Macrophage Dvl2 deficiency promotes NOD1-Driven pyroptosis and exacerbates inflammatory liver injury.

Dishevelled 2 (Dvl2) is a key mediator of the Wingless/Wnt signaling pathway that regulates cell proliferation, migration, and immune function. However, little is known about the role of macrophage Dvl2 in modulating NOD1-mediated pyroptosis and hepatocyte death in oxidative stress-induced inflammatory liver injury. In a mouse model of oxidative stress-induced liver inflammation, mice with myeloid-specific Dvl2 knockout (Dvl2) displayed exacerbated ischemia/reperfusion (IR) stress-induced hepatocellular damage with increased serum ALT levels, oxidative stress, and proinflammatory mediators.

IL-17 Signaling in Keratinocytes Orchestrates the Defense against Staphylococcus aureus Skin Infection.

Keratinocytes (KCs) form the outer epithelial barrier of the body, protecting against invading pathogens. Mice lacking the IL-17RA or both IL-17A and IL-17F develop spontaneous Staphylococcusaureus skin infections. We found a marked expansion of T cells, comprised of RORγt-expressing γδ T cells and T helper 17 cells in the skin-draining lymph nodes of these mice.

Early screening model for mild cognitive impairment based on resting-state functional connectivity: a functional near-infrared spectroscopy study.

Significance: As an early stage of Alzheimer's disease (AD), the diagnosis of amnestic mild cognitive impairment (aMCI) has important clinical value for timely intervention of AD. Functional near-infrared spectroscopy (fNIRS)-based resting-state brain connectivity analysis, which could provide an economic and quick screening strategy for aMCI, remains to be extensively investigated.

Aim: This study aimed to verify the feasibility of fNIRS-based resting-state brain connectivity for evaluating brain function in patients with aMCI, and to determine an early screening model for auxiliary diagnosis.

Decreased Hemodynamic Responses in Left Parietal Lobule and Left Inferior Parietal Lobule in Older Adults with Mild Cognitive Impairment: A Near-Infrared Spectroscopy Study.

Background: The brain activation patterns of mild cognitive impairment (MCI) are still unclear and they involve multiple brain regions. Most previous studies have focused on abnormal activation in the frontal and temporal lobes, with few investigating the entire brain.

Objective: To identify and compare the changes in cerebral hemodynamics and abnormal activation patterns in the entire brain of MCI patients and healthy older adults.

Macrophage Notch1 inhibits TAK1 function and RIPK3-mediated hepatocyte necroptosis through activation of β-catenin signaling in liver ischemia and reperfusion injury.

Background: Notch signaling is highly conserved and critically involved in cell differentiation, immunity, and survival. Activation of the Notch pathway modulates immune cell functions during the inflammatory response. However, it remains unknown whether and how the macrophage Notch1 may control the innate immune signaling TAK1, and RIPK3-mediated hepatocyte necroptosis in liver ischemia and reperfusion injury (IRI).

Novel role of macrophage TXNIP-mediated CYLD-NRF2-OASL1 axis in stress-induced liver inflammation and cell death.

Background & Aims: The stimulator of interferon genes (STING)/TANK-binding kinase 1 (TBK1) pathway is vital in mediating innate immune and inflammatory responses during oxidative/endoplasmic reticulum (ER) stress. However, it remains unknown whether macrophage thioredoxin-interacting protein (TXNIP) may regulate TBK1 function and cell death pathways during oxidative/ER stress.

Methods: A mouse model of hepatic ischaemia/reperfusion injury (IRI), the primary hepatocytes, and bone marrow-derived macrophages were used in the myeloid-specific TXNIP knockout (TXNIP) and TXNIP-proficient (TXNIP) mice.

Erratum: Myeloid Nrf2 deficiency aggravates non-alcoholic steatohepatitis progression by regulating YAP-mediated NLRP3 inflammasome signaling.

[This corrects the article DOI: 10.1016/j.isci.

Myeloid Nrf2 deficiency aggravates non-alcoholic steatohepatitis progression by regulating YAP-mediated NLRP3 inflammasome signaling.

Nuclear-erythroid-2-related factor 2 (Nrf2) is involved in the pathogenesis of different liver diseases. Herein, we first demonstrated that Nrf2 expression was diminished in nonalcoholic steatohepatitis (NASH) liver macrophages. In myeloid Nrf2-deficiency mice, aggravated liver steatosis and inflammation in high-fat-diet (HFD)-fed mice were observed compared with the chow-diet group.

The cGAS-STING Pathway: Novel Perspectives in Liver Diseases.

Liver diseases represent a major global health burden accounting for approximately 2 million deaths per year worldwide. The liver functions as a primary immune organ that is largely enriched with various innate immune cells, including macrophages, dendritic cells, neutrophils, NK cells, and NKT cells. Activation of these cells orchestrates the innate immune response and initiates liver inflammation in response to the danger signal from pathogens or injured cells and tissues.

CD47-Mediated Hedgehog/SMO/GLI1 Signaling Promotes Mesenchymal Stem Cell Immunomodulation in Mouse Liver Inflammation.

Background And Aims: The cluster of differentiation 47 (CD47)-signal regulatory protein alpha (SIRPα) signaling pathway plays important roles in immune homeostasis and tissue inflammatory response. Activation of the Hedgehog/smoothened (SMO)/GLI family zinc finger 1 (Gli1) pathway regulates cell growth, differentiation, and immune function. However, it remains unknown whether and how the CD47-SIRPα interaction may regulate Hedgehog/SMO/Gli1 signaling in mesenchymal stem cell (MSC)-mediated immune regulation during sterile inflammatory liver injury.

Cancer-associated fibroblasts enhance the chemoresistance of CD73 hepatocellular carcinoma cancer cells via HGF-Met-ERK1/2 pathway.

Background: Cancer-associated fibroblasts (CAFs) are a major component of hepatocellular carcinoma (HCC) stroma that are critically involved in HCC cancer chemoresistance, but the mechanism has not been elucidated. Previous studies have reported CD73 exerted an immunosuppressive function in cancer. Here, we explored the mechanism by which CAFs regulates CD73 HCC cells and clarified whether CAFs promote chemoresistance of CD73 cells.

Traf6 inhibitor boosts antitumor immunity by impeding regulatory T cell migration in Hepa1-6 tumor model.

Tumors escape immune attacks via various mechanisms, among which activation of regulatory pathways in effector immune cells and recruitment of immunosuppressive cells are usually employed. Traf6 is a member of the family of tumor necrosis factor receptor-associated factors and involved in many signaling pathways. While it plays important roles in both tumor biology and immune system, the potential therapeutic role of Traf6 in tumor immunotherapy hasn't ever been assessed.

TRAF6 directs FOXP3 localization and facilitates regulatory T-cell function through K63-linked ubiquitination.

Regulatory T cells (Tregs) are crucial mediators of immune control. The characteristic gene expression and suppressive functions of Tregs depend considerably on the stable expression and activity of the transcription factor FOXP3. Transcriptional regulation of the Foxp3 gene has been studied in depth, but both the expression and function of this factor are also modulated at the protein level.

Mangiferin ameliorates fatty liver via modulation of autophagy and inflammation in high-fat-diet induced mice.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally. The progression of NAFLD is complex and associated with inflammation, oxidative stress, autophagy, endoplasmic reticulum stress, and insulin resistance. Mangiferin, a natural C-glucosyl xanthone, has been reported to show multiple biological activities.