👤 Jordan Metz

Macrophages differentiated with macrophage colony-stimulating factor (M-CSF) (M-Mac) are widely used as an experimental model. Interleukin 27 (IL-27)-polarized M-Mac (27M-Mac) suppresses HIV replication; however, the effects of IL-27 polarization on granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced macrophages (GM-Mac) remain less investigation. Here, we compare multiple functional properties and gene expression profiles of 27M-Mac and IL-27-polarized GM-Mac (27GM-Mac). M-Mac and GM-Mac were generated from monocytes of healthy donors and subsequently treated with IL-27 for three days. HIV replication in 27M-Mac, GM-Mac, and 27GM-Mac was suppressed to nearly 10% of that in M-Mac; however, single-cell RNA sequencing showed that M-Mac clustered with GM-Mac, and 27M-Mac clustered with 27GM-Mac. Expression of CD38 and secretion of CXCL9 and C1q were significantly increased in 27M-Mac and 27GM-Mac compared with M-Mac and GM-Mac. Although CD16 and CD64 expression increased in 27M-Mac and 27GM-Mac relative to their respective controls, phagocytic activity in 27M-Mac and 27GM-Mac was 30% of that in M-Mac. Autophagy was promoted 3.7-fold more strongly in 27M-Mac than in M-Mac, reaching levels comparable to those in GM-Mac and 27GM-Mac. Collectively, these findings indicate that IL-27 polarizes M-Mac and GM-Mac toward transcriptionally and functionally similar subtypes, providing insight into the role of IL-27 in macrophage polarization and plasticity. Show less

The human brain functions as a highly integrated system. Interconnected cellular and molecular networks within this system process sensory information, cognitive functions, and motor responses. The brain also exhibits a remarkable potential for plasticity-driven adaptive learning and memory. Importantly, neuroplasticity serves as a key mechanism of neuroprotection while also enabling the brain to compensate for injury through adaptive structural remodeling. Understanding the brain as a dynamic system requires examining how its components interact to produce adaptive physiological responses and complex behaviors, such as social interactions. Key molecules, such as brain-derived neurotrophic factor (BDNF) and oxytocin (OT), play pivotal roles in maintaining the brain's dynamic complexity and integrative functioning. In this review, we introduce the concept of "neurosocial plasticity", which refers to the brain's ability to adapt both neural circuitry and social behavior through the dynamic interaction between BDNF and OT. This concept highlights how BDNF-OT interactions may support both neural plasticity and the capacity for adaptive social functioning. We then explore how their co-localization, co-expression, and co-regulation may regulate neural and social plasticity, ultimately shaping the brain's adaptability and the development of social behaviors across various contexts. Show less

Type 1 diabetes (T1D) results from an autoimmune attack of the pancreatic β cells that progresses to dysglycemia and symptomatic hyperglycemia. Current biomarkers to track this evolution are limited, with development of islet autoantibodies marking the onset of autoimmunity and metabolic tests used to detect dysglycemia. Therefore, additional biomarkers are needed to better track disease initiation and progression. Multiple clinical studies have used proteomics to identify biomarker candidates. However, most of the studies were limited to the initial candidate identification, which needs to be further validated and have assays developed for clinical use. Here we curate these studies to help prioritize biomarker candidates for validation studies and to obtain a broader view of processes regulated during disease development. This systematic review was registered with Open Science Framework (DOI 10.17605/OSF.IO/N8TSA). Using PRISMA guidelines, we conducted a systematic search of proteomics studies of T1D in the PubMed to identify putative protein biomarkers of the disease. Studies that performed mass spectrometry-based untargeted/targeted proteomic analysis of human serum/plasma of control, pre-seroconversion, post-seroconversion, and/or T1D-diagnosed subjects were included. For unbiased screening, 3 reviewers screened all the articles independently using the pre-determined criteria. A total of 13 studies met our inclusion criteria, resulting in the identification of 251 unique proteins, with 27 (11%) being identified across 3 or more studies. The circulating protein biomarkers were found to be enriched in complement, lipid metabolism, and immune response pathways, all of which are found to be dysregulated in different phases of T1D development. We found a subset of 3 proteins (C3, KNG1 & CFAH), 6 proteins (C3, C4A, APOA4, C4B, A2AP & BTD) and 7 proteins (C3, CLUS, APOA4, C6, A2AP, C1R & CFAI) have consistent regulation between multiple studies in samples from individuals at pre-seroconversion, post-seroconversion and post-diagnosis compared to controls, respectively, making them strong candidates for clinical assay development. Biomarkers analyzed in this systematic review highlight alterations in specific biological processes in T1D, including complement, lipid metabolism, and immune response pathways, and may have potential for further use in the clinic as prognostic or diagnostic assays. Show less

Inadequate magnesium (Mg) intake is a widespread problem, with over 50% of women of reproductive age consuming less than the Recommended Dietary Allowance (RDA). Because pregnancy increases the requirement for Mg and the beneficial effects of magnesium sulfate for preeclampsia/eclampsia and fetal neuroprotection are well described, we examined the outcomes of Mg deficiency during pregnancy. Briefly, pregnant Swiss Webster mice were fed either control or Mg-deficient diets starting on gestational day (GD) 6 through euthanasia on GD17. Mg-deficient dams had significantly reduced weight gain and higher plasma adipokines, in the absence of inflammation. Livers of Mg-deficient dams had significantly higher saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) and lower polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) (P < 0.0001) and arachidonic acid (AA) (P < 0.0001). Mechanistically, Mg deficiency was accompanied by enhanced desaturase and elongase mRNA expression in maternal livers along with higher circulating insulin and glucose concentrations (P < 0.05) and increased mRNA expression of Srebf1 and Chrebp, regulators of fatty acid synthesis (P < 0.05). Fetal pups exposed to Mg deficiency were growth-restricted and exhibited reduced survival. Mg-deficient fetal livers showed lower MUFAs and higher PUFAs, with lower desaturase and elongase mRNA expression than controls. In addition, DHA concentrations were lower in Mg-deficient fetal brains (P < 0.05). These results indicate that Mg deficiency during pregnancy influences both maternal and fetal fatty acid metabolism, fetal growth and fetal survival, and support better understanding maternal Mg status before and during pregnancy. Show less