decoction group.The corresponding library was constructed and OTU clustering and microbial community diversity and abundance analysis were carried out to determine the composition of intestinal flora and the changes of species and diversity among groups. RESULTS AND CONCLUSION:Luzhongjiangu decoction could significantly increase the expression of osteocalcin,osteopontin and other osteogenic related factors,alleviate the destruction of bone trabeculae,increase bone mineral density,and had a significant therapeutic effect on osteonecrosis of the femoral head,of which the middle dose group showed the most significant effect.The results of intestinal flora sequencing showed that Luzhongjiangu decoction improved the flora disorder of rats with osteonecrosis of the femoral head to some extent,and screened out different colonies such as Bacillus,Desulfurizans,Desulfurization,Isobacteria,Bifidobacterium and so on;it could up-regulate the abundance of beneficial bacteria such as Bifidobacterium,down-regulate the abundance of harmful bacteria such as Desulfovibrio,and improve the structure of intestinal flora.Functional prediction analysis indicated that Luzhongjiangu decoction could mainly affect amino acid metabolism and energy metabolism.Correlation analysis showed that the differential bacteria of Bifidobacterium and Intestinimonas in the middle dose group of Luzhongjiangu decoction were positively correlated with vitamin D3,estradiol and calcitonin,and negatively correlated with prostaglandin E2.In the model group,Escherichia-Shigella,Desulfovibrio,Globicatella and Streptococcus were positively correlated with prostaglandin E2 and negatively correlated with vitamin D3,estradiol and calcitonin.To conclude,Luzhongjiangu decoction may play a role in the treatment of osteonecrosis of the femoral head by regulating the structure of intestinal flora,up-regulating the abundance of beneficial bacteria and affecting the secretion of vitamin D3,estradiol,calcitonin and prostaglandin E2.
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Objective@#To explore the moderating role of estradiol in the relationship between parenting styles and preschool children's behavioral problems, so as to provide a theoretical basis for improving the development of human s emotional health development in early life stage.@*Methods@#During September to November in 2022, 354 children aged 3-6 years and their parents from two kindergartens in Bengbu City were chosen by using stratified cluster sampling method for the questionnaire survey. The Parenting Style Scale and the Child Behavior Checklist (CBCL) were used to collect information on parenting style and child behavioral problems. Salivary estradiol of children was collected and tested. Independent samples t test was applied to compare the scores of the scale for parental up bringing and children s behavioral problems, and Pearson correlation analysis was conducted to explore the relationship among parental upbringing, estradiol and children s behavioral problems.@*Results@#Parents doting, laissez faire, autocratic, and inconsistent parenting styles were positive associated with child behavior problems( r =0.14-0.70); fathers democratic parenting style was negatively associated with child behavior problems( r =-0.14，-0.22，-0.21，-0.17，-0.27，-0.20); mothers democratic parenting styles was negatively correlated with scores on all five dimensions of child behavior problems except the withdrawal dimension ( r =-0.14，-0.12，-0.13，-0.21，-0.12)( P <0.05). Estradiol levels had significant moderating effects on maternal doting parenting style and children s withdrawal ( β =0.68) as well as social problems ( β =-1.00), also moderating laissez faire parenting styles and children s withdrawal problems ( β =0.75)( P <0.05). For children with low levels of estradiol, withdrawal problem scores were negatively associated with mother s doting parenting style and positively associated with laissez faire parenting style, and socialization problem scores were associated with mother s doting parenting style; for children with high levels of estradiol, withdrawal problem scores were positively associated with mother s doting parenting style, and socialization problem scores were associated with mother s doting parenting style ( t=2.84, 6.24, 3.16 , 2.37, 4.49, P <0.05).@*Conclusions@#Parenting styles are strongly associated with child behavioral problems; estradiol levels play a moderating role in mothers doting, laissez faire parenting styles and children s withdrawal problems and social problems.Parents should adopt more positive parenting styles and focus on the role of estradiol levels in maternal education to reduce the occurrence of behavioral problems in children.
