ABSTRACT
ABSTRACT Purpose: This study aimed to determine the effect of serum G receptor-mediated protein-1 levels on the development of retinopathy in patients with diabetes in comparison with healthy individuals. Methods: The study enrolled patients with diabetic retinopathy (Group 1), patients without diabetic retinopathy (Group 2), and healthy individuals (Group 3). Levels of serum progesterone, serum G receptor-mediated protein-1, estradiol, oxidant/antioxidants, and thyroid-releasing hormones were analyzed and compared among the groups. Post-hoc analysis was performed to compare the subgroups in which significant differences were found. Results: Groups 1, 2, and 3 each included 40 patients. A significant difference was found among all groups in terms of serum G receptor-mediated protein-1, oxidant/antioxidant, and estradiol levels (p<0.01), but no significant difference was found in terms of thyroid-releasing hormone or progesterone (p=0.496, p=0.220, respectively). In the post-hoc analysis of the groups with significant differences, another significant difference was found among all groups for serum G receptor-mediated protein-1 and oxidant/antioxidant levels (p<0.05). Serum G receptor-mediated protein-1 and oxidant levels were positively correlated, whereas serum G receptor-mediated protein-1 and antioxidant levels were negatively correlated (r=0.622/p<0.01, r=0.453/p<0.01, r=0.460/p<0.01, respectively). The multiple regression analysis showed that increased levels of serum G receptor-mediated protein-1 may help prevent diabetic retinopathy. Conclusions: Serum G receptor-mediated protein-1 levels, which were the highest in the diabetic retinopathy Group, increased as the oxidant/antioxidant balance changed in favor of oxidative stress. This appears to be a defense mechanism for preventing neuronal damage.
RESUMO Objetivo: Esta pesquisa buscou determinar o impacto dos níveis de proteína G sérica no desenvolvimento da retinopatia em pacientes diabéticos, comparando-os a indivíduos saudáveis. Métodos: Foram incluídos, no estudo, 40 pacientes com retinopatia diabética (Grupo 1), 40 pacientes sem retinopatia diabética (Grupo 2) e 40 indivíduos saudáveis (Grupo 3). Os níveis hormonais de progesterona sérica, de proteína G sérica, estradiol, oxidante/antioxidante e hormônio liberado pela tireoide foram analisados e comparados. A análise post hoc foi realizada para comparar os subgrupos nos quais diferenças estatisticamente significativas foram encontradas. Resultados: Uma diferença significativa foi encontrada entre todos os grupos em termos de proteína G sérica, oxidante/antioxidante e níveis de estradiol (p<0.01), mas nenhuma diferença significativa foi encontrada em termos de hormônio liberado pela tireoide ou progesterona (p=0,496, p=0,220, respectivamente). Na análise post hoc dos grupos com diferenças estatisticamente significativas, outra diferença significativa foi encontrada entre todos os grupos para proteína G sérica e níveis oxidantes/antioxidantes (p<0,05). Os níveis de proteína G sérica e os níveis de oxidante foram positivamente correlacionados, enquanto os níveis de proteína G sérica e os níveis de antioxidantes foram negativamente correlacionados (r=0,622/p<0,01, r=0,453/p<0,01, r=0,460/p<0,01, respectivamente). A análise de regressão múltipla mostrou que o aumento da proteína G sérica pode ajudar a prevenir a retinopatia diabética. Conclusões: Os níveis de proteína G sérica que eram mais altos no grupo de retinopatia diabética, aumentaram à medida que o equilíbrio oxidante/antioxidante mudou em favor do estresse oxidativo. Este parece ser um mecanismo de defesa para prevenir danos neuronais.
