Comparison of dietary inflammatory index and inflammatory biomarkers between vegetarians and omnivores in Chinese population.

Most previous studies on the association between vegetarian diet and inflammation have used only one inflammatory biomarker e.g., C-reactive protein (CRP) and the findings were generally inconsistent. Therefore, we conducted a cross-sectional study to investigate the correlation between diet and inflammation in Chinese vegetarians using dietary indices and multiple inflammatory biomarkers. 279 vegetarians and omnivores of the same sex and age recruited in Shanghai, 2016. 24-h dietary review questionnaire was collected and used to calculate Dietary inflammatory index (DII) and Energy-adjusted inflammatory index (E-DII) of both groups. In addition, energy intake matched vegetarian and omnivore recipes were designed by registed dietitions and used to calculate a theoretical DII. Five serum inflammatory biomarkers CRP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were measured. We found that vegetarians had significantly lower E-DII and theoretical DII than omnivores (P < 0.001). In contrast, the raw DII of vegetarians was almost the same with that of omnivores, probably due to lower energy intake in vegetarians than in omnivores (1367.97 ± 479.75 vs. 1724.78 ± 568.13, P < 0.001). Levels of TNF-α, IL-6, NLR and PLR were significantly higher in vegetarians than in omnivores while no statistical differences were found in CRP. In conclusion, a theoretical vegetarian diet with adequate energy intake as well as a balanced dietary intake showed good anti-inflammatory effects, though this was not fully reflected in vegetarian population in the real world, probably due to insufficient energy intake in the vegetarian population.

Macrophage lineage cells-derived migrasomes activate complement-dependent blood-brain barrier damage in cerebral amyloid angiopathy mouse model.

Accumulation of amyloid beta protein (Aß) in brain vessels damages blood brain barrier (BBB) integrity in cerebral amyloid angiopathy (CAA). Macrophage lineage cells scavenge Aß and produce disease-modifying mediators. Herein, we report that Aß40-induced macrophage-derived migrasomes are sticky to blood vessels in skin biopsy samples from CAA patients and brain tissue from CAA mouse models (Tg-SwDI/B and 5xFAD mice). We show that CD5L is packed in migrasomes and docked to blood vessels, and that enrichment of CD5L impairs the resistance to complement activation. Increased migrasome-producing capacity of macrophages and membrane attack complex (MAC) in blood are associated with disease severity in both patients and Tg-SwDI/B mice. Of note, complement inhibitory treatment protects against migrasomes-mediated blood-brain barrier injury in Tg-SwDI/B mice. We thus propose that macrophage-derived migrasomes and the consequent complement activation are potential biomarkers and therapeutic targets in CAA.

FOXP3+ macrophage represses acute ischemic stroke-induced neural inflammation.

Proper termination of cell-death-induced neural inflammation is the premise of tissue repair in acute ischemic stroke (AIS). Macrophages scavenge cell corpses/debris and produce inflammatory mediators that orchestrate immune responses. Here, we report that FOXP3, the key immune-repressive transcription factor of Tregs, is conditionally expressed in macrophages in stroke lesion. FOXP3 ablation in macrophages results in detrimental stroke outcomes, emphasizing the beneficial role of FOXP3+ macrophages. FOXP3+ macrophages are distinct from the M1 or M2 subsets and display superactive efferocytic capacity. With scRNAseq and analysis of FOXP3-bound-DNA isolated with CUT & RUN, we show that FOXP3 facilitates macrophage phagocytosis through enhancing cargo metabolism. FOXP3 expression is controlled by macroautophagic/autophagic protein degradation in resting macrophages, while initiation of LC3-associated phagocytosis (LAP) competitively occupies the autophagic machineries, and thus permits FOXP3 activation. Our data demonstrate a distinct set of FOXP3+ macrophages with enhanced scavenging capability, which could be a target in immunomodulatory therapy against AIS.Abbreviations: ADGRE1/F4/80: adhesion G protein-coupled receptor E1; AIF1/Iba1: allograft inflammatory factor 1; AIS: acute ischemic stroke; ARG1: arginase 1; ATP: adenosine triphosphate; BECN1/Beclin1: Beclin 1, autophagy related; BMDM: bone marrow-derived macrophages; CKO: conditional knockout; CSF1/M-CSF: colony stimulating factor 1 (macrophage); CSF2/GM-CSF: colony stimulating factor 2; CSF3/G-CSF: colony stimulating factor 3; CUT & RUN: cleavage under targets and release using nuclease; CyD: cytochalasin D; DAMP: danger/damage-associated molecular pattern; DIL: dioctadecyl-3,3,3,3-tetramethylin docarbocyanine; ELISA: enzyme linked immunosorbent assay; GO: Gene Ontology; FCGR3/CD16: Fc receptor, IgG, low affinity III; HMGB1: high mobility group box 1; IFNG/IFNγ: interferon gamma; IP: immunoprecipitation; KEGG: Kyoto Encyclopedia of Genes and Genomes; ITGAM/CD11b: integrin subunit alpha M; ITGAX/CD11c: integrin subunit alpha X; LAP: LC3-associated phagocytosis; LC-MS: liquid chromatography-mass spectrometry; LPS: lipopolysaccharide; MRC1/CD206: mannose receptor, C type 1; O4: oligodendrocyte marker O4; PBMC: peripheral blood mononuclear cells; RBC: red blood cells; PTPRC/CD45: protein tyrosine phosphatase, receptor type, C; RBFOX3/NeuN: RNA binding protein, fox 1 homolog (C. elegans) 3; RUBCN/Rubicon: RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein; scRNAseq: single cell RNA sequencing; SQSTM1/p62 (sequestosome 1); TGFB/TGFß: transforming growth factor, beta; tMCAO: transient middle cerebral artery occlusion; TNF/TNFα: tumor necrosis factor; Treg: regulatory T cell.