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Aim To investigate the molecular mechanism by which quercetin inhibits the malignant behavior of breast cancer cells. Methods Breast cancer cell lines MCF-7 and MB231 were used as the research models. Lentiviral transfection was employed to establish tumor cells with high expression of ERa and MAL-AT-1. The expression of MALAT-1 was assessed using RT-qPCR,and ERa expression was determined through Western blot. Subsequently, CCK-8 assay and colony formation assay were conducted to evaluate cell proliferation. PI staining and adenovirus transfection were performed to observe the inhibitory effects of quercetin on breast cancer cell proliferation. Results 17|3-es-tradiol ( E2 ) promoted the proliferation of MCF-7 breast cancer cells, while 5 jjunol L quercetin reversed the promoting effect of E2 on proliferation ( P 0. 05 ) . Quercetin had no effect on MB231 breast cancer cells. Overexpression of ERa significantly inhibited the pro-proliferative effect of E2 on MB231-ERa cells, and quercetin further suppressed this effect. Additionally , quercetin inhibited the expression of MALAT-1. However,this inhibitory effect was reversed by overexpression of MALAT-1, leading to enhanced cell proliferation , cell cycle progression, and clonal formation a-bility. Conclusions Quercetin exerts its anti-tumor effects on breast cancer cells by regulating MALAT-1, dependent on the presence of estrogen receptor. Quercetin shows potential as a therapeutic drug for breast cancer targeting the estrogen receptor.
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ABSTRACT Purpose: This study aimed to determine the effect of serum G receptor-mediated protein-1 levels on the development of retinopathy in patients with diabetes in comparison with healthy individuals. Methods: The study enrolled patients with diabetic retinopathy (Group 1), patients without diabetic retinopathy (Group 2), and healthy individuals (Group 3). Levels of serum progesterone, serum G receptor-mediated protein-1, estradiol, oxidant/antioxidants, and thyroid-releasing hormones were analyzed and compared among the groups. Post-hoc analysis was performed to compare the subgroups in which significant differences were found. Results: Groups 1, 2, and 3 each included 40 patients. A significant difference was found among all groups in terms of serum G receptor-mediated protein-1, oxidant/antioxidant, and estradiol levels (p<0.01), but no significant difference was found in terms of thyroid-releasing hormone or progesterone (p=0.496, p=0.220, respectively). In the post-hoc analysis of the groups with significant differences, another significant difference was found among all groups for serum G receptor-mediated protein-1 and oxidant/antioxidant levels (p<0.05). Serum G receptor-mediated protein-1 and oxidant levels were positively correlated, whereas serum G receptor-mediated protein-1 and antioxidant levels were negatively correlated (r=0.622/p<0.01, r=0.453/p<0.01, r=0.460/p<0.01, respectively). The multiple regression analysis showed that increased levels of serum G receptor-mediated protein-1 may help prevent diabetic retinopathy. Conclusions: Serum G receptor-mediated protein-1 levels, which were the highest in the diabetic retinopathy Group, increased as the oxidant/antioxidant balance changed in favor of oxidative stress. This appears to be a defense mechanism for preventing neuronal damage.
RESUMO Objetivo: Esta pesquisa buscou determinar o impacto dos níveis de proteína G sérica no desenvolvimento da retinopatia em pacientes diabéticos, comparando-os a indivíduos saudáveis. Métodos: Foram incluídos, no estudo, 40 pacientes com retinopatia diabética (Grupo 1), 40 pacientes sem retinopatia diabética (Grupo 2) e 40 indivíduos saudáveis (Grupo 3). Os níveis hormonais de progesterona sérica, de proteína G sérica, estradiol, oxidante/antioxidante e hormônio liberado pela tireoide foram analisados e comparados. A análise post hoc foi realizada para comparar os subgrupos nos quais diferenças estatisticamente significativas foram encontradas. Resultados: Uma diferença significativa foi encontrada entre todos os grupos em termos de proteína G sérica, oxidante/antioxidante e níveis de estradiol (p<0.01), mas nenhuma diferença significativa foi encontrada em termos de hormônio liberado pela tireoide ou progesterona (p=0,496, p=0,220, respectivamente). Na análise post hoc dos grupos com diferenças estatisticamente significativas, outra diferença significativa foi encontrada entre todos os grupos para proteína G sérica e níveis oxidantes/antioxidantes (p<0,05). Os níveis de proteína G sérica e os níveis de oxidante foram positivamente correlacionados, enquanto os níveis de proteína G sérica e os níveis de antioxidantes foram negativamente correlacionados (r=0,622/p<0,01, r=0,453/p<0,01, r=0,460/p<0,01, respectivamente). A análise de regressão múltipla mostrou que o aumento da proteína G sérica pode ajudar a prevenir a retinopatia diabética. Conclusões: Os níveis de proteína G sérica que eram mais altos no grupo de retinopatia diabética, aumentaram à medida que o equilíbrio oxidante/antioxidante mudou em favor do estresse oxidativo. Este parece ser um mecanismo de defesa para prevenir danos neuronais.
