Inhalable Textile Microplastic Fibers Impair Airway Epithelial Differentiation.

Rationale: Microplastics are a pressing global concern, and inhalation of microplastic fibers has been associated with interstitial and bronchial inflammation in flock workers. However, how microplastic fibers affect the lungs is unknown. Objectives: Our aim was to assess the effects of 12 × 31 µm nylon 6,6 (nylon) and 15 × 52 µm polyethylene terephthalate (polyester) textile microplastic fibers on lung epithelial growth and differentiation. Methods: We used human and murine alveolar and airway-type organoids as well as air-liquid interface cultures derived from primary lung epithelial progenitor cells and incubated these with either nylon or polyester fibers or nylon leachate. In addition, mice received one dose of nylon fibers or nylon leachate, and, 7 days later, organoid-forming capacity of isolated epithelial cells was investigated. Measurements and Main Results: We observed that nylon microfibers, more than polyester, inhibited developing airway organoids and not established ones. This effect was mediated by components leaching from nylon. Epithelial cells isolated from mice exposed to nylon fibers or leachate also formed fewer airway organoids, suggesting long-lasting effects of nylon components on epithelial cells. Part of these effects was recapitulated in human air-liquid interface cultures. Transcriptomic analysis revealed upregulation of Hoxa5 after exposure to nylon fibers. Inhibiting Hoxa5 during nylon exposure restored airway organoid formation, confirming Hoxa5's pivotal role in the effects of nylon. Conclusions: These results suggest that components leaching from nylon 6,6 may especially harm developing airways and/or airways undergoing repair, and we strongly encourage characterization in more detail of both the hazard of and the exposure to microplastic fibers.

Prenatal influenza vaccination rescues impairments of social behavior and lamination in a mouse model of autism.

BACKGROUND: Prenatal infection is a substantial risk factor for neurodevelopmental disorders such as autism in offspring. We have previously reported that influenza vaccination (VAC) during early pregnancy contributes to neurogenesis and behavioral function in offspring. RESULTS: Here, we probe the efficacy of VAC pretreatment on autism-like behaviors in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) mouse model. We show that VAC improves abnormal fetal brain cytoarchitecture and lamination, an effect associated with promotion of intermediate progenitor cell differentiation in MIA fetal brain. These beneficial effects are sufficient to prevent social deficits in adult MIA offspring. Furthermore, whole-genome analysis suggests a strong interaction between Ikzf1 (IKAROS family zinc-finger 1) and neuronal differentiation. Intriguingly, VAC rescues excessive microglial Ikzf1 expression and attenuates microglial inflammatory responses in the MIA fetal brain. CONCLUSIONS: Our study implies that a preprocessed influenza vaccination prevents maternal bacterial infection from causing neocortical lamination impairments and autism-related behaviors in offspring.

Long Non-Coding RNA Prostate Cancer-Associated Transcript 7 (PCAT7) Induces Poor Prognosis and Promotes Tumorigenesis by Inhibiting mir-134-5p in Non-Small-Cell Lung (NSCLC).

BACKGROUND Long non-coding RNA PCAT7 has been revealed to participate in tumorigenesis of various cancers. However, the mechanism of PCAT7 in non-small cell lung cancer (NSCLC) has not been identified. Hence, this study aimed to determine the function of PCAT7 in NSCLC. MATERIAL AND METHODS The expression level of PCAT7 in 96 pairs of NSCLC tissues and 6 cell lines was detected by qRT-PCR. Proliferation assay, flow cytometric analysis, transwell/migration assay, and Western blotting assay were performed to detect the relation between PCAT7 and malignant behaviors of NSCLC cells in vitro, including cell proliferation, apoptosis, migration, invasion, and epithelial-to-mesenchymal transition (EMT). Rescue assays were carried out to confirm the contribution of PCAT7 to the progression of NSCLC cells by targeting miR-134-5p. RESULTS PCAT7 was found to be overexpressed in NSCLC tissues (compared with corresponding non-tumor tissues) and NSCLC cells (compared with normal cell line 16-HBE). Overexpression of PCAT7 resulted in the promotion of tumor cell proliferation, inhibition of cells apoptosis, facilitation of cells metastasis, and formation of EMT phenotype, while PCAT7 expression deletion remarkably prohibited cell proliferation, accelerated their apoptosis, weakened metastasis, and reversed EMT to MET. miR-134-5P, as a target gene of PCAT7, restored the effects of down-regulation of PCAT7. CONCLUSIONS These findings demonstrate that PCAT7 participates in tumor progression in NSCLC by inhibiting miR-134-5p.

