Abdominal aortic aneurysm (AAA) is often clinically silent before rupture characterized by extensive vascular inﬂammation and degenerative elasticity of aortic wall. MCPIP1 exhibits anti-infllammatory and pro-apoptotic effects involved in atherogenesis. However, little is known about the expression and the contribution of MCPIP1 in AAA. In the present study, we collected clinical AAA specimens and constructed AAA mice model through Ang-Ⅱ infusion, and found apparently increased MCPIP1 expression and severe inflammatory infiltration in AAA aortic membrane as evidenced by elevated levels of MCP1, IL-1β and NF-κB, as well as HE staining. The elasticity of aortic tunica media was impaired along with multiple apoptosis of vascular smooth muscle cells (VSMCs) in Ang-II-induced aneurysmal mouse. In vitro Ang-II administration of VSMCs induced MCPIP1 expression, accompanied by upregulation of MMP-2 and MMP-9, as well as enhancement of VSMCs proliferation and apoptosis, which may cause damage of intima-media elasticity. Silencing MCPIP1 reversed above effects to further restore the balance of proliferation and apoptosis in VSMCs. Overall, our data indicated that upregulation of MCPIP1 may become a promising candidate for the diagnosis of AAA, and specific knockdown MCPIP1 in VSMCs could inhibit VSMCs apoptosis and downregulate MMPs to maintain vascular wall elasticity. Therefore, knockdown of MCPIP1 may serve as a potential target for gene therapy of AAA.
Background: Postpartum depression (PPD) is a common serious mental health problem. Recent studies have demonstrated that hormone therapy serves as a promising therapeutic approach in managing PPD. The present study aims at exploring the role of thyroid hormone (TH), estrogen and progestogen in patients with PPD. Methods: Initially, PPD patients were enrolled and a PPD mouse model was established. The serum levels of estradiol (E2), progesterone (P), triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were subsequently measured. Next, in order to identify the effects of TH, estrogen and progestogen on PPD progression, mice were administrated with E2, P, contraceptives (CA), Euthyrox and methimazole (MMI). Besides, the body weight, activities, basolateral amygdala (BLA) neuron cell structure and the related gene expression of mice were analyzed. Results: The PPD patients and the mice showed elevated serum levels of T3, T4, FT3 and FT4 along with diminished E2, P and TSH levels. In the mice administered with a combination of E2, P, and MMI, decreased TH and increased estrogen and progestogen were detected, which resulted in increased body weight, normal activities, and BLA neuron cell structure. Moreover, brain-derived neurotrophic factor (BDNF) and cAMP-responsive element-binding protein (CREB) were both up-regulated in PPD mice administrated with a combination of E2, P, and MMI, which was accompanied by decreased TH and elevated estrogen and progestogen. Conclusion: Taken together, reduced TH combined with enhanced estrogen and progestogen confers neuroprotection in PPD, highlighting a potential target in prevention and treatment of PPD.
Better understanding of epigenetic regulation of hepatocellular carcinoma (HCC) will help us to cure this most common malignant liver cancer worldwide. The underlying mechanisms of HCC tumorigenesis are genomic aberrations regulated by genetic and epigenetic modifications. Histone H3 lysine modifications regulate histone structure and modulate transcriptional factor binding with target gene promoters. Targetting genes include VASH2, fatty acids synthase, RIZ1, FBP1, MPP1/3, YAP, which affect tumorigenesis, metabolisms, angiogenesis, and metastasis. Signal pathway studies demonstrate that the HGF-MET-MLL axis, phosphatase and tensin homolog (PTEN)-PI3K-Akt axis; WNT-β-catenin signal pathway is involved in histone H3 modification. A variety of factors such as virus infection, reactive oxygen species, food-borne toxins, irradiation, or non-coding RNA cause hepatocellular DNA damage or modification. Dysfunctional DNA repair mechanisms, including those at the epigenetic level are also major causes of HCC tumorigenesis. The development of therapies based on epigenetic regulatory mechanisms has great potential to advance the care of HCC patients in the future.
Fibroblast-like synoviocytes (FLSs) play a crucial role in rheumatoid arthritis (RA) pathogenesis. While miRNA (miR)-506 has been implicated in the progression of multiple diseases, its role in RA remains to be explored. The present study evaluated the function of miR-506 in the regulation of RA-FLSs. FLSs were prepared from RA and healthy synovial tissues. The expression of miR-506 was measured by quantitative real time PCR (qRT-PCR). The effects of miR-506 on RA-FLSs proliferation and apoptosis were detected by cell counting Kit-8 and flow cytometry assays, respectively. The determination of TNF-α, IL-6, and IL-1β concentrations in RA-FLSs supernatant were done by ELISA. The levels of miR-506 were detected to be significantly lower in the synovial tissues and FLSs of RA than in the synovial tissues and FLSs of healthy controls. The miR-506 up-regulation in RA-FLSs significantly inhibited the proliferation and promoted cell cycle arrest at the G 0 /G 1 phase. The overexpression of miR-506 induced apoptosis, along with an increase in activities of caspase-3 and -8. A target gene Toll-like receptor 4 ( TLR4 ) under the direct regulation of miR-506 was identified through the luciferase assay, qRT-PCR and western blot analysis. Forced overexpression of TLR4 in the rescue experiments showed that TLR4 effectively reversed the effect on proliferation and apoptosis in miR-506-overexpressing RA-FLSs. Thus, miR-506 may be a potential target for RA prevention and therapy of RA.