RESUMEN
Although pregnancy is initiated and maintained through highly complex mechanisms, it is essential to understand the events that occur before and during early pregnancy to understand a healthy implantation process. The Notch signal, thought to be involved in this process, is frequently the subject of research with its different aspects. To better understand the role of Notch signaling in the peri-implantation period of the mouse uterus, we investigated the state of expression and localization of Notch 3, Notch 4, Rbp-J, Hes1, Hes7, Hey2, HeyL, and Fbw7 in the uterus and implantation sites in early pregnancy. Balb/C mice were divided into groups D1, D4, D5, D6, and D8. For D5 and D6 groups, implantation sites were identified by intravenous injection of Chicago blue. IHC, WB, and QRT-PCR methods were used. Notch 3 was very strong positive on the 4th day of pregnancy. Notch 4 was highly expressed on days 4, 5, 6, and 8 of pregnancy when P4 levels were high. Hes 1 level was at the lowest on the 4th day of pregnancy. Hes 7 protein expression gradually increased from D1 to D8 in the uteri and implantation sites. Hey 2 expression was at the highest level on the 1st and 4th days. Hey L expression was on the apical of the glands. Fbxw7 that expression was high on the 1st and 4th days of pregnancy. Notch signaling may play an essential role in regulating endometrial receptivity. In addition, our Hes7 results are new to the literature.
Asunto(s)
Implantación del Embrión , Factores de Transcripción , Embarazo , Femenino , Ratones , Animales , Factores de Transcripción/metabolismo , Útero , Endometrio/metabolismo , Transducción de Señal , Receptores Notch/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genéticaRESUMEN
PURPOSE: Develop a spectroscopic method to assess cartilage thickness during the arthroscopic examination. METHODS: Currently, arthroscopy assesses cartilage damage visually; outcomes are based on the surgeon's subjective experience. Light reflection spectroscopy is a promising method for measuring cartilage thickness based on the absorption of light by the subchondral bone. In the presented study, in vivo diffuse optical back reflection spectroscopic measurements were acquired by gently placing an optical fibre probe on different locations of the articular cartilage of 50 patients during complete knee replacement surgery. The optical fibre probe consists of two optical fibers with a diameter of 1 mm to deliver the light and detect back-reflected light from the cartilage. Centre to centre distance between the source and the detector fibers was 2.4 mm. Actual thicknesses of the articular cartilage samples were measured under microscopy using histopathological staining. RESULTS: Using half of the samples in the patient data, a linear regression model was formed to estimate cartilage thicknesses from the spectroscopic measurements. The regression model was then used to predict the cartilage thickness in the second half of the data. The cartilage thickness was predicted with a mean error of 8.7% if the actual thickness was less than 2.5 mm (R2 = 0.97). CONCLUSION: The outer diameter of the optical fibre probe was 3 mm, which can fit into the arthroscopy channel and can be used to measure the cartilage thickness in real-time during the arthroscopic examination of the articular cartilage.
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Cartílago Articular , Humanos , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Análisis Espectral/métodos , Artroscopía/métodos , Modelos LinealesRESUMEN
Nuclear factor-erythroid 2-related factor- 2 (Nrf2) is a nuclear transcription factor that facilitates transcription of genes for detoxification enzymes and antioxidant proteins. We investigated the distribution and expression of Nrf2 during the peri-implantation period. We detected Nrf2 in uteri of mice during estrus (control) and on days 1, 4, 5, 6 and 8 of pregnancy using immunohistochemistry, quantitative real-time polymerase chain reaction and western blotting. Nrf2 immunostaining was significantly greater on days 1, 5 and 6 of pregnancy compared to controls, and on days 4 and 8 of pregnancy; western blotting results were consistent with immunohistochemical observations. Nrf2 mRNA levels on days 5 and 8 were significantly higher than for control uteri. Increased expression of Nrf2 on days 1, 5 and 6 of pregnancy may be important for uterine receptivity, implantation and decidualization by protecting the developing embryo and uterus from the adverse effects of oxidative stress.
