Expression of Cannabinoid Receptors in Myometrium and its Correlation With Dysmenorrhea in Adenomyosis

2019 ◽  
Vol 26 (12) ◽  
pp. 1618-1625 ◽  
Author(s):  
Xue Shen ◽  
Hua Duan ◽  
Sha Wang ◽  
Wei Hong ◽  
Yu-Yan Wang ◽  
...  

The myometrium, especially the junctional zone (JZ), is now well documented to have a role in the pathogenesis of adenomyosis. Cannabinoid receptors have been shown to participate in the establishment of endometriosis and its pain perception. However, its relation to adenomyosis has not been identified yet. The aim of this study was to investigate the expression of cannabinoid receptor type I (CB1) and type II (CB2) in myometrium of uteri with and without adenomyosis and determine the correlation between their levels and clinical parameters of adenomyosis. We collected tissue samples of JZ and the outer myometrium from 45 premenopausal women with adenomyosis and 34 women without adenomyosis. CB1 and CB2 messenger RNA (mRNA) and protein expression levels were evaluated by the use of Western blotting and real-time quantitative polymerase chain reaction from all samples. Clinical information on the severity of dysmenorrhea and other data were collected. We found both CB1 and CB2 mRNA and protein levels in women with adenomyosis were significantly higher than those of controls, and CB1 expression levels in JZ were positively correlated with the severity of dysmenorrhea. These data suggest that cannabinoid receptor CB1 may be involved in the pathogenesis of dysmenorrhea in adenomyosis and may be a potential therapeutic target.

2021 ◽  
Vol 15 ◽  
Author(s):  
Alejando Fuerte-Hortigón ◽  
Jaime Gonçalves ◽  
Laura Zeballos ◽  
Rubén Masa ◽  
Ricardo Gómez-Nieto ◽  
...  

The endocannabinoid system modulates epileptic seizures by regulating neuronal excitability. It has become clear that agonist activation of central type I cannabinoid receptors (CB1R) reduces epileptogenesis in pre-clinical animal models of epilepsy. The audiogenic seizure-prone hamster GASH/Sal is a reliable experimental model of generalized tonic-clonic seizures in response to intense sound stimulation. However, no studies hitherto had investigated CB1R in the GASH/Sal. Although the distribution of CB1R has been extensively studied in mammalian brains, their distribution in the Syrian golden hamster brain also remains unknown. The objective of this research is to determine by immunohistochemistry the differential distribution of CB1R in the brains of GASH/Sal animals under seizure-free conditions, by comparing the results with wild-type Syrian hamsters as controls. CB1R in the GASH/Sal showed a wide distribution in many nuclei of the central nervous system. These patterns of CB1R-immunolabeling are practically identical between the GASH/Sal model and control animals, varying in the intensity of immunostaining in certain regions, being slightly weaker in the GASH/Sal than in the control, mainly in brain regions associated with epileptic networks. The RT-qPCR analysis confirms these results. In summary, our study provides an anatomical basis for further investigating CB1R in acute and kindling audiogenic seizure protocols in the GASH/Sal model as well as exploring CB1R activation via exogenously administered cannabinoid compounds.


2020 ◽  
Vol 19 ◽  
pp. 153303382091795
Author(s):  
Liang Zhong Yao ◽  
Yan Li Zhu ◽  
Jun Jie Liu

