The Roles of T cells in Immune Checkpoint Inhibitor-Induced Arthritis.

Immune checkpoint inhibitor (ICI) therapy, a novel anti-tumor strategy, can specifically eliminate tumors by activating the immune system and inhibiting tumor immune escape. However, ICI therapy can lead to notable negative outcomes known as immune-related adverse events (irAEs). ICI-induced arthritis, also known as ICI arthritis, stands as the prevailing form of irAEs. The purpose of this review is to highlight the crucial functions of T cells in the progression of ICI arthritis. Under the influence of different signaling molecules, T cells could gather in large numbers within the synovial membrane of joints, releasing inflammatory substances and enzymes that harm healthy tissues, ultimately causing ICI arthritis. Moreover, considering the functions of T cells in triggering ICI arthritis, this review suggests several treatments to prevent ICI arthritis, including inhibiting the overstimulation of T cells at the synovial sac of joints, enhancing the precision of ICI medications, and directing ICI drugs specifically towards tumor tissues instead of joints. Collectively, T lymphocytes play a vital role in the onset of ICI arthritis, offering a hopeful perspective on treating ICI arthritis through the specific targeting of T cells within the affected joints.

Cavitation-on-a-Chip Enabled Size-Specific Liposomal Drugs for Selective Pharmacokinetics and Pharmacodynamics.

The size of liposomal drugs has been demonstrated to strongly correlate with their pharmacokinetics and pharmacodynamics. While the microfluidic method successfully achieves the production of liposomes with well-controlled sizes across various buffer/lipid flow rate ratio (FRR) settings, any adjustments to the FRR inevitably influence the concentration, encapsulation efficiency (EE), and stability of liposomal drugs. Here we describe a controllable cavitation-on-a-chip (CCC) strategy that facilitates the precise regulation of liposomal drug size at any desired FRR. The CCC-enabled size-specific liposomes exhibited striking differences in uptake and biodistribution behaviors, thereby demonstrating distinct antitumor efficacy in both tumor-bearing animal and melanoma patient-derived organoid (PDO) models. Intriguingly, as the liposome size decreased to approximately 80 nm, the preferential accumulation of liposomal drugs in the liver transitioned to a predominant enrichment in the kidneys. These findings underscore the considerable potential of our CCC approach in influencing the pharmacokinetics and pharmacodynamics of liposomal nanomedicines.

Mimicking Tumor Metastasis Using a Transwell-Integrated Organoids-On-a-Chip Platform.

The mortality rate among cancer patients is primarily attributed to tumor metastasis. The evaluation of metastasis potential provides a powerful framework for personalized therapies. However, little work has so far been undertaken to precisely model tumor metastasis in vitro, hindering the development of preventive and therapeutic interventions. In this work, a tumor-metastasis-mimicked Transwell-integrated organoids-on-a-chip platform (TOP) for precisely evaluating tumor metastatic potential is developed. Unlike the conventional Transwell device for detecting cell migration, the engineered device facilitates the assessment of metastasis in patient-derived organoids (PDO). Furthermore, a novel Transwell chamber with a hexagon-shaped structure is developed to mimic the migration of tumor cells into surrounding tissues, allowing for the evaluation of tumor metastasis in a horizontal direction. As a proof-of-concept demonstration, tumor organoids and metastatic clusters are further evaluated at the protein, genetic, and phenotypic levels. In addition, preliminary drug screening is undertaken to highlight the potential for using the device to combat cancers. In summary, the tumor-metastasis-mimicked TOP offers unique capabilities for evaluating the metastasis potential of tumor organoids and contributes to the development of personalized cancer therapies.

Association of multiple air pollutants with oxygen saturation during sleep in COPD patients: Effect modification by smoking status and airway inflammatory phenotypes.

Air pollution contributes substantially to the development of chronic obstructive pulmonary disease (COPD). To date, the effect of air pollution on oxygen saturation (SpO2) during sleep and potential susceptibility factors remain unknown. In this longitudinal panel study, real-time SpO2 was monitored in 132 COPD patients, with 270 nights (1615 h) of sleep SpO2 recorded. Exhaled nitric oxide (NO), hydrogen sulfide (H2S) and carbon monoxide (CO) were measured to assess airway inflammatory characteristics. Exposure levels of air pollutants were estimated by infiltration factor method. Generalized estimating equation was used to investigate the effect of air pollutants on sleep SpO2. Ozone, even at low levels (<60 µg/m3), was significantly associated with decreased SpO2 and extended time of oxygen desaturation (SpO2 < 90%), especially in the warm season. The associations of other pollutants with SpO2 were weak, but significant adverse effects of PM10 and SO2 were observed in the cold season. Notably, stronger effects of ozone were observed in current smokers. Consistently, smoking-related airway inflammation, characterized by higher levels of exhaled CO and H2S but lower NO, significantly augmented the effect of ozone on SpO2 during sleep. This study highlights the importance of ozone control in protecting sleep health in COPD patients.