AEBP1 upregulation contributes to cervical cancer progression by facilitating cell proliferation, migration, and invasion.

BACKGROUND: Aberrant expression of adipocyte enhancer-binding protein 1 (AEBP1) has been demonstrated to be involved in the tumorigenesis and progression of numerous cancers. This study was aimed to investigate the mechanism of AEBP1 in the development of cervical cancer. METHODS: The expression of AEBP1 in cervical cancer was assessed by immunohistochemistry. The function of AEBP1 on cell proliferation, migration, and invasion was determined by methyl thiazolyl tetrazolium assay, colony formation, and transwell assay. The activation of related signaling pathway was determined by western blot. The bioinformatics analysis was performed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: Higher protein expression of AEBP1 was observed in patients with cervical cancer. Overexpressed AEBP1 promoted cell proliferation, migration, and invasion abilities in cervical cancer cells. Moreover, the research manifested that AEBP1 activated the phosphorylation of STAT3. GO and KEGG analysis showed that genes positively related to AEBP1 were highly enriched in functions like epithelial cell proliferation, muscle cell migration, myoblast migration, smooth muscle tissue development, ECM-receptor interaction, transcriptional misregulation in cancer, and proteoglycans in cancer. While genes negatively related to AEBP1 were associated with immunity, including inflammatory response, external-stimulus response, neutrophil, granulocyte, and macrophage chemotaxis. CONCLUSIONS: This study suggested that AEBP1 acts as an oncogened and might be a potential therapeutic target for the treatment of cervical cancer.

GLP1R inhibits the progression of endometrial carcinoma through activation of cAMP/PKA pathway.

BACKGROUND: This study strived to explore the role and mechanism of glucagon-like peptide-1 receptor (GLP1R) in endometrial carcinoma (EC). METHODS: In detail, after transfection of GLP1R overexpression vector and small interfering RNA targeting PKA, the mRNA expressions of GLP1R and PKA in EC cells (Ishikawa and RL95-2) were quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The cell biological behaviors, including proliferation, migration, invasion, and apoptosis, were detected using 5-ethynyl-2'-deoxyuridine (EdU), wound healing, transwell, and flow cytometry assays, respectively. The cyclic adenosine monophosphate (cAMP) content and related protein expressions (GLP1R, p-PKA, and PKA) were determined by enzyme-linked immunosorbent assay (ELISA) and western blot. The effects of GLP1R and PKA on tumorigenesis were evaluated by measuring the tumor volume and weight of mice bearing EC. RESULT: According to the results, GLP1R expression was downregulated in EC tissues and cells, and there was a positive correlation between GLP1R and PKA expressions. Upregulation of GLP1R promoted apoptosis and activated the cAMP/PKA signaling pathway in EC cells, while hindering the EC cell proliferation, invasion, migration, and the growth of tumor in mice. However, these effects were blunted by downregulation of PKA, which also accelerated the progression of EC in vitro and in vivo via inhibiting the activation of cAMP/PKA signaling pathway. CONCLUSION: Collectively, upregulation of GLP1R impeded EC progression via inducing the activation of cAMP/PKA signaling pathway, which may be a potential treatment for EC.