Asunto(s)
Implantación del Embrión , Factor 2 Relacionado con NF-E2 , Embarazo , Femenino , Ratones , Animales , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Útero/metabolismo , ARN Mensajero/metabolismo , Regulación de la Expresión GénicaRESUMEN
BACKGROUND: Fertilization, pre-implantation embryo development, implantation, and decidualization are critical for a healthy pregnancy. Successful implantation requires a competent blastocyst and a receptive uterus. Apelin was purified from the bovine stomach in 1998. Apelin receptor (APJ) is a member of G protein-coupled receptors. Apelin/APJ system's physiological role was shown in cardiovascular system, immune response, stress response, fluid regulation, nutrient uptake, angiogenesis, and adipoinsular axis; however, whether apelin/APJ system plays a role in implantation is unknown. In our study, we aimed to evaluate the localization and expressions of the apelin/APJ system in the peri-implantation period mouse uterus. METHODS: Uteri and implantation sites were collected from mice on the estrous phase and the 1st, 4th, 5th, 6th, and 8th days of pregnancy. Also, inter-implantation sites were collected from the 5th day of the pregnancy group. Localization and expressions of apelin and APJ were determined by immunohistochemistry and Western blot, respectively. RESULTS: Apelin and APJ were expressed in the luminal and gland epithelium, the stroma of all experimental groups. Two isoforms of apelin-8 and 16 kDa were detected by Western blot. While apelin expression increased from the estrous to the 8th day of pregnancy, APJ expression increased from the estrous to the 4th day of pregnancy, reached the highest expression level, then decreased. CONCLUSIONS: Our findings suggest that the apelin/APJ system might be involved in implantation and decidualization. Our findings will guide further studies and may help elucidate the underlying causes of implantation failure and pregnancy loss.
Asunto(s)
Receptores de Apelina , Apelina , Implantación del Embrión , Animales , Bovinos , Femenino , Ratones , Embarazo , Apelina/genética , Receptores de Apelina/genética , Endometrio/metabolismo , Péptidos y Proteínas de Señalización Intercelular , Receptores Acoplados a Proteínas G/metabolismo , Regulación del Desarrollo de la Expresión GénicaRESUMEN
PURPOSE: Events in the uterus during the peri-implantation period include embryo development, acquisition of uterine receptivity, implantation and decidualization. Hippo signaling pathway regulates cell proliferation, apoptosis and differentiation. We aimed to determine localization and expressions of pYAP (Phospho Yes-associated protein), YAP (Yes-associated protein), TEAD1 (TEA domain family member 1) and CTGF (Connective tissue growth factor), members of the Hippo signaling pathway, in the mouse uterus during the peri-implantation period. METHODS: Pregnant mice were randomly separated into 5 groups: 1st, 4th, 5th, 6th, and 8th days of pregnancy groups. Non-pregnant female mice in estrous phase were included in the estrous group. Uteri and implantation sites were collected. Also, inter-implantation sites were collected from the 5th day of pregnancy group. pYAP, YAP, TEAD-1 and CTGF were detected by immunohistochemistry and Western blotting. RESULTS: We observed that the expressions of YAP, TEAD-1 and CTGF were increased in the luminal and glandular epithelium on the 1st and 4th days of pregnancy when epithelial proliferation occurred. pYAP expression was high, and YAP and CTGF expressions were low in the luminal epithelium of the implantation sites on the 5th day of pregnancy, when epithelial differentiation occurred. pYAP expression was low, YAP and CTGF expressions were high at implantation sites on the 6th and 8th days of pregnancy, where decidua was formed. CONCLUSION: Our findings suggest that the Hippo signaling pathway might be involved in implantation and decidualization. Our findings will guide further studies and may help to elucidate underlying causes of implantation failure and pregnancy loss.
Asunto(s)
Vía de Señalización Hippo , Proteínas Señalizadoras YAP , Embarazo , Femenino , Ratones , Animales , Implantación del Embrión/fisiología , Útero/fisiología , Desarrollo EmbrionarioRESUMEN
PURPOSE: This study aims to investigate whether indomethacin (IND) delays preterm birth by regulating the Notch pathway, Tlr receptors, and Sp-A in the placenta in lipopolysaccharide (LPS)-induced preterm labor (PTL) model. METHODS: CD-1 mice were distributed to the pregnant control (PC), Sham, PBS, IND (2 mg/kg; i.p.), LPS (25 µg/100 µl; intrauterine), and LPS + IND groups. The injections were performed on day 14.5 of pregnancy. Placentae were collected on day 15.5 of pregnancy, and immunohistochemical analyzes were performed. Differences in staining intensities between the Cox-1, Notch-1 (N1), Dll-1, Jagged-2 (Jag-2), Tlr-2, and Tlr-4 proteins were compared. RESULTS: Preterm labor rates were 100% and 66% (preterm delivery delayed 5 h) in the LPS and LPS + IND groups, respectively. In LPS-treated mice, a general morphological deterioration was observed in the placenta. Total placental mid-sagittal measurement was significantly reduced in the LPS-treated group, while it was similar to the PC group in the LPS + IND group. Cox-1 expression in the LZ increased, and Sp-A expression decreased after LPS injection, and IND administration diminished this increase. N1 expression increased in the labyrinth zone (LZ) and the junctional zone (JZ). Dll-1 and Jag-2 expression increased in the JZ after LPS injection (p < 0.0001). IND administration diminished Tlr-2 expression in the LZ and Tlr-4 expression in the JZ after LPS injection. CONCLUSION: In conclusion, PG (prostaglandin) inhibition may alter Notch signaling, Tlr, and Sp-A protein expression and may be associated with delayed labor in LPS-induced mice.