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SUMMARY: Estradiol and progesterone receptors play an essential role in the changes occurring in the uterus during the estrus cycle in dogs (Canis lupus familiaris). In order to investigate the potential effect of progestational agent medroxyprogesterone acetate (MPA) when is used during anestrus on the expression of estradiol receptors [ER], progesterone receptors [PR] and nuclear protein Ki67, we evaluated uterine tissue immunohistochemically. Uteri were grouped as nulliparous (control, n=11), multiparous (n=11) and treated with MPA (n=11; nulliparous with two treatments; 5mg/kg; i.m.). The amount and location of PR, ER and Ki67 were studied on the epithelial surface, apical and basal regions of the endometrium and myometrium using immunohistochemical techniques with a spectral confocal microscope and analyzed by ANOVA. Differences in ER were observed between the multiparous and MPA-treated groups in the apical region of the endometrium (p=0.0022). Differences in cell proliferation were detected between the nulliparous and multiparous groups (p=0.0037) and nulliparous and MPA-treated groups (p=0.0003) in the basal region of the endometrium. In conclusion, two doses of MPA (5mg/kg; i.m.) do not have a significant effect on the expression of ER and PR; however, they inhibit cell proliferation in the basal region of the endometrium, which includes the stroma, subepithelial cell layer, compact layer, and spongy layer. The clinical and long-term effect of this treatment should be evaluated in subsequent studies.
Los receptores de estradiol y progesterona juegan un rol fundamental en los cambios que se producen en el útero durante el ciclo estral de las perras (Canis lupus familiaris). El objetivo de este estudio fue evaluar las expresiones de ER-a y PR en el útero y la proliferación de células endometriales detectando la expresión nuclear de la proteína Ki67 en perras expuestas a la progestina sintética MPA y compararlas con perras nulíparas y multíparas expuestas a progesterona luteal. Úteros fueron agrupados como nulíparas (control, n=11), multíparas (n=11) y tratadas con MPA (n=11; nulíparas con dos tratamientos; 5 mg/kg; i.m.). La expresión de PR, ER-a y Ki67 fue evaluada en la regiones apicales y basales del endometrio y miometrio con un microscopio confocal espectral. Se observó diferencias en ER-a entre los grupos multíparas y tratados con MPA en la región apical del endometrio (p=0,0022). Se detectaron diferencias en la proliferación celular entre los grupos de nulíparas y multíparas (p=0,0037) y los grupos de nulíparas y tratados con MPA (p=0,0003) en la región basal del endometrio. En conclusión, dos dosis de MPA (5mg/kg; i.m.) no tienen un efecto significativo sobre la expresión de ER y PR; sin embargo, inhiben la proliferación celular en la región basal del endometrio, el cual incluye a estroma, capa de células subepiteliales, estratos compacto y esponjoso. El efecto clínico a largo plazo de este tratamiento debe ser evaluado en estudios posteriores.
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Animals , Female , Dogs , Progesterone/metabolism , Uterus/metabolism , Receptors, Estrogen/metabolism , Ki-67 Antigen/metabolism , Immunohistochemistry , Medroxyprogesterone Acetate/metabolismABSTRACT
Abstract Objective: To evaluate hypothalamic-pi- tuitary-gonadal (HPG) axis alterations at 1 and 12 months after kidney transplan- tation (KT) and their association with in- sulin resistance. Methods: A retrospective clinical study was conducted in a tertiary care center in kidney transplantation recipients (KTRs) aged 18- 50 years with primary kidney disease and stable renal graft function. LH, FSH, E2/T, and HOMA-IR were assessed at 1 and 12 months after KT. Results: Twenty-five KTRs were included; 53% were men, and the mean age was 30.6±7.7 years. BMI was 22.3 (20.4-24.6) kg/m2, and 36% had hypogonadism at 1 month vs 8% at 12 months (p=0.001). Re- mission of hypogonadism was observed in all men, while in women, hypogonadotropic hypogonadism persisted in two KTRs at 12 months. A positive correlation between go- nadotrophins and age at 1 and 12 months was evident. Fifty-six percent of patients had insulin resistance (IR) at 1 month and 36% at 12 months (p=0.256). HOMA-IR showed a negative correlation with E2 (r=- 0.60; p=0.050) and T (r=-0.709; p=0.049) at 1 month, with no correlation at 12 months. HOMA-IR at 12 months after KT correlated positively with BMI (r=0.52; p=0.011) and tacrolimus dose (r=0.53; p=0.016). Conclusion: Successful KT restores the HPG axis in the first year. Hypogonadism had a negative correlation with IR in the early pe- riod after KT, but it was not significant at 12 months.
