• Casey Burnett posted an update 6 months ago

    During the last century, our battle against cancer has been inaugurated upon three main approaches; surgery, radiation and chemotherapy. The latest findings on the effectiveness of immunotherapy in cancer management offer a ray of hope after decades of research and studies on the best treatment methods. Immunotherapy has proven effective in the surveillance and destruction of cancer-causing cells, demonstrating its ability to suppress cancer through controlling the well-established immune-editing process. Immuno-editing is a process that comprises three principal elements; namely elimination, equilibrium, and escape, and is paramount to the comprehension of checkpoint inhibition. Cancer cells employ various approaches to evade the elimination step leading to its immune-escape. The escape mechanism encompasses the upregulation of negative co-signals that block successful activation of cancer-eradicating immune cells, developing cytokine background that favors the immunosuppressive tumor microenvironment (TME), or dropping the expression of tumor-specific proteins known as neo-antigens, therefore reducing the immunogenic activity against cancer cells. Today, checkpoint inhibitors are considered as a main approach in our fight against cancer. Strategies targeting the inhibitory roles of checkpoint inhibitors have been shown effective against different cancer types and stages, and some already gained the FDA’s approval. This review seeks to comprehensively cover the historical background as well as the most recent updates for the role of immune checkpoint regulators in the maintenance of immune homeostatic balance as well as keeping the tumorigenic cells in check. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.Dementia is an important issue in western societies, and in the following years, this problem will also rise in the developing regions, such as Africa and Asia. The most common types of dementia in adults are Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD) and vascular dementia (VaD), of which, AD accounts for more than half of the cases. The most prominent symptom of AD is cognitive impairment, currently treated with four drugs donepezil, rivastigmine, and galantamine, enhancing cholinergic transmission; as well as memantine, protecting neurons against glutamate excitotoxicity. Fluvastatin Despite ongoing efforts, no new drugs in the treatment of AD have been registered for the last ten years, thus multiple studies have been conducted on genetic factors affecting the efficacy of antidementia pharmacotherapy. The researchers investigate the effects of variants in multiple genes, such as ABCB1, ACE, CHAT, CHRNA7, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, CYP3A7, NR1I2, NR1I3, POR, Prs; For any queries, please email at epub@benthamscience.net.BACKGROUND Cognitive capacities in Alzheimer’s disease (AD) are impaired by an epigenetic blockade mediated by histone deacetylase 2 (HDAC2), which prevents the transcription of genes that are important for synaptic plasticity. OBJECTIVE Investigation of the functional relationship between cell adhesion molecule L1 and HDAC2 in AD. METHODS Cultures of dissociated cortical and hippocampal neurons from wild-type or L1-deficient mice were treated with Aβ1- 42 for 24 h. After removal of Aβ1-42 cells were treated with the recombinant L1 extracellular domain (rL1) for 24 h followed by immunohistochemistry, western blotting, and reverse transcription PCR to evaluate the interaction between L1 and HDAC2. RESULTS Aβ and HDAC2 protein levels were increased in APPSWE/L1+/- mutant brains compared to APPSWE mutant brains. Administration of the recombinant extracellular domain of L1 to cultured cortical and hippocampal neurons reduced HDAC2 mRNA and protein levels. In parallel, reduced phosphorylation levels of glucocorticoid receptor 1 (GR1), which is implicated in regulating HDAC2 levels, was observed in response to L1 administration. Application of a glucocorticoid receptor inhibitor reduced Aβ-induced GR1 phosphorylation and prevented the increase in HDAC2 levels. HDAC2 protein levels were increased in cultured cortical neurons from L1-deficient mice. This change could be reversed by the administration of the recombinant extracellular domain of L1. CONCLUSION Our results suggest that some functionally interdependent activities of L1 and HDAC2 contribute to ameliorating the phenotype of AD by GR1 dephosphorylation, which leads to reduced HDAC2 expression. The combined findings encourage further investigations on the beneficial effects of L1 in the treatment of AD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND Immunoglobulin G and A, transferrin, haptoglobin and alpha-1-antitrypsin are representing approximately 85% of the human serum glycoproteome and their N-glycosylation analysis may lead to discover important molecular disease markers. However, due to the labile nature of the sialic acid residues, the desialylated subset of the serum N-glycoproteome has been traditionally utilized for diagnostic applications. OBJECTIVE Creating a five-protein model to deconstruct the overall N-glycosylation fingerprints in inflammatory and malignant lung diseases. METHODS The N-glycan pool of human serum and the five high abundant serum glycoproteins were analyzed. Simultaneous endoglycosidase/sialidase digestion was followed by fluorophore labeling and separation by CE-LIF to establish the model. Pooled serum samples from patients with COPD, lung cancer (LC) and their comorbidity were all analyzed. RESULTS Nine significant (>1%) asialo-N-glycan structures were identified both in human serum and the standard protein ence.net.BACKGROUND Different clinical studies have given inconsistent results on whether the use of antipsychotics increases the risk of thromboembolism. In this paper, we reviewed all relevant literature to provide suggestions for clinical diagnosis and treatment. METHOD PubMed, Web of Science, EMBASE, MEDLINE, Cochrane and Scopus databases were thoroughly searched up to June 2019. Two researchers independently searched the literature, extracted data. Data were analyzed by Stata 12.0 software. RESULT A total of 22 studies involving 31514226 subjects were included. This meta-analysis showed that patients taking the first- or second-generation antipsychotics had a higher risk of venous thromboembolism and pulmonary embolism than those who did not, and low potency first-generation agents increased the risk of venous thromboembolism more than high potency antipsychotics, and olanzapine, clozapine, haloperidol, perphenazine and risperidone also significantly increased the risk of it. The risk of venous thrombosis in obese people was higher than that in overweight people, patients not less than 65 years old had an increased risk compared with younger patients.

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