Asunto(s)
Trabajo de Parto Prematuro , Nacimiento Prematuro , Animales , Femenino , Humanos , Recién Nacido , Lipopolisacáridos/toxicidad , Ratones , Placenta/metabolismo , Embarazo , Prostaglandinas/efectos adversos , Prostaglandinas/metabolismo , Tensoactivos/efectos adversos , Tensoactivos/metabolismo , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , ÚteroRESUMEN
Although it is thought that there is a close relationship between Notch signal and preterm birth, the functioning of this mechanism in the cervix is unknown. The efficacy of surfactants and prostaglandin inhibitors in preterm labor is also still unclear. In this study, 48 female CD-1 mice were distributed to pregnant control (PC), Sham, PBS, indomethacin (2 mg/kg; intraperitoneally), lipopolysaccharides (LPS) (25 µg/100 µl; intrauterine), LPS + IND, and Surfactant Protein A Block (SP-A Block: SP-A B; the anti-SP-A antibody was applied 20 µg/100µl; intrauterine) groups. Tissues were examined by immunohistochemistry, immunofluorescence, and Western blot analysis. LPS administration increased the expression of N1 Dll-1 and Jagged-2 (Jag-2). Although Toll-like receptor (Tlr)-2 significantly increased in the LPS-treated and SP-A-blocked groups, Tlr-4 significantly increased only in the LPS-exposed groups. It was observed that Jag-2 is specifically expressed by mast cells. Overall, this experimental model shows that some protein responses increase throughout the uterus, starting at a specific point on the cervix epithelium. Surfactant Protein A, which we observed to be significantly reduced by LPS, may be associated with the regulation of the epithelial response, especially during preterm delivery due to infection. On the contrary, prostaglandin inhibitors can be considered an option to delay infection-related preterm labor with their dose-dependent effects. Finally, the link between mast cells and Jag-2 could potentially be a control switch for preterm birth.
Asunto(s)
Cuello del Útero/efectos de los fármacos , Indometacina/farmacología , Proteína Jagged-2/metabolismo , Mastocitos/efectos de los fármacos , Nacimiento Prematuro/tratamiento farmacológico , Animales , Cuello del Útero/metabolismo , Cuello del Útero/patología , Femenino , Lipopolisacáridos/farmacología , Mastocitos/metabolismo , Mastocitos/patología , Ratones , Nacimiento Prematuro/metabolismo , Nacimiento Prematuro/patología , Proteína A Asociada a Surfactante Pulmonar/antagonistas & inhibidores , Proteína A Asociada a Surfactante Pulmonar/metabolismo , Receptores Notch/antagonistas & inhibidores , Receptores Notch/metabolismoRESUMEN
PURPOSE: Implantation is essential for a successful pregnancy. Despite the increasing number of studies, implantation is still an unknown process. This study aimed to determine whether sirtuin-1 has a role in embryo implantation in oxidative stress-induced mice. METHODS: Pregnant mice were separated into 5 groups: control, vehicle, paraquat, SRT1720, and SRT1720+Paraquat. Paraquat is a herbicide and is used to induce oxidative stress. SRT1720 is a specific sirtuin-1 activator. Implantation and inter-implantation sites were removed in the morning of the 5th day of pregnancy after Chicago blue injection was performed. Sirtuin-1 and Forkhead box O1 (FoxO1) were detected by immunohistochemistry and Western blot while acetylated lysine was evaluated by Western blot analysis. Reactive oxygen and nitrogen species (ROS/RNS) and superoxide dismutase (SOD) activity were determined by fluorometric and spectrometric methods, respectively. RESULTS: Although there was no embryo implantation in paraquat-treated mice, 5 out of 9 SRT1720+Paraquat-treated mice had implantation sites which were significantly higher compared to the paraquat-treated group. Sirtuin-1 and FoxO1 expressions were increased at implantation sites of SRT1720-treated mice. ROS/RNS levels were decreased, while deacetylated FoxO1 levels and SOD activity were increased in SRT1720-treated mice. CONCLUSION: Our findings suggest that sirtuin-1 may play a role in embryo implantation against oxidative stress through FoxO1-SOD signaling.