Guizhi Fuling Capsule ameliorates endometrial hyperplasia through promoting p62-Keap1-NRF2-mediated ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Guizhi Fuling Capsule (GFC) is a classical traditional Chinese medicine officially recorded in Synopsis of the Golden Chamber and has long been used to treat gynecological diseases in China. However, scientific evidence for the anti-endometrial hyperplasia potential of GFC used in traditional medicine is lacking. AIM OF THE STUDY: This study evaluated whether GFC protects against endometrial hyperplasia and its potential mechanism in mice. METHODS AND MATERIALS: We used estrogen (estradiol) to induce endometrial hyperplasia in mice. C57BL/6 mice were treated with estradiol subcutaneously for 21 days, and GFC (75 mg/kg and 150 mg/kg) was given intragastric administration from the first day of the modeling. H&E staining is used to evaluate endometrial tissue structure change. Malondialdehyde was measured to explore lipid peroxidation. Western blot, immunohistochemistry and immunofluorescence were performed to observe the expressions of GPX4, p62, Keap1 and NRF2. RESULTS: The degree of ferroptosis in endometrial tissue of patients with endometrial hyperplasia was lower than normal endometrial tissue. In addition, ferroptosis inducer imidazole ketone erastin could improve endometrial hyperplasia in mice. Interestingly, GFC significantly alleviated endometrial hyperplasia through triggering ferroptosis. Furthermore, GFC inhibited p62-Keap1-NRF2 pathway in estradiol-induced endometrial hyperplasia model. CONCLUSIONS: GFC may attenuate estrogen-induced endometrial hyperplasia in mice through triggering ferroptosis via inhibiting p62-Keap1-NRF2 pathway. These findings suggest that GFC might act as a promising traditional Chinese medicine to treat endometrial hyperplasia.

Curcumin analogue AI-44 alleviates MSU-induced gouty arthritis in mice via inhibiting cathepsin B-mediated NLRP3 inflammasome activation.

NOD-like receptors (NLRs), as a part of intracellular pattern recognition receptors (PRR), are important regulators in innate immune system. The NLRP3 inflammasome which is a member of NLRs has been linked to several human inflammatory diseases. Gouty arthritis is triggered when the deposition of monosodium urate (MSU) crystals in joints induces acute inflammation characterized by the recruitment of macrophages and neutrophils. In this study, we explored the curcumin analogue AI-44 alleviated the gouty arthritis in mice via suppressing MSU engaging NLRP3 inflammasome activation. Furthermore, we demonstrated that AI-44 inhibited the interaction of cathepsin B and NLRP3 to prevent the activation of NLRP3 inflammasome. Moreover, we found AI-44 inhibited the enzyme activity of cathepsin B and bound to the key residue E122 in cytoplasm but not in lysosome. Collectively, these data suggest that AI-44 is a novel drug candidate for the treatment of gouty arthritis through targeting cathepsin B and inhibiting NLRP3 inflammasome activation.

[Effects of buyang huanwu decoction on the sarcoplasmic reticulum calcium uptake in abdominal aortic constriction induced myocardial hypertrophic rats].

UNLABELLED: objective: To investigate effects of buyang huanwu decoction (BYHWD) on the rats' myocardial hypertrophic model induced by abdominal aortic constriction, and to clarify the molecular regulatory mechanisms for sarcoplasmic reticulum calcium uptake. METHODS: Hypertrophic myocardium rat model was induced by abdominal aorta constriction (AAC). Four weeks after modeling, rats were randomly divided into the sham-operation group (Group S), the AAC model group (Group M), the Enalapril group (Group E), and the BYHWD treatment group (Group BYHWD), respectively. The left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), + dp/dtmax,-dp/dtmax, cardiac output (CO), heart mass index (HMI), and left ventricular mass index (LVMI) were observed in each group after 12-week medication. The serum contents of the atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were detected using ELISA. The SERCA2a activity, the ex- pressions of SERCA2a, phospholamban (PLN), and PLN phosphorylation were observed finally. RESULTS: Compared with Group S, LVSP and LVEDP significantly increased,-dp/dtmax and CO obviously decreased, the myocardial tissue was obviously thickened, the serum contents of ANP and BNP increased, the activity and expression of SERCA2a decreased, the SERCA2a/PLN ratio and PLN phosphorylation degree decreased in Group M (all P <0.05). Compared with Group M, LVEDP obviously decreased, -dp/dtmax and CO obviously increased, the hypertrophy myocardial tissue was obviously lessened, the serum contents of ANP and BNP decreased, the activity of SERCA2a increased, the relative expression contents of SERCA2a, Ser16, and Thrl7 were elevated in Group BYHWD (all P <0.05). BYHWD had significant roles in elevating the SERCA2a/PLN ratio and PLN phosphorylation degree (P <0.05). CONCLUSION: BYHWD could significantly improve hemodynamics of heart failure rats, elevate CO, lessen cardiac hypertrophy, and improve the capabilities for sarcoplasmic reticulum calcium uptake.

