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It is critical to find efficient non-invasive prognostic factor for osteosarcoma. In this study, we demonstrated that serum protein of pro-surfactant protein B (pro-SFTPB) may be a potential diagnostic indicator in osteosarcoma. We found that serum pro-SFTPB was highly expressed in osteosarcoma patients and presented good diagnostic value to discern osteosarcoma patients from non-osteosarcoma control subjects. Serum pro-SFTPB was also significantly correlated with advanced clinical stage, distant metastasis, and shorter overall survival. In addition, serum pro-SFTPB was demonstrated to be an independent prognostic factor for osteosarcoma. Overall, our study demonstrated that serum pro-SFTPB may be a useful diagnostic factor for osteosarcoma. Key words: osteosarcoma, pro-SFTPB diagnosis, survival, prognosis, Introduction Osteosarcoma is one type of bone cancers that mostly occur in young people, including children and adolescents (Jafari et al. 2020; Sadykova et al. 2020). Osteosarcoma has a high [...]

Epithelial cell dysfunction has emerged as a central component of the pathophysiology of diffuse parenchymal diseases including idiopathic pulmonary fibrosis (IPF). Alveolar type 2 (AT2) cells represent a metabolically active lung cell population important for surfactant biosynthesis and alveolar homeostasis. AT2 cells and other distal lung epithelia, like all eukaryotic cells, contain an elegant quality control network to respond to intrinsic metabolic and biosynthetic challenges imparted by mutant protein conformers, dysfunctional subcellular organelles, and dysregulated telomeres. Failed AT2 quality control components (the ubiquitin-proteasome system, unfolded protein response, macroautophagy, mitophagy, and telomere maintenance) result in diverse cellular endophenotypes and molecular signatures including ER stress, defective autophagy, mitochondrial dysfunction, apoptosis, inflammatory cell recruitment, profibrotic signaling, and altered progenitor function that ultimately converge to drive downstream fibrotic remodeling in the IPF lung. As this complex network becomes increasingly better understood, opportunities will emerge to identify targets and therapeutic strategies for IPF., Introduction Fibrosis is a common pathological manifestation of chronic disease in a variety of organ systems, including liver, kidney, and skin. In the distal lung, fibrotic remodeling represents a major [...]

Electronic nicotine delivery systems (ENDS) or e-cigarettes have emerged as a popular recreational tool among adolescents and adults. Although the use of ENDS is often promoted as a safer alternative to conventional cigarettes, few comprehensive studies have assessed the long-term effects of vaporized nicotine and its associated solvents, propylene glycol (PG) and vegetable glycerin (VG). Here, we show that compared with smoke exposure, mice receiving ENDS vapor for 4 months failed to develop pulmonary inflammation or emphysema. However, ENDS exposure, independent of nicotine, altered lung lipid homeostasis in alveolar macrophages and epithelial cells. Comprehensive lipidomic and structural analyses of the lungs revealed aberrant phospholipids in alveolar macrophages and increased surfactant- associated phospholipids in the airway. In addition to ENDS-induced lipid deposition, chronic ENDS vapor exposure downregulated innate immunity against viral pathogens in resident macrophages. Moreover, independent of nicotine, ENDS- exposed mice infected with influenza demonstrated enhanced lung inflammation and tissue damage. Together, our findings reveal that chronic e-cigarette vapor aberrantly alters the physiology of lung epithelial cells and resident immune cells and promotes poor response to infectious challenge. Notably, alterations in lipid homeostasis and immune impairment are independent of nicotine, thereby warranting more extensive investigations of the vehicle solvents used in e-cigarettes., Introduction The electronic nicotine delivery system (ENDS), or e-cigarette, entered the US market in the mid-2000s and rapidly gained popularity among tobacco smokers and never-smokers (1). Currently, an estimated 10 [...]

