“…It is of particular interest in biological psychiatry as a molecular substrate of emotional, neuropsychiatric, and neurodegenerative disorders [ 24 , 25 ] and an important target for psychotropic drugs [ 26 , 27 ]. In addition, HTR2A has been implicated in the pathophysiology of cardiovascular disorders [ 28 , 29 ], diabetes [ 30 ], and obesity [ 31 ].…”
The serotonin receptor 2A gene (HTR2A) is a strong candidate for the fetal programming of future behavior and metabolism. Maternal obesity and gestational diabetes mellitus (GDM) have been associated with an increased risk of metabolic and psychological problems in offspring. We tested the hypothesis that maternal metabolic status affects methylation of HTR2A in the placenta. The prospective study included 199 pairs of mothers and healthy full-term newborns. Genomic DNA was extracted from feto-placental samples and analyzed for genotypes of two polymorphisms (rs6311, rs6306) and methylation of four cytosine residues (−1665, −1439, −1421, −1224) in the HTR2A promoter region. Placental HTR2A promoter methylation was higher in male than female placentas and depended on both rs6311 and rs6306 genotypes. A higher maternal pre-gestational body mass index (pBMI) and, to a lesser extent, diagnosis of GDM were associated with reduced HTR2A promoter methylation in female but not male placentas. Higher pBMI was associated with reduced methylation both directly and indirectly through increased GDM incidence. Tobacco use during pregnancy was associated with reduced HTR2A promoter methylation in male but not female placentas. The obtained results suggest that HTR2A is a sexually dimorphic epigenetic target of intrauterine exposures. The findings may contribute to a better understanding of the early developmental origins of neurobehavioral and metabolic disorders associated with altered HTR2A function.
“…It is of particular interest in biological psychiatry as a molecular substrate of emotional, neuropsychiatric, and neurodegenerative disorders [ 24 , 25 ] and an important target for psychotropic drugs [ 26 , 27 ]. In addition, HTR2A has been implicated in the pathophysiology of cardiovascular disorders [ 28 , 29 ], diabetes [ 30 ], and obesity [ 31 ].…”
The serotonin receptor 2A gene (HTR2A) is a strong candidate for the fetal programming of future behavior and metabolism. Maternal obesity and gestational diabetes mellitus (GDM) have been associated with an increased risk of metabolic and psychological problems in offspring. We tested the hypothesis that maternal metabolic status affects methylation of HTR2A in the placenta. The prospective study included 199 pairs of mothers and healthy full-term newborns. Genomic DNA was extracted from feto-placental samples and analyzed for genotypes of two polymorphisms (rs6311, rs6306) and methylation of four cytosine residues (−1665, −1439, −1421, −1224) in the HTR2A promoter region. Placental HTR2A promoter methylation was higher in male than female placentas and depended on both rs6311 and rs6306 genotypes. A higher maternal pre-gestational body mass index (pBMI) and, to a lesser extent, diagnosis of GDM were associated with reduced HTR2A promoter methylation in female but not male placentas. Higher pBMI was associated with reduced methylation both directly and indirectly through increased GDM incidence. Tobacco use during pregnancy was associated with reduced HTR2A promoter methylation in male but not female placentas. The obtained results suggest that HTR2A is a sexually dimorphic epigenetic target of intrauterine exposures. The findings may contribute to a better understanding of the early developmental origins of neurobehavioral and metabolic disorders associated with altered HTR2A function.
“…ANP is a circulating peptide secreted by the atrium that can be activated during CH development; it is a component of the natriuretic peptide system and is often used as a prognostic marker in patients with compensatory heart failure or CH [ 40 ]. Furthermore, overexpression of β-MHC in the heart leads to impaired myocardial function, and the inhibition of β-MHC expression can prevent the occurrence of ISO-induced CH [ 41 ]. An increasing amount of evidence has shown that the levels of ANP, BNP, and β-MHC as well as the cell surface area are increased in CH [ 42 , 43 ].…”
Cardiac hypertrophy (CH) is a result of the physiological adaptation of the heart to coronary heart disease, hypertension, and other cardiovascular diseases. Sinomenine is extracted from
Caulis Sinomenii
. This study aimed to explore the specific mechanism of the action of sinomenine in cardiac hypertrophy (CH) via Nrf2/ARE signaling pathway
in vivo
and
in vitro
. To establish a model of CH, H9C2 cells were treated with angiotensin II (Ang II) and intraperitoneally injected with isoproterenol. Then the cells were treated with 50 and 100 μM sinomenine. TUNEL, HE, rhodamine-labeled phalloidin, and immunohistochemical staining were performed. Flow cytometry was used to measure apoptosis rates. mRNA expression of ANP, BNP, and β-MHC was determined by qRT-PCR. Furthermore, western blotting was performed to analyze protein expression. After sinomenine treatment, the surface area and apoptosis rates were decreased. Furthermore, the mRNA expression of ANP, BNP, and β-MHC, levels of reactive oxygen species and malondialdehyde, and protein expression of Caspase3 and Bax were down-regulated, and the protein expression of Bcl-2 was upregulated. Sinomenine activates the Nrf2/ARE signaling pathway, and inhibition of this signaling pathway reversed the effects of sinomenine. In animal experiments, sinomenine decreased the heart weight and left ventricular weight indices, as well as the expression of ANP, BNP, and β-MHC. Furthermore, sinomenine reduced the apoptosis rate and relieved CH-related oxidative stress by activating the Nrf2/ARE signaling pathway. Together, these findings reveal that sinomenine is a potential candidate drug for CH treatment and further research is required to generalize the result in human subjects.
“…FFAR4 can promote cell proliferation and migration and has been identified as a potential prognostic biomarker for laryngeal cancer ( 35 ). HTR2A encodes one of the serotonin receptors and could activate the PI3K-Akt-MTOR signal ( 36 ). SH3KBP1 is involved in several cellular processes, such as apoptosis, cytoskeletal rearrangement, and cell adhesion ( 37 ).…”
BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most fatal cancers in the world. The 5-year survival rate of ESCC is <30%. However, few biomarkers can accurately predict the prognosis of patients with ESCC. We aimed to identify potential survival-associated biomarkers for ESCC to improve its poor prognosis.MethodsImmuneAI analysis was first used to access the immune cell abundance of ESCC. Then, ESTIMATE analysis was performed to explore the tumor microenvironment (TME), and differential analysis was used for the selection of immune-related differentially expressed genes (DEGs). Weighted gene coexpression network analysis (WGCNA) was used for selecting the candidate DEGs. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to build the immune-cell-associated prognostic model (ICPM). Kaplan–Meier curve of survival analysis was performed to evaluate the efficacy of the ICPM.ResultsBased on the ESTIMATE and ImmuneAI analysis, we obtained 24 immune cells’ abundance. Next, we identified six coexpression module that was associated with the abundance. Then, LASSO regression models were constructed by selecting the genes in the module that is most relevant to immune cells. Two test dataset was used to testify the model, and we finally, obtained a seven-genes survival model that performed an excellent prognostic efficacy.ConclusionIn the current study, we filtered seven key genes that may be potential prognostic biomarkers of ESCC, and they may be used as new factors to improve the prognosis of cancer.
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