scholarly journals Macrophage Activation by a Substituted Pyrimido[5,4-b]Indole Increases Anti-Cancer Activity

2019 ◽  
Author(s):  
Joseph Hardie ◽  
Javier A. Mas-Rosario ◽  
Siyoung Ha ◽  
Erik M. Rizzo ◽  
Michelle E. Farkas
Keyword(s):  
Small Molecule ◽  
Macrophage Activation ◽  
Expression Patterns ◽  
Inflammatory Factors ◽  
New Approach ◽  
Anti Cancer ◽  
Macrophage Activator ◽  
Specific Manner ◽  
Tlr Agonist ◽  
Complementary Strategy

ABSTRACTImmunotherapy has become a promising new approach for cancer treatment due to the immune system’s ability to remove tumors in a safe and specific manner. Many tumors express anti-inflammatory factors that deactivate the local immune response or recruit peripheral macrophages into pro-tumor roles. Because of this, effective and specific ways of activating macrophages into anti-tumor phenotypes is highly desirable for immunotherapy purposes. Here, the use of a small molecule TLR agonist as a macrophage activator for anti-cancer therapy is reported. This compound, referred to as PBI1, demonstrated unique activation characteristics and expression patterns compared to treatment with LPS, through activation of TLR4. Furthermore, PBI1 treatment resulted in anti-tumor immune behavior, enhancing macrophage phagocytic efficiency five-fold versus non-treated macrophages. Additive effects were observed via use of a complementary strategy (anti-CD47 antibody), resulting in ∼10-fold enhancement of phagocytosis, suggesting this small molecule approach could be used in conjunction with other therapeutics.

Synthesis and characterization of fluorescent chitosan–ZnSe/ZnS nanoparticles for potential drug carriers

RSC Advances ◽  
2015 ◽  
Vol 5 (49) ◽  
pp. 38810-38817 ◽  
Author(s):  
Yeping Li ◽  
Jingbo Xu ◽  
Yun Xu ◽  
Liying Huang ◽  
Junli Wang ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Drug Carrier ◽  
Drug Carriers ◽  
Cancer Drug ◽  
Synthesis And Characterization ◽  
Potential Drug ◽  
Zns Nanoparticles ◽  
New Approach ◽  
Anti Cancer

The objective of the study is to describe a new approach of combining quantum dots into chitosan as an anti-cancer drug carrier.

Industry Watch

2004 ◽  
Vol 08 (06) ◽  
pp. 297-308
Keyword(s):  
Phase Ii ◽  
Cancer Vaccine ◽  
Phase Ii Trial ◽  
Invasive Cancer ◽  
Pharmaceutical Sector ◽  
Regional Office ◽  
New Approach ◽  
Bird Flu ◽  
Non Invasive ◽  
Anti Cancer

Ai Scientific Awarded R&D Start Grant. CSIRO Drug Effective against Bird Flu. AustCancer Commences Anti-cancer Vaccine Phase II Trial. New Approach against Cancer. Non-invasive Cancer Test. China’s Chemical Pharmaceutical Sector Q1 2003 Performance. International Generic Companies Target India’s Manufacture Infrastructure. Cardinal Health Sets up Regional Office in Singapore. BRV Enters Agreement with Genedata.

scholarly journals miR-124-3p Inhibits Microglial Secondary Inflammation After Basal Ganglia Hemorrhage by Targeting TRAF6 and Repressing the Activation of NLRP3 Inflammasome

2021 ◽  
Vol 12 ◽  
Author(s):  
Yudan Fang ◽  
Xiaoqin Hong
Keyword(s):  
Basal Ganglia ◽  
Cell Viability ◽  
Healthy Volunteers ◽  
Nlrp3 Inflammasome ◽  
Cell Model ◽  
Expression Patterns ◽  
Cell Activity ◽  
Inflammatory Factors ◽  
High Morbidity ◽  
Apoptosis Rate

