Simonsenbaird0681

ERBB2 is a well-studied oncogene that promotes progression of multiple cancers, especially in breast cancer. However, the expression status of ERBB2, the values of ERBB2 on prognosis, and its molecular characterization in glioma have not been well examined. We explored the expression of ERBB2 and its clinical and molecular immune characterization in human glioma samples using the extracted genetic and clinical data from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases. Immunohistochemistry (IHC) performed on the tissue microarray slide was used to validate the expression and clinical and prognostic values of ERBB2 in glioma. Higher ERBB2 expression was found in patients with higher grades gliomas than in patients with lower grades gliomas. Besides, patients with higher ERBB2 expression showed poor prognosis. The IHC and clinical data next validated the expression pattern and prognostic value of ERBB2 in glioma. Further analysis showed that there was a strong positive correlation between ERBB2 and common immune checkpoints as well as immune markers of various immune cells in both TCGA and CGGA databases, and the IHC data further validated the positive correlation between ERBB2 and PD-L1 expression. Besides, analysis of ERBB2-related immune genes and signatures showed the significant role of ERBB2 in mediating tumor immune response in glioma. To sum up, our findings summarize the expression pattern and clinical characteristics of ERBB2 in glioma, which may be useful for expanding our understanding of the critical role of ERBB2 in antitumor therapy in glioma.Estrogen receptors alpha (ERα), a member of the nuclear receptor protein family, was found to play an important role in maintaining bone mass. Its downstream signaling proteins such as ERK and NF-κB were reported to be involved in development of osteoporosis, which meant that targeting ERα might be an effective strategy for searching for new drugs to prevent bone loss. In this study, we demonstrate that isobavachalcone (ISO), as one of bioactive compounds isolated from Psoralea corylifoliaLinn, has high affinity with ERα. 2-Deoxy-D-glucose mw The effects of ISO are investigated on receptor activator of NF-κB ligand (RANKL)-induced osteocalstogenesis. It is reported that ISO inhibits the RANKL-mediated increase of osteoclast-related genes MMP9, cathepsink and TRAR in RAW264.7 cells. Moreover, in vitro experiment shows that ISO exhibits an inhibitory effect on ERK and NF-κB signaling pathway, and suppresses RANKL-induced expression of osteoclast-related transcription factors NFATc1 and c-Fos. However, the impact of ISO in these molecules is eliminated by the application of ERα antagonist AZD9496.We further verified pharmacological effects of ISO in ovariectomized osteoporotic mice, and ISO significantly prevented bone loss and decreased M1 polarization of macrophages from marrow and spleen. Collectively, our data suggest that ISO prevents osteoporosis via suppressing activation of ERK and NF-κB signaling pathways as well as M1 polarization of macrophages.MicroRNA-181b (miR-181b) has been well noted with anti-inflammatory properties in several pathological conditions. It has also been suggested to be downregulated in patients with asthma. In this study, we explored the function of miR-181b in airway remodeling in asthmatic mice and the molecular mechanism. A mouse model with asthma was induced by ovalbumin (OVA) challenge, and miR-181b was found to be downregulated in lung tissues in the OVA-challenged mice. Overexpression of miR-181b was introduced in mice, after which the respiratory resistance, inflammatory infiltration, mucus production, and epithelial-mesenchymal transition (EMT) and fibrosis in mouse airway tissues were decreased. The integrated bioinformatics analysis suggested long non-coding RNA (lncRNA) TUG1 as a sponge for miR-181b. miR-181 directly targeted high mobility group box 1 (HMGB1) mRNA. HMGB1 was suggested to enhance activation of the nuclear factor kappa B (NF-κB) signaling. Further upregulation of lncRNA TUG1 blocked the protective functions of miR-181b in asthmatic mice. To conclude, this study evidenced that lncRNA TUG1 reinforces HMGB1 expression through sequestering microRNA-181b, which activates the NF-κB signaling pathway and promotes airway remodeling in asthmatic mice. This study may provide novel ideas in asthma management.Cyclophilin A (CypA) is a pro-inflammatory factor with multiple immunomodulating effects. Here, we investigated the effects of recombinant human CypA (rhCypA) as a factor of antitumor host defense. Our results demonstrated that rhCypA dramatically inhibited the growth of murine transplantable tumors (mammary adenocarcinoma Ca755, melanoma B16, Lewis lung carcinoma (LLC), and cervical cancer CC-5). In the B16 model, rhCypA effects were observed only when tumor cells were transplanted at the significantly reduced injection dose, indicating that antitumor properties of rhCypA are more effective at the initial stages of cancer development. Antitumor effect of rhCypA in the CC-5 model was comparable to the action of 5-fluorouracil (5FU), and rhCypA administration prevented 5FU - induced leukopenia in the blood of tumor-bearing mice. In the LLC model, rhCypA injection before but not after tumor resection significantly suppressed the formation of post-surgical metastases. RhCypA exhibited no direct cytotoxic effects in vitro on human leukemia cells (K-562, HL-60, KG-1), indicating that rhCypA antitumor action could be mediated by its immunomodulating activity. In the B16 model, rhCypA had no impact on tumor angiogenesis and gene expression of several MMPs, endogenous CypA, and CD147, which play a crucial role in cancer progression. However, in this model, rhCypA stimulated gene expression of MMPs 8, 9, and 12 that could contribute to malignancy growth inhibition. Here, our findings pointed out CypA as one of the factors of antitumor host defense that can effectively control the initial stages of tumor and metastases formation by regulating the action of MMPs and changing the tumor microenvironment.We integrate time-inconsistent decision making due to hyperbolic discounting into a gerontologically founded life cycle model with endogenous aging and longevity. Individuals can slow down aging and postpone death by health investments and by reducing unhealthy consumption, conceptualized as smoking. We show that individuals continuously revise their original plans to smoke less and invest more in their health. Consequently, they accumulate health deficits faster and die earlier than originally planned. This fundamental health consequence of time-inconsistency has not been addressed in the literature so far. Because death is endogenous, any attempt to establish the time-consistent first-best solution by manipulating the first order conditions through (sin-) taxes and subsidies is bound to fail. We calibrate the model with U.S. data for an average American in the year 2012 and estimate that time-inconsistent health behavior causes a loss of about 4 years of life. We show how price policy can nudge individuals to behave more healthy such that they actually realize the longevity and value of life planned at age 20.