Alzheimer's disease (AD) is a neurodegenerative disorder and leading cause of dementia, which begins with impaired memory. The neuropathological hallmarks of AD include destructive alterations of neurons by neurofibrillary tangles, neuritic amyloid plaques, and neuroinflammatory process in the brain. Chemokines have a major role in inflammatory cell attraction and glial cell activation and/or modulation in the central nervous system. Moreover, the clinical and immunopathological evidence could show dual key role of chemokines in their pro- and anti-inflammatory properties in AD. However, their effects in neurodegeneration and/or neuroprotection remain an area of investigation. This review article provides an overview of characteristic, cellular source and activity of chemokines, and their roles in neuronal glial cell interaction in AD.

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The human dental pulp stem cells (hDPSCs) are one of the readily available sources of multipotent mesenchymal stem cells (MSCs) and can be considered as a type of tool cells for cell-based therapies. However, the main limitation in the clinical use of these cells is DPSC senescence, which can be induced by lipopolysaccharide (LPS) of oral pathogenic bacteria. Up to now, far little attention has been paid to exploring the molecular mechanisms of senescence in DPSCs. So, the current study aimed to investigate the underlying molecular mechanism of senescence in hDPSCs stimulated with Porphyromonas gingivalis (P. gingivalis) and Escherichia coli (E. coli)-derived LPSs, by evaluating both mRNA and protein expression of four important senescence-related genes, including TP53, CDKN1A, CDKN2A and SIRT1. To this purpose, hDPSCs were stimulated with different LPSs for 6, 24 and 48 h and then the gene expression was evaluated using quantitative real-time polymerase chain reaction (qPCR) and western blotting. Following stimulation with P. gingivalis and E. coli-derived LPSs, the relative mRNA and protein expression of all genes were significantly up-regulated in a timedependent manner, as compared with unstimulated hDPSCs. Moreover, the hDPSCs stimulated with P. gingivalis LPS for 6 and 24 h had the highest mRNA expression of CDKN1A and SIRT1, respectively (p < 0.0001), whereas the highest mRNA expression of CDKN2A and TP53 was seen in hDPSCs stimulated with E. coli LPS for 48 h (p < 0.0001). In summary, because DPSCs have been reported to have therapeutic potential for several cell-based therapies, targeting molecular mechanisms aiming at preventing DPSC senescence could be considered a valuable strategy.

Abstract:Introduction: Silibinin, a polyphenolic flavonoid isolated from the milk thistle plant (Silybummarianum), has various applications in cancer therapy. This investigation aimed to examine the effects of silibinin on proliferation and chemokine receptor expression on MDA-MB-231 cells, a highly metastatic human breast cancer cell line. Methods: The cytotoxic effect of silibinin on MDA-MB-231 cells was determined by micro-culture tetrazolium test (MTT) assay. In addition, the expression of chemokine receptors CXCR3, CCR5 and CCR7 genes in response to silibinin was evaluated by Real-Time PCR. Results: Data analysis from MTT assay showed that silibinin had dose-dependent and time-dependent inhibitory effects on MDA-MB-231 cell line. Moreover, Real-Time PCR analysis showed that silibinin not only had no inhibitory effects on CXCR3, CCR5 and CCR7 gene expressions, but also could increase significantly the expression of these genes in a dose and time-dependent manner. Conclusion: These results revealed for the first time the increased possibility of CXCR3, CCR5 and CCR7 genes expression in response to silibinin in human breast cancer cells.

Treatment of Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, is currently considered a challenging issue since it causes substantial disability, poor quality of life, and mortality. Despite remarkable progress in advanced conventional therapeutic interventions,the global burden of the disease has nearly doubled, prompting us to assess the risk-effectiveness of different treatment modalities. Each protocol could be considered as the best alternative treatment depending on the patient’s situation. Prescription of Levodopa, the most effective available medicine for this disorder, has been associated with many complications, i.e., multiple episodes of "off-time", and treatment resistance. Other medications, which are typically used in combination with levodopa, may have several adverse effects as well. As a result, the therapies that are more in line with human physiology and make the least interference with other pathways are worth investigating. On the other hand, remaining and persistent symptoms after therapy and the lack of effective response to the conventional approaches have raised expectations towards innovative alternative approaches such as stem cell-based therapy. It is critical not to overlook the unexplored side effects of innovative approaches due to the limited number of research. In this review, we aimed to compare the efficacy and risk of advanced therapies with innovative cell-based and stem-cell-based modalities in PD patients. This paper recapitulated the underlying factors/conditions, which could lead us to more practical and established therapeutic outcomes with more advantages and few complications. It could be an initial step to reconsider the therapeutic blueprint for patients with Parkinson’s disease.