Objectives: Intracerebral hemorrhage (ICH) represents a serious central nervous system emergency with high morbidity and mortality, and the basal ganglia is the most commonly affected brain region. Differentially expressed microRNAs (miRs) have recently been highlighted to serve as potential diagnostic biomarkers and therapeutic targets for ICH. This study investigated the mechanism of miR-124-3p in microglial secondary inflammation after ICH.Methods: In this study, 48 patients with primary basal ganglia ICH and 48 healthy volunteers were selected and venous blood was collected from all patients on the second morning of admission (within 24 h of stroke onset). The expression of miR-124-3p in serum was detected by RT-qPCR. Three months after ICH, the patients were assessed by modified Rankin Scale (mRS), and the correlation between miR-124-3p expression and mRS score was analyzed by Pearson. The inflammatory response of microglia was induced by lipopolysaccharide (LPS) to establish the cell model of microglial inflammation. miR-124-3p expression patterns were detected in the serum of ICH patients and healthy volunteers, normal microglia, and LPS-induced microglia. The miR-124-3p mimic was transfected into LPS-induced microglia, followed by measurement of the inflammatory factors, apoptosis rate, and cell viability. The target gene of miR-124-3p was predicted and verified. The expression patterns of tumor necrosis factor receptor-associated factor 6 (TRAF6) were detected. pcDNA3.1 and pcDNA3.1-TRAF6 were transfected into LPS-induced HMC3 cells, and nucleotide-binding oligomerization domain-like receptor (NLR) pyrin domain-containing 3 (NLRP3) expression patterns were determined. Lastly, the effects of TRAF6 overexpression on apoptosis, cell viability, and inflammation in HMC3 cells were measured.Results: miR-124-3p was downregulated in the serum of basal ganglia ICH patients and LPS-induced microglia, and miR-124-3p expression was negatively correlated with mRS. Overexpression of miR-124-3p reduced the inflammatory factors and apoptosis rate and promoted cell activity in LPS-induced microglia. miR-124-3p was found to target TRAF6. Overexpression of TRAF6 enhanced the expression of NLRP3 inflammasome, inflammatory factors and apoptosis rate, and reduced cell viability.Conclusion: Our findings indicate that miR-124-3p repressed the activation of NLRP3 inflammasome by targeting TRAF6, thus inhibiting microglial secondary inflammation after ICH in basal ganglia.

Small Molecule Restores Itaconate Sensitivity inSalmonella enterica: A Potential New Approach to Treating Bacterial Infections

ChemBioChem ◽  
2016 ◽  
Vol 17 (16) ◽  
pp. 1513-1517 ◽  
Author(s):  
Fabien Hammerer ◽  
Justin H. Chang ◽  
Dustin Duncan ◽  
Angel Castañeda Ruiz ◽  
Karine Auclair
Keyword(s):  
Small Molecule ◽  
Bacterial Infections ◽  
New Approach

Role of Different Doses of Ketamine in Postoperative Neurocognitive Function in Aged Mice Undergoing Partial Hepatectomy by Regulating the Bmal1/NMDA/NF-Κb Axis

2021 ◽  
pp. 1-14
Author(s):  
Xiaoli Niu ◽  
Simin Zheng ◽  
Siyuan Li ◽  
Hongtao Liu
Keyword(s):  
Partial Hepatectomy ◽  
Calcium Binding ◽  
Expression Patterns ◽  
Microglia Activation ◽  
Inflammatory Factors ◽  
Aged Patients ◽  
Aged Mice ◽  
Aryl Hydrocarbon ◽  
Different Doses ◽  
Synapsin 1

<b><i>Background:</i></b> The current study set out to probe the function of different doses of ketamine in postoperative neurocognitive disorder (PND) in aged mice undergoing partial hepatectomy (PH) with the involvement of the brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1)/n-methyl-D-aspartate (NMDA)/nuclear factor-kappa B (NF-κB) axis. <b><i>Methods:</i></b> First, aged mice were intraperitoneally injected with different doses of ketamine prior to surgery, followed by hepatic lobectomy. Afterward, mice cognitive function was assessed. In addition, Bmal1 mRNA expression patterns were quantified, while NMDA 2B receptor, NF-κB p65, synapsin 1, and postsynaptic density 95 (PSD95) levels were determined; the release of inflammatory factors was detected, and ionized calcium-binding adapter molecule-1 expression was measured to quantify microglia activation. In addition, Bmal1-knockout (Bmal1-KO) mice were intraperitoneally injected with a subanesthetic dose of ketamine to verify the mechanism of Bmal1 in regulating the NMDA 2B subunit (NR2B)/NF-κB axis to affect PH in aged patients. <b><i>Results:</i></b> After PH, hippocampal-dependent memory was impaired, and synapsin 1 and PSD95 levels were downregulated. On the other hand, PH diminished Bmal1 expression but elevated NR2B and NF-κB p65 levels and anesthetic doses of ketamine further regulated the Bmal1/NMDA/NF-κB axis. In Bmal1-KO mice, the NMDA/NF-κB axis was activated, the release of inflammatory cytokines was promoted, and hippocampus-dependent memory was impaired, which were reversed by a subanesthetic dose of ketamine. <b><i>Conclusion:</i></b> Altogether, findings obtained in our study indicated that a subanesthetic dose of ketamine activated Bmal1, downregulated the NMDA/NF-κB axis, and reduced inflammation and microglia activation to alleviate PND in aged mice undergoing PH.

