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The migration of leukocytes into the CNS drives the neuropathology of multiple sclerosis (MS). This penetration likely utilizes energy resources that remain to be defined. Using the experimental autoimmune encephalomyelitis (EAE) model of MS, we determined that macrophages within the perivascular cuff of post-capillary venules are highly glycolytic as manifested by strong expression of lactate dehydrogenase A (LDHA) that converts pyruvate to lactate. These macrophages expressed prominent levels of monocarboxylate transporter-4 (MCT-4) specialized in secreting lactate from glycolytic cells. The functional relevance of glycolysis was confirmed by siRNA-mediated knockdown of LDHA and MCT-4, which decreased lactate secretion and macrophage transmigration. MCT-4 was in turn regulated by EMMPRIN (CD147) as determined through co-expression/co-immunoprecipitation studies, and siRNA-mediated EMMPRIN silencing. The functional relevance of MCT-4/EMMPRIN interaction was affirmed by lower macrophage transmigration in culture using the MCT-4 inhibitor, α-cyano-4-hydroxy-cinnamic acid (CHCA), a cinnamon derivative. CHCA also reduced leukocyte infiltration and the clinical severity of EAE. Relevance to MS was corroborated by the strong expression of MCT-4, EMMPRIN and LDHA in perivascular macrophages in MS brains. These results detail the metabolism of macrophages for transmigration from perivascular cuffs into the CNS parenchyma and identifies CHCA and diet as potential modulators of neuro-inflammation in MS.

The formation of the body of any space can be derived from the prevailing behaviors and diverse lifestyle patterns and the physical support of the type of space from specific activities or diverse uses. Each space has a different meaning that emerges based on the body that surrounds it. Traditional markets as the support of commercial centers have components that are derived and show the physical design and spatial behavior that are directly related. This research was formed with the aim of extracting physical-spatial components and classifying them in the markets of Kerman. The research method is a combination of nested qualitative and quantitative type. In the qualitative part, semi-structured interviews with scholars and snowball sampling are used, in which 28 experts are interviewed. In order to reduce the data, coding is used in ATLASTI software. It is a causal-comparative quantitative method that uses the components of the previous stage to develop a questionnaire and distribute it among 384 space users. The results are entered into the GRAPHER 16 software for analysis and are analyzed with inferential statistics. The results show that the most important factors in the body-behavior components in the formation of the traditional market of Kerman city include the response of the wise in the form, the support of the body to the activity, the cover Plant is with a value of (1.000) and the lowest factor contribution is related to inviting elements with a value of (0.295). Also, all the components have a significant relationship to explain the factor contribution, except for the flooring component, whose factor contribution is (0.467) but it does not have a significant relationship. To facilitate the review of the results, a summary chart of the determined coefficients has been presented. [ABSTRACT FROM AUTHOR]

Background: The role of tumor-associated macrophages (TAMs) in glioblastoma (GBM) disease progression has received increasing attention. Recent advances have shown that TAMs can be re-programmed to exert a pro-inflammatory, anti-tumor effect to control GBMs. However, imaging methods capable of differentiating tumor progression from immunotherapy treatment effects have been lacking, making timely assessment of treatment response difficult. We showed that tracking monocytes using iron oxide nanoparticle (USPIO) with MRI can be a sensitive imaging method to detect therapy response directed at the innate immune system. Methods: We implanted syngeneic mouse glioma stem cells into C57/BL6 mice and treated the animals with either niacin (a stimulator of innate immunity) or vehicle. Animals were imaged using an anatomical MRI sequence, R2* mapping, and quantitative susceptibility mapping (QSM) before and after USPIO injection. Results: Compared to vehicles, niacin-treated animals showed significantly higher susceptibility and R2*, representing USPIO and monocyte infiltration into the tumor. We observed a significant reduction in tumor size in the niacin-treated group 7 days later. We validated our MRI results with flow cytometry and immunofluoresence, which showed that niacin decreased pro-inflammatory Ly6C high monocytes in the blood but increased CD16/32 pro-inflammatory macrophages within the tumor, consistent with migration of these pro-inflammatory innate immune cells from the blood to the tumor. Conclusion: MRI with USPIO injection can detect therapeutic responses of innate immune stimulating agents before changes in tumor size have occurred, providing a potential complementary imaging technique to monitor cancer immunotherapies. Manuscript highlight: We show that iron oxide nanoparticles (USPIOs) can be used to label innate immune cells and detect the trafficking of pro-inflammatory monocytes into the glioblastoma. This preceded changes in tumor size, making it a more sensitive imaging technique. [ABSTRACT FROM AUTHOR]

The article focuses on PD-1 independent of PD-L1 ligation promotes glioblastoma growth through the NFkB pathway. Topics include the brain tumor–initiating cells (BTICs) drive glioblastoma growth through not fully understood mechanisms, the cells within the human glioblastoma microenvironment coexpress programmed cell death 1 (PD-1) and BTIC marker, and the gain- or loss-of-function studies revealed that tumor-intrinsic PD-1 promoted proliferation and self-renewal of BTICs.