Asunto(s)
Implantación del Embrión/fisiología , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Estrés Oxidativo , Paraquat/toxicidad , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 1/metabolismo , Animales , Implantación del Embrión/efectos de los fármacos , Femenino , Herbicidas/toxicidad , Ratones , Ratones Endogámicos BALB C , Embarazo , Sirtuina 1/química , Sirtuina 1/genéticaRESUMEN
BACKGROUND: Prostate cancer is the most common cancer in men. A Notch signaling pathway is an important pathway in cell proliferation, differentiation, and fate. However, currently, the effects of abiraterone based-anti-androgene therapy and docetaxel, the most commonly used standard chemotherapy in prostate cancer treatment, on Notch signaling pathway are unknown. This study aimed to investigate the effects of abiraterone acetate and docetaxel on the expression of Notch1, Jagged1 and Hes1 in prostate cancer cell lines. METHODS: In vitro effects of abiraterone acetate and docetaxel were examined on Notch1, Jagged1, and Hes1 expression in LNCaP and PC3 PCa cell lines by immunofluorescence, Western blot, and qRT-PCR. MTT proliferation assay was used to evaluate cell proliferation and survival. RESULTS: We found that in the treatment of PC3 cells with abiraterone acetate, docetaxel, and their combination, only mRNA expressions of Notch1, Jagged1 and Hes1 were affected compared to control, but these expression differences were not observed in protein expression. In LNCaP cells, abiraterone acetate and the combination groups reduced Notch1 protein expression. All treatment groups did not alter Jagged1 expression compared to control, but significantly increased the Hes1 gene and protein expression. CONCLUSION: Our findings suggest that abiraterone and docetaxel treatments affects the expression of Notch signal pathway proteins. But these drugs especially cause significant upregulation in Hes1 expression in PCa cells. Therefore, co-application of Notch signaling inhibitors together with docetaxel and abiraterone chemotherapy, it was thought that decreased Hes1 expression could be stopped the deterioration of the prognosis of the patient.
Asunto(s)
Antagonistas de Andrógenos/farmacología , Androstenos/farmacología , Docetaxel/farmacología , Proteína Jagged-1/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptor Notch1/metabolismo , Factor de Transcripción HES-1/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Metástasis de la Neoplasia , Neoplasias de la Próstata/genética , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Varicocele, which is one of the causes of infertility in men, can be defined as the expansion of spermatic cord veins. The presence of apelin and apelin receptor (APJ) in many tissues and the effects of apelin have been reported in several studies. There is no study showing apelin and APJ protein expressions in normal and varicocele-induced testicular tissues. In this study, we aimed to demonstrate varicocele-induced changes in apelin and APJ expressions in testicular tissue by immunohistochemical and western blotting techniques. In our study, Wistar male rats were randomly divided into three groups as control, varicocele, and sham. While the control group rats were not subjected to any treatment, the unilateral varicocele model was created under anesthesia in the varicocele group. In the sham group, the left abdominal region was opened and closed to exclude the effect of the surgical procedure. At the 13th postoperative week, the left testes were obtained under anesthesia in all groups, and the immunohistochemistry and Western blotting techniques were used to detect apelin and APJ expressions. In our study; apelin and APJ were significantly expressed in control group's testicular tissue; apelin in testicular tissues of varicocele groups increased compared to the control group, whereas APJ expression decreased. In conclusion, the presence of apelin/APJ system in normal testis and the increased expression of apelin in varicocele-induced testicular tissue suggested that apelin may have a role in the varicocele etiopathogenesis.
