TFEB SUMOylation in Airway Epithelial Cells Impairs Lysosomal Biogenesis to Promote Asthma Development.

Lysosomal dysfunction is the primary cause of various immune disorders. Transcription factor EB (TFEB) SUMOylation is critically involved in the lysosomal biogenesis. Whether TFEB SUMOylation-associated lysosomal dysfunction contributes to asthma pathogenesis remain to be determined.

Autologous transplantation of P63 lung progenitor cells in patients with bronchiectasis: A randomized, single-blind, controlled trial.

Non-cystic fibrosis bronchiectasis is a progressive respiratory disease with limited treatment options, prompting the exploration of regenerative therapies. This study investigates the safety and efficacy of autologous P63 progenitor cell transplantation in a randomized, single-blind, controlled, phase 1/2 trial. Thirty-seven patients receive bronchoscopic airway clearance (B-ACT) (n = 19) or B-ACT plus P63 progenitor cells (n = 18).

Non-bacterial cystitis caused by pembrolizumab therapy for adenocarcinoma of the lung: a case report.

Immune checkpoint inhibitors (ICIs) including anti-programmed death cell protein 1 (anti-PD1) and anti-programmed cell death-ligand 1 (PD-L1), by disinhibiting the antitumor responses of lymphocytes, have extended survival benefits for patients in lung cancer. ICIs can also lead to a wide spectrum of immune-related adverse events (irAEs), due to dysregulation of immune reactions. Here, we report a 27-year-old female patient with adenocarcinoma of the lung treated with pembrolizumab-combined chemotherapy treatment, who complained of urinary irritation symptoms.

ASCs Activate cGAS-Type I IFNs-IL-7 Axis Via Pseudomonas aeruginosa-Derived Outer Membrane Vesicles to Resolve Pneumonia.

Mesenchymal stem cells (MSCs) therapy could efficiently attenuate LPS-induced acute lung injury and Pseudomonas aeruginosa (PA)-induced acute pneumonia. However, the underlying molecular mechanisms are still elusive. Here, we report that PA-derived outer membrane vesicles (OMVs) trigger mouse primary adipose tissue-derived mesenchymal stem cells (ASCs) to upregulate cyclic GMP-AMP synthase (cGAS) for sensing of double-stranded DNA (dsDNA) and the expression of interleukin (IL)-7.

CD69 mediates the protective role of adipose tissue-derived mesenchymal stem cells against Pseudomonas aeruginosa pulmonary infection.

Background: Our previous study shows that Adipose tissue-derived mesenchymal stem cells (ASCs) are a promising strategy for cell-based therapy against pulmonary infection with Pseudomonas aeruginosa (P. aeruginosa), but the underlying mechanisms remain unclear.

Methods: cDNA microarray assay was performed to explore the transcriptome of ASCs primed by P.

Distinct immune signatures discriminate between asymptomatic and presymptomatic SARS-CoV-2 subjects.

Increasing numbers of SARS-CoV-2-positive (SARS-CoV-2) subjects are detected at silent SARS-CoV-2 infection stage (SSIS). Yet, SSIS represents a poorly examined time-window wherein unknown immunity patterns may contribute to the fate determination towards persistently asymptomatic or overt disease. Here, we retrieved blood samples from 19 asymptomatic and 12 presymptomatic SARS-CoV-2 subjects, 47 age/gender-matched patients with mild or moderate COVID-19 and 27 normal subjects, and interrogated them with combined assays of 44-plex CyTOF, RNA-seq and Olink.

Epithelial exosomal contactin-1 promotes monocyte-derived dendritic cell-dominant T-cell responses in asthma.

Background: Exosomes have emerged as a vital player in cell-cell communication; however, whether airway epithelial cell (AEC)-generated exosomes participate in asthma development remains unknown.

Objective: Our aims were to characterize the AEC-secreted exosomes and the potentially functional protein(s) that may contribute to the proinflammatory effects of AEC exosomes in the dendritic cell (DC)-dominant airway allergic models and to confirm their clinical significance in patients with asthma.

Methods: Mice were treated with exosomes derived from house dust mite (HDM)-stimulated AECs (HDM-AEC-EXOs) or monocyte-derived DCs primed by HDM and/or contactin-1 (CNTN1).

Shuxuening injection protects against myocardial ischemia-reperfusion injury through reducing oxidative stress, inflammation and thrombosis.

Background: Shuxuening injection (SXNI) has a good effect on cardiovascular and cerebrovascular diseases. Here, our study aims to investigate whether SXNI have the protective effect on myocardial ischemia-reperfusion injury (MIRI) and elucidate the mechanism of SXNI's cardiac protection.

Methods: In this experiment, the coronary arteries of Sprague-Dawley (SD) rats were ligated for the induction of a MIRI model.

Integrated liquid chromatography-mass spectrometry and nuclear magnetic resonance spectra for the comprehensive characterization of various components in the Shuxuening injection.