[Research progress of sarcolipin-a new regulatory protein of sarcoplasmic reticulum Ca2+ ATPase].

Sarcolipin (SLN) is a 3 kD membrane protein found in sarcoplasmic reticulum (SR). It has 31 amino acid residues; SLN and phopholamban (PLB) are belong to the same protein family, so they have similar physiological functions. SLN inhibits sarcoplasmic reticulum Ca(2+) ATPase (SERCA) activity and reduces its affinity of Ca(2+), resulting in dysfunction of myocardial contraction and heart failure. However, much remains to be elucidated. SLN independently or in conjunction with PLB affects SERCA activity, imbalancing intracellular calcium homeostasis, and reducing myocardial contractivity; these effects promote the development of heart failure.

[Protective effects of Leonurus japonicas on myocardial remodeling induced by isoproterenol in rats].

OBJECTIVE: To investigate the effects of Leonurus japonicas on myocardial remodeling induced by isoproterenol (ISO) in rats. METHODS: The model of rat myocardial remodeling was established by subcutaneous injection of ISO (20,10 and 5 mg/kg for 3 days, subsequently 3 mg/kg for 7 days). Rats were randomly divided into five groups: Control, ISO, ISO + enalapril, ISO + Leonurus 8 g/ kg and ISO + Leonurus 16 g/kg. Recorded the values of LVSP, LVEDP, +/- dp/dt (max), cardiac output ( CO). Weighed the body weight (BW), heart weight (HW) and left ventricular weight (LVW) of rats to calculate the values of HW/BW and LVW/BW. The hydroxyproline contents were investigated by spectrophotometric measurement. The contents of type I collagen and type III collagen and ratio of I/III collagen were assessed by immunohistochemical stain. RESULTS: Leonurus (16 g/kg x day(-1)) could increased the value of LVSP, + dp/dt(max), CO (P < 0.05). Leonurus (8 g/kg) could increased the value of -dp/dt(max), decreased the ratios of HW/BW and LVW/BW (P < 0.05), the contents of hydroxyproline, type I collagen, type III collagen and the ratios of I/III collagen (P < 0.05). CONCLUSIONS: Leonurus at a dosage of 16 g/kg may improve the systolic function; Leonurus at a dosage of 8 g/kg may improve the diastolic function, down-regulate the expression of collagen and normalize the ratio of I/III collagen.

[Dynamic study on inhibition of qi-benefiting, blood-activating recipe on myocardial hypertrophy induced by ISO in rats].

OBJECTIVE: To observe the effect of Qi-Benefiting, Blood-Activating Recipe on the different pathologic stage of myocardial hypertrophy induced by ISO in rats. METHODS: Myocardial hypertrophy rats were induced by isoproterenol, and treated with Qi-Benefiting, Blood-Activating Recipe for 5,10 and 15 weeks, hemodynamic parameters, LVMI, HMI were determined, ANP and BNP were analysed. RESULTS: Qi-Benefiting, Blood-Activating Recipe could increase cardiac output and improve hemodynamic parameters all after 5, 10 and 15 weeks' treatment (P<0.05). It could decrease the contents of ANP and BNP after 5, 10 and 15 weeks' treatment (P<0.05). Qi-Benefiting, Blood-Activating Recipe could significantly decrease the levels of HWI and LVMI after 5, 10 and 15 weeks' treatment (P<0.05). CONCLUSION: Qi-Benefiting, Blood-Activating Recipe can significant improve hemodynamic status, increase cardiac output and decrease the level of neurohormonal factors.