Electronic nicotine delivery systems (ENDS) are rapidly increasing in popularity due to the perception that they may represent a safe alternative to conventional cigarettes. However, a growing body of evidence indicates that ENDS exposure can disrupt maintenance of pulmonary immune homeostasis and antimicrobial immunity. In this issue of the JCI, Madison et al. demonstrate that in mice, chronic ENDS exposure induces profound alterations in lipid homeostasis. ENDS-exposed mice showed irregularities in the surfactant-secreting lamellar bodies within type 2 alveolar cells and increased intracellular phospholipid accumulation within alveolar macrophages. Moreover, ENDS-exposed mice displayed greater inflammation and tissue damage in response to influenza A, which may be due to downregulated expression of a viral pattern-recognition receptor in alveolar macrophages. Collectively, the results of this study identify previously unrecognized adverse effects of ENDS exposure on pulmonary lipid metabolism, although the implication of these effects on long-term respiratory health requires future exploration., Electronic nicotine delivery systems-what's the harm? The adverse health consequences of long-term cigarette smoking are well established, and it remains the leading cause of preventable death worldwide (1). Although tobacco [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2010.11.028 Byline: Katarina Moravcevic (1)(2), Jeannine M. Mendrola (1), Karl R. Schmitz (2), Yu-Hsiu Wang (4)(5), David Slochower (2)(5), Paul A. Janmey (2)(3)(5), Mark A. Lemmon (1)(2) Abstract: Phospholipid-binding modules such as PH, C1, and C2 domains play crucial roles in location-dependent regulation of many protein kinases. Here, we identify the KA1 domain (kinase associated-1 domain), found at the C terminus of yeast septin-associated kinases (Kcc4p, Gin4p, and Hsl1p) and human MARK/PAR1 kinases, as a membrane association domain that binds acidic phospholipids. Membrane localization of isolated KA1 domains depends on phosphatidylserine. Using X-ray crystallography, we identified a structurally conserved binding site for anionic phospholipids in KA1 domains from Kcc4p and MARK1. Mutating this site impairs membrane association of both KA1 domains and intact proteins and reveals the importance of phosphatidylserine for bud neck localization of yeast Kcc4p. Our data suggest that KA1 domains contribute to 'coincidence detection,' allowing kinases to bind other regulators (such as septins) only at the membrane surface. These findings have important implications for understanding MARK/PAR1 kinases, which are implicated in Alzheimer's disease, cancer, and autism. Author Affiliation: (1) Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA (2) Graduate Group in Biochemistry and Molecular Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA (3) Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA (4) Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA (5) Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA Article History: Received 19 March 2010; Revised 3 August 2010; Accepted 1 November 2010 Article Note: (miscellaneous) Published: December 9, 2010

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2010.11.028 Byline: Katarina Moravcevic (1)(2), Jeannine M. Mendrola (1), Karl R. Schmitz (2), Yu-Hsiu Wang (4)(5), David Slochower (2)(5), Paul A. Janmey (2)(3)(5), Mark A. Lemmon (1)(2) Abstract: Phospholipid-binding modules such as PH, C1, and C2 domains play crucial roles in location-dependent regulation of many protein kinases. Here, we identify the KA1 domain (kinase associated-1 domain), found at the C terminus of yeast septin-associated kinases (Kcc4p, Gin4p, and Hsl1p) and human MARK/PAR1 kinases, as a membrane association domain that binds acidic phospholipids. Membrane localization of isolated KA1 domains depends on phosphatidylserine. Using X-ray crystallography, we identified a structurally conserved binding site for anionic phospholipids in KA1 domains from Kcc4p and MARK1. Mutating this site impairs membrane association of both KA1 domains and intact proteins and reveals the importance of phosphatidylserine for bud neck localization of yeast Kcc4p. Our data suggest that KA1 domains contribute to 'coincidence detection,' allowing kinases to bind other regulators (such as septins) only at the membrane surface. These findings have important implications for understanding MARK/PAR1 kinases, which are implicated in Alzheimer's disease, cancer, and autism. Author Affiliation: (1) Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA (2) Graduate Group in Biochemistry and Molecular Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA (3) Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA (4) Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA (5) Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA Article History: Received 19 March 2010; Revised 3 August 2010; Accepted 1 November 2010 Article Note: (miscellaneous) Published: December 9, 2010

