جستجوی مقالات مرتبط با کلیدواژه « receptors » در نشریات گروه « پزشکی »

 Current therapies for depression are moderately effective, as response and remission rates were reported at 50% and 15-40%, following the first trial with current medications, respectively, and electroconvulsive therapy is not beneficial for more than half of the resistant patients. Recent research suggests that medication with glutamatergic modulatory properties may have antidepressant effects and would be of benefit to refractory patients. This study aims to review the efficacy of these medications in the treatment of unipolar depression. Ketamine, as the leading drug acting through the glutamatergic system, appears to be effective in treating depression IV and orally and in combination with electroconvulsive therapy. There is also clinical evidence of the promising effects of amantadine and lanicemine. Supplements and herbs such as L-carnosine, Crocus sativus (saffron), and Cinnamomum tamala, which were reported to be effective in randomized controlled trials on patients with depression, may act through this system as an antidepressant. Taken together, glutamate receptor modulators are alternative drugs for patients with resistant depression. Further high-quality clinical studies are recommended.

Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism. 

Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey’s post hoc test and Chi square test. P<0.05 was considered statistically significant.

Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high post-implantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001).

Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects.

A solitary fibrous tumor (SFT) of the pleura is a rare chest wall mesenchymal neoplasm which usually arises from CD34-positive sub-mesothelial mesenchymal cells of visceral pleura. It is rare, accounting for less than 5% of all pleural neoplasms. Recently, steroid hormone receptors were recognized in the cells of extra-pleural SFT. Progesterone may participate as a growth factor in many CD34 (+) stromal neoplasms. During pregnancy, the amount of plasma progesterone gradually increases. As a result, it could promote the development of cancers that rely on progesterone. However, the link between SFT and pregnancy has not yet been established. There are only six extra-thoracic SFT-reported cases with accelerated growth during pregnancy, on the literature. Hence, we reported an interesting case of SFT which is the first reported case of thoracic SFT presenting during pregnancy. Moreover, we attempted to clarify the mechanism of this tumor's rapid growth by examining its hormonal receptors status in the cells of this tumor.

 Due to the lack of research on pediatric urolithiasis (PU) in Iran, this case-control study aimed to assess the correlation of vitamin D receptor (VDR) gene polymorphisms in the Iranian population living in Kerman, Iran.

 This study was conducted on 90 outpatients with urinary calculi (49 female and 41 male subjects with a mean age of 4.55 ± 3.005 years) and 90 healthy children (39 female and 51 male subjects with a mean age of 5.6 ± 3.67 years) without a history of urolithiasis as the control group. Deoxyribonucleic acid was extracted from the blood samples of all patients and healthy subjects, and TaqI genotyping was performed via the restriction fragment length polymorphism method.

 TaqI single-nucleotide polymorphisms (rs731236) were shown to be associated with a higher incidence of PU. Multivariable logistic regression analysis demonstrated that carriers with the C allele of TaqIrs731236 had a considerably higher risk of PU than the control group (odds ratio = 1.94; 95% confidence interval = 1.24 - 2.96; P = 0.004).

 The obtained findings demonstrated that C allele (rs731236) and CC variant genotypes were considerably linked with a higher risk of PU in children in the Iranian population.