Asunto(s)
Receptores de Apelina/genética , Apelina/genética , Cordón Espermático/metabolismo , Varicocele/genética , Animales , Modelos Animales de Enfermedad , Regulación del Desarrollo de la Expresión Génica/genética , Humanos , Infertilidad Masculina/genética , Infertilidad Masculina/patología , Masculino , Ratas , Cordón Espermático/irrigación sanguínea , Testículo/crecimiento & desarrollo , Testículo/metabolismo , Testículo/patología , Varicocele/metabolismo , Varicocele/patologíaRESUMEN
Apelin is a peptide that plays a role in physiological processes such as angiogenesis, apoptosis, and proliferation. The aim of this study was to investigate the role of capsaicin-sensitive afferent neurons and vagus in the effect of apelin against ischemia/reperfusion (I/R) injury. The experimental groups were (1) control, (2) I/R, (3) apelin + I/R, (4) vagotomy + I/R, (5) vagotomy + apelin + I/R, (6) capsaicin + I/R, (7) capsaicin + apelin + I/R, (8) lorglumide + I/R, and (9) lorglumide + apelin + I/R. To test the potential gastroprotective effect of apelin-13, apelin-13 (2 mg/kg i.v.) was administered just before both ischemia and reperfusion. A vagotomy was performed 1 week before I/R in the vagotomized groups; capsaicin (125 mg/kg s.c.) was administrated 2 weeks before I/R in the capsaicin-treated groups and lorglumide (5 mg/kg i.p.) was administered 30 min before I/R in the lorglumide-treated groups. After I/R, a variety parameters in gastric tissue were analyzed. cfos expression was determined in brainstem samples. In the I/R group, the lesion index, myeloperoxidase activity, lipid peroxidation, nitric oxide, and tumor necrosis factor-α increased, and mucosal blood flow, prostaglandin-E2, and calcitonin gene related peptide decreased. Apelin prevented the damaging effects of I/R and increased cfos expression in brainstem areas. Vagotomy, capsaicin, and lorglumide largely eliminated the gastroprotective effects of apelin-13. This study showed that sensory nerves and the vagus play regulatory roles in apelin-induced gastroprotection. Cholecystokinin may play a role in the effect of apelin through sensory neurons.
Asunto(s)
Péptidos y Proteínas de Señalización Intercelular/farmacología , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/fisiopatología , Células Receptoras Sensoriales/efectos de los fármacos , Estómago/efectos de los fármacos , Estómago/inervación , Nervio Vago/efectos de los fármacos , Animales , Citoprotección/efectos de los fármacos , Dinoprostona/metabolismo , Relación Dosis-Respuesta a Droga , Masculino , Óxido Nítrico/metabolismo , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Receptor de Colecistoquinina B/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Células Receptoras Sensoriales/patología , Nervio Vago/fisiopatologíaRESUMEN
Wide application of gonadotropin-releasing hormone (GnRH) agonists and antagonists for clinical purposes determines their effects on ovarian signaling pathways. Our study aimed to determine the localization, expression levels of Wnt signaling members in the pubertal and adult mouse ovary and the impact of GnRH antagonist cetrorelix on these signaling members. 0.5 mg/kg of cetrorelix was injected to 3-and 6-week-old mice for 2 weeks. At the end of injection, ovaries from 5 (5Ce)- to 8-week (8Ce)-old mice were embedded in paraffin for immunohistochemistry and homogenized for western blot to compare with control (5C-8C) and sham groups (5S-8S). WNT2 and WNT4 showed higher expression in thecal and stromal cells in adult mouse ovaries and only WNT4 expression was affected by cetrorelix. FZD1 was localized mainly in oocytes of pubertal ovaries and granulosa cells and oocytes of adult ovaries. FZD1 was reduced by cetrorelix in pubertal ovaries. FZD4 was abundantly localized in thecal and stromal cells of all groups and protein level was not affected by cetrorelix. LRP-6 was expressed mainly in oocytes and stromal cells of pubertal, oocytes of adult ovaries and its expression was reduced by cetrorelix in adult ovaries. CTNNB1 intensity in granulosa cells was the lowest in pubertal and the highest in adult ovaries and its expression was decreased by cetrorelix in adult ovaries. Cetrorelix affected the expression of specific members of the Wnt signaling depending on the developmental stage of mice, pointing out its possible interaction with gonadotropins during pubertal and adult stages.
