Lamontejlersen1807

The carcinogenic function of arachidonate lipoxygenase12 (Alox12) has been reported in various cancers. However, little is known on the role of Alox12 in lung cancer. Here, we demonstrate that Alox12 is upregulated and contributes to biological activities of lung cancer through multiple mechanisms. We found that Alox12 mRNA and protein levels were increased by 2.5-fold in a panel of lung cancer cell lines compared to normal lung cells. The expression of Alox12 varied among lung cancer cell lines. The immunohistochemistry analysis on paired normal and tumor lung tissues from twenty patients showed that Alox12 protein level is higher in lung cancer than normal lung tissues from the majority of patients. We further observed the upregulation of Alox12-12-HETE signaling axis in lung cancer tissues. Givinostat HDAC inhibitor Overexpression of Alox12 promoted growth and migration in normal lung cells and lung cancer cells. In contrast, Alox12 inhibition via genetic and pharmacological approaches suppressed growth and migration, induced apoptosis, and sensitized lung cancer cells to chemotherapy. This is through suppressing RhoA signaling, inhibiting epithelial-to-mesenchymal transition (EMT) and NF-κB activity. Our work reveals the therapeutic value of inhibiting Alox12 in overcoming chemoresistance in lung cancer. β-Amyloid (Aβ) plaque in the brains of patients with Alzheimer's disease (AD) is mainly caused by impaired clearance of Aβ by glial cells, including microglia and astrocytes. Because microglia play an important protective role in the central nervous system, many efforts have been made to identify agents that effectively improve microglial Aβ phagocytosis. This study found that TLQP-21, which is cleaved from VGF (VGF nerve growth factor inducible) precursor protein, enhanced Aβ phagocytosis and degradation by microglial BV2 cells. TLQP-21 also improved microglial phagocytic activity and promoted fibrillar amyloid-β (fAβ) uptake by microglial BV2 cells via a C3AR1-dependent mechanism. Moreover, TLQP-21 stimulated Aβ degradation by enhancing lysosome activity, thereby enhancing fAβ clearance. These results suggest that treatment with TLQP-21 may be a novel therapeutic strategy to efficiently enhance microglial Aβ clearance in AD. This review is devoted to comparative pharmacological analysis of synthetic drugs such as memantine and its isomers, as well as tacrine, velnacrine, rivastigmine, and donepezil, with natural alkaloids, terpenoids, and triterpenoid peroxides, which are used to treat dementia, Alzheimer's and Parkinson's diseases, myasthenia gravis and other neurodegenerative diseases. Recently discovered by French scientists from Marseille triterpenoid hydroperoxides demonstrate high activity as potential therapeutic agents for the treatment of dementia. The information presented in this review is of great interest to pharmacologists, medical chemists, physiologists, neurologists and doctors, as well as for the pharmaceutical industry. Crown All rights reserved.Apoptosis of osteoblasts plays a crucial role in osteomyelitis. Hydrogen sulfide (H2S) levels are increased in the pathophysiological processes of osteomyelitis. However, the effect of H2S on the apoptosis of osteoblasts remains unclear. To investigate the specific role of H2S in osteoblast apoptosis, MC3T3-E1 and hFOB cells were treated with NaHS or Na2S, a donor of H2S, and lipopolysaccharide (LPS), during osteomyelitis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, flow cytometry analysis, western blotting, immunofluorescence, polymerase chain reaction, and Alizarin red staining were performed to examine the effects of H2S on osteoblast cell apoptosis, cell osteogenic differentiation, and AKT kinase (AKT)/nuclear factor kappa B (NF-κB) signaling. Hydrogen sulfide increased cell apoptosis, and inhibited the proliferation and osteogenic differentiation of osteoblast cells impaired by LPS. H2S increased apoptosis through upregulation of the FAS ligand (FASL) signaling pathway. H2S-induced apoptosis was alleviated using a FAS/FASL signaling pathway inhibitor. Treatment with NaHS also increased cell apoptosis by downregulating AKT/NF-κB signaling. In addition, treatment with an AKT signaling pathway activator decreased apoptosis and reversed the inhibitory effects of H2S on osteogenic differentiation. Hydrogen sulfide promotes LPS-induced apoptosis of osteoblast cells by inhibiting AKT/NF-κB signaling. Chromatin organization starts from a "beads-on-a string" 10 nm fiber, a basic nucleosomal structure consisting of DNA and core histones. Given its regular nucleosome array on DNA backbone where N-terminal tails of each histone are exposed on the surface of chromatin fiber, we hypothesized that chromatin can be utilized as a heterologous peptide carrier to elicit a peptide-specific immune response. The plasmid DNA containing the Widom's clone 601 sequence and the recombinant chimeric histones containing the peptide derived from ras oncogene (G12V) were used to assemble the chromatin fiber in vitro. The immunogenicity of the assembled chromatin was tested in mice as a single vaccine component or formulated with adjuvants. G12V tagged-chromatin co-administered with adjuvants induced higher antibody responses against the G12V peptide than vaccination with adjuvant alone, while chimeric histones did not generate a significant antibody response. Interestingly, splenocytes from mice vaccinated with the G12V tagged-chromatin vaccine did not generate significant antigen-specific cytokine responses. Our studies suggest that chromatin can be utilized as an effective carrier of antigenic peptides for inducing specific antibody responses. Inflammatory bowel disease (IBD) is a risk factor for the development of colorectal cancer (CRC) for which mutation to p53 is an early event leading to dysplasia. Interestingly, P2RY6 mRNA increases in both pathologies. In this study, we investigated if p53 and p53R273H mutant, commonly found in CRC and IBD, were involved in the transcriptional regulation of P2RY6. First, the P2RY6 promoter was defined as a region corresponding to -1600 to +273 nucleotides relative to the putative TATA-less transcriptional starting site found at position 73,264,505 of NCBI reference sequence NC_000010.11. We cloned this promoter region along with 5'-deletion constructs in the pGL4.10[luc2] vector for luciferase assays to delineate the minimal promoter region. We observed that p53 wt and p53R273H differentially regulated the transcription of the P2RY6 gene. In fact, increasing quantity of p53R273H enhanced the capacity of p53 wt to stimulate the transactivation of the P2RY6 promoter but this cooperative effect was lost when p53R273H was present in a ratio of 31.