The objective of this article is to study the effect of inhibiting phosphatase and tensin homolog deleted chromatosome 10 gene on phosphoinositide 3-kinase/protein kinase B ( Akt)/Forkhead homeobox O3a signaling pathway in human nasopharyngeal carcinoma HK-1 cells. Nasopharyngeal carcinoma HK-1 cell lines were divided into PTEN gene interference group (siPTEN), nonspecific small interfering RNA group (siNC), empty vector group (Vector), and no transfection control group (Normal). The mRNA and protein expression levels of PTEN, PI3K, p-Akt, and FoxO3a were detected by real-time fluorescence quantitative polymerase chain reaction and Western blot. Immunofluorescence was used to detect the subcellular localization of PTEN, PI3K, p-Akt, and FoxO3a in HK-1 cells. The proliferation of HK-1 cells was detected by MTT assay, and the apoptosis of HK-1 cells was detected by flow cytometry. Compared with the siNC group, the expression levels of PTEN, FoxO3a messenger RNA, and protein in the siPTEN group were significantly decreased ( P < .05), while the expression levels of PI3K, p-Akt messenger RNA, and protein were significantly increased ( P < .05). The growth rate of HK-1 cells in the siPTEN group was significantly higher than the siNC group ( P < .05), while the apoptosis rate was significantly lower than that of the siNC group ( P < .05). Small interfering RNA can inhibit the expression of PTEN in HK-1 cells, and PTEN can participate in the development of NPC by affecting PI3K/Akt/FoxO3a signaling pathway.


2020 ◽  
Vol 18 ◽  
pp. 205873922093460
Author(s):  
Junhua Li ◽  
Andong Li

It is suggested that programmed cell death protein-1 (PD-1) is involved in hepatitis B virus (HBV) infection, the leading cause of hepatocellular carcinoma globally. This study was multi-aimed, that is, to investigate the role of microRNA (miR) 4717 and its target, PD-1 and to determine how the rs10204525 polymorphism in the 3′ untranslated region (3′UTR) of PD-1 affects its interaction with miR-4717. The expression levels of miR-4717 with various single-nucleotide polymorphisms were measured by reverse transcription–quantitative polymerase chain reaction (RT-qPCR). A total of 54 tissue samples from HBV-infected individuals were collected, genotyped, and categorized into three groups; AA (n = 32), AG (n = 18), and GG (n = 4). The expression levels of gene PDCD1 and its corresponding PD-1 protein were significantly declined in the AA group as compared to AG and GG groups. There was a negative linear association between PDCD1 and miR-4717 in the tissue samples. HEPG2 cells transfected with an miR-4717 mimic or PD-1 small interfering (si)RNA exhibited significantly reduced expression levels of PDCD1 and PD-1, whereas cells transfected with an inhibitor of miR-4717 demonstrated greater expression levels of PDCD1 and PD-1 compared with the scramble control. In addition, cell viability and apoptosis were assessed in cells transfected with an miR-4717 mimic, PD-1 siRNA, or an miR-4717 inhibitor. Results revealed that treatment with the miR-4717 mimic or PD-1 siRNA enhanced viability of cells and reduced apoptosis. The results of this study suggest that rs10204525 polymorphism interferes with the interaction between PD-1 and miR-4717 and therefore induces apoptosis in liver cancer cells.


2019 ◽  
Vol 20 (10) ◽  
pp. 781-784 ◽  
Author(s):  
Meizhen Zhao ◽  
Li Juanjuan ◽  
Fan Weijia ◽  
Xie Jing ◽  
Huang Qiuhua ◽  
...  

Background: This study aimed to investigate the expression levels of microRNA (miRNA)-125b in serum exosomes and its diagnostic efficacy for asthma severity. Methods: The study included 80 patients with untreated asthma and 80 healthy volunteers. The patients were divided into 4 groups according to disease severity: 20 with the intermittent state, 20 with the mildly persistent state, 20 with the moderately persistent state, and 20 with the severely persistent state. The expression levels of miRNA-125b in serum exosomes of each group were detected using a quantitative polymerase chain reaction and compared. The Spearman correlation analysis was used to study the correlation between the expression levels of miRNA-125b in serum exosomes and asthma severity. The diagnostic efficacy of the expression levels of miRNA-125b in exosomes for asthma severity was evaluated using the Receiver Operating Characteristic (ROC) curve. Results: The expression levels of miRNA-125b in serum exosomes of patients with intermittent, mildly persistent, moderately persistent, and severely persistent asthma were all higher than those in the healthy control group, with statistically significant differences. The expression levels of miRNA-125b were also statistically significantly different among patients in each group. The Spearman correlation analysis showed a positive correlation of the relative expression of miRNA-125b in serum exosomes with asthma severity. The area under the ROC curve of the diagnostic efficacy of miRNA-125b in serum exosomes for patients with intermittent, mildly, moderately, and severely persistent asthma was 0.7770, 0.8573, 0.9111, and 0.9995, respectively. Conclusion: The expression levels of miRNA-125b in serum exosomes had a high diagnostic efficacy and might serve as a noninvasive diagnostic marker for asthma severity.


