Association between healthy eating index-2015 and abdominal aortic calcification: A population-based cross-sectional study

Background: An association between the healthy eating index (HEI)-2015 and risk of abdominal aortic calcification (AAC) is unclear in the general population of the United States (U.S.). Therefore, we examined the relationship between HEI-2015 and AAC risk in our research. Methods: A cross-sectional study of National Health and Nutrition Examination Surveys (NHANES) participants between 2013 and 2014 was conducted. For the analysis of the association between HEI-2015 and AAC, the restricted cubic spline (RCS) plot and multivariable logistic regression models were used. In addition, we also conducted subgroup analysis for the relationship between HEI-2015 and AAC. Results: There was a total of 1162 individuals. As shown by the RCS plot, HEI-2015 was linked with AAC risk in a U-shaped pattern (P for nonlinearity < 0.05). Taking into account known confounding variables, compared with the lowest quartiles, the odds ratios with 95% confidence intervals for AAC across the quartiles were 0.637 (0.425,0.956), 0.763 (0.499, 1.167), and 0.842 (0.561, 1.265). Based on the results of subgroup analysis, the HEI-2015 and AAC risk were U-curve correlated among all age groups, sex, with or without hypertension or DM, and BMI of <30 kg/m2. The greens and beans, and whole fruits are independent protective factor for AAC. Conclusions: The U-shaped relationships exist between HEI-2015 and prevalence of AAC in the general U.S. population. Consequently, prevalence of AAC may be mitigated with reasonable and balanced diet

Virus Infection and Death Receptor-Mediated Apoptosis

Virus infection can trigger extrinsic apoptosis. Cell-surface death receptors of the tumor necrosis factor family mediate this process. They either assist persistent viral infection or elicit the elimination of infected cells by the host. Death receptor-mediated apoptosis plays an important role in viral pathogenesis and the host antiviral response. Many viruses have acquired the capability to subvert death receptor-mediated apoptosis and evade the host immune response, mainly by virally encoded gene products that suppress death receptor-mediated apoptosis. In this review, we summarize the current information on virus infection and death receptor-mediated apoptosis, particularly focusing on the viral proteins that modulate death receptor-mediated apoptosis

Interleukin 16 contributes to gammaherpesvirus pathogenesis by inhibiting viral reactivation.

Gammaherpesviruses have evolved various strategies to take advantage of host cellular factors or signaling pathways to establish a lifelong latent infection. Like the human gammaherpesvirus Epstein-Barr virus, murine gammaherpesvirus 68 (MHV68) establishes and maintains latency in the memory B cells during infection of laboratory mice. We have previously shown that MHV68 can immortalize fetal liver-derived B cells that induce lymphomas when injected into immunodeficient mice. Here we identify interleukin 16 (IL16) as a most abundantly expressed cytokine in MHV68-immortalized B cells and show that MHV68 infection elevates IL16 expression. IL16 is not important for MHV68 lytic infection but plays a critical role in MHV68 reactivation from latency. IL16 deficiency increases MHV68 lytic gene expression in MHV68-immortalized B cells and enhances reactivation from splenic latency. Correlatively, IL16 deficiency increases the frequency of MHV68-infected plasma cells that can be attributed to enhanced MHV68 reactivation. Furthermore, similar to TPA-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus, IL16 deficiency markedly induces Tyr705 STAT3 de-phosphorylation and elevates p21 expression, which can be counteracted by the tyrosine phosphatase inhibitor orthovanadate. Importantly, orthovanadate strongly blocks MHV68 lytic gene expression mediated by IL16 deficiency. These data demonstrate that virus-induced IL16 does not directly participate in MHV68 lytic replication, but rather inhibits virus reactivation to facilitate latent infection, in part through the STAT3-p21 axis

Neutrophils resist ferroptosis and promote breast cancer metastasis through aconitate decarboxylase 1

Metastasis causes breast cancer-related mortality. Tumor-infiltrating neutrophils (TINs) inflict immunosuppression and promote metastasis. Therapeutic debilitation of TINs may enhance immunotherapy, yet it remains a challenge to identify therapeutic targets highly expressed and functionally essential in TINs but under-expressed in extra-tumoral neutrophils. Here, using single-cell RNA sequencing to compare TINs and circulating neutrophils in murine mammary tumor models, we identified aconitate decarboxylase 1 (Acod1) as the most upregulated metabolic enzyme in mouse TINs and validated high Acod1 expression in human TINs. Activated through the GM-CSF-JAK/STAT5-C/EBPβ pathway, Acod1 produces itaconate, which mediates Nrf2-dependent defense against ferroptosis and upholds the persistence of TINs. Acod1 ablation abates TIN infiltration, constrains metastasis (but not primary tumors), bolsters antitumor T cell immunity, and boosts the efficacy of immune checkpoint blockade. Our findings reveal how TINs escape from ferroptosis through the Acod1-dependent immunometabolism switch and establish Acod1 as a target to offset immunosuppression and improve immunotherapy against metastasis.</p