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The Tongmai Yangxin pill (TMYX) has potential clinical effects on no-reflow (NR); however, the effective substances and mechanisms by which this occurs remain unclear. This study evaluates the cardioprotective effects and molecular mechanisms of TMYX against NR. We used a myocardial NR rat model (2 h after myocardial ischemia and 2 h after reperfusion) to confirm the effect and mechanism of action of TMYX in alleviating NR. In vitro studies in isolated coronary microvasculature of NR rats and in silico network pharmacology analyses were performed to reveal the underlying mechanisms of TMYX and determine the main components, targets, and pathways of TMYX, respectively. The experiment was approved by the Ethics Committee of Hunan University of Chinese Medicine (LLBH-202212160001). TMYX showed therapeutic effects on NR by improving cardiac structure and function, reducing NR, ischemic areas, and cardiomyocyte injury, and decreasing the content of cardiac troponin I (cTnI). Moreover, the mechanism of TMYX predicted by network pharmacology is related to the hypoxia inducible factor-1 (HIF-1), nuclear factor kappa-B (NF-κB), and tumor necrosis factor (TNF) signaling pathways. TMYX increased the expression of G protein-coupled estrogen receptor (GPER), phospho-extracellular signal-regulated kinase (p-ERK), and HIF-1α. In vitro, TMYX enhanced the diastolic function of coronary microvascular cells; however, this effect was inhibited by GPER inhibitor (G-15), eNOS inhibitor (L-NAME), and sGC inhibitor (ODQ). This study integrates pharmacology and experimental evaluation to reveal that TMYX activates HIF-1α/eNOS signaling pathway by upregulating GPER to relax coronary microvessels, thereby significantly alleviating NR.
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Objective In this study, a meta-analysis of the expression of G-protein-coupled estrogen receptor (GPER) in breast cancer (BC) and its role in prognosis was conducted to understand the effect of this expression on the survival and clinicopathological characteristics of patients with BC. Methods Identical search strategies were used to search relevant literature in electronic databases updated to November 24, 2022. Individual hazard ratios (HRs) and odds ratios (ORs) with their 95%CI were extracted and pooled to evaluate the strength of the association between positive GPER expression and survival results, the clinicopathological features of patients with BC. Begg's tests, Egger's tests, and funnel plots were used to evaluate publication bias. Heterogeneity and sensitivity were also assessed. All works were completed using Review Manager 5.4.1. Results GPER expression had a favorable effect on OS (HR=0.77; 95%CI: 0.49-1.22; Z=01.10; P=0.27) and an unfavorable effect on DFS/RFS/DDFS (HR=1.03; 95%CI: 0.64-1.65; Z=00.13; P=0.90) in patients with BC. GPER expression was not significantly related to the prognosis of patients with BC, and GPER expression was not an independent prognostic factor. Furthermore, GPER expression was significantly associated with TNM staging (OR=0.31, 95%CI: 0.06-0.55, Z=02.43, P=0.02), distant metastasis (OR=6.82, 95%CI: 1.89-24.55, Z=02.94, P=0.003), histological grade (OR=0.009, 95%CI: −0.16-0.01, Z=02.16, P=0.03), ER expression (OR=1.77, 95%CI: 1.15-2.72, Z=02.59, P=0.009), and PR expression (OR=1.36, 95%CI: 1.00-1.84, Z=01.95, P=0.05). Conclusion GPER may not be an independent prognostic factor for BC. GPER expression was significantly related to some clinicopathological features of patients with BC, including TNM staging, distant metastasis, histological grade, ER expression, and PR expression.
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The aim of this paper is to study the molecular mechanism of Shaofu Zhuyu decoction in treating dysmenorrhea of endometriosis based on GPER2/MAPK/STAT1 axis. In this study, HE staining was used to observe the pathological changes of the rats in each group. The levels of TNF-α and IL-6 were detected by ELISA assay. The mRNA expressions of neurotransmitter receptor (NK1) and GPER were detected by qPCR. The protein contents of MAPK and STAT1 were detected by Western blot. According to the results, compared with the model group, Shaofu Zhuyu decoction could significantly improve the inflammation of the ectopic uterine cavity tissue, decrease the contents of TNF-α and IL-6 in the uterine cavity, the mRNA expressions of NK1 and GPER, and the protein expressions of MAPK and STAT1. In conclusion, Shaofu Zhuyu decoction could effectively inhibit the expressions of GPER2, MAPK and STAT1, decrease the levels of TNF-α, IL-6 and NK1 mRNA and relieve the inflammatory pain in patients with endometriosis.