Cirrhotic cardiomyopathy is a well-recognized cardiac dysfunction in cirrhotic patients. Studies have confirmed the protective effects of silymarin in different types of cardiac injury. This study aimed to examine the effectiveness and molecular mechanism of silymarin against myocardial dysfunction and hypertrophy in a rat model of cirrhosis.  The experiment was performed at Alborz University of Medical Sciences (Karaj, Iran) during 2020-2021. Thirty-two male Wistar rats were randomly divided into four groups of Sham-operated (control group for surgical procedures), Bile Duct Ligated (BDL), and two Silymarin extract (SE)-treated groups of 300 and 600 mg/Kg/day. After 28 days, serum levels of AST, ALT, GGT, and ALP, liver histopathological status, as well as cardiac mechanical function, were assessed. Cardiac β1-adrenergic receptors (β1-AR), L-type voltage-dependent calcium channels (L-VDCC), and GATA4 mRNA expression were also determined using real-time RT-PCR. Data analysis was performed using the one-way ANOVA followed by Duncan’s multiple range test. Histological data has been analyzed with Kruskal-Wallis nonparametric test. The analysis was performed at P≤0.05. BDL was associated with a significant elevation in serum AST, ALT, GGT, and ALP, development of necrosis and fibrosis of the liver texture, increased Heart Weight and Heart Weight to Body Weight ratio, enhanced cardiac mechanical function as well as a significant up-regulation of ventricular β1-AR and L-VDCC. Administration of SE600, but not SE300, significantly reduced the serum levels of the enzymes and alleviated signs of liver necrosis and fibrosis. Cirrhotic-induced cardiac dysfunction was also restored by SE600, but not by the lower dose. In addition, cardiac expression of the β1-AR and L-VDCC was down-regulated toward normal values by either higher or lower doses of the SE.  Silymarin treatment in higher dose attenuated cirrhosis-associated cardiac remodeling and reduced cardiac mechanical dysfunctions.

Metastasis is an important factor in the survival estimate of patients with breast cancer. The present study aimed to examine the frequency of epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression in relation to the metastatic site, pattern, and tumor size in patients with metastatic breast cancer (MBC). In this retrospective study, the medical records of patients diagnosed with MBC at Motahari Clinic (Shiraz, Iran) during 2017-2019 were examined. Metastasis was confirmed using computed tomography, and a total of 276 patients were included in the study. Based on the expression of receptors, the patients were categorized into luminal A, luminal B, HER2, and TNBC groups. The frequency and percentage of receptors in relation to the metastatic site, size, and pattern were compared using the Chi square test. P<0.05 was considered statistically significant. The frequency of receptor positivity in the 276 selected medical records were of the subtype HER2-enriched (n=48), luminal A (n=43), luminal B (n=146), and TNBC (n=39). The most common metastatic sites were the bones (47.1%), lungs (34.4%), liver (27.9%), brain (20.3%), and other organs (12.7%). The first site of metastasis occurred in the bones (36.6%), lungs (17.4%), liver (15.6%), brain (10.5%), and other organs (7.6%). The frequency of receptor expression was different in relation to the first metastatic site (P=0.024). There was a statistically significant difference between the frequency of receptor expression in patients with bone (P=0.036), brain (P=0.031), and lung (P=0.020) metastases. The frequency of receptor expression was also significantly different in relation to the size of liver metastasis (P=0.009). Luminal A and B subtypes showed higher rates of bone metastasis as the first metastatic site. The difference in the frequency of receptor expression in relation to the metastatic site and tumor size can be used as predictive and prognostic factors in patients with breast cancer.

Glucocorticoids are pivotal components of immunosuppressive regimens in solid organ transplantations. This study aimed to assess the possible association between the ER22/23EK, N363S, and Bcl1 polymorphisms, and short-term clinical outcomes, including acute rejection and delayed graft function (DGF), in kidney transplantation recipients.

A case-control study was conducted in a two-year period on adults with transplanted kidneys, comprised of subjects without rejection (n=50, control) and those with documented rejection within one year after transplantation (n=50, case), between April 2017 and September 2018, in Shiraz, Iran. Demographic characteristics and clinical and paraclinical findings were gathered. The genotyping of the ER22/23EK, N363S, and Bcl1 polymorphisms was carried out via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The association between the genotypes and DGF as well as rejection types was evaluated using either the Chi square test or Fisher exact test. A stepwise logistic regression analysis was conducted to determine the independent factors of acute rejection within the first year after transplantation.

The study population consisted of 64 men and 36 women. The frequency of mutated alleles was 0.32 for G (Bcl1), 0.02 for S (N363S), and 0.065 for A (ER22/23EK). There was no significant association either between the studied polymorphisms and acute rejection or between the Bcl1 (P=0.17), N363S (P=0.99), and ER22/23EK (P=0.99) genotypes and DGF. The length of hospital stay after kidney transplantation was slightly more in N363N and ER22/23EK wild allele carriers. However, this difference was not statistically significant.

