The CCR6-CCL20 Axis Promotes Regulatory T-cell Glycolysis and Immunosuppression in Tumors.

Regulatory T cells (Treg) are important players in the tumor microenvironment. However, the mechanisms behind their immunosuppressive effects are poorly understood. We found that CCR6-CCL20 activity in tumor-infiltrating Tregs is associated with greater glycolytic activity and ablation of Ccr6 reduced glycolysis and lactic acid production while increasing compensatory glutamine metabolism.

PP2Ac/STRN4 negatively regulates STING-type I IFN signaling in tumor-associated macrophages.

Stimulator of IFN genes type I (STING-Type I) IFN signaling in myeloid cells plays a critical role in effective antitumor immune responses, but STING agonists as monotherapy have shown limited efficacy in clinical trials. The mechanisms that downregulate STING signaling are not fully understood. Here, we report that protein phosphatase 2A (PP2A), with its specific B regulatory subunit Striatin 4 (STRN4), negatively regulated STING-Type I IFN in macrophages.

The Role of Myeloid Cells in GBM Immunosuppression.

Gliomas are intrinsic brain tumors that originate from glial cells. Glioblastoma (GBM) is the most aggressive glioma type and resistant to immunotherapy, mainly due to its unique immune environment. Dimensional data analysis reveals that the intra-tumoral heterogeneity of immune cell populations in the glioma microenvironment is largely made up of cells of myeloid lineage.

Functional Change of Effector Tumor-Infiltrating CCR5CD38HLA-DRCD8 T Cells in Glioma Microenvironment.

Human glioma facilitates an impaired anti-tumor immunity response, including defects in circulation of T lymphocytes. The level of CD8 T-cell activation acts as an immune regulator associated with disease progression. However, little is known about the characteristics of peripheral and tumor-infiltrating CD8 T cells in patients with glioma.

Regulatory effects of caffeic acid phenethyl ester on neuroinflammation in microglial cells.

Microglial activation has been widely demonstrated to mediate inflammatory processes that are crucial in several neurodegenerative disorders. Pharmaceuticals that can deliver direct inhibitory effects on microglia are therefore considered as a potential strategy to counter balance neurodegenerative progression. Caffeic acid phenethyl ester (CAPE), a natural phenol in honeybee propolis, is known to possess antioxidant, anti-inflammatory and anti-microbial properties.

Naringenin Suppresses Neuroinflammatory Responses Through Inducing Suppressor of Cytokine Signaling 3 Expression.

Accumulating evidence suggests that neuroinflammation is closely associated with the pathogenesis of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. The hallmark of neuroinflammation is considered to be microglial activation in the central nervous system (CNS). Activated microglia release pro-inflammatory cytokines which cause neuroinflammation and progressive neuronal cell death.

Exogenous endothelin-1 induces cell migration and matrix metalloproteinase expression in U251 human glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common and lethal type of primary brain tumor characterized by its rapid infiltration to surrounding tissues during the early stages. The fast spreading of GBM obscures the initiation of the tumor mass making the treatment outcome undesirable. Endothelin-1 is known as a secretory protein presented in various types of brain cells, which has been indicated as a factor for cancer pathology.

Anti-neuroinflammatory effects of the calcium channel blocker nicardipine on microglial cells: implications for neuroprotection.

Background/objective: Nicardipine is a calcium channel blocker that has been widely used to control blood pressure in severe hypertension following events such as ischemic stroke, traumatic brain injury, and intracerebral hemorrhage. However, accumulating evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play important roles in neurodegeneration, and the effect of nicardipine on microglial activation remains unresolved.

Methodology/principal Findings: In the present study, using murine BV-2 microglia, we demonstrated that nicardipine significantly inhibits microglia-related neuroinflammatory responses.

In-group bias in residency selection.

Background: More than half of all Canadian medical graduates match to residency programs within the same university as their medical school. Here we describe two studies designed to explore whether there is partiality for internal applicants in the resident selection process.

Methods: We first performed an observational study in which we compared the ratings of 14 'internal' and 89 'external' applicants to the University of Calgary Internal Medicine Training Program by resident and faculty raters.

Rater variables associated with ITER ratings.

Advocates of holistic assessment consider the ITER a more authentic way to assess performance. But this assessment format is subjective and, therefore, susceptible to rater bias. Here our objective was to study the association between rater variables and ITER ratings.

Rapid evaluation after high-risk TIA is associated with lower stroke risk.

Background: Current 'standard of care' for patients presenting with a 'high-risk' TIA varies, with use of several outpatient and inpatient approaches. We describe the clinical outcomes and costs for high risk TIA patients who received care in a 'rapid evaluation unit', and compare these to a historical 'high-risk' cohort.

Methods: The study cohort was comprised of patients with TIA admitted to a 'rapid evaluation unit' during the period March 2002 to April 2003.

Early risk of stroke after transient ischemic attack: a systematic review and meta-analysis.

Background: Recent observational studies suggest that the risk for stroke may be high in the first 90 days after transient ischemic attack (TIA). This finding may, however, not be consistent across existing studies assessing stroke risk after TIA. The objectives of our study were to conduct a systematic review and meta-analysis of observational studies estimating the risk of stroke at 2, 30, and 90 days after TIA and to explore clinical and methodological factors that may explain variability in findings across studies.

Transplanting kidneys from CMV-seropositive donors to CMV-seronegative recipients is not associated with poorer renal allograft function or survival.

Background: Cytomegalovirus (CMV)-seronegative recipients of renal allografts from CMV-seropositive donors (D+/R-) have a higher rate of acute rejection than other renal transplant recipients. A relationship between CMV infection/disease and chronic allograft nephropathy (CAN) has been proposed from animal studies, although human studies have been inconclusive. The objective of this study was to determine if CMV seromatching has an effect on renal allograft function and allograft survival.

Cytomegalovirus seromismatching increases the risk of acute renal allograft rejection.

Background: There is an association between cytomegalovirus (CMV) infection or disease and acute allograft rejection in the setting of renal transplantation. There is, however, debate regarding the nature of this association, with evidence supporting both a "forward" relationship (CMV infection or disease precedes acute rejection) and a "backward" relationship (CMV infection or disease follows acute rejection). The objective of this study was to determine whether CMV matching had an independent effect on the risk of acute renal allograft rejection, which would support the view that CMV infection or disease is a risk factor for acute rejection.