Relationship between immune cells and the development of chronic lung allograft dysfunction.

A major cause of death for lung transplant recipients (LTRs) is the advent of chronic lung allograft dysfunction (CLAD), which has long plagued the long-term post-transplant prognosis and quality of survival of transplant patients. The intricacy of its pathophysiology and the irreversibility of its illness process present major obstacles to the clinical availability of medications. Immunotherapeutic medications are available, but they only aim to slow down the course of CLAD rather than having any therapeutic impact on the disease's development. For this reason, understanding the pathophysiology of CLAD is essential for both disease prevention and proven treatment. The immunological response in particular, in relation to chronic lung allograft dysfunction, has received a great deal of interest recently. Innate immune cells like natural killer cells, eosinophils, neutrophils, and mononuclear macrophages, as well as adaptive immunity cells like T and B cells, play crucial roles in this process through the release of chemokines and cytokines. The present review delves into changes and processes within the immune microenvironment, with a particular focus on the quantity, subtype, and characteristics of effector immune cells in the peripheral and transplanted lungs after lung transplantation. We incorporate and solidify the documented role of immune cells in the occurrence and development of CLAD with the advancements in recent years.

Bridging Smart Nanosystems with Clinically Relevant Models and Advanced Imaging for Precision Drug Delivery.

Intracellular delivery of nano-drug-carriers (NDC) to specific cells, diseased regions, or solid tumors has entered the era of precision medicine that requires systematic knowledge of nano-biological interactions from multidisciplinary perspectives. To this end, this review first provides an overview of membrane-disruption methods such as electroporation, sonoporation, photoporation, microfluidic delivery, and microinjection with the merits of high-throughput and enhanced efficiency for in vitro NDC delivery. The impact of NDC characteristics including particle size, shape, charge, hydrophobicity, and elasticity on cellular uptake are elaborated and several types of NDC systems aiming for hierarchical targeting and delivery in vivo are reviewed. Emerging in vitro or ex vivo human/animal-derived pathophysiological models are further explored and highly recommended for use in NDC studies since they might mimic in vivo delivery features and fill the translational gaps from animals to humans. The exploration of modern microscopy techniques for precise nanoparticle (NP) tracking at the cellular, organ, and organismal levels informs the tailored development of NDCs for in vivo application and clinical translation. Overall, the review integrates the latest insights into smart nanosystem engineering, physiological models, imaging-based validation tools, all directed towards enhancing the precise and efficient intracellular delivery of NDCs.

Nanoparticle-Exposure-Triggered Virus Reactivation Induces Lung Emphysema in Mice.

Nanoparticles (NPs) released from engineered materials or combustion processes as well as persistent herpesvirus infection are omnipresent and are associated with chronic lung diseases. Previously, we showed that pulmonary exposure of a single dose of soot-like carbonaceous NPs (CNPs) or fiber-shaped double-walled carbon nanotubes (DWCNTs) induced an increase of lytic virus protein expression in mouse lungs latently infected with murine γ-herpesvirus 68 (MHV-68), with a similar pattern to acute infection suggesting virus reactivation. Here we investigate the effects of a more relevant repeated NP exposure on lung disease development as well as herpesvirus reactivation mechanistically and suggest an avenue for therapeutic prevention. In the MHV-68 mouse model, progressive lung inflammation and emphysema-like injury were detected 1 week after repetitive CNP and DWCNT exposure. NPs reactivated the latent herpesvirus mainly in CD11b+ macrophages in the lungs. In vitro, in persistently MHV-68 infected bone marrow-derived macrophages, ERK1/2, JNK, and p38 MAPK were rapidly activated after CNP and DWCNT exposure, followed by viral gene expression and increased viral titer but without generating a pro-inflammatory signature. Pharmacological inhibition of p38 activation abrogated CNP- but not DWCNT-triggered virus reactivation in vitro, and inhibitor pretreatment of latently infected mice attenuated CNP-exposure-induced pulmonary MHV-68 reactivation. Our findings suggest a crucial contribution of particle-exposure-triggered herpesvirus reactivation for nanomaterial exposure or air pollution related lung emphysema development, and pharmacological p38 inhibition might serve as a protective target to alleviate air pollution related chronic lung disease exacerbations. Because of the required precondition of latent infection described here, the use of single hit models might have severe limitations when assessing the respiratory toxicity of nanoparticle exposure.