Modulating and Imaging Macrophage Reprogramming for Cancer Immunotherapy.

Cancer immunotherapy has made great progress in effectively attacking or eliminating cancer. However, the challenges posed by the low reactivity of some solid tumors still remain. Macrophages, as a key component of the tumor microenvironment (TME), play an important role in determining the progression of solid tumors due to their plasticity and heterogeneity.

Development of Self-Adjuvants in mRNA Vaccine and Its Application in Disease Prevention and Treatment.

Adjuvants augment the immunogenicity of vaccines when co-administered with messenger RNA (mRNA) antigens. In recent years, nanotechnology and nanoscience have seen significant growth, resulting in the discovery of synthetic small molecule compounds, natural extracts, and nanomaterials with self-adjuvant properties for nano delivery. The materials exhibit robust immune activity and efficiently activate various innate immune signaling pathways.

Excessive Lipid Peroxidation in Uterine Epithelium Causes Implantation Failure and Pregnancy Loss.

The uterine epithelium undergoes a dramatic spatiotemporal transformation to enter a receptive state, involving a complex interaction between ovarian hormones and signals from stromal and epithelial cells. Redox homeostasis is critical for cellular physiological steady state; emerging evidence reveals that excessive lipid peroxides derail redox homeostasis, causing various diseases. However, the role of redox homeostasis in early pregnancy remains largely unknown.

Melittin-Carrying Nanoparticle Suppress T Cell-Driven Immunity in a Murine Allergic Dermatitis Model.

Allergic contact dermatitis (ACD) and atopic dermatitis (AD) are the most common human skin disorders. Although corticosteroids have been widely used to treat ACD and AD, the side effects of corticosteroids encourage researchers to explore new immunoregulatory treatments. Here, an immunomodulatory approach based on lipid nanoparticles carrying α-helical configurational melittin (α-melittin-NP) is developed to overcome T cell-mediated inflammatory reactions in an oxazolone (OXA)-induced contact hypersensitivity mouse model and OXA-induced AD-like mouse model.

Mesoscale visualization of three-dimensional microvascular architecture and immunocyte distribution in intact mouse liver lobes.

The complex vascular architecture and diverse immune cells of the liver are critical for maintaining liver homeostasis. However, quantification of the network of liver vasculature and immunocytes at different scales from a single hepatic lobule to an intact liver lobe remains challenging. Here, we developed a fast and fluorescence-preserving transparency method, denoted liver-CUBIC, for systematic and integrated analysis of the microcirculation and the three-dimensional distribution of dendritic cells (DCs)/macrophages in intact liver lobes.

The CXCR4-CXCL12 axis promotes T cell reconstitution via efficient hematopoietic immigration.

T cells play a critical role in immunity to protect against pathogens and malignant cells. T cell immunodeficiency is detrimental, especially when T cell perturbation occurs during severe infection, irradiation, chemotherapy, and age-related thymic atrophy. Therefore, strategies that enhance T cell reconstitution provide considerable benefit and warrant intensive investigation.

Pyroptosis and Its Regulation in Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DbCM) is a prevalent disease, characterized by contractile dysfunction and left ventricular hypertrophy. Patients with DbCM have high morbidity and mortality worldwide. Recent studies have identified that pyroptosis, a kind of cell death, could be induced by hyperglycemia involved in the formation of DbCM.

Stable overexpression of mutated PTEN in Chinese hamster ovary cells enhances their performance and therapeutic antibody production.

Chinese hamster ovary (CHO) cells with a high viable cell density (VCD), resilience to culture stress, and the capacity to continuously express recombinant proteins are highly desirable. Phosphatase and tension homology deleted on chromosome ten (PTEN) functions as a key negative regulator of the PI3K/Akt signaling pathway, mediating cell growth and survival. Its oncogenic mutant endows cells with an enhanced proliferation rate and resistance to death.

Ikzf1 regulates embryonic T lymphopoiesis via Ccr9 and Irf4 in zebrafish.

Ikzf1 is a Krüppel-like zinc-finger transcription factor that plays indispensable roles in T and B cell development. Although the function of Ikzf1 has been studied extensively, the molecular mechanism underlying T lymphopoiesis remains incompletely defined during the embryonic stage. Here we report that the genetic ablation of in mutant zebrafish resulted in abrogated embryonic T lymphopoiesis.

MiR-106b promotes therapeutic antibody expression in CHO cells by targeting deubiquitinase CYLD.

MicroRNAs (miRNAs) function as important regulators of major cellular processes, such as cell cycle, proliferation, development, and apoptosis. Recently, miRNA engineering of Chinese hamster ovary (CHO) cells has emerged as a promising strategy for enhancing therapeutic antibody production. Previously, we have reported that inhibition of deubiquitinase cylindromatosis (CYLD) remarkably enhanced the therapeutic antibody production in CHO cells.

Visualizing DC morphology and T cell motility to characterize DC-T cell encounters in mouse lymph nodes under mTOR inhibition.

Mammalian target of rapamycin (mTOR), a serine/threonine kinase orchestrating cellular metabolism, is a crucial immune system regulator. However, it remains unclear how mTOR regulates dendritic cell (DC) function in vivo, especially DC-T cell encounters, a critical step for initiating adaptive immune responses. We dynamically visualized DC-T contacts in mouse lymph node using confocal microscopy and established an encounter model to characterize the effect of mTOR inhibition on DC-T cell encounters using DC morphology.

Inactivation of deubiquitinase CYLD enhances therapeutic antibody production in Chinese hamster ovary cells.

Chinese hamster ovary (CHO) cells are promising host engineering cells for industry manufacturing of therapeutic antibodies. However, cell death due to apoptosis remains a huge challenge to augment antibody production, and developing CHO cells with enhanced anti-apoptosis and proliferation ability is fundamental for cell line development and high-yielding bioprocesses. Deubiquitinase cylindromatosis (CYLD) has been proved to be a tumor suppressor by negatively regulating NF-κB and Wnt/β-catenin signaling pathways.