Our data suggested no statistically significant association between the genotypes of the studied polymorphisms and early clinical outcomes after kidney transplantation.

Based on this point that some of the cancers do not appropriately respond to conventional therapy and there is the possibility of relapse, immunotherapy is currently under investigation. Cancer immunotherapies are widely recognized as transformational for several cancers and enable to move to the front-line therapy with few side effects. One of its new branches is treatment with T-cells that have been changed their receptor. The research on these cells is generally according to the design of a receptor against a specific tumor antigen. Also, manipulation of regulatory T-cell (Tregs), as the barriers to useful immune responses in the tumor microenvironment, will promote Tregs -targeted therapeutic opportunities and improve the efficacy of the current cancer treatment, such as radiation and chemotherapy. This review attempts to show novel insights into the roles of Tregs in cancer which can be considered as a promising anticancer therapeutic strategy for targeting them and approaches for generation of tumor antigen-specific T lymphocytes (AST) using chimeric antigen receptors.

The release of dopamine (DA) in the posterior ventral tegmental area (pVTA) plays an important role in cue-related learning, reward, and relapse. On the other hand, studies have shown that the use of N-methyl-D-aspartate receptor (NMDAR) antagonist (AP5) inhibits the expression of morphine (5 mg/kg, s. c) conditioned place preference (CPP). In this study, we have tried to show the interaction effect of the DA stimulatory agents through D1-like receptor (D1R) agonist (SKF38393) and D2-like receptor (D2R) antagonist (eticlopride; through disinhibition) with NMDAR antagonist into the pVTA on the expression of morphine CPP.

The SKF38393 and eticlopride, individually and simultaneously (in ineffective doses), were injected into the pVTA with the AP5 in rats, and animals were then placed in a CPP apparatus.

Concomitant administration of D1R agonist (4 μg/rat) with NMDAR antagonist (1 μg/rat) induced the expression of morphine CPP, but the administration of D2R antagonist with NMDAR antagonist was unaffected on the expression of morphine CPP. Furthermore, concomitant administration of ineffective doses of D1R agonist and D2R antagonist with NMDAR antagonist had no effect on the expression of morphine CPP.

The results showed using higher doses of D1R agonist with NMDAR antagonist could reverse the blocked expression of morphine CPP by NMDAR antagonists, while, the use of D2R antagonist with NMDAR antagonist could not. Therefore, presynaptic receptors such as D1R probably through releasing other stimulatory neurotransmitters can play a vital role in the expression of morphine CPP and cue-related learning.

Leptin and leptin receptor (Ob-R) are associated with worse prognosis, distant metastasis, and poor survival of breast cancer. We investigated the cytotoxic effect of silibinin and curcumin, individually and combined, on Ob-R expression in MCF-7 cells.

This study was performed from October 2017 to April 2018 at the Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. The cytotoxic effect of silibinin and curcumin, individually and combined, and their corresponding half-maximal inhibitory concentration (IC50) values were determined using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. The cells were treated with different concentrations of silibinin (50-400 μM), curcumin (10-35 μM), and their combinations for 24 and 48 hours. The expression of Ob-R was measured using the Western blot analysis by treating the cells with different concentrations of curcumin (10-25 μM), silibinin (50-250 μM), and their respective combinations. The difference in mean cell viability between the groups was calculated using one-way ANOVA followed by Tukey’s post hoc test.

Silibinin and curcumin exerted time- and dose-dependent cytotoxic effect on MCF-7 cells. After treatment with silibinin, the IC50 values were about 250 and 50 μM at 24 and 48 hours, respectively. In terms of treatment with curcumin, the IC50 values were about 25 and 15 μM at 24 and 48 hours, respectively. Following treatment with silibinin, the Western blot analysis showed that Ob-R expression significantly decreased at 150 μM (P=0.031) and 200 μM (P=0.023) concentrations. Curcumin did not significantly decrease the Ob-R expression, however, the expression significantly decreased (P=0.004) when it was combined with silibinin.

