IL-33: Friend or foe in transplantation?

Several reports have highlighted the dichotomous nature of the Interleukin-33 (IL-33) system in cardiac and lung disease, where this cytokine can exert both protective effects and drive pro-inflammatory responses in a context-specific manner. This State-of-the-Art review focuses on preclinical mechanistic studies of the IL-33 system in development of allograft rejection in heart and lung transplantation. We address the scope of potential cellular sources of IL-33 and pathways for cellular release that may impact the study of this cytokine system in transplant models. We then highlight soluble IL-33 receptor as a biomarker in cardiac allograft rejection and detail preclinical models that collectively demonstrate a role for this cytokine in driving type-2 immune programs to protect cardiac allografts. We contrast this with investigation of IL-33 in lung transplantation, which has yielded mixed and somewhat conflicting results when comparing human studies with preclinical models, which have implicated the IL-33 system in both allograft tolerance and acceleration of chronic rejection. We summarize and interpret these results in aggregate and provide future directions for study of IL-33 in heart and lung transplantation.

The impact of obesity on ventilator-associated pneumonia, a US nationwide study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the leading causes of mortality in patients with critical care illness. Since obesity is highly prevalent, we wanted to study its impact on the outcomes of patients who develop VAP. METHODS: Using the National Inpatient Sample (NIS) database from 2017 to 2020, we conducted a retrospective study of adult patients with a principal diagnosis of VAP with a secondary diagnosis with or without obesity according to 10th revision of the International Statistical Classification of Diseases (ICD-10) codes. Several demographics, including age, race, and gender, were analyzed. The primary endpoint was mortality, while the secondary endpoints included tracheostomy, length of stay in days, and patient charge in dollars. Multivariate logistic regression model analysis was used to adjust for confounders, with a p-value less than 0.05 considered statistically significant. RESULTS: The study included 3832 patients with VAP, 395 of whom had obesity. The mean age in both groups was around 58 years, and 68% of the group with obesity were females compared to 40% in females in the group without obesity. Statistically significant comorbidities in the obesity group included a Charlson Comorbidity Index score of three and above, diabetes mellitus, hypertension, chronic kidney disease, and sleep apnea. Rates and odds of mortality were not significantly higher in the collective obesity group 39 (10%) vs. 336 (8.5%), p-value 0.62, adjusted odds ratio 1.2, p-value 0.61). The rates and odds of tracheostomy were higher in the obesity group but not statistically significant. Obese patients were also found to have a longer hospitalization. Upon subanalysis of the data, no evidence of racial disparities was found in the care of VAP for both the obese and control groups. CONCLUSIONS: Obesity was not found to be an independent risk factor for worse outcomes in patients who develop VAP in the intensive care unit.

Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease.

IL-33 is a cytokine central to type 2 immune pathology in chronic airway disease. This cytokine is abundantly expressed in the respiratory epithelium and increased in disease, but how expression is regulated is undefined. Here we show that increased IL33 expression occurs from multiple noncanonical promoters in human chronic obstructive pulmonary disease (COPD), and it facilitates production of alternatively spliced isoforms in airway cells. We found that phorbol 12-myristate 13-acetate (PMA) can activate IL33 promoters through protein kinase C in primary airway cells and lines. Transcription factor (TF) binding arrays combined with RNA interference identified activator protein (AP) TFs as regulators of baseline and induced IL33 promoter activity. ATAC-Seq and ChIP-PCR identified chromatin accessibility and differential TF binding as additional control points for transcription from noncanonical promoters. In support of a role for these TFs in COPD pathogenesis, we found that AP-2 (TFAP2A, TFAP2C) and AP-1 (FOS and JUN) family members are upregulated in human COPD specimens. This study implicates integrative and pioneer TFs in regulating IL33 promoters and alternative splicing in human airway basal cells. Our work reveals a potentially novel approach for targeting IL-33 in development of therapeutics for COPD.

Enhancing porphyrin photostability when locked in metal-organic frameworks.

Porphyrins have been widely used in many optical devices given their unique photochemical properties. Their poor photostability has, however, limited their wide applications in bioimaging and biosensing schemes. Herein, we report the remarkable photostability enhancement of the porphyrin, carboxyphenyl porphyrin (TCPP-H2) when locked in a zirconium based metal-organic framework (MOF-525). Steady-state ensemble fluorescence spectroscopy experiments showed minimal changes (2%) in the recorded signal when MOF-525 was continuously illuminated as compared to a 16% decrease for free porphyrins. Single particle fluorescence imaging revealed bright microparticles with exceptional photostability and no-blinking within the experiment window. This study highlights the use of metal-organic frameworks for preparing photostable microstructures by leveraging on their unique self-assembly properties.

Silver-Modified Cross-Linked Polyvinylpyrrolidone and Its Antibacterial Activity.

There is an increasing need to develop new antibacterial materials for treating contaminated potable water, particularly for addressing increasing bacterial resistance, which is predicted to be a major threat to human health in the future, especially for high-risk groups and populations displaced in conflict regions. In addition, a material that can be easily separated from solutions is highly desirable to allow for the fast and efficient recovery of the bactericidal material. In this study, we reported the preparation of microsized cross-linked PVP (PVPP) decorated with silver nanoparticles. The silver particles grew to sizes between 100 and 700 nm with average diameters of 534 ± 72 nm (N = 70), 265 ± 66 nm (N = 70), and 255 ± 75 nm (N = 70) for the 0.5, 1, and 10 mg/mL concentrations of PVPP, respectively. The prepared complexes were easily separated from water by gravity. The minimum inhibitory concentrations against E. coli were calculated to be approximately 100, 65, and 60 µg/mL Ag+ for the 10, 1, and 0.5 mg/mL concentrations of PVPP, respectively. The PVPP/AgNP microparticles retained their antibacterial activity after they were collected from a bacterial culture, washed, and then recycled into a second batch of freshly prepared microorganism solution.