Exploring feasible drugs for the treatment of pathological cardiac hypertrophy has always been a focus of cardiovascular disease research. Paeoniflorin (PF) and β-Ecdysterone (β-Ecd) are the main active components of Paeonia lactiflora and Achyranthes bidentata, which can be used for the treatment of cardiovascular diseases, but their mechanism of action remains unclear. This study focused on oxidative stress and ferroptosis to investigate the protective effects of PF and β-Ecd on cardiac hypertrophy in primary cardiomyocytes and C57BL/6 mice, utilizing the integration of CCK8 assays, ros detection, molecular docking, real-time quantitative PCR, western blot, immunofluorescence, etc. The result of combination indices demonstrated a significant synergistic protective effect of PF and β-Ecd on cardiac hypertrophy. Furthermore, in vitro and in vivo studies further showed that the combination of PF and β-Ecd could improve the abnormalities of cell surface area, ANP, β-MHC, MDA, SOD, calcium ion, mitochondrial membrane potential and so on induced by cardiac hypertrophy through the inhibition effects of oxidative stress and iron metabolism, which might be closely related to the impact on the Nrf2/HO-1 and SLC7A11/GPX4 pathways. Altogether, this work revealed the mechanism of the combination of PF and β-Ecd in the treatment of cardiac hypertrophy from the aspects of suppressing oxidative stress and ferroptosis, aiming to promote effective treatment of the disease and the clinical application of PF and β-Ecd.

Cardiac hypertrophy is frequently associated with ventricular dysfunction and heart failure. Paeoniflorin, has been widely used to treat cardiovascular dysfunction-related diseases. However, the underlying mechanism has been unclear. Here, we investigated the potential inhibitory effects and mechanism of paeoniflorin on oxidative stress of cardiac hypertrophy induced by angiotensin II (AngII) in vitro. Using MTS assay, qRT-PCR, WGA staining assay, and western blot, different dosages (50-400 & mu;M) of paeoniflorin were utilized to examine the antihypertrophy effects on H9c2 cells. Western blot examination revealed the presence of apoptosis-related proteins Bax, Bcl2, and Cytc, antioxidative stress-related proteins Nrf2, HO-1, SOD, and CAT, and mitophagyrelated proteins PINK1 and Parkin. qRT-PCR was used to detect the mRNA expression of Bax, Bcl2, Nrf2, and HO-1. TUNEL, caspase3/9 enzyme viability, and MDA, T-AOC, and superoxide levels were all evaluated using commercial kits.The fluorescent probes DCFH-DA and JC-1 were employed to measure cellular ROS and MMP levels. Nrf2 siRNA was utilized to investigate Nrf2's role in paeoniflorin-treated cardiac hypertrophy. Paeoniflorin dramatically reduced cell section area (CSA) and hypertrophic marker (ANP, BNP) expression while inhibiting oxidative stress by modulating ROS and MDA, CAT, SOD, and T-AOC levels. Furthermore, in AngIIinduced cardiomyocyte hypertrophy, paeoniflorin restores H9c2 apoptosis by restoring Bax, Bcl-2 Cyt-C, Caspase 3, and Caspase 9 levels. Paeoniflorin also restored Nrf2/HO-1 and PINK1/Parkin expression, and its antiAngII activities were mediated by Nrf2, which was regulated by Nrf2 knockdown. In conclusion, Our data confirm that paeoniflorin alleviates cardiac hypertrophy through modulating oxidative stress and Nrf2 signaling pathway in vitro.

Background: Ovarian cancer (OC) is a highly malignant disease, and due to its high recurrence rate, high chemotherapy resistance, and lack of effective early diagnostic methods, effective targets for early screening, treatment, and prognosis prediction are necessary for research in this field. This study aimed to investigate the mechanism of periplakin (PPL) in malignant development of ovarian cancer and provide references for the treatment of ovarian cancer.Methods: We performed a The Cancer Genome Atlas (TCGA) analysis of RNA seq data from clinical tumor sample, and ana-lyzed PPL expression levels in tumors and adjacent tissues in Clinical Proteomic Tumor Analysis Consortium (CPTAC) data. We obtained information related to PPL and patient prognosis in clinical tumor samples of ovarian cancer from the TCGA database, including the expression level of PPL in various epithelial cell cancers and the correlation between PPL expression and patient survival. Then, we analyzed the relationship between PPL expression and ovarian cancer development. Also, we collected clinical tumor samples and used the enzyme-linked immunosorbent assay (ELISA) to detect the difference in PPL expression between tumor tissue and adjacent tissues. We constructed a stable knockdown SKOV3 ovarian cancer cell line with PPL. The western blot (WB) technique was used to detect the expression level of PPL and the protein kinase A (AKT) in the experimental group and control group after downregulation. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was utilized to detect the changes in the growth and proliferation of SKOV3 ovarian cancer cell lines in the control (shctrl) and experimental (shPPL#1, shPPL#2, and PPL Flag) groups after knocking down PPL. The control (BALB/c shctrl) and the experimental (BALB/c shPPL#1 and BALB/c shPPL#2) groups were used to detect the effect of knocking down PPL on the growth of ovarian cancer cells in situ transplanted into mouse models.Results: Among various human tumors, the majority of people suffer from ovarian cancer. We found that the relative expression level of PPL gene in ovarian cancer is high. Analysis of CPTAC data showed an increase in PPL expression levels in ovarian cancer tissues compared to normal tissues. Knocking down PPL significantly affects the growth of ovarian cancer cells and inhibits the proliferation and migration of ovarian cancer cells. PPL knockdown significantly alters the phosphorylation level of AKT in the SKOV3 ovarian cancer cell line. The results of orthotopic transplantation were similar to those in cell lines. The tumor weight and volume in the experimental group were smaller than those in the control group. Knocking down PPL could reduce the p-AKT activity of transplanted mice.Conclusions: PPL plays a crucial role in the proliferation and migration of ovarian cancer tumors. It regulates the phosphorylation of AKT and affects the proliferation and migration of ovarian cancer cells. Targeting PPL may serve as a new therapeutic target in ovarian cancer patients.