Several Long-Evans rat substrains carrying the phenotype of oculo-cutaneous albinism and bleeding diathesis are a rat model of Hermansky-Pudlak syndrome (HPS). The mutation responsible for the phenotype (Ruby) was identified as a point mutation in the initiation codon of Rab38 small GTPase that regulates intracellular vesicle transport. As patients with HPS often develop life-limiting interstitial pneumonia accompanied by abnormal morphology of alveolar type II cells, we investigated lung surfactant system in Long-Evans Cinnamon rats, one strain of the Ruby rats. The lungs showed conspicuous morphology of type II cells containing markedly enlarged lamellar bodies. Surfactant phosphatidylcholine and surfactant protein B were increased in lung tissues and lamellar bodies but not in alveolar lumen. Expression levels of mRNA for surfactant proteins A, B, C, and D were not altered. Isolated type II cells showed aberrant secretory pattern of newly synthesized [[sup.3]H]phosphatidylcholine, i.e., decreased basal secretion and remarkably amplified agonist-induced secretion. [[sup.3]H]phosphatidylcholine synthesis and uptake by type II cells were not altered. Thus Rab38-deficient type II cells appear to carry abnormality in lung surfactant secretion but not in synthesis or uptake. These results suggest that aberrant lung surfactant secretion may be involved in the pathogenesis of interstitial pneumonia in HPS. Ruby; Long-Evans Cinnamon rat; alveolar type II cells; lamellar body doi: 10.1152/ajplung.00242.2009

Most research on growing bacterial colonies on agar plates has concerned the effect of genetic or morphotype variation. Some studies have indicated that there is a correlation between microscopic bacterial motion and macroscopic colonial expansion, especially for swarming strains, but no measurements have been obtained for a single strain to relate the microscopic scale to the macroscopic scale. We examined here a single strain (Paenibacillus dendritiformis type T; tip splitting) to determine both the macroscopic growth of colonies and the microscopic bacterial motion within the colonies. Our multiscale measurements for a variety of growth conditions revealed that motion on the microscopic scale and colonial growth are largely independent. Instead, the growth of the colony is strongly affected by the availability of a surfactant that reduces surface tension.

Pseudomonas aeruginosa produces extracellular glycolipids composed of L-rhamnose and 3-hydroxyalkanoic acid called rhamnolipids. Although these compounds are usually regarded as biosurfactants or haemolysins, their exact physiological function is not well understood. Rhamnolipids are synthesized by a rhamnosyltransferase, encoded by the rhlAB operon, which catalyses the transfer of TDP-L-rhamnose to 3-(3-hydroxyalkanoyloxy)alkanoic acid (HAA) moieties of various lengths. RhlB is the catalytic protein of the rhamnosyltransferase, rhlA is indispensable for rhamnolipid synthesis, but its function is unknown. Using a liquid chromatography/mass spectrometry method, the production of extracellular HAAs by P. aeruginosa was detected previously and it was demonstrated that they are the actual precursors of rhamnolipid biosynthesis. In this report, evidence is presented indicating that rhlA is required for production of HAAs and that these HAAs display potent surface-active properties. P. aeruginosa can colonize surfaces by swarming motility, a form of organized translocation requiring the production of wetting agents. Using rhlA and rhlB mutants it was observed that swarming requires the expression of the rhlA gene but does not necessitate rhamnolipid production, as HAAs act as surfactants. Finally, it was shown that the use of ammonium instead of nitrate as source of nitrogen and an excess of available iron both decrease rhlA expression and swarming motility.