Asunto(s)
Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Antagonistas de Hormonas/farmacología , Oocitos/efectos de los fármacos , Pubertad/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacos , Animales , Femenino , Hormona Liberadora de Gonadotropina/administración & dosificación , Hormona Liberadora de Gonadotropina/química , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Liberadora de Gonadotropina/farmacología , Antagonistas de Hormonas/administración & dosificación , Antagonistas de Hormonas/química , Ratones , Ratones Endogámicos BALB C , Oocitos/metabolismo , Pubertad/metabolismoRESUMEN
Parkinson's disease (PD) is a degenerative disorder of the human central and peripheral nervous systems. n-3 fatty acids docosahexaenoic acid (DHA, C22: 6n-3) and eicosapentaenoic acid (EPA) as well as apelin have anti-inflammatory effects in various cells. At the same time, apelin has anti-oxidative and anti-apoptotic effects. The study was conducted to determine the effect of DHA on the distribution of apelin and apelin receptor (APJ) in the central nervous system in 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP)-induced PD model. DHA treatment decreased the return time and total down time in the Parkinson group which were measured by pole test. Besides, the ambulatory activity, distance and total locomotor activity were increased by DHA in the PD model of animals. The time mice remained on the rotating rod mile was also significantly increased by DHA treatment in MPTP injected animals. The apelin expression in the pons of mice in the Parkinson, DHA and Parkinson + DHA groups were lower compared to the Control group. When apelin and apelin receptor expressions in cerebrum were examined, there was no statistically significant difference between the groups. When apelin receptor expression in cerebellum was examined, the difference between the Control and Parkinson + DHA, Parkinson and Parkinson + DHA, DHA and Parkinson + DHA groups were statistically significant. Apelin receptor expressions in pons of the Parkinson, DHA and Parkinson + DHA groups were lower compared to the Control group. Apelin protein levels of cerebellum and pons were found to be decreased in DHA group compare with Control group. In conclusion; DHA has been implicated in the expression of the apelin receptor and has reduced the expression of APJ receptor.
Asunto(s)
Receptores de Apelina/genética , Apelina/genética , Enfermedad de Parkinson/tratamiento farmacológico , Trastornos Parkinsonianos/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Ácidos Docosahexaenoicos/administración & dosificación , Ácido Eicosapentaenoico/administración & dosificación , Regulación de la Expresión Génica , Humanos , Ratones , Sistema Nervioso/efectos de los fármacos , Fármacos Neuroprotectores/administración & dosificación , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/patología , Trastornos Parkinsonianos/genética , Trastornos Parkinsonianos/patologíaRESUMEN
The complex and multifactorial mechanisms that initiate and sustain the early labor process in the human uterus and cervix are still not well defined. Cervical maturation or ripening is likely to play a key role in preparing for birth. Prostaglandins have many different functions, including the regulation of uterine contractility and structure during pregnancy. The prostaglandin E1 analogue misoprostol is frequently used as a uterotonic and cervical ripening agent. Notch is a transmembrane receptor family responsible for basic functions such as cell survival, cell-cell communication, and differentiation and decidualization in pregnancy. However, our understanding of the effect of Notch signaling on the cervical ripening process is limited. This study was conducted in 20 pregnant women aged at 12 to 20 weeks of gestation undergoing medical abortion for fetal or maternal indications. True-Cut needle biopsies were taken from the anterior cervix 4 hours after oral ingestion of 200-µg misoprostol or before the ingestion of misoprostol in the control group. Cervical expression of Notch receptors and ligands changed during the early phase of prostaglandin-induced preterm labor. Four hours after the administration of misoprostol, it was seen that N1 expression increased in muscle, while DLL1 and J2 expression increased in blood vessels, and N4 expression increased in macrophages. Knowing the mechanisms that initiate preterm birth is the most important step in planning the treatments and actions to prevent premature birth. As a signal that affects and perhaps directs preterm labor, Notch is prone to be an important actor in this process.
Asunto(s)
Abortivos no Esteroideos/uso terapéutico , Aborto Inducido , Cuello del Útero/efectos de los fármacos , Misoprostol/uso terapéutico , Receptores Notch/metabolismo , Contracción Uterina/efectos de los fármacos , Adulto , Proteínas de Unión al Calcio/metabolismo , Cuello del Útero/metabolismo , Femenino , Humanos , Proteína Jagged-2/metabolismo , Proteínas de la Membrana/metabolismo , Embarazo , Receptor Notch1/metabolismo , Transducción de SeñalRESUMEN
ABSTRACT Objective: To evaluate the effect of intravesical hyaluronic acid (HA) treatment on inflammatory cells and the severity of inflammation in an interstitial cystitis rat model created with hydrogen chloride (HCL) via immunohistochemical studies and myeloperoxidase activity for the first time in the literature. Materials and Methods: A total of 30 adult female white Rattus Norvegicus rats were divided into 3 groups as the HCL group, hyaluronic acid treatment (HCL-HA) group and control group. Chemical cystitis was created by administering HCL(400 microL,10 mM) except control group. A single dose of intravesical HA(0.5 mL,0.8 mg/mL) was administered to the treatment group. The bladder tissues of all subjects were immunohistochemically stained. The cell surface markers were used to evaluate inflammatory cell infiltration. Mast cell activation and IL-6 was evaluated to assess the inflammation and severity of inflammation, respectively. Myeloperoxidase activity was measured as it shows neutrophil density. Statistical significance was accepted as P<0.05. Results: It was observed that there was rich monocyte, T lymphocyte, B lymphocyte, and Natural Killer cells infiltration and high IL-6 levels in the bladder tissue after the intravesical hydrogen chloride instillation, especially in the stroma layer(p<0.005). In the HCL-HA group, severity of inflammation had statistically significantly regressed to the levels of the control group(p<0.005). An increase was observed in the bladder myeloperoxidase activity of the HCL group compared to the other two groups(p<0.05). Conclusions: Single dose intravesical hyluronic acid instillation reduces inflammatory cell infiltration and the severity of bladder inflammation in the rat model of bladder pain syndrome/interstitial cystitis.