Resumo Objetivo: Avaliar as alterações do eixo hipotálamo-hipófise-gonadal (HHG) em 1 e 12 meses após transplante renal (TR) e sua associação com a resistência à insulina. Métodos: Foi realizado um estudo clínico retrospectivo em um centro de cuidados terciários em receptores de transplante renal (RTR) com idade entre 18-50 anos com doença renal primária e função do enxerto renal estável. LH, FSH, E2/T e HOMA-IR foram avaliados em 1 e 12 meses após o TR. Resultados: foram incluídos 25 RTR; 53% eram homens e a média de idade foi de 30,6±7,7 anos. O IMC foi de 22,3 (20,4-24,6) kg/m2 e 36% apresentaram hipogonadismo em 1 mês vs 8% aos 12 meses (p=0,001). A remissão do hipogonadismo foi observada em todos os homens, enquanto nas mulheres, o hipogonadismo hipogonadotrófico persistiu em dois RTR aos 12 meses. Ficou evidente uma correlação positiva entre gonadotrofinas e idade em 1 e 12 meses. Cinquenta e seis por cento dos pacientes apresentaram resistência à insulina (RI) em 1 mês e 36% aos 12 meses (p=0,256). O HOMA-IR mostrou uma correlação negativa com E2 (r=-0,60; p=0,050) e T (r=-0,709; p=0,049) em 1 mês, sem correlação em 12 meses. O HOMA-IR aos 12 meses após TR correlacionou-se positivamente com o IMC (r=0,52; p=0,011) e a dose de tacrolimus (r=0,53; p=0,016). Conclusão: O TR bem-sucedido restaura o eixo HHG no primeiro ano. O hipogonadismo apresentou uma correlação negativa com a RI no período inicial após o TR, mas essa correlação não foi significativa aos 12 meses.
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Resumen El trabajo de parto es la transición de un estado de inactividad y relajación muscular a un estado de excitación, en el cual la capa muscular del útero (miometrio) realiza crecientes contracciones coordinadas para llevar a cabo la expulsión del feto y la placenta. Durante el inicio del trabajo de parto, el miometrio experimenta una serie de cambios fisiológicos, bioquímicos y moleculares, pasando de un estado de quiescencia a un fenotipo contráctil que inducirá el parto. En parte, esto es provocado por la acción de las hormonas progesterona, estradiol y oxitocina. En general, la progesterona mantiene la quiescencia del miometrio durante el embarazo al inhibir la expresión de moléculas proinflamatorias y proteínas asociadas a la contracción, mientras que al término del embarazo, el estradiol induce la expresión de dichas moléculas. Por su parte, la oxitocina induce un aumento en la concentración de calcio intracelular para llevar a cabo las contracciones de los miocitos uterinos. El objetivo del presente trabajo es presentar un resumen acerca de los mecanismos moleculares involucrados en la regulación de la actividad de las células miometriales por medio de las hormonas progesterona, estradiol y oxitocina, así como discutir las perspectivas de esta interesante área de investigación.
Abstract Labor is the transition from a state of inactivity and muscle relaxation to a state of muscle excitation, in which the muscular layer of the uterus (myometrium) performs increasingly coordinated contractions to deliver the fetus and expel the placenta. During the onset of labor, the myometrium undergoes a series of physiological, biochemical, and molecular changes, allowing the tissue to transition from a quiescent state to a contractile phenotype that will support labor. This is partly caused by the action of the hormones progesterone, estradiol, and oxytocin. In general, progesterone maintains the quiescence of the myometrium during pregnancy by decreasing the expression of proinflammatory molecules and contraction-associated proteins. In contrast, at the end of pregnancy, estradiol induces the expression of these molecules. For its part, oxytocin induces an increase in intracellular calcium concentration to carry out the contractions of uterine myocytes. The objective of this review is to present a summary of the molecular mechanisms involved in regulating myometrial cell activity through the hormones progesterone, estradiol and oxytocin, as well as to discuss the perspectives of this exciting area of research.
