Mitochondria in Focus: From Function to Therapeutic Strategies in Chronic Lung Diseases

Mitochondria are essential organelles for cell metabolism, growth, and function. Mitochondria in lung cells have important roles in regulating surfactant production, mucociliary function, mucus secretion, senescence, immunologic defense, and regeneration. Disruption in mitochondrial physiology can be the central point in several pathophysiologic pathways of chronic lung diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and asthma. In this review, we summarize how mitochondria morphology, dynamics, redox signaling, mitophagy, and interaction with the endoplasmic reticulum are involved in chronic lung diseases and highlight strategies focused on mitochondrial therapy (mito-therapy) that could be tested as a potential therapeutic target for lung diseases.

Intratracheal Keratinocyte Growth Factor Enhances Surfactant Protein B Expression in Mechanically Ventilated Preterm Pigs

Bronchopulmonary dysplasia (BPD) is a devastating disease of prematurity that is associated with mechanical ventilation and hyperoxia. We used preterm pigs delivered at gestational day 102 as a translational model for 26–28-week infants to test the hypothesis administering recombinant human keratinocyte growth factor (rhKGF) at initiation of mechanical ventilation will stimulate type II cell proliferation and surfactant production, mitigate ventilator induced lung injury, and reduce epithelial to mesenchymal transition considered as a precursor to BPD. Newborn preterm pigs were intubated and randomized to receive intratracheal rhKGF (20 μg/kg; n = 6) or saline (0.5 ml 0.9% saline; control; n = 6) before initiating 24 h of ventilation followed by extubation to nasal oxygen for 12 h before euthanasia and collection of lungs for histopathology and immunohistochemistry to assess expression of surfactant protein B and markers of epithelial to mesenchymal transition. rhKGF pigs required less oxygen during mechanical ventilation, had higher tidal volumes at similar peak pressures indicative of improved lung compliance, and survival was higher after extubation (83% vs. 16%). rhKGF increased surfactant protein B expression (p < 0.05) and reduced TGF-1β (p < 0.05), that inhibits surfactant production and is a prominent marker for epithelial to mesenchymal transition. Our findings suggest intratracheal administration of rhKGF at initiation of mechanical ventilation enhances surfactant production, reduces ventilator induced lung injury, and attenuates epithelial-mesenchymal transition while improving pulmonary functions. rhKGF is a potential therapeutic strategy to mitigate pulmonary responses of preterm infants that require mechanical ventilation and thereby reduce the incidence and severity of bronchopulmonary dysplasia.

Ultra-low dioxane in ethoxy sulphate products

The progressive reduction of the permitted content of 1,4-dioxane in ethoxy sulphates presents an increased challenge for surfactant producers. This article discusses technical solutions that can be put in place based on the chemistry of the 1,4-dioxane molecule and its formation mechanism during surfactant production. Desmet Ballestra’s “ultra-low dioxane technology” is discussed in detail, with emphasis on the technical features, advantages, and achievable quality. Technologies for 1,4-dioxane degradation and disposal into water effluent streams are also illustrated.

Competitive advantage of oral streptococci for colonization of the middle ear mucosa

The intermittent aeration of the middle ear seeds its mucosa with saliva aerosols and selects for a distinct community of commensals adapted to the otic microenvironment. We gained insights into the selective forces that enrich for specific groups of oral migrants in the middle ear mucosa by investigating the phylogeny and physiology of 19 strains enriched (Streptococcus) or transiently present (Staphylococcus, Neisseria and actinobacterial Micrococcus and Corynebacterium) in otic secretions. Phylogenetic analyses of full length 16S rRNA sequences resolved close relationships between the streptococcal strains and oral commensals as well as between the transient migrants and known nasal and oral species. Physiological functions that facilitate mucosal colonization (swarming motility, surfactant production) and nutrition (mucin and protein degradation) were widespread in all the otic cultivars, as was the ability of most of the isolates to grow both aerobically and anaerobically. However, streptococci stood out for their enhanced biofilm-forming abilities under oxic and anoxic conditions and for their efficient fermentation of mucosal substrates into lactate, a key metabolic intermediate in the otic trophic webs. Additionally, the otic streptococci inhibited the growth of common otopathogens, an antagonistic interaction that could exclude competitors and protect the middle ear mucosa from infections by transient pathobionts. These adaptive traits allow streptococcal migrants to colonize the otic mucosa and grow microcolonies with syntrophic anaerobic partners, establishing trophic webs with other commensals similar to those formed by the oral ancestors in buccal biofilms.

