جستجوی مقالات مرتبط با کلیدواژه "17β-estradiol" در نشریات گروه "پزشکی"

 Exosomes are natural nanoparticles that participate in intercellular communication through molecular transport. Recently, due to their membrane vesicular structure and surface proteins, exosomes have been used extensively in the research field of drug delivery. Osteoporosis is an inflammation in which the cellular balance of bone tissue is disturbed that reduces bone density and making bone prone to abnormal fractures with small amount of force. Utilizing estrogen is one of the main therapeutic strategies for osteoporosis. Despite the positive effects of estrogen on bone tissue, changes in the natural estrogen levels of the body can cause a number of diseases such as different types of cancer. Therefore, designing a therapeutic system which controls more accurate tissue targeting of estrogen seems to be a rational and promising practical approach.

 In this study, bone marrow mesenchymal stem cells (BMMSCs)-derived exosomes were loaded by estradiol using two different methods of drug loading, namely incubation and sonication methods and then the survival effects of the drug loaded exosomes on BMMSCs was investigated.

 Examination of size, shape, and surface factors of exosomes in different states (pure exosomes and drug-loaded exosomes) showed that the round morphology of exosomes was preserved in all conditions. However, the particles size increased significantly when loaded by sonication method. The increased survival of BMMSCs was noted with estradiol-loaded exosomes when compared to the control group.

 The results suggest that estradiol-loaded exosomes have potential to be used as nano-drug carriers in the treatment of osteoporosis.

TNF-α, as a pro-inflammatory cytokine in the tumor microenvironment is able to regulate the expression and function of various ATP binding cassette (ABC) transporters involved in clinical drug resistance and among them, ABCC2 transporter is represented to contribute to cancer multidrug resistance (MDR) by drug efflux.

In this study, we aimed to evaluate the effects of TNF-α and/or E2 (17β-estradiol) on the mRNA and protein expression levels of ABCC2 and NF-κB (p65) transcription factor in estrogen receptor positive (ER+) MCF-7 cells by QRT-PCR and Western blot analysis. Also, we used MTT assay to study the cell sensitivity against the active form of tamoxifen (4OH-TAM), a hypothetical substrate and Cisplatin (Cis), a well-known substrate for ABCC2 used in endocrine and chemo-therapy of breast cancers, respectively. Data were analyzed by one-way ANOVA and Tukey tests. Significance was considered in P-values < 0.05.

The expression levels of ABCC2 and the active form of NF-κB (p65) were significantly increased following 20-day concomitant treatment with TNF-α and E2, compared to untreated cells as control. Also, the viability assay showed that 20-day TNF-α+E2 treatment led to more sensitivity reduction of MCF-7 cells to Cis and 4OH-TAM compared to E2-treated and untreated cells.

Based on our findings, there is a positive correlation between ABCC2 overexpression, over-activity of NF-ҡB/p65 and decreasing the sensitivity of MCF-7 cells to Cis and 4OH-TAM following TNF-α treatment in MCF-7 cells. Further experiments are needed to elucidate possible mechanistic relationship of these findings and their clinical significance in order to circumvent the drug-resistance in breast tumors.

Breast cancer is a hormone-dependent malignancy that is associated with estrogen and progesterone interactions. The liver is the most important organ to be affected by the metastasis of breast cancer, which causes functional impairment. We compared levels of obesity, 17β-estradiol, and secreted proteins in postmenopausal women with breast cancer but without hepatic symptoms to those in healthy postmenopausal women.
We recruited 105 postmenopausal women with breast cancer but without any clinical hepatic symptoms based on a physician’s diagnosis, and 105 healthy postmenopausal women. After taking blood samples, we separated the serum and determined the levels of alanine aminotransferase (ALT), enzyme aspartate aminotransferase (AST), sex hormone-binding globulin (SHBG), and 17β-estradiol using an enzyme-linked immunosorbent assay (ELISA). The results were statistically analyzed using SPSS.
The mean ages of the subjects in the cancer and control groups were 60.88 ± 0.85 and 55.56 ± 0.81 years, respectively. The exception ages (p=0.002), body mass index (BMI) values (p=0.033), serum glutamic oxaloacetic transaminase (SGOT) levels/AST levels (p=3.1*10-4), serum glutamic pyruvic transaminase (SGPT) levels/ALT levels(p=0.001), SHBG levels(p=0.014), and 17β-estradiol levels(p=0.003) in the serum differed significantly between the groups. Moreover, the mean serum 17β-estradiol (E2) levels and weights were higher in the cancer group than in the control group. Nevertheless, the mean serum levels of synthetic liver enzymes (SHBG, ALT, and AST) were lower in the cancer group than in the control group.
In general, the postmenopausal cancer patients had higher serum estrogen levels and BMIs than their healthy counterparts. Furthermore, the levels of liver enzymes apparently decreased in the cancer group, probably owing to liver malfunction.