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Objective:To explore the role of 17β-estradiol(17β-E2) derived from the hippocampus and gonad in the cognitive memory during the reconsolidation period of fear memory in rats with post-traumatic stress disorder(PTSD).Methods:The 8-week-old clean grade female SD rats were used for this study. Single prolonged stress combined with context fear conditioning was used to prepare the rat PTSD model.(1) Gonad estradiol experiment: 50 female rats were randomly divided into blank control group, model group, sham ovariectomy group, ovariectomy group, and ovariectomy+ estradiol group by random number table method, with 10 rats in each group. The rats in model group, sham ovariectomy group, ovariectomy group, and ovariectomy+ estradiol group were established PTSD model. Rats in ovariectomy group and ovariectomy+ estradiol group underwent ovariectomy, while rats in sham ovariectomy group only were removed adipose tissue of the same mass around the ovaries. And the rats in ovariectomy+ estradiol group were injected with 17β-E2(1 mg/kg, once a day for 14 days) 7 days after ovariectomy.(2) Hippocampal estradiol experiment: 40 female rats were randomly divided into blank control group, model group, hippocampal solvent control group and hippocampal estradiol inhibitor group by random number table method, with 10 rats in each group.The rats in model group, hippocampal solvent control group and hippocampal estradiol inhibitor group were established PTSD model.Rats in hippocampal estradiol inhibitor group were given letrozole once(bilateral, 0.5 μL per side) during the fear memory consolidation period) and rats in the hippocampus solvent control group were injected once with dimethyl sulfoxide in the hippocampus(bilateral, 0.5 μL per side) . The open field test and elevated cross maze test were used to evaluate the anxiety level and autonomous exploration ability, the freeze test was used to evaluate the fear memory, the new object recognition test was used to evaluate the non-spatial memory, and ELISA was used to detect serum 17β-E2 level. SPSS 25.0 software was used for data analysis, and one-way ANOVA was used for inter group comparisons, LSD test was used for further pairwise comparisons.Results:(1)In the gonad estradiol experiment, there were statistical differences in various indicators among the five groups of rats in the open field test, elevated cross maze test, freeze test, and new object recognition test( F=20.200, 12.702, 7.514, 10.094, 7.899, 13.211, all P<0.05). The number of upright times, central area activity time, distance and frequency of entering the open arm, and cognitive index of the model group rats were all lower than those of the blank control group(all P<0.05), and the freezing time was higher than that of the blank control group( P<0.05). The number of upright positions((11.20±1.55) times), central area activity time((11.33±1.80) s), distance((1.49±0.26) m) and times((10.00±1.50) times) entering the open arm, the freezing time((92.20±6.07) s) and cognitive index((60.40±3.71)%) in ovariectomy+ estradiol group were all higher than those of ovariectomy group((4.90±0.65) times, (4.31±1.07) s, (0.49±0.06) m, (3.10±0.62) times, (60.30±5.28) s, (32.60±8.08)%)(all P<0.05). (2) In the hippocampal estradiol experiment, there were statistical differences in various indicators among the four groups in the open field test, elevated cross maze test, freeze test, and new object recognition test( F=40.831, 5.553, 9.087, 5.848, 7.657, 9.191, all P<0.05). The numbers of upright positions, distance and frequency of entering open arms of the model group rats were lower than those of the blank control group(all P<0.05). The number of upright positions((3.00 ± 0.39) times), distance of entering open arm((1.17±0.37) m), freezing time((46.70±3.57)s), and cognition index((29.60±2.70)%) in the hippocampal estradiol inhibitor group were all lower than those in the hippocampal solvent control group((10.10±1.40) times, (4.02±0.79) m, (93.70±9.73) s, (54.20±5.08)%)(all P<0.05). Conclusion:17β-E2 derived from the hippocampus and gonad both had ameliorative effect on cognitive memory and anxiety-like behavior in the reconsolidation period of fear memory in PTSD model rats.