Statistical Approach to Optimize Production of Biosurfactant by Achromobacter Xylos

This study aimed to optimize medium composition biosurfactant production of achromobacter xylos using response surface quadratic model . Lipoprotein and lipopeptides are used in many industries such as petroleum refining, pharmaceutical, mining, agriculture and bioprocess industries. The point of this assessment was to pull out and portray the biosurfactant passing on restriction of microorganisms from oil corrupted soil and considering their advancement energy at various temperatures and pH. The separation and growth study was directed in MSM medium using lamp fuel oil as sole carbon hotspot for bacterial turn of events. Confined strains were found to be Gram positive bacillus and in general Gram's positive minuscule life forms can convey lipopeptides type biosurfactants. The ideal conditions for achromobacteria xylos growth were discovered to be at pH seven (7) and temperature 30oC. Central composite design (CCD) was utilized to pick the following medium components (MgSO4, NaNO3, CaCl2, (NH4)2SO4, FeSO4, and KH2PO4). Central composite arrangement (CCD) of RSM was utilized to analyze the four parts at five stages, and biosurfactant fixation was evaluated as reaction. Backslide coefficients were directed by backslide examination, and the quadratic model condition was settled. R2 an impetus for bio-surfactant was endeavored to be 0.7527, showing that the quadratic model was basic with the exploratory outcomes. Confirmation of the numerical model was driven by playing out the assessment with the normal overhauled values, and bio-surfactant production was found to be 10.53 g/L. Underwriting of the normal quadratic model was 97.3% exact with the test results facilitated under the ideal conditions. CaCl2, (NH4)2SO4, FeSO4, and KH2PO4 were perceived as successful portions for bio-surfactant delivering 98% of achromobacter xylos microorganism.

FGF10 and Lipofibroblasts in Lung Homeostasis and Disease: Insights Gained From the Adipocytes

Adipocytes not only function as energy depots but also secrete numerous adipokines that regulate multiple metabolic processes, including lipid homeostasis. Dysregulation of lipid homeostasis, which often leads to adipocyte hypertrophy and/or ectopic lipid deposition in non-adipocyte cells such as muscle and liver, is linked to the development of insulin resistance. Similarly, an altered secretion profile of adipokines or imbalance between calorie intake and energy expenditure is associated with obesity, among other related metabolic disorders. In lungs, lipid-laden adipocyte-like cells known as lipofibroblasts share numerous developmental and functional similarities with adipocytes, and similarly influence alveolar lipid homeostasis by facilitating pulmonary surfactant production. Unsurprisingly, disruption in alveolar lipid homeostasis may propagate several chronic inflammatory disorders of the lung. Given the numerous similarities between the two cell types, dissecting the molecular mechanisms underlying adipocyte development and function will offer valuable insights that may be applied to, at least, some aspects of lipofibroblast biology in normal and diseased lungs. FGF10, a major ligand for FGFR2b, is a multifunctional growth factor that is indispensable for several biological processes, including development of various organs and tissues such as the lung and WAT. Moreover, accumulating evidence strongly implicates FGF10 in several key aspects of adipogenesis as well as lipofibroblast formation and maintenance, and as a potential player in adipocyte metabolism. This review summarizes our current understanding of the role of FGF10 in adipocytes, while attempting to derive insights on the existing literature and extrapolate the knowledge to pulmonary lipofibroblasts.