Asunto(s)
Animales , Femenino , Ratas , Vejiga Urinaria/efectos de los fármacos , Cistitis Intersticial/tratamiento farmacológico , Ácido Hialurónico/uso terapéutico , Vejiga Urinaria/patología , Índice de Severidad de la Enfermedad , Administración Intravesical , Cistitis Intersticial/inducido químicamente , Cistitis Intersticial/patología , Modelos Animales de Enfermedad , Ácido ClorhídricoRESUMEN
OBJECTIVE: To evaluate the effect of intravesical hyaluronic acid (HA) treatment on inflammatory cells and the severity of inflammation in an interstitial cystitis rat model created with hydrogen chloride (HCL) via immunohistochemical studies and myeloperoxidase activity for the first time in the literature. MATERIALS AND METHODS: A total of 30 adult female white Rattus Norvegicus rats were divided into 3 groups as the HCL group, hyaluronic acid treatment (HCL-HA) group and control group. Chemical cystitis was created by administering HCL(400 microL,10 mM) except control group. A single dose of intravesical HA(0.5 mL,0.8 mg/mL) was administered to the treatment group. The bladder tissues of all subjects were immunohistochemically stained. The cell surface markers were used to evaluate inflammatory cell infiltration. Mast cell activation and IL-6 was evaluated to assess the inflammation and severity of inflammation, respectively. Myeloperoxidase activity was measured as it shows neutrophil density. Statistical significance was accepted as P<0.05. RESULTS: It was observed that there was rich monocyte, T lymphocyte, B lymphocyte, and Natural Killer cells infiltration and high IL-6 levels in the bladder tissue after the intravesical hydrogen chloride instillation, especially in the stroma layer(p<0.005). In the HCL-HA group, severity of inflammation had statistically significantly regressed to the levels of the control group(p<0.005). An increase was observed in the bladder myeloperoxidase activity of the HCL group compared to the other two groups(p<0.05). CONCLUSIONS: Single dose intravesical hyluronic acid instillation reduces inflammatory cell infiltration and the severity of bladder inflammation in the rat model of bladder pain syndrome/interstitial cystitis.
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Cistitis Intersticial/tratamiento farmacológico , Ácido Hialurónico/uso terapéutico , Vejiga Urinaria/efectos de los fármacos , Administración Intravesical , Animales , Cistitis Intersticial/inducido químicamente , Cistitis Intersticial/patología , Modelos Animales de Enfermedad , Femenino , Ácido Clorhídrico , Ratas , Índice de Severidad de la Enfermedad , Vejiga Urinaria/patologíaRESUMEN
Hypertension is an important health problem that is manifested by systemic arterial blood pressure being permanently elevated and leading to serious complications. Hypertension is the basis for coronary heart diseases, heart failure, kidney damage, cerebrovascular diseases. Due to ethical concerns, there is no detailed study of the mechanism, side effects and treatment of hypertension in humans. For this reason, specific studies related to the organ of hypertension are performed in experimental animals. The heart and kidney tissue, which are the most important organs that hypertension has damaged, have formed specific organs of our work. In our experimental study, a total of 35 (hypertensive group: 20, control group: 15) Rattus Norvegicus Wistar albino rats were used. In order to obtain our hypertension model, our experimental animals were given L-NAME together with drinking water for six weeks. After six weeks, the experimental procedures were terminated. Heart and kidney tissues of the hypertensive and control group were obtained. Expression of apelin and apelin receptor (APJ) was demonstrated by immunohistochemical and Western Blot protocols. Hypertrophic cardiac atrium of the hearts of the large cavities, interventricular septum and myocardium to the disintegration, as well as an increase in the diameter of the coronary artery has been observed. In general, kidney tissues of the hypertensive group showed narrowing in cortical renal structures and enlargement in structures in the renal medulla. As a result, in hypertensive cases, there was an increase in expression of Apelin and APJ receptor in heart tissue, and a decrease in expression of Apelin and APJ receptor in kidney tissue. We think that our findings may contribute to experimental or clinical studies related to hypertension and apelin.