Shuxuening injection (SXNI) is made from the extract of Ginkgo biloba, and used for curing coronary heart disease, stenocardia and cerebral vasospasm. However, the flavonoids and terpene trilactones (TTLs) only account for about 30% of the dry weight of SXNI according to the current quality control standard. Thus, systematic investigation of the chemical composition of SXNI is needed to guarantee the drug safety.

Heme oxygenase-1 protects airway epithelium against apoptosis by targeting the proinflammatory NLRP3-RXR axis in asthma.

Asthma is thought to be caused by malfunction of type 2 T helper cell (Th2)-mediated immunity, causing excessive inflammation, mucus overproduction, and apoptosis of airway epithelial cells. Heme oxygenase-1 (HO-1) functions in heme catabolism and is both cytoprotective and anti-inflammatory. We hypothesized that this dual function may be related to asthma's etiology.

Airway epithelial TSLP production of TLR2 drives type 2 immunity in allergic airway inflammation.

Epithelial cells (ECs)-derived cytokines are induced by different stimuli through pattern recognition receptors (PRRs) to mount a type-2-cell-mediated immune response; however, the underlying mechanisms are poorly characterized. Here, we demonstrated asthmatic features in both primary bronchial epithelial cells (pBECs) and mouse model using several allergens including ovalbumin (OVA), house dust mite (HDM), or Alternaria alternata. We found that toll-like receptor 2 (TLR2) was highly induced in ECs but not dendritic cells (DCs) by various allergens, leading to recruitment of circulating basophils into the lung via C-C chemokine ligand-2 (CCL2).

Heme oxygenase-1 inhibits basophil maturation and activation but promotes its apoptosis in T helper type 2-mediated allergic airway inflammation.

The anti-inflammatory role of heme oxygenase-1 (HO-1) has been studied extensively in many disease models including asthma. Many cell types are anti-inflammatory targets of HO-1, such as dendritic cells and regulatory T cells. In contrast to previous reports that HO-1 had limited effects on basophils, which participate in T helper type 2 immune responses and antigen-induced allergic airway inflammation, we demonstrated in this study, for the first time, that the up-regulation of HO-1 significantly suppressed the maturation of mouse basophils, decreased the expression of CD40, CD80, MHC-II and activation marker CD200R on basophils, blocked DQ-ovalbumin uptake and promoted basophil apoptosis both in vitro and in vivo, leading to the inhibition of T helper type 2 polarization.

Basophil-associated OX40 ligand participates in the initiation of Th2 responses during airway inflammation.

Asthma is characterized by increased airway submucosal infiltration of T helper (Th) cells and myeloid cells that co-conspire to sustain a chronic inflammation. While recent studies have demonstrated that the myeloid basophils promote Th2 cells in response to various types of allergens, the underlying mechanisms are poorly understood. Here, we found for the first time that in a mouse model of allergic asthma basophils highly expressed OX40 ligand (OX40L) after activation.

Heme oxygenase-1 ameliorates dextran sulfate sodium-induced acute murine colitis by regulating Th17/Treg cell balance.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a group of autoimmune diseases characterized by nonspecific inflammation in the gastrointestinal tract. Recent investigations suggest that activation of Th17 cells and/or deficiency of regulatory T cells (Treg) is involved in the pathogenesis of IBD. Heme oxygenase (HO)-1 is a protein with a wide range of anti-inflammatory and immune regulatory function, which exerts significantly protective roles in various T cell-mediated diseases.

Basophils as a primary inducer of the T helper type 2 immunity in ovalbumin-induced allergic airway inflammation.

Antigen-induced allergic airway inflammation is mediated by T helper type 2 (Th2) cells and their cytokines, but the mechanism that initiates the Th2 immunity is not fully understood. Recent studies show that basophils play important roles in initiating Th2 immunity in some inflammatory models. Here we explored the role of basophils in ovalbumin (OVA) -induced airway allergic inflammation in BALB/c mice.

Heme oxygenase-1 exerts a protective role in ovalbumin-induced neutrophilic airway inflammation by inhibiting Th17 cell-mediated immune response.

Allergic asthma is conventionally considered as a Th2 immune response characterized by eosinophilic inflammation. Recent investigations revealed that Th17 cells play an important role in the pathogenesis of non-eosinophilic asthma (NEA), resulting in steroid-resistant neutrophilic airway inflammation. Heme oxygenase-1 (HO-1) has anti-inflammation, anti-oxidation, and anti-apoptosis functions.

Spatial and seasonal variations of pesticide contamination in agricultural soils and crops sample from an intensive horticulture area of Hohhot, North-West China.

The spatial variability and temporal trend in concentrations of the organochlorine pesticides (OCPs), hexachlorocyclohexane (HCH) and dichlorodiphenyltrichloroethane (DDT), in soils and agricultural corps were investigated on an intensive horticulture area in Hohhot, North-West China, from 2008 to 2011. The most frequently found and abundant pesticides were the metabolites of DDT (p,p'-DDE, p,p'-DDT, o,p'-DDT and p,p'-DDD). Total DDT concentrations ranged from ND (not detectable) to 507.