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AIM To study the therapeutic effects of Neiyi Kangfu Tablets (Trionycis Carapax,Ostreae concha,Rhei Radix et Rhizoma,etc.) on adenomyosis and its possible mechanism of action.METHODS The mouse model for adenomyosis was set up by the pituitary allograft,and received the gavage of Neiyi Kangfu Tablets,Dan'e Fukang Decoction (Salviae miltiorrhizae Radix et Rhizoma,Curcumae Rhizoma,Paeoniae Radix rubra,etc.) and gestrinone,respectively,for three months.Western blot,real-time PCR,IHC were used to measure the expression of GPER-Ras-STAT3 in ectopic endometrium and entopic endometrium.RESULTS High doses of Neiyi Kangfu Tablets could significantly lower GPER protein and gene expression;down-regulate the Ras and STAT3 protein expression;reduce the lesion severity score of ectopic tissue morphology.Its curative effect was better than Dan'e Fukang Decoction and gestrinone.CONCLUSION Neiyi Kangfu Tablets may control the development of ectopic lesions by inhibiting the GPER-Ras-STAT3 pathway activity and weakening the production of estrogen.
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BACKGROUND: Endometriosis, pro-inflammatory and invasive benign disease estrogen dependent, abnormally express in endometria the enzyme P450Arom, positively regulated by steroid factor-1 (SF-1). Our objective was to study the nuclear protein contents of upstream stimulating factor 2 (USF2a and USF2b), a positive regulator of SF-1, throughout the menstrual cycle in eutopic endometria from women with and without (control) endometriosis and the involvement of nuclear estrogen receptors (ER) and G-coupled protein estrogen receptor (GPER)-1. RESULTS: Upstream stimulating factor 2 protein contents were higher in mid (USF2b) and late (USF2a and USF2b) secretory phase in eutopic endometria from endometriosis than control (p < 0.05). In isolated control epithelial cells incubated with E2 and PGE2, to resemble the endometriosis condition, the data showed: (a) significant increase of USF2a and USF2b nuclear protein contents when treated with E2, PPT (specific agonist for ERa) or G1 (specific agonist for GPER1); (b) no increase in USF2 binding to SF-1 E-Box/DNA consensus sequence in E2-treated cells; (c) USF2 variants protein contents were not modified by PGE2; (d) SF-1 nuclear protein content was significantly higher than basal when treated with PGE2, E2 or G1, stimulation unaffected by ICI (nuclear ER antagonist); and (e) increased (p < 0.05) cytosolic protein contents of P450Arom when treated with PGE2, E2, PPT or G1 compared to basal, effect that was additive with E2 + PGE2 together. Nevertheless, in endometriosis cells, the high USF2, SF-1 and P450Arom protein contents in basal condition were unmodified. CONCLUSION: These data strongly suggest that USF2 variants and P450Arom are regulated by E2 through ERa and GPER1, whereas SF-1 through GPER1, visualized by the response of the cells obtained from control endometria, being unaffected the endogenously stimulated cells from endometriosis origin. The lack of E2 stimulation on USF2/SF-1 E-Box/DNA-sequence binding and the absence of PGE2 effect on USF2 variants opposite to the strong induction that they exert on SF1 and P450 proteins suggest different mechanisms and indirect regulations. The sustained USF2 variants protein expression during the secretory phase in eutopic endometria from women with endometriosis may participate in the pathophysiology of this disease strongly associated with infertility and its characteristic endometrial invasion to ectopic sites in the pelvic cavity.