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Objective To investigate the predictive value of vitamin D,sex hormones and their receptors in the development and regression of male patients with clinical isolated syndrome(CIS).Methods A total of 40 male CIS patients were included in the CIS group and 30 healthy subjects matched in age and long-term res-idence were included in the control group.The levels of vitamin D[1,25(OH)2D2 and 1,25(OH)2D3]inpe-ripheral blood of the included individuals and the first relapsed multiple sclerosis patients(MS group)were detected by ultra-high-performance liquid chromatography-tandem mass spectrometry.The levels of testoster-one(T),progesterone(P),and estradiol(E2)in peripheral blood were detected by electrochemiluminescence.Estrogen receptor(ERα,ERβ),androgen receptor(AR)and vitamin D receptor(VDR)levels in lymphocyte supernatant were detected by enzyme-linked immunosorbent assay(ELISA).Results After a median follow-up of 31.5 months,29 patients(72.5％)with CIS were converted to multiple sclerosis.Compared with pa-tients with non-recurrent CIS patients,patients with multiple sclerosis had a younger age of onset and were prone to positive oligoclonal bands.Compared with HC group,vitamin D levels were reduced in CIS patients,and the difference was statistically significant(P＜0.05).When CIS patients reverted to multiple sclerosis,se-rum levels of E2,ERα,and ERβ were elevated compared with those before relapse,and the levels of testosteroneand AR were decreased,and the difference was statistically significant(P＜0.05).Correlation analysis showed no correlation between peripheral blood levels of vitamin D,sex hormones and their receptors and EDSS in CIS patients.Conclusion Male CIS patients with younger onset age and positive oligoclonal bands are prone to transition to multiple sclerosis.The decrease of vitamin D level may be associated with the onset of male CIS.Vitamin D,sex hormones,and their receptors have no predictive value in the conversion of CIS to multiple sclerosis.
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Objective:To analyze the safety and effectiveness of superselective embolization of the uterine arteries in the treatment of uterine fibroids.Methods:The clinical data of 60 patients with uterine fibroids who were admitted to Zhejiang Veteran Hospital from February 2020 to February 2022 were retrospectively analyzed. These patients were divided into a control group and an observation group ( n = 30/group) according to different surgical methods. The control group underwent conventional surgery. The observation group underwent superselective embolization of the uterine arteries. Uterine size, uterine fibroid size, postoperative hormone level, and complications were compared between the two groups. Results:There was no significant difference in total response rate between the observation and control groups [93.33 (28/30) vs. 83.33 (25/30), χ2 = 1.46, P > 0.05]. After surgery, serum estradiol, luteinizing hormone, follicle-stimulating hormone, and progesterone levels in the observation group were (164.14 ± 19.97) ng/L, (2.43 ± 1.47) IU/L, (2.51 ± 1.14) IU/L, and (5.05 ± 0.43) μg/L, respectively, which were significantly lower than (190.23 ± 21.62) ng/L, (3.78 ± 1.63) IU/L, (3.94 ± 1.23) IU/L, (8.22 ± 1.35) μg/L in the control group ( t = 4.86, 3.37, 4.67, 12.25, all P < 0.05). The incidence of postoperative complications in the observation group was significantly lower than that in the control group [3.33% (1/30) vs. 20.00% (6/30), χ2 = 4.04, P < 0.05). Conclusion:Compared with conventional surgery, superselective embolization of the uterine arteries is more effective on uterine fibroids, better keep postoperative hormone level stable, and reduce or avoid short- and long-term complications. Therefore, superselective embolization of the uterine arteries for the treatment of uterine fibroids deserves the clinical promotion.
