Alzheimer’s disease (AD) is a debilitating neurological disorder, and currently, there is no cure for it. Several pathologic alterations have been described in the brain of AD patients, but the ultimate causative mechanisms of AD are still elusive. The classic hallmarks of AD, including amyloid plaques (Aβ) and tau tangles (tau), are the most studied features of AD. Unfortunately, all the efforts targeting these pathologies have failed to show the desired efficacy in AD patients so far. Neuroinflammation and impaired autophagy are two other main known pathologies in AD. It has been reported that these pathologies exist in AD brain long before the emergence of any clinical manifestation of AD. Microglia are the main inflammatory cells in the brain and are considered by many researchers as the next hope for finding a viable therapeutic target in AD. Interestingly, it appears that the autophagy and mitophagy are also changed in these cells in AD. Inside the cells, autophagy and inflammation interact in a bidirectional manner. In the current review, we briefly discussed an overview on autophagy and mitophagy in AD and then provided a comprehensive discussion on the role of these pathways in microglia and their involvement in AD pathogenesis.

Natural killer (NK) cell therapy is one of the most promising treatments for Glioblastoma Multiforme (GBM). However, this emerging technology is limited by the availability of sufficient numbers of fully functional cells. Here, we investigated the efficacy of NK cells that were expanded and treated by interleukin-2 (IL-2) and heat shock protein 70 (HSP70), both in vitro and in vivo. Proliferation and cytotoxicity assays were used to assess the functionality of NK cells in vitro, after which treated and naïve NK cells were administrated intracranially and systemically to compare the potential antitumor activities in our in vivo rat GBM models. In vitro assays provided strong evidence of NK cell efficacy against C6 tumor cells. In vivo tracking of NK cells showed efficient homing around and within the tumor site. Furthermore, significant amelioration of the tumor in rats treated with HSP70/Il-2-treated NK cells as compared to those subjected to nontreated NK cells, as confirmed by MRI, proved the efficacy of adoptive NK cell therapy. Moreover, results obtained with systemic injection confirmed migration of activated NK cells over the blood brain barrier and subsequent targeting of GBM tumor cells. Our data suggest that administration of HSP70/Il-2-treated NK cells may be a promising therapeutic approach to be considered in the treatment of GBM.

Natural killer (NK) cell therapy is one of the most promising treatments for Glioblastoma Multiforme (GBM). However, this emerging technology is limited by the availability of sufficient numbers of fully functional cells. Here, we investigated the efficacy of NK cells that were expanded and treated by interleukin-2 (IL-2) and heat shock protein70 (HSP70), both in vitro and in vivo. Proliferation and cytotoxicity assays were used to assess the functionality of NK cells in vitro, after which treated and naïve NK cells were administrated intra-cranially and systemically to compare the potential antitumor activities in our in vivo rat GBM models. In vitro assays provided strong evidence of NK cell efficacy against C6 tumor cells. In vivo tracking of NK cells showed efficient homing around and within the tumor site. Furthermore, significant amelioration of the tumor in rats treated with HSP70/Il-2 treated NK cells as compared to those subjected to non-treated NK cells, as confirmed by MRI, proved the efficacy of adoptive NK cell therapy. Moreover, results obtained with systemic injection confirmed migration of activated NK cells over the blood brain barrier and subsequent targeting of GBM tumor cells. Our data suggest that administration of HSP70/Il-2 treated NK cells may be a promising therapeutic approach to be considered in the treatment of GBM.

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent and debilitating condition with unclear etiology. Increasing evidence implicates immune dysregulation, yet the molecular mechanisms underlying impaired immune regulation remain poorly defined. This study investigated the role of adaptive immune responses and DNA methylation in CP/CPPS pathogenesis. Methods: Voided bladder 3 (VB3) urine samples from CP/CPPS patients and healthy controls were analyzed for CD4 T cell markers and lineage-defining transcription factors. DNA methylation profiling of peripheral blood mononuclear cells (PBMCs) and purified CD4 T cells was performed using targeted methylation arrays. Functional assays evaluated IL-10 production following lipopolysaccharide (LPS) stimulation, with or without azacitidine (AZA), a DNA methyltransferase inhibitor that reverses methylation-dependent gene silencing. In vivo relevance was assessed using the experimental autoimmune prostatitis (EAP) mouse model. Results: VB3 samples from CP/CPPS patients demonstrated elevated CD4 T cell transcripts with a Th17/Th1 (RORgammaT/TBET) bias and reduced FOXP3 expression. DNA methylation analysis revealed hypermethylation of IL10 and FOXP3 promoters and hypomethylation of inflammatory genes including CD274, ITGAL, and TNF. PBMCs from patients exhibited diminished IL-10 secretion in response to LPS, which was restored by azacitidine treatment. In the EAP model, recombinant IL-10 administration failed to attenuate pelvic allodynia, whereas azacitidine significantly reduced pain sensitivity. Conclusions: CP/CPPS is associated with widespread epigenetic reprogramming of immune regulatory genes leading to impaired IL10 mediated immune regulation. Pharmacologic inhibition of DNA methylation restored IL10 responses and alleviated pain in vivo, supporting demethylation therapy as a potential strategy for treating chronic prostatic inflammation and pelvic pain.

Background: Breast carcinoma represents the most frequent malignancy in women in Canada. The intrinsic or acquired drug resistance significantly contributes to in-creased risk of recurrence and metastasis. Although, front-line therapy is multimodal, chemoresistance remains a major hurdle in treatment and therapy. Intake of natural compounds issued from the fermentation processes are now considered a god strategy to help overcome chemoresistance. Materials and Methods: Extracellular vehicles (EVs) from Mesenchymal Stro-mal/Stem Cells (MSCs) pretreated with Lentinula edodes cultured extract (AHCC) were used to study the effect on reducing chemoresistance and modulating mi-croRNAs in cell lines, MCF-7 and MCF-7/DOX cells by EVs derived from MSCs under AHCC treatment. Characterization of EVs was done by using nanoparticles tracking analysis. MicroRNas and the formation of cancer stem cells were studied. Results: miRNA analysis revealed that AHCC remarkably affected the expression of several microRNAs, amongst which are miR-155, miR-34a, miR-Let7 and miR-200c. In vitro experiments showed inhibition of cancer stem cell proliferation after challenging the cells with EVs pretreated with AHCC. Conclusion: Our data demonstrated that AHCC may contribute to the modulation of tumor microenvironment, thus influenc-ing the development of cancer stem cells.