MiR-27a-3p Targeting GSK3ß Promotes Triple-Negative Breast Cancer Proliferation and Migration Through Wnt/ß-Catenin Pathway.

BACKGROUND: Dysregulation of microRNAs (miRNAs) was found to play crucial roles in varieties of cancers, which affect tumor proliferation and migration. MiR-27a-3p has been identified as a tumor-related miRNA in liver cancer, lung cancer, and colorectal cancer. However, the function of miR-27a-3p in triple-negative breast cancer (TNBC) and its possible molecular mechanisms have still not been elucidated. METHODS: QRT-PCR technique was used to detect the expression of miR-27a-3p in TNBC and normal breast cell lines or the effects of miR-27a-3p knockdown and overexpression in TNBC cell lines. Proliferation and migration were measured by CCK-8 method, colony formation, wound healing, and Transwell assays, respectively. Furthermore, we used a dual-luciferase reporter gene assay and Western blot analysis to identify GSK3ß as a target of miR-27a-3p. RESULTS: In this study, we found that miR-27a-3p expression was significantly elevated in TNBC cell lines. Database analysis suggested that TNBC patients with a high expression of miR-27a-3p have poorer overall survival possibilities. Overexpression of miR-27a-3p promotes TNBC cells proliferation, colony formation, and cell migration in vitro. Nevertheless, dual-luciferase reporter result showed that miR-27a-3p directly targeted the 3'-UTR regions of GSK3ß mRNA and negatively regulated its expression. Lastly, we demonstrated that miR-27a-3p inactivates Wnt/ß-catenin signaling pathway via targeting GSK3ß. CONCLUSION: These results indicate that expression of miR-27a-3p was highly expressed in TNBC and promoted tumor progression through attenuating GSK3ß and may have a potential molecular-targeted strategy for TNBC therapy.

A comparative study of three nutritional risk screening tools in surgical inpatients with laryngeal cancer.

BACKGROUND AND OBJECTIVES: Nutritional screening has been recommended for hospitalized patients. The goal of this study was to compare the screening value of Nutritional Risk Screening 2002 (NRS-2002), Malnutrition Universal Screening Tool (MUST), and Malnutrition Screening Tool (MST) in inpatients with laryngeal cancer, and to identify which is the most accurate. METHODS AND STUDY DESIGN: An observational cross-sectional study of 197 laryngeal cancer patients admitted for surgery was conducted using continuous sampling. NRS-2002, MUST, and MST were used to screen the nutritional risk of patients after admission and before discharge. Diagnostic information and the length-of-hospital stay (LOS) data were extracted from the hospital HIS system. RESULTS: The detection rates of NRS-2002, MUST, and MST in admission or discharge patients were 14.7%/27.9%, 22.3%/26.9%, and 4.6%/11.2%, respectively. Using NRS-2002 as the reference, high sensitivity (82.8%) and a Kappa coefficient (k=0.584) were achieved using MUST in admission patients, while MST presented the lowest sensitivity (17.3%) and Kappa coefficient (k=0.208). MST maintained low sensitivity (25.5%) and Kappa coefficient (k=0.243) in discharge patients. NRS-2002 ≥3 was an independent risk factor for longer LOS in patients with laryngeal cancer (odds ratio (OR)=5.59, 95% confidence interval (CI)=1.86-16.81, p=0.002). The MUST and MST scores did not predict long LOS. CONCLUSIONS: Compared with NRS-2002, MUST is superior to MST in sensitivity, specificity, and Kappa coefficient. NRS-2002 better identified patients at risk for longer LOS, but a consistent conclusion was not reached with MUST and MST. Further validation in larger samples is needed.