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Objective:To investigate the efficacy of Qingruxiao granules combined with tamoxifen in the treatment of breast hyperplasia and its effect on serum hypoxia-inducible factor-alpha (HIF-α), angiopoietin-2 (Ang-2) and prolactin (PRL) levels. Methods:Ninety-eight patients with breast hyperplasia admitted to Xi'an No.3 Hospital from June 2020 to January 2022 were retrospectively included in this study. They were divided into control and observation groups ( n = 49/group) according to different treatments. The control group was treated with tamoxifen alone. The observation group was treated with Qingruxiao granules combined with tamoxifen. Clinical efficacy, symptom score, ultrasound parameters (glandular layer thickness, longest diameter of mass, maximum diameter of hypoechoic area, inner diameter of lactating tube), endocrine hormone levels (estradiol, progesterone, and prolactin), HIF-α, and Ang-2 pre- and post-treatment, as well as the incidence of adverse reactions were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [93.88% (4/49) vs. 77.55%, χ2 = 5.33, P < 0.05). After treatment, breast mass score, breast pain, systemic accompanying symptom, and nipple discharge in the observation group were (1.34 ± 0.29) points, (1.02 ± 0.36) points, (0.68 ± 0.17) points, (0.97 ± 0.15) points, respectively, which were significantly lower than (1.57 ± 0.23) points, (1.45 ± 0.41) points, (0.95 ± 0.26) points, and (1.28 ± 0.26) points, respectively, in the control group ( t = 4.35, 5.52, 6.08, 7.23, all P < 0.001). The glandular layer thickness, the longest diameter of mass, the maximum diameter of hypoechoic area, and the inner diameter of lactating duct in the observation group were (9.45 ± 1.67) mm, (11.46 ± 3.68) mm, (14.37 ± 4.22) mm, and (1.23 ± 0.39) mm, respectively, which were significantly lower than (11.26 ± 2.51) mm, (16.33 ± 4.01) mm, (19.87 ± 5.01) mm, (1.54 ± 0.48) mm in the control group ( t = 4.20, 2.26, 5.88, 3.51, all P < 0.001). Serum estradiol and prolactin levels in the observation group were (122.35 ± 29.76) ng/L and (205.64 ± 36.42) IU/L, respectively, which were significantly lower than (139.76 ± 30.48) ng/L and (251.49 ± 41.87) IU/L in the control group ( t = 2.86, 5.78, both P < 0.05). Serum progesterone level in the observation group was (9.22 ± 1.57) μg/L, which was significantly higher than (7.18 ± 1.21) μg/L in the control group ( t = -7.20, P < 0.05). Serum HIF-α and Ang-2 levels in the observation group were (0.15 ± 0.05) ng/L and (0.98 ± 0.11) ng/L, respectively, which were significantly lower than (0.24 ± 0.07) ng/L and (1.49 ± 0.22) ng/L in the control group ( t = 7.32, 14.51, both P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Qingruxiao granules combined with tamoxifen can effectively improve clinical symptoms, reduce tumor size, regulate endocrine hormone levels, decrease the expression of angiogenic factors in patients with breast hyperplasia, and is highly safe.
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OBJECTIVE@#To investigate the effect of Heliotropium indicum L. (H. indicum L.) on uterine involution and its underlying mechanisms in both in vivo and in vitro study.@*METHODS@#For in vivo studies, postpartum rats were randomly divided into 2 groups (n=24 for each): control group and treated group which were orally and daily administered with ethanolic extract of H. indicum L. (250 mg/kg body weight) until day 5 of postpartum. Uteri were collected for analysis of weight, cross-sectional area, collagen cross-sectional area, and collagen content on postpartum day 1, 3, and 5 (n=8 for each) from both groups. Blood samples were collected for hepatotoxicity and 17β-estradiol (E2) measurement. For in vitro studies, the extract effects on uterine contraction at half maximum effective concentration of 2.50 mg/mL were studied in organ bath system for at least 20 min.@*RESULTS@#Uterine parameters were significantly decreased after treated with extract of H. indicum L. (P<0.05). H. indicum L. extract significantly accelerated the reduction of those parameters and significantly decreased E2 (P<0.05). The extract facilitated uterine involution with no hepatotoxicity. H. indicum L. extract significantly stimulated uterine contraction (P<0.05) and synergized with oxytocin, prostaglandin and its precursor, linoleic acid. By investigating the different sequencing of the extract with the additional stimulants (added before or after), the two showed antagonistic effects, but still showed potentiated force when compared with control (without the stimulants).@*CONCLUSIONS@#The underlying mechanisms by which H. indicum L. facilitated uterine involution might be due to reducing E2 which induces collagenase activity, leading to decreases in uterine weight and size and stimulating uterine contraction. Our study provides new findings for future drug development for facilitating uterine involution with H. indicum L.
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Pregnancy , Female , Rats , Animals , Heliotropium , Uterus , Plant Extracts/pharmacology , Oxytocin , Collagen/pharmacologyABSTRACT
Objective To study the effect and mechanism of estradiol (E