The combination of silibinin and curcumin significantly reduced Ob-R expression in MCF-7 cells compared with their individual effects.

Intense stress can change pain perception and induce hyperalgesia; a phenomenon called stress-induced hyperalgesia (SIH). However, the neurobiological mechanism of this effect remains unclear. The present study aimed to investigate the effect of the spinal cord µ-opioid receptors (MOR) and α2-adrenergic receptors (α2-AR) on pain sensation in rats with SIH.

Eighteen Sprague-Dawley male rats, weighing 200- 250 g, were randomly divided into two groups (n=9 per group), namely the control and stress group. The stress group was evoked by random 1-hour daily foot-shock stress (0.8 mA for 10 seconds, 1 minute apart) for 3 weeks using a communication box. The tail-flick and formalin tests were performed in both groups on day 22. The real-time RT-PCR technique was used to observe MOR and α2-AR mRNA levels at the L4-L5 lumbar spinal cord. Statistical analysis was performed using the GraphPad Prism 5 software (San Diego, CA, USA). Student’s t test was applied for comparisons between the groups. P<0.05 was considered statistically significant.

There was a significant (P=0.0014) decrease in tailflick latency in the stress group compared to the control group. Nociceptive behavioral responses to formalin-induced pain in the stress group were significantly increased in the acute (P=0.007) and chronic (P=0.001) phases of the formalin test compared to the control group. A significant reduction was also observed in MOR mRNA level of the stress group compared to the control group (P=0.003). There was no significant difference in α2-AR mRNA level between the stress and control group.

The results indicate that chronic stress can affect nociception and lead to hyperalgesia. The data suggest that decreased expression of spinal cord MOR causes hyperalgesia.

The innate immune system against malignancies is mainly orchestrated by natural killer cells, which carry out killing mechanisms by using their receptors, such as killer immunoglobulin-like receptors (KIRs). This study was designed to determine the diversity of KIR genes in non-melanoma skin cancers. A total of 160 subjects with skin cancer, including 60 cases of squamous cell carcinoma and 100 cases of basal cell carcinoma (BCC), and 270 healthy subjects formed the study groups. The sequence-specific polymerase chain reaction was carried out to detect the presence or absence of 16 KIR genes. KIR3DL1 (p = 0.0381, OR = 4.78, 95% CI = 1.108 to 20.62) increased in BCC patients compared to healthy controls. We concluded that the higher frequency of KIR3DL1 in BCC patients compared with healthy controls may increase the probability of developing BCC in Iranians.

Crocin, a component of saffron, showed hypotensive which is perhaps due to vascular smooth muscle relaxant effect. The relaxant effects of saffron on tracheal smooth muscle also could be due to its constituent, crocin. In the present study, the relaxant effects of crocin and its possible mechanisms on rat tracheal smooth muscle were investigated. The relaxant effects of three cumulative concentrations of crocin (30, 60, and 120 μM) or theophylline (0.2, 0.4, 0.6 mM) as positive control was examined on pre-contracted tracheal smooth muscle by methacholine or KCl in non-incubated or incubated conditions with different agents including atropine, chlorpheniramine, indomethacin, diltiazem, glibenclamide and propranolol. In non-incubated tracheal smooth muscle, crocin showed significant relaxant effects on KCl induced muscle contraction (p