2020 ◽  
Vol 20 (7) ◽  
pp. 518-523
Author(s):  
Rugül Köse Çinar

Objective: Neuroserpin is a serine protease inhibitor predominantly expressed in the nervous system functioning mainly in neuronal migration and axonal growth. Neuroprotective effects of neuroserpin were shown in animal models of stroke, brain, and spinal cord injury. Postmortem studies confirmed the involvement of neuroserpin in Alzheimer’s disease. Since altered adult neurogenesis was postulated as an aetiological mechanism for bipolar disorder, the possible effect of neuroserpin gene expression in the disorder was evaluated. Methods: Neuroserpin mRNA expression levels were examined in the peripheral blood of bipolar disorder type I manic and euthymic patients and healthy controls using the polymerase chain reaction method. The sample comprised of 60 physically healthy, middle-aged men as participants who had no substance use disorder. Results: The gene expression levels of neuroserpin were found lower in the bipolar disorder patients than the healthy controls (p=0.000). The neuroserpin levels did not differ between mania and euthymia (both 96% down-regulated compared to the controls). Conclusion: Since we detected differences between the patients and the controls, not the disease states, the dysregulation in the neuroserpin gene could be interpreted as a result of the disease itself.


2019 ◽  
Vol 16 (10) ◽  
pp. 1167-1174 ◽  
Author(s):  
Kamil J. Kuder ◽  
Tadeusz Karcz ◽  
Maria Kaleta ◽  
Katarzyna Kiec-Kononowicz

Background: : One of the best known to date GPCR class A (Rhodopsin) includes more than 100 orphan receptors for which the endogenous ligand is not known or is unclear. One of them is N-arachidonyl glycine receptor, named GPR18, a receptor that has been reported to be activated by Δ9-THC, endogenous cannabinoid receptors agonist anandamide and other cannabinoid receptor ligands suggesting it could be considered as third cannabinoid receptor. GPR18 activity, as well as its distribution might suggest usage of GPR18 ligands in treatment of endometriosis, cancer, and neurodegenerative disorders. Yet, so far only few GPR18 antagonists have been described, thus only ligand-based design approaches appear to be most useful to identify new ligands for this orphan receptor. Methods: : Main goal of this study, GPR18 inactive form homology model was built on the basis of the evolutionary closest homologous template: Human P2Y1 Receptor crystal structure. Results: : Obtained model was further evaluated and showed active/nonactive ligands differentiating properties with acceptable confidence. Moreover, it allowed for preliminary assessment of proteinligand interactions for a set of previously described ligands. Conclusion:: Thus collected data might serve as a starting point for a discovery of novel, active GPR18 blocking ligands.


Reproduction ◽  
2017 ◽  
Vol 154 (1) ◽  
pp. 79-92 ◽  
Author(s):  
Min An ◽  
Dong Li ◽  
Ming Yuan ◽  
Qiuju Li ◽  
Lu Zhang ◽  
...  

Endometrial cells and microenvironment are two important factors in the pathogenesis of adenomyosis. Our previous study demonstrated that macrophages can induce eutopic epithelial cells of adenomyosis to suffer from epithelial–mesenchymal transition (EMT). The aim of this study is to detect whether macrophages interacting with epithelial cells equally induce the EMT process in normal and eutopic endometria of healthy and adenomyotic patients; and whether macrophages parallelly polarize to M2. We investigated the expression levels of epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), cytokeratin7 (CK7), vimentin, transforming growth factor-β1 (TGFB1), SMAD3 and pSMAD3 using immunohistochemistry and western blot, and then estimated the genetic levels of CD163, IL10 and MMP12 using real-time quantitative polymerase chain reaction (RT-PCR) in macrophages. Eutopic and normal endometrial tissues were obtained from 20 patients with adenomyosis and 11 control patients without adenomyosis, respectively. The immunohistochemical analysis shows distinct EMT in eutopic endometria in secretory phase; the expression levels of TGFB1, SMAD3 and pSMAD3 that indicate signal pathway of EMT were also higher in secretory phase. Macrophages can induce EMT process in primary endometrial epithelial cells derived from normal and eutopic endometria. After co-culturing, THP-1-derived macrophages polarized to M2. Compared with the eutopic endometrium group, further polarization to M2 was observed in the normal endometrium group. These results indicate that adenomyosis may be promoted by the pathologic EMT of epithelial cells, which is induced by macrophages that incapably polarize to M2.


