Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2023.01.31.526405

Bei Mu Gua Lou San facilitates mucus expectoration by increasing surface area and hydration levels of airway mucus in an air-liquid-interface cell culture model of the respiratory epithelium

Groiss, S.·Somvilla, I.·Daxboeck, C.·Stueckler, M.·Pritz, E.·Brislinger, D.
View original source ↗Export metadata ↓

Abstract

Bei Mu Gua Lou San (BMGLS) is an ancient formulation known for its moisturizing and expectorant properties, but the underlying mechanisms remain unknown. We investigated dose-dependent effects of BMGLS on its rehydrating and mucus-modulating properties using an air-liquid-interface (ALI) cell culture model of the Calu-3 human bronchial epithelial cell line and primary normal human bronchial epithelial cells (NHBE), and specifically focused on quantity and composition of the two major mucosal proteins MUC5AC and MUC5B. ALI cultures were treated with BMGLS at different concentrations over three weeks and evaluated by means of histology, immunostaining and electron microscopy. MUC5AC and MUC5B mRNA levels were assessed and quantified on protein level using an automated image-based approach. Additionally, expression levels of the major mucus-stimulating enzyme 15-lipoxygenase (ALOX15) were evaluated. BMGLS induced dose-dependent morphological changes in NHBE but not Calu-3 ALI cultures that resulted in increased surface area via the formation of herein termed intra-epithelial structures (IES). While cellular rates of proliferation, apoptosis or degeneration remained unaffected, BMGLS caused swelling of mucosal granules, increased the area of secreted mucus, decreased muco-glycoprotein density, and dispensed MUC5AC. Additionally, BMGLS reduced expression levels of MUC5AC, MUC5B and the mucus-stimulating enzyme 15-lipoxygenase (ALOX15). Our studies suggest that BMGLS rehydrates airway mucus while stimulating mucus secretion by increasing surface areas and regulating goblet cell differentiation through modulating major mucus-stimulating pathways.

Source connections

Explore related subjects

molecular biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Groiss, S., Somvilla, I., Daxboeck, C., Stueckler, M., Pritz, E., Brislinger, D.. 2023-01-31. Bei Mu Gua Lou San facilitates mucus expectoration by increasing surface area and hydration levels of airway mucus in an air-liquid-interface cell culture model of the respiratory epithelium. https://doi.org/10.1101/2023.01.31.526405

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

LOca-1: A minimal calcium-activated arginyl-specific orthocaspase from the Loki's Castle hydrothermal vent field

Orthocaspases are prokaryotic homologs of metacaspases within the C14 family of cysteine proteases, yet their biochemical properties and cellular roles remain poorly understood. Here, we report the discovery and comprehensive characterization of LOca-1, a metagenome-derived orthocaspase from the Loki's Castle hydrothermal vent field. LOca-1 consists primarily of a single, conserved p20 catalytic domain and undergoes calcium-dependent activation through cleavage at a conserved arginine residue. Once activated, LOca-1 displays strict arginyl-specific proteolytic activity and strong selectivity for residues surrounding the cleavage site. The enzyme is both thermoactive and thermostable, exhibiting maximal activity at 65 {degrees}C and a melting temperature of approximately 72 {degrees}C. Structural modelling revealed conservation of the catalytic core relative to plant metacaspases despite substantial sequence divergence. To our knowledge, LOca-1 is only the second biochemically characterized orthocaspase and the first reported from a deep-sea hydrothermal vent environment. LOca-1 expands the known biochemical diversity of prokaryotic metacaspase homologs and provides insights into the properties of a minimal p20-domain orthocaspase. Together, our findings establish LOca-1 as a thermostable, calcium-activated arginyl-specific orthocaspase and provide a foundation for future studies of orthocaspase function in prokaryotes.

molecular biology↗
bioRxiv2026

A TMEM175 Mutation Disrupts the Lysosomal-Mitochondrial Axis Causing Short QT Syndrome and Sudden Cardiac Death

Short QT Syndrome (SQTS) is a rare cardiac channelopathy characterized by abnormally short QTc intervals and increased sudden cardiac death (SCD) risk. Only 20-30% of SQTS cases have been linked to genetic mutations, typi-cally in surface membrane ion channels. We identified a novel lysosomal TMEM175 gene mutation (p.Arg377His) in 7 patients in a family with SQTS and SCD. Genetic analyses, including whole exome sequencing in the family and rare-variant burden testing in [~]118,000 UK Biobank participants, sug-gested an association between TMEM175 rare variants and QT interval short-ening. Functional studies in CRISPR-engineered mice and patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) revealed that TMEM175R377H causes shortened QT intervals and hastened repolariza-tion, respectively, as well an increased arrhythmia susceptibility. Isolated TMEM175R377H cardiomyocytes showed action potential duration (APD) abbre-viation, confirmed in whole TMEM175R377H mouse hearts and patient-specific iPSC-CM monolayers. In silico and electron microscopy studies showed that TMEM175R377H disrupts lysosomal-mitochondrial interactions, leading to mito-chondrial dysfunction, as evidenced by the reduced maximal respiration and spare respiratory capacity, with reduced ATP production, IKATP activation, and APD shortening. This mutation represents the first non-sarcolemmal ion chan-nel defect associated with SQTS and high SCD risk, potentially expanding the genetic landscape of the disease.

molecular biology↗
bioRxiv2026

Protecting host mitochondria with vitamin B3 preserves bioenergetics and thermogenesis during antibiotic treatment

Antibiotics that target bacterial translation can also impair mitochondrial function because mitochondria retain bacterial-like ribosomes. As antibiotic resistance continues to increase and the use of several broad-spectrum antibiotics has been limited by their mitochondrial toxicity, there is a growing need to understand their off-target effects in host physiology, and to identify strategies that can mitigate antibiotic-induced mitochondrial dysfunction. We demonstrate that antibiotic chloramphenicol (CA) induces a dose-dependent reduction in mitochondrial respiration and mitochondrial thermogenesis in Drosophila S2 cells, human HEK293T cells and in developing Drosophila larvae. In vivo, CA exposure triggers female-biased aberrant innate immune activation of hosts carrying naturally occurring mitochondrial rRNA variants. Metabolomic profiling revealed alterations in vitamin B3 metabolism in Drosophila during and following CA exposure. Among the vitamin B3 vitamers examined, nicotinamide (NAM) exhibited the strongest protective effect, mitigating the CA-induced impairments in mitochondrial respiration and thermogenesis, as well as aberrant immune activation. We identify mitochondrial thermogenesis as a previously unrecognized target of antibiotic-induced mitochondrial perturbation and a sensitive marker of mitochondrial stress. Furthermore, we demonstrate that co-supplementation of CA with NAM mitigates antibiotic-induced mitochondrial toxicity through evolutionarily conserved mitochondrial pathways. Finally, we establish Drosophila as a powerful model for investigating antibiotic-induced mitochondrial dysfunction and for developing therapeutic strategies to protect host mitochondria during antibiotic treatment.

molecular biology↗