Breast cancer is an important cause of death among women. Prevention of cancer through dietary intervention has recently received increasing interest. Lately, dietary polyphenols have gained much attention for their health benefits, including anticancer properties. Dalbergin as a polyphenol is synthesized from a common neoflavene intermediate. This study aimed to examine whether dalbergin can be useful in the chemotherapy of estrogen receptor-positive T47D cell line. This experimental study was performed at the Laboratory of Biophysics and Molecular Biology, the Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran, from October 2017 to November 2019. The doubling time of T47D cells was obtained from the growth curve. The cytotoxic effect of dalbergin on T47D breast cancer cells was evaluated. To assess the clonogenic ability, T47D cells were treated with dalbergin for 48 hours and then, the colony assay was performed. A Real-Time PCR was used to determine the transcription levels of p53, Bcl-2, and STAT3 genes. The doubling time of T47D cells was 28.02 ± 4.22 hours (P < 0.05). Dalbergin decreased the viability of the T47D cell line. The half-maximal inhibitory concentration (IC50) values of dalbergin for T47D cells were found to be 1 µM in 24 hours, 0.001 µM in 48 hours, and 0.00001 µM in 72 hours of treatment (P < 0.05). In the clonogenic assay, 0.001 µM dalbergin for 48 hours could reduce the surviving fraction of T47D cells (P < 0.05). Additionally, dalbergin could change the mRNA levels of p53, Bcl-2, and STAT3 genes (P < 0.05). Our results indicated that dalbergin has some anticancer effects probably through inducing apoptosis in cancerous cells by changing mRNA levels of apoptosis-related proteins.

Cancer is the second leading cause of death globally, and it was responsible for almost 9.6 million deaths in 2018. Breast cancer (BC) is the most common cancer among women with almost two million new cases worldwide in 2018. Thus, it is necessary to study new methods to estimate the survival predictive factors in BC patients. This cohort study aimed to fit a Cox model to BC data using partial likelihood (PL) and new maximum penalized likelihood (MPL) methods in order to determine the predictive factors of survival time and compare the accuracy of these two methods. This prospective cohort study used the data of 356 women with BC registered at the Cancer Research Center of Shahid Beheshti University of Medical Sciences in Tehran, Iran. The patients were identified from 1999 to 2015. The Cox model by new MPL and PL methods was used with variables such as the stage of cancer, tumor grade, estrogen receptor, and several other variables for univariate and multiple analyses. The mean age ± standard deviation (SD) of patients at diagnosis was about 48 ± 11.27 years ranging from 24 to 84 years. Using the new MPL method, in addition to lymphovascular invasion and recurrence variables, estrogen receptor (P = 0.045) also had a statistically significant relationship with survival. The standard errors of most variables were smaller when using the MLP method than the PL method. The overall one-year, two-year, five-year, and 10-year survival rates based on the baseline hazard estimate were 96%, 92%, 70%, and 51%, respectively. In the analysis of BC data, new MPL method can help identify the factors that affect the survival of patients more accurately than usual methods do. This method decreases the standard error of most variables and can be applied for identifying predictive factors more accurately than previous methods.

Promising therapeutic agents for the symptoms in animal models of fragile X syndrome (FXS) have not resulted in similar advances in clinical trials of humans with FXS due to the dearth of tools to quantify their key cognitive and behavioral outcomemeasures with optimal validity and reliability. Therefore, experts strongly recommended an effort to develop and implement use of biomarkers in unfolding clinical trials in FXS. Molecular imaging provides a spectrum of agents to serve as biomarkers to confirm that humans with FXS exhibit the molecular abnormalities of animal models of FXS. Thus, molecular imaging provides the mechanism to establish target engagement in humans for clinical trials of novel agents for FXS.

Postoperative pain is a major complication in patients undergoing eye surgery. N-methyl-D-aspartate (NMDA) receptor antagonists are widely used to manage postoperative pains. Dextromethorphan, as an NMDA antagonist, is commonly used as an oral drug. This study was conducted to evaluate the effect of Dextromethorphan on post-operation pain and sedative effect in comparison to placebo. A double-blinded, placebo-controlled, randomized clinical trial, upon 60 patients undergoing vitrectomy surgery was done. Thirty patients received 30 mg oral Dextromethorphan before the operation, and 30 patients received a placebo. Post-operation pain and sedation were evaluated after zero, one, two, and six hours. Post-operation pain was significantly lower in patients who received Dextromethorphan at zero, one, and two hours after operation (P < 0.001); however, not at six hours after operation (P = 0.11). Sedative effect was higher in the Dextromethorphan group at zero (P = 0.03) and one hour (P = 0.01) after operation. Prescribing oral Dextromethorphan before a vitrectomy surgery could reduce postoperative pain. It also has postoperative sedation effects.