Types A and B Niemann-Pick disease (NPD) are lipid storage disorders caused by the deficient activity of acid sphingomyelinase (ASM). In humans, NPD is associated with the dysfunction of numerous organs including the lung. Gene targeting of the ASM gene in transgenic mice produced an animal model with features typical of NPD, including pulmonary inflammation. To assess mechanisms by which ASM perturbed lung function, we studied lung morphology, surfactant content, and metabolism in ASM-deficient mice in vivo. Pulmonary inflammation, with increased cellular infiltrates and the accumulation of alveolar material, was associated with alterations in surfactant content. Saturated phosphatidylcholine (SatPC) content was increased twofold, and sphingomyelin content was increased 5.5-fold in lungs of the ASM knockout (ASMKO) mice. Additional sphingomyelin enhanced the sensitivity of surfactant inhibition by plasma proteins. Clearance of SatPC from the lungs of ASMKO mice was decreased. Catabolism of SatPC by alveolar macrophages from the ASMKO mouse was significantly decreased, likely accounting for decreased pulmonary SatPC in vivo. In summary, ASM is required for normal surfactant catabolism by alveolar macrophages in vivo. Alterations in surfactant composition, including increased sphingomyelin content, contributed to the abnormal surfactant function observed in the ASM-deficient mouse. surface activity; surfactant catabolism; saturated phosphatidylcholine; surfactant proteins; alveolar macrophage

Research hasa beeen conducted on surfactant films. The role of cholesterol in these films, its effect on the maximum and minimum surface tension under dynamic conditions in captive bubble surfactometer and on the surface-associated reservoir topography have been investigated via the use of atomic force microscopy and the details are reported.

Research has been conducted on th surfactant protein A. The identification of the functional importance of the distinct chain types in human surfactant protein A has been carried out and the details are reported.

Research has been conducted on hexadecane biodegradation by Pseudomonas aeruginosa. The ability of the rhamnolipid to stimulate this biodegradation has been investigated via the use of the hydrophobic fluorescent probe and the details are reported.

The author reviews the publications on aqueous surfaces and interfaces. The topics of interest include the adsorbates' molecular structure at aqueous surfaces, small molecules adsorbed at aqueous surfaces and vibrational sum frequency studies of alkyl surfactants adsorbed at vapor/water and organic/water surfaces.

Research has been conducted on the surfactant protein B, a lung surfactant component. The results of the circular dichroism analysis and the solution structure of this protein dissolved in CD (sub)3 OH are presented.

Research has ben conducted on the pulmatory surfactant, a thin lipid/protein film. The study of the protein secondary structure and of the lipid acyl chain conformational order aquired from the monolayer films' lipid and protein constituents at the water and air interface has been carried out via the use of the infrared reflection-absorption spectroscopy.

The authors review the publications on organophosphorus compounds. The topics of interest include structure, bonding and nucleophilic reactivity of o-lodosylcarboxylates, and modeling nerve agents.

The authors review the publications on liquid crystals and surfactants. The topics of interest include calamitic liquid crystals, layered compounds and magnetic anisotropy and magnetic alignment of liquid crystals.

Research has been conducted on the lung surfactant's abundant lipid, cholesterol. The role of the cellular cholesteroil content in the palmitic acid esterification and uptake and in the fatty acid translocase cellular distribution has been investigated and the details are discussed.

Research has been conducted on the solvatochromic neutral alcohol and ionic sulfate homologous series. The methods used in producing surfactants' homologous series which can probe changes in the solvent environment on molecular length scales are described.

Research has been conducted on the muscarinic cholinergic receptors. The binding of the antagonists to M (sub)2 muscarinic receptors has been carried out and investigated in the porcine-atria's detergent-solubilized extracts and the results are described.

Research has been conducted on the collagen binding proteins. The identification of these proteins from Lactobacillus fermentum RC-14 biosurfactant has been carried out via the ProteinChip tandem mass spectrometry and the results are reported.

Research has been conducted on the nonstoichiometric and stoichiometric copper selenides. The synthesis of the selenides' nanocrystallites has been carried out in various solutions via the sonochemical irradiation and the effect of the solvents, surfactants and ultrasonic irradiation on the phase and morphology of the products have been analyzed.

Research has been conducted on the tetraarylporphyrins. The synthesis and structural characterization of these compounds have been carried out and the results are reported.