D4-Chip Reveals Impaired T Cell Function in Sepsis: Insights from Plasma Microenvironment Analysis and Mitochondrial Targeted Therapy.

Background: Sepsis, a systemic inflammation syndrome initiated by infection, poses significant challenges due to its intricate pathophysiology. T cells play a crucial role in combating infections during sepsis. Despite previous observations indicating T cell dysfunction in sepsis, reliable in-vitro detection methods were lacking, and the factors influencing these impairments remained unclear.

T Cells Chemotaxis Migration Studies with a Multi-Channel Microfluidic Device.

Immune surveillance is dependent on lymphocyte migration and targeted recruitment. This can involve different modes of cell motility ranging from random walk to highly directional environment-guided migration driven by chemotaxis. This study protocol describes a flow-based microfluidic device to perform quantitative multiplex cell migration assays with the potential to investigate in real time the migratory response of T cells at the population or single-cell level.

Investigations on T cell transmigration in a human skin-on-chip (SoC) model.

A microfluidics-based three-dimensional skin-on-chip (SoC) model is developed in this study to enable quantitative studies of transendothelial and transepithelial migration of human T lymphocytes in mimicked skin inflammatory microenvironments and to test new drug candidates. The keys results include 1) CCL20-dependent T cell transmigration is significantly inhibited by an engineered CCL20 locked dimer (CCL20LD), supporting the potential immunotherapeutic use of CCL20LD for treating skin diseases such as psoriasis; 2) transepithelial migration of T cells in response to a CXCL12 gradient mimicking T cell egress from the skin is significantly reduced by a sphingosine-1-phosphate (S1P) background, suggesting the role of S1P for T cell retention in inflamed skin tissues; and 3) T cell transmigration is induced by inflammatory cytokine stimulated epithelial cells in the SoC model. Collectively, the developed SoC model recreates a dynamic multi-cellular micro-environment that enables quantitative studies of T cell transmigration at a single cell level in response to physiological cutaneous inflammatory mediators and potential drugs.

Mucus-penetrating PEGylated polysuccinimide-based nanocarrier for intravaginal delivery of siRNA battling sexually transmitted infections.

Intravaginal delivery of siRNA for prevention of sexually transmitted infections faces obstacles such as the acidic environment and vaginal mucus barrier. To achieve effective protection and delivery of siRNA, we developed a polysuccinimide (PSI)-based nanocarrier (PSI-PEG-API-PMA, PPAP) by conjugating methoxy polyethylene glycol amine (Me-PEG-NH, Mw 5000), 1-(3-aminopropyl)imidazole (API), and 1-pyrenemethylamine hydrochloride (PMA) to PSI. PPAP demonstrated a spherical self-assembled nanostructure before and after encapsulation of a model siRNA.

TILRR Promotes Migration of Immune Cells Through Induction of Soluble Inflammatory Mediators.

TILRR has been identified as an important modulator of inflammatory responses. It is associated with NF-κB activation, and inflammation. Our previous study showed that TILRR significantly increased the expression of many innate immune responsive genes and increased the production of several pro-inflammatory cytokines/chemokines by cervical epithelial cells.

Applications of microfluidic devices in advancing NK-cell migration studies.

Understanding how NK cells interact with tumor cells under specific microenvironment will be informative in development of NK-cell based immunotherapy. Applications of microfluidic devices in in vitro studies of NK-cell migrations offer unique opportunities to examine NK-cell migrations at single-cell under controlled cellular microenvironments. Novel devices can be created and engineered to present precise configuration that mimics cellular microenvironments for cell migration studies.

Sputum from chronic obstructive pulmonary disease patients inhibits T cell migration in a microfluidic device.

Chronic obstructive pulmonary disease (COPD) is a common lung disease characterized by narrowed airways, resulting in serious breathing difficulty. Previous studies have demonstrated that inflammatory infiltration of leukocytes in the airway is associated with the pathogenesis of COPD. In the present study, we employed a microfluidic approach to assess the effect of COPD sputum on activated human peripheral blood T cell migration and chemotaxis under well-controlled gradient conditions.

Cell Migration Research Based on Organ-on-Chip-Related Approaches.

Microfluidic devices have been widely used for cell migration research over the last two decades, owing to their attractive features in cellular microenvironment control and quantitative single-cell migration analysis. However, the majority of the microfluidic cell migration studies have focused on single cell types and have configured microenvironments that are greatly simplified compared with the in-vivo conditions they aspire to model. In addition, although cell migration is considered an important target for disease diagnosis and therapeutics, very few microfluidic cell migration studies involved clinical samples from patients.

Targeting the WASF3-CYFIP1 Complex Using Stapled Peptides Suppresses Cancer Cell Invasion.

Activation of the WASF3 protein by extracellular stimuli promotes actin cytoskeleton reorganization and facilitates cancer cell invasion, whereas WASF3 depletion suppresses invasion and metastasis. In quiescent cells, the interaction between WASF3 and a complex of proteins, including CYFIP1, acts as a conformational restraint to prevent WASF3 activation. Therefore, we took advantage of this endogenous regulatory mechanism to investigate potential sites that disrupt WASF3 function.

Lens defects and age-related fiber cell degeneration in a mouse model of increased AbetaPP gene dosage in Down syndrome.

Early-onset cataract and Alzheimer's disease occur with high frequency in Down syndrome (trisomy 21), the most common chromosome duplication in human live births. Previously, we used in vivo and lens organ culture models to demonstrate Alzheimer pathophysiology in oxidative stress-related lens degeneration. Currently, well-characterized Alzheimer transgenic mouse models are used to extend these findings.