Background:The aim of this paper was to investigate the clinical significance of periplakin (PPL) expression in ovarian cancer (OV) tissues and to explore the influence and possible mechanism of PPL on OV apoptosis.Methods:PPL expression in OV tissues was detected by western blotting, and its correlation with the clinicopathological parameters and prognosis of OV patients was analyzed. The influence of PPL expression on the growth of OV cell lines was analyzed using the DepMap database. The biological function of PPL and related genes in tumors was studied using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis based on The Cancer Genome Atlas (TCGA) database. PPL expression in OV cell lines was detected by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The expression of apoptosis-related proteins in each group after PPL knockdown was detected by western blotting.Results:PPL expression in OV tissues was higher than that in normal ovarian tissues (P<0.05). PPL messenger RNA (mRNA) expression was highest in the OV cell line CAOV-4 and lowest in the OV cell line CoC1. PPL expression was decreased in the si-PPL-1, si-PPL-2, and si-PPL-3 groups, with significant inhibition in the si-PPL-1 and si-PPL-3 groups. Compared to that in the si-NC group, the cell proliferation rate in the si-PPL-1 and si-PPL-3 groups was decreased, and the apoptosis rate was increased. The expression of active caspase 3 and BCL-2-associated X (BAX) was increased, while that of B-cell lymphoma 2 (BCL-2) was decreased.Conclusions:PPL was highly expressed in OV tissues and cell lines, and this was related to the prognosis of OV patients. PPL might promote cancers by inhibiting OV apoptosis and could be a potential target of therapy for OV.

Cervical cancer (CC), a common gynecological carcinoma, is a serious threat to women's health. The dysregulation of circular RNAs (circRNAs) is associated with the pathogenesis of cervical cancer. Therefore, we explored the role of circ-ATP8A2 in CC cell development and progression. Circ-ATP8A2 profiles in CC specimens and cells were detected using real-time PCR. In addition, cell counting kit-8 (CCK-8), acridine orange/ethidium bromide (AO/EB), flow cytometric, and Transwell experiments were carried out on HeLa and SW756 cells to determine cell proliferation, apoptosis, migration and invasion. Furthermore, the mechanism of circ-ATP8A2 was explored by dual-luciferase reporter system. Circ-ATP8A2 was significantly enhanced in CC specimens and cells. Knockdown of circ-ATP8A2 inhibited cell proliferation, migratory and invasive capacities and increased apoptotic cells. Ectopically expressed circ-ATP8A2 induced the opposite effects. For the mechanism exploration, circ-ATP8A2 sponges miR-433 to release its suppression on epidermal growth factor receptor (EGFR) expression at post-transcriptional level. What's more, circ-ATP8A2 could promote cell progression by miR-433/EGFR axis in CC cells. Collectively, this work might offer a potential treatment target for CC.

Retinoblastoma (RB) is the most common intraocular malignancy in infants and children with high mortality rate in developing countries. Emerging evidence demonstrated that abnormally expressed circular RNAs (circRNAs) are involved in tumorigenesis and progression in several malignancies. However, their clinical values, biological functions and mechanisms in RB has not been reported before. Recently, hsa_circ_0001649 was found to play imperative roles in cholangiocarcinoma, gastric cancer, and hepatocellular carcinoma. In the current study, qRT-PCR was performed to detect the expression of hsa_circ_0001649 in RB samples and cells. The correlations between hsa_circ_0001649 expression and clinicopathologic characteristics were further analyzed. In addition, we up-regulated hsa_circ_0001649 in Y79 cells and knocked down hsa_circ_0001649 in WERI-Rb1 cells to explore its effect on cell proliferation and apoptosis. The animal study was performed to confirm the in vitro results. Furthermore, AKT/mTOR signaling pathway was detected to clarify the molecular mechanisms of hsa_circ_0001649 exerts in RB cell growth. The results indicated that hsa_circ_0001649 was decreased in RB tissues and cells, and this downregulation was associated with larger tumor size and advanced intraocular international retinoblastoma classify (IIRC) stage in RB patients. Additionally, hsa_circ_0001649 could act as an independent prognostic predictor for overall survival in patients with RB. Moreover, hsa_circ_0001649 inhibits cell growth and promotes cell apoptosis in RB cells. AKT/mTOR signaling pathway is involved in the cell growth alteration affected by hsa_circ_0001649. Overall, hsa_circ_0001649 might be a potentially useful prognostic biomarker and therapeutic target for RB.