2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098154
Author(s):  
Xin Yuan ◽  
Yize Zhang ◽  
Zujiang Yu

Objective To investigate the association between microRNA-3615 (miR-3615) expression and the prognosis and clinicopathological features in patients with hepatocellular carcinoma (HCC). Methods We obtained clinicopathological and genomic data and prognostic information on HCC patients from The Cancer Genome Atlas (TCGA) database. We then analyzed differences in miR-3615 expression levels between HCC and adjacent tissues using SPSS software, and examined the relationships between miR-3615 expression levels and clinicopathological characteristics. We also explored the influence of miR-3615 expression levels on the prognosis of HCC patients using Kaplan–Meier survival curve analysis. Results Based on data for 345 HCC and 50 adjacent normal tissue samples, expression levels of miR-3615 were significantly higher in HCC tissues compared with adjacent tissues. MiR-3615 expression levels in HCC patients were negatively correlated with overall survival time and positively correlated with high TNM stage, serum Ki-67 expression level, and serum alpha-fetoprotein level. There were no significant correlations between miR-3615 expression and age, sex, and pathological grade. Conclusion MiR-3615 may be a promising new biomarker and prognostic factor for HCC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fan Liu ◽  
Hua Li ◽  
Junwei Wu ◽  
Bin Wang ◽  
Na Tian ◽  
...  

AbstractThe LOX genes have been identified and characterized in many plant species, but studies on the banana LOX genes are very limited. In this study, we respectively identified 18 MaLOX, 11 MbLOX, and 12 MiLOX genes from the Musa acuminata, M. balbisiana and M. itinerans genome data, investigated their gene structures and characterized the physicochemical properties of their encoded proteins. Banana LOXs showed a preference for using and ending with G/C and their encoded proteins can be classified into 9-LOX, Type I 13-LOX and Type II 13-LOX subfamilies. The expansion of the MaLOXs might result from the combined actions of genome-wide, tandem, and segmental duplications. However, tandem and segmental duplications contribute to the expansion of MbLOXs. Transcriptome data based gene expression analysis showed that MaLOX1, 4, and 7 were highly expressed in fruit and their expression levels were significantly regulated by ethylene. And 11, 12 and 7 MaLOXs were found to be low temperature-, high temperature-, and Fusarium oxysporum f. sp. Cubense tropical race 4 (FocTR4)-responsive, respectively. MaLOX8, 9 and 13 are responsive to all the three stresses, MaLOX4 and MaLOX12 are high temperature- and FocTR4-responsive; MaLOX6 and MaLOX17 are significantly induced by low temperature and FocTR4; and the expression of MaLOX7 and MaLOX16 are only affected by high temperature. Quantitative real-time PCR (qRT-PCR) analysis revealed that the expression levels of several MaLOXs are regulated by MeJA and FocTR4, indicating that they can increase the resistance of banana by regulating the JA pathway. Additionally, the weighted gene co-expression network analysis (WGCNA) of MaLOXs revealed 3 models respectively for 5 (MaLOX7-11), 3 (MaLOX6, 13, and 17), and 1 (MaLOX12) MaLOX genes. Our findings can provide valuable information for the characterization, evolution, diversity and functionality of MaLOX, MbLOX and MiLOX genes and are helpful for understanding the roles of LOXs in banana growth and development and adaptations to different stresses.


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