A comprehensive cancer-associated microRNA expression profiling and proteomic analysis of human umbilical cord mesenchymal stem cell derived exosomes.

2021 ◽  
Author(s):  
Ganesan Jothimani ◽  
Surajait Pathak ◽  
Suman Dutta ◽  
Asim K. Duttaroy ◽  
Antara Banerjee
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Umbilical Cord ◽  
Expression Patterns ◽  
Functional Enrichment ◽  
Human Umbilical Cord ◽  
Human Mscs ◽  
Anti Cancer

Abstract Background The mesenchymal stem cells (MSCs) have enormous therapeutic potential owing to their multi-lineage differentiation and self-renewal properties. MSCs express growth factors, cytokines, chemokines, and non-coding regulatory RNAs with immunosuppressive, anti-tumor, and migratory properties. MSCs also release several anti-cancer molecules via extracellular vesicles, that act as pro-apoptotic/tumor suppressor factors. This study aimed to identify the stem cell-derived secretome that could exhibit anti-cancer properties through molecular profiling of cargos in MSC-derived exosomes. Methods Human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated from umbilical cord tissues and cultured expanded. After that, exosomes were isolated from the hUCMSC conditioned medium. The miRNA profiling of hUCMSCs and hUCMSC-derived exosomes was performed, followed by functional enrichment analysis. Results The miRNA expression profile and gene ontology (GO) depicts the differential expression patterns of high and less-expressed miRNAs that are delineated to be involved in the regulation of the apoptosis process. The LCMS/MS data and GO analysis indicate that hUCMSC secretomes are involved in several oncogenic and inflammatory signaling cascades. Conclusion Primary human MSCs releases miRNAs and growth factors via exosomes that are increasingly implicated in intercellular communications, and hUCMSC-exosomal miRNAs may have a critical influence in regulating cell death and apoptosis of cancer cells.

scholarly journals The Antiasthma Medication Ciclesonide Suppresses Breast Cancer Stem Cells through Inhibition of the Glucocorticoid Receptor Signaling-Dependent YAP Pathway

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 6028 ◽  
Author(s):  
Su-Lim Kim ◽  
Hack Sun Choi ◽  
Ji-Hyang Kim ◽  
Dong-Sun Lee
Keyword(s):  
Breast Cancer ◽  
Glucocorticoid Receptor ◽  
Underlying Mechanism ◽  
Tissue Growth ◽  
New Approach ◽  
Ru 486 ◽  
Mammosphere Formation ◽  
Cysteine Rich Protein ◽  
Anti Cancer ◽  
Interfering Rna

Ciclesonide is an FDA-approved glucocorticoid used to treat asthma and allergic rhinitis. However, whether it has anticancer and anti-cancer stem cell (CSC) effects is unknown. This study focused on investigating the effect of ciclesonide on breast cancer and CSCs and determining its underlying mechanism. Here, we showed that ciclesonide inhibits breast cancer and CSC formation. Similar glucocorticoids—dexamethasone and prednisone—did not inhibit CSC formation. Ciclesonide-induced glucocorticoid receptor (GR) degradation was dependent on ubiquitination. We showed via GR small interfering RNA (siRNA) that GR plays an important role in CSC formation. We showed via western blot and immunofluorescence assays that ciclesonide reduces the nuclear level of GR. The GR antagonist RU-486 also inhibited CSC formation. Ciclesonide reduced the protein level of the Hippo transducer Yes-associated protein (YAP). GR siRNA induced a decrease in YAP protein expression and inhibited mammosphere formation. The YAP inhibitor verteporfin inhibited CSC formation and transcription of the connective tissue growth factor and cysteine-rich protein 61 genes. The GR/YAP1 pathway regulated breast CSC formation. We showed that the GR/YAP signaling pathway regulates breast CSC formation and revealed a new approach for targeting GR and YAP to inhibit CSC formation.

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