جستجوی مقالات مرتبط با کلیدواژه "receptors" در نشریات گروه "پزشکی"

Developing a practical method to predict active systemic lupus erythematosus (SLE) in patients with inactive/mild status at the onset of the disease could lead to appropriate treatment that ultimately prevents future relapses. The development of SLE is influenced by steroid hormones and probably the receptors of these hormones. Therefore, we aimed to investigate the predictive effect of the levels of estradiol and testosterone hormones and their receptors on the severity of SLE disease. Serum samples were taken from 59 female patients with inactive SLE in Golestan province in northern Iran. The concentration of estradiol (E2) and testosterone (T) hormones and their receptors, estrogen receptors (ER) and androgen receptors (AR), was measured at the beginning of the study after sampling. After a one-year follow-up (2021 to 2022), the patients were divided into active and inactive SLE groups based on the clinical criteria of the SLE activity index. T test and Mann-Whitney U-test were used to analyze the difference of variables. The correlation was analyzed using Pearson and Spearman tests. Discriminative power was measured, and a cut-off point was suggested. There was a significant difference in the average E2+ER/T+AR ratio between active and inactive SLE groups (P<0.001). It was also found that this ratio has a significant correlation with the severity of the disease (r=0.546, P<0.001). Despite the normal concentration of each steroid hormone and its receptors, the E2+ER/T+AR ratio may be a good indicator of the development of active SLE.

Stress during pregnancy significantly impacts offspring early physiological programming. Herbal remedies are frequently used by pregnant women to enhance their wellbeing. Moringa oleifera Leaf Extract (MoLE) is believed to have both anti-stress and antioxidant properties which can act as a Selective Estrogen Receptor Modulator (SERM) that regulate activities of estrogen, and can have different effects on different tissues. Goal of this study is to compile information on molecular docking analysis of phytochemicals found in MoLE targeting Estrogen Receptor-alpha (ER-α) and assess effects of MoLE administration on dam's and fetal brain tissues and placenta, during gestational stress.

Phytochemical study of MoLE was determined using Gas Chromatography-Mass Spectrometry. Molecular docking technique was employed to predict aspects of interaction and binding affinities energy of bioactive phytocompounds in protein site of ER-α using autodock tools. 30 apparently healthy pregnant Albino-Wistar rats were randomly placed into 6 groups of 5 rats per group and exposed to Chronic Unpredictable Stress (CUS) protocol for two weeks, as follows: Group I (water and normal rat chow ad libitum), Group II (CUS protocol only), Group III (5 mg/kg body weight/day of MoLE), Group IV (10 mg/kg body weight/day of MoLE), Group V (CUS protocol +5 mg/kg body weight/day of MoLE), Group VI (CUS protocol +10 mg/kg body weight/ day of MoLE).

This study found that 1-Propanol, 3,3'-oxy bis- and 1, 2, 3-Trimethyldiazir-idine are most potent ligands for ER-α among all 41 compounds. Photomicrograph examination of tissues from stressed rats showed mild to severe alterations in histology. Consumption of MoLE during chronic stress showed mild to moderate protective effects.

These findings suggest that 1-Propanol, 3,3'-oxy bis- and 1, 2, 3-Trimethyldiaziridine can be further investigated for development of novel therapeutics.

The aim of this study is to review the role of renin-angiotensin in skin regeneration and wound healing with a focus on molecular mechanisms. Angiotensin receptor type 1 (AT1R) are abundant in the wounded area, and thus, lead to the activation of ERK, STAT1, and STAT3 which can lead to epidermal self-renewal. The expression of Renin Angiotensin System (RAS) components was significantly lower in wounds caused by burning, rather than intact skin, noting that RAS is involved in the re-epithelialization of skin. ERK, STAT and STAT3 are the targets of Ang II, indicating that RAS active components are involved in fibroblast, stem cells and keratinocyte migration. The effect of inhibiting the RAS on wound healing is context-dependent. On one hand, it is suggested that inhibiting RAS during this phase may slow down wound healing speed. On the other hand, studies have shown that RAS inhibition in this phase can lead to α-SMA activation, ultimately accelerating the wound healing process. Most of the investigations indicate that the inhibition of RAS with Angiotensin Receptor Blockers (ARBs) and Angiotensin Converting Enzyme (ACE) plays a significant role in tissue remodeling in the last phase of wound healing. It has been shown that the inhibition of RAS can inhibit scar formation and fibrosis through the downregulation of inflammatory and fibrogenic agents, such as TGF-β, SMAD2/3, and TAK1, PDGF-BB, and HSP47. To sum up, that local administration of RAS regulators might lead to less scar formation and inflammation in the last phase of wound closure.

 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