Estrogen is a steroid hormone that plays a key role in the development and regulation of reproductive system. It has been shown that estrogen is related to breast cancer development through binding to its receptors. In order to uncover the estrogen effects on adenosine receptor expression, estrogen-positive MCF-7 cells were used to treat with agonist and antagonist of estrogen and then the mRNA expression of adenosine receptor subtypes were evaluated. Estrogen-positive MCF-7 cells were treated with various concentrations of 17β estradiol (E2) as an estrogen agonist, and ICI 182,780 as an estrogen antagonist. The gene expression of adenosine receptor subtypes were detected by real time RT-PCR. The results of MTT assay showed that E2 increased cell viability in a dose dependent manner. The expression pattern of all adenosine receptor subtypes are as follow; A2b > A1 > A2a > A3 in untreated MCF-7 cells. Obtained results showed that E2 incubation at 0.001-0.01 µM led to up-regulation of A1ARs, A2aARs and A3ARs dose dependently. E2 at 0.001 µM also had no significant effect on A2bARs expression but, at higher doses induced a considerable decrease in mRNA A2bARs expression. Treatment with antagonist confirmed that up-regulation of these receptors is mediated by estrogen receptor. Taken together, our results indicate that treatment of MCF-7cells with E2 led to up-regulation of adenosine receptors. However, these effects were partially restored by treatment with antagonist suggesting that such effects are mediated by estrogen receptors.

The 17β-estradiol acts as a neurosteroid in the brain and modulates nociception by binding to the estrogen receptors and also by allosteric interaction with other membrane-bound receptors like glutamate receptors. Paragigantocellularis lateralis nucleus (LPGi) is one of the important brain regions implicated in the pain modulation. So, this study was designed to evaluate the possible involvement of the membrane-bound AMPA receptors of LPGi nucleus in the pain modulatory effect of intra-LPGi 17β-estradiol in the male rats.
In order to study the pain modulatory effect of intra-LPGi microinjection of 17β-estradiol, cannulation into the LPGi nucleus was performed. Then, 500 nl of saline, 17β-estradiol and CNQX- the AMPA receptor antagonist- were unilaterally administered into the right LPGi by injection cannula and Hamilton syringe. In addition, for assessing the role of the AMPA receptors in the pain modulation by 17β-estradiol, 17β-estradiol was injected 15 min after the intra-LPGi administration of CNQX. Then, 50 μl of 4% formalin was subcutaneously injected into the plantar surface of contralateral hind paw and the number of paw jerking behavior was observed for 60 min.
The results showed that intra-LPGi injection of 0.8 μmol of 17β-estradiol attenuated the chronic phase (P Considering the results of this study, it can be concluded that the analgesic effect of intra-LPGi injection of 17β-estradiol might be mediated via AMPA receptors.

The nucleus paragigantocellularis lateralis (LPGi) is involved in the descending pain modulation. The neurostreoid, 17β-estradiol found in the PGi nucleus and modulates nociception by binding to estrogen receptors and also by allosteric interaction with NMDA receptors. In this study, the role of NMDA receptors in the 17β-estradiol-induced pain modulation was investigated by assessing the inflammatory pain responses changes after blockade of the LPGi nucleus’ NMDA receptors.
In order to study the antinociceptive effect of intra-LPGi microinjection of 17β-estradiol, a guide cannula was implanted into the right LPGi nucleus. 500 nl of drugs were administered 15 minutes prior to formalin (50 μl of 4%) injection. Then, formalin-induced paw jerking behaviour was recorded for 60 min. For assessing the role of the NMDA receptors in the pain modulation by 17β-estradiol, it was injected 15 min after the intra-LPGi administration of 0.5 nmol of AP5 (the NMDA receptor antagonist); and paw jerking frequency was recorded for 1 h.
The results of the present study showed that intra-LPGi injection of 0.8 μmol of 17β-estradiol attenuated the chronic phase (P According to the results of this study, it can be concluded that the analgesic effect of intra-LPGi injection of 17β-estradiol on the formalin-induced inflammatory pain might be mediated via NMDA receptors.

Previous studies have demonstrated the potential of monotherapy with either mesenchymal stem cells (MSCs) or estrogen in autoimmune and cuprizone models of multiple sclerosis (MS). The aim of this study was to examine the effects of co-administration of 17β-estradiol (E2) and adipose-derived mesenchymal stem cells (ADSCs) on remyelination of corpus callosum axons in a cuprizone model of MS. Forty eight male C57BL/6 mice were fed cuprizone (0.2%) for 6 weeks. At day 0 after cuprizone removal, animals were randomly divided into four groups. The E2 monotherapy, ADSCs monotherapy, E2/ADSCs combined therapy and vehicle control. Some mice of the same age were fed with their normal diet to serve as healthy control group. E2 pellets, designed to release 5.0 mg E2 over 10 days, were implanted subcutaneously. 106 PKH26 labeled ADSCs were transplanted into lateral tail. The extent of demyelination, remyelination, and cell type's composition of host brain were examined at 10 days post-transplantation in the body of the corpus callosum. Transplanted cells migrated to the corpus callosum injury. Histological examination revealed efficacy of intravenous ADSCs transplantation in remyelination of mouse cuprizone model of MS can be significantly enhanced by E2 administration. Flow cytometry showed that the mean percentages of expression of Iba-1, Olig2 and O4 were significantly increased in E2/ADSCs combined therapy in comparison with ADSCs monotherapy. In conclusion, the findings of this study revealed that E2 administration enhanced efficacy of intravenous ADSCs transplantation in remyelination of corpus callosum axons in mouse cuprizone model of MS.