Starting the Engine and Releasing the Brakes of T-Cell Responses: A Biomimetic Dendritic Cell Nanoplatform for Improved Glioblastoma Immunotherapy.

Glioblastoma (GBM), the most aggressive primary brain tumor, remains a challenge for immunotherapies, like immune checkpoint blockade (ICB), due to the blood-brain barrier (BBB) and immunosuppressive tumor microenvironment (TME) deficient in cytotoxic T-cells and effective T-cell-dendritic cell (DC) interactions. Herein, we engineer a biomimetic nanoplatform comprising paclitaxel (PTX) nanoparticles (NPs) encapsulated in a tumor-associated antigen-loaded DC membrane modified with ICB antibodies. The DC membrane not only facilitates BBB penetration and GBM targeting but also directly engages with T-cells reminiscent of T-cell-antigen-presenting cell (APC) clusters.

Clearance of senescent vascular smooth muscle cells retards aging-related restenosis following bioresorbable scaffolds implantation.

In contrast to bioinert metal stents, the degradation of bioresorbable scaffolds (BRS) induces complex mechanical changes and accumulation of degradation products, potentially leading to adverse events following implantation into stenotic arteries. Atherosclerosis (AS) is a typical age-related disease, plaque formation and changes in vascular mechanical properties can significantly affect the process of restenosis and vascular repair after BRS implantation. The aging of vascular smooth muscle cells (VSMCs) is earlier than that of endothelial cells (ECs) and plays a decisive role in the mechanical properties of blood vessels.

Multiple synergistic anti-aging effects of vascular cell adhesion molecule 1 functionalized nanoplatform to improve age-related neurodegenerative diseases.

Aging is a critical factor in the onset and progression of neurodegenerative diseases and cognitive decline, with aging-related neuroinflammation and cellular senescence being major contributors. In the aging brain, the cerebral vascular endothelium overexpresses vascular cell adhesion molecule 1 (VCAM1), activating microglia and leading to neuroinflammation and cognitive impairment. Quercetin, a natural neuroprotective agent widely used for treating neurodegenerative diseases, their therapeutic efficacy, however, is limited by its poor water solubility and inability to penetrate the blood-brain barrier (BBB).

Tumor-Antigen Activated Dendritic Cell Membrane-Coated Biomimetic Nanoparticles with Orchestrating Immune Responses Promote Therapeutic Efficacy against Glioma.

Immunotherapy has had a profound positive effect on certain types of cancer but has not improved the outcomes of glioma because of the blood-brain barrier (BBB) and immunosuppressive tumor microenvironment. In this study, we developed an activated mature dendritic cell membrane (aDCM)-coated nanoplatform, rapamycin (RAPA)-loaded poly(lactic--glycolic acid) (PLGA), named aDCM@PLGA/RAPA, which is a simple, efficient, and individualized strategy to cross the BBB and improve the immune microenvironment precisely. cells uptake and the transwell BBB model revealed that the aDCM@PLGA/RAPA can enhance homotypic-targeting and BBB-crossing efficiently.

Ubiquitin-specific peptidase 53 inhibits the occurrence and development of clear cell renal cell carcinoma through NF-κB pathway inactivation.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent malignant diseases in the urinary system with more than 140,000 related deaths annually. Ubiquitination-deubiquitination homeostasis is an important factor in ccRCC progression; ubiquitin-specific peptidase 53 (USP53) belongs to the family of deubiquitinating enzymes, but its functions are rarely reported.

Methods: Databases obtained from GEO and TCGA were analyzed to reveal the role of USP53 in ccRCC.

Hepatocyte TNF Receptor-Associated Factor 6 Aggravates Hepatic Inflammation and Fibrosis by Promoting Lysine 6-Linked Polyubiquitination of Apoptosis Signal-Regulating Kinase 1.

Activation of apoptosis signal-regulating kinase 1 (ASK1) is a key driving force of the progression of nonalcoholic steatohepatitis (NASH) and represents an attractive therapeutic target for NASH treatment. However, the molecular and cellular mechanisms underlying ASK1 activation in the pathogenesis of NASH remain incompletely understood. In this study, our data unequivocally indicated that hyperactivated ASK1 in hepatocytes is a potent inducer of hepatic stellate cell (HSC) activation by promoting the production of hepatocyte-derived factors.