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Receptores de Apelina/metabolismo , Apelina/metabolismo , Hipertensión , Riñón/metabolismo , Miocardio/metabolismo , Animales , Western Blotting , Peso Corporal , Modelos Animales de Enfermedad , Electroforesis en Gel de Poliacrilamida , Hipertensión/inducido químicamente , Inmunohistoquímica , NG-Nitroarginina Metil Éster/toxicidad , Ratas , Ratas Wistar , Estándares de ReferenciaRESUMEN
BACKGROUND: The cardiovascular system is a primary target of stress and stress is the most important etiologic factor in cardiovascular diseases. Stressors increase expressions of atrial natriuretic peptide (ANP) and apelin in cardiac tissue. AIM: The aim of the present study was to investigate whether stress-induced apelin has an effect on the expression of ANP in the right atrium of rat heart. METHODS: The rats were divided into the control, stress and F13A+stress groups. In the stress and F13A+stress groups, the rats were subjected to water immersion and restraint stress (WIRS) for 6h. In the F13A+stress group, apelin receptor antagonist F13A, was injected intravenously immediately before application of WIRS. The plasma samples were obtained for the measurement of corticosterone and atrial natriuretic peptide. The atrial samples were used for immunohistochemistry and western blot analysis. RESULTS: F13A administration prevented the rise of plasma corticosterone and ANP levels induced by WIRS. While WIRS application increased the expressions of apelin, HIF-1α and ANP in atrial tissue, while F13A prevented the stress-induced increase in the expression of HIF-1α and ANP. CONCLUSION: Stress-induced apelin induces ANP expression in atrial tissue and may play a role in cardiovascular homeostasis by increasing ANP expression under WIRS conditions.
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Receptores de Apelina/metabolismo , Apelina/metabolismo , Factor Natriurético Atrial/biosíntesis , Miocardio/metabolismo , Estrés Psicológico/metabolismo , Animales , Homeostasis/fisiología , Ratas , Ratas WistarRESUMEN
The objective of this study was to explore the role of apelin in the healing of gastric lesions induced by stress. Male Wistar rats were exposed to water immersion and restraint stress (WIRS) for 6 h with or without the apelin receptor antagonist F13A. The rats were killed on the 1st, 3rd, 5th or 10th day after the end of stress induction. Apelin and hypoxia-inducible factor-1α expression was increased on the 1st day after the end of stress exposure and was decreased daily thereafter. However, F13A retarded the healing of gastric lesions by preventing the improvement of mucosal blood flow, prostaglandin E2 production and vascular endothelial growth factor expression in rats exposed to WIRS. Additionally, F13A increased the gastric 4-hydroxynonenol + malondialdehyde content on the 1st and 3rd days after the end of stress induction but did not affect the change in gastric mucosal nitric oxide levels. In conclusion, apelin may be a regulatory protein involved in the healing mechanism of stress-induced gastric damage.
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Deshidratación/metabolismo , Mucosa Gástrica/metabolismo , Inmersión/fisiopatología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Restricción Física/fisiología , Estrés Fisiológico/fisiología , Animales , Apelina , Deshidratación/fisiopatología , Mucosa Gástrica/fisiopatología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Masculino , Malondialdehído/metabolismo , Óxido Nítrico/metabolismo , Ratas , Ratas Wistar , Estómago/fisiopatología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Agua/metabolismoRESUMEN
PURPOSE: To investigate the effect of medical ozone treatment on the experimental acute distal colitis in rats. METHODS: Eighteen rats were randomly distributed into three equal groups; control, acute distal colitis (ADC) without and with medical ozone treatment. Rats in the control group were taken saline. ADC was performed by rectal way with 4% acetic acid in groups 2 and 3, and the group 3 was treated with medical ozone for three weeks both rectally and intraperitoneally. At the twenty second day the distal colons samples were obtained for malondialdehyde and myeloperoxidase, blood samples were obtained to measure the levels of TNF-α and IL-1ß levels. Histolopatological examination was evaluated with Ki-67, IL-1ß and VEGF immunostaining densities. RESULTS: There was significant increase in tissue MDA, MPO activity, TNF-α and IL-1ß after ozone administration. There was also a significant difference at immunostaining densities of histopathological examination. CONCLUSIONS: Medical ozone treatment ameliorated the experimental acute distal colitis induced by acetic acid in rats. Its possible effect is by means of decreasing inflammation, edema, and affecting the proliferation and the vascularization.