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1.
World J Microbiol Biotechnol ; 38(11): 216, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36056983

RESUMO

The increasing influence of human activity and industrialization has adversely impacted the environment via pollution with organic contaminants, which are minimally soluble in water. These hydrophobic organopollutants may be present in sediment, water or biota and have created concern due to their toxic effects in mammals. The ability of microorganisms to degrade pollutants makes their use the most effective, inexpensive and ecofriendly method for environmental remediation. Microorganisms have the ability to produce natural surfactants (biosurfactants) that increase the bioavailability of hydrophobic organopollutants, which enables their use as carbon and energy sources. Due to microbial diversity in production, and the biodegradability, nontoxicity, stability and specific activity of the surfactants, the use of microbial surfactants has the potential to overcome problems associated with contamination by hydrophobic organopollutants.This review provides an overview of the current state of knowledge regarding microbial surfactant production, mode of action in the biodegradation of hydrophobic organopollutants and biosynthetic pathways as well as their applications using emergent strategy tools to remove organopollutants from the environment. It is also specified for the first time that biosurfactants are produced either as growth-associated products or secondary metabolites, and are produced in different amounts by a wide range of microorganisms.


Assuntos
Carbono , Tensoativos , Animais , Biodegradação Ambiental , Humanos , Interações Hidrofóbicas e Hidrofílicas , Mamíferos/metabolismo , Tensoativos/metabolismo , Água
2.
Sci Immunol ; 7(75): eabj0140, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36112694

RESUMO

Pulmonary alveolar proteinosis (PAP) is a syndrome characterized by accumulation of surfactant lipoproteins within the lung alveoli. Alveolar macrophages (AMs) are crucial for surfactant clearance, and their differentiation depends on colony-stimulating factor 2 (CSF2), which regulates the establishment of an AM-characteristic gene regulatory network. Here, we report that the transcription factor CCAAT/enhancer binding protein ß (C/EBPß) is essential for the development of the AM identity, as demonstrated by transcriptome and chromatin accessibility analysis. Furthermore, C/EBPß-deficient AMs showed severe defects in proliferation, phagocytosis, and lipid metabolism, collectively resulting in a PAP-like syndrome. Mechanistically, the long C/EBPß protein variants LAP* and LAP together with CSF2 signaling induced the expression of Pparg isoform 2 but not Pparg isoform 1, a molecular regulatory mechanism that was also observed in other CSF2-primed macrophages. These results uncover C/EBPß as a key regulator of AM cell fate and shed light on the molecular networks controlling lipid metabolism in macrophages.


Assuntos
Macrófagos Alveolares , Surfactantes Pulmonares , Cromatina/metabolismo , Metabolismo dos Lipídeos , Lipoproteínas/metabolismo , Macrófagos Alveolares/metabolismo , PPAR gama/metabolismo , Isoformas de Proteínas/metabolismo , Surfactantes Pulmonares/metabolismo , Tensoativos/metabolismo
3.
J Oleo Sci ; 71(9): 1309-1318, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36047240

RESUMO

The conditions that significantly affect the biodegradability of linear alkylbenzene sulfonate (LAS) based on previous studies were categorized. Among these previous studies, we focused on those that used activated sludge and river water as inocula in biodegradation studies. Analyzing the results of these studies revealed two types of methylene blue active substances (MBAS) removal curves in primary biodegradation, and the study conditions that differentiated the two types were analyzed, along with verification studies. The effects of the LAS concentration and interfacial activity during biodegradation were analyzed to set the concentration of LAS in this study. Surface tension was measured as an indicator of interfacial activity and biodegradation was measured by oxygen demand. Two widely used surfactants, alcohol ethoxylate and sodium dodecyl sulfate, were evaluated to clarify the significance of the effective concentration range of LAS. The concentration of LAS was set at 10 or 20 mg/L in the verification study. Acclimatization and the concentration balance of LAS and river water were the strongest factors in studies using activated sludge and river water, respectively. Our classification chart may be helpful in analyzing and comparing the conditions of previous and current studies. Such understanding of the study conditions and practical evaluation may aid in avoiding misleading environmental impact assessments of LAS.


Assuntos
Ácidos Alcanossulfônicos , Esgotos , Biodegradação Ambiental , Tensoativos/metabolismo , Água
4.
J Environ Manage ; 321: 115868, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35985258

RESUMO

The effect of six important factors on the anaerobic biodegradation of linear alkylbenzene sulphonate (LAS) was evaluated using a response surface methodology. The factors were: (i) co-substrate concentration (CC), (ii) contact time between LAS and microorganisms, (iii) temperature, (iv) hardness, (v) pH, and (vi) LAS source. The results showed that individually or combined, CC with chemical oxygen demand (COD) ≤50 mg L-1 was the factor that mostly favoured LAS biodegradation; whereas at COD >50 mg L-1, adsorption to sludge and solubilisation in the aqueous medium were favoured. Two-factor interactions promoted the highest percentages of biodegradation (45-52%), adsorption (43-45%), and solubilisation (18-25%). The three-factor interactions resulted in small percentage increases of up to 11%, 5%, and 13% for biodegradation, adsorption, and solubilisation, respectively, compared to those of two-factor interactions. The interactions of four, five, and six factors resulted in a non-significant effect on LAS biodegradation, adsorption, and solubilisation, with percentages close to those quantified for the two- and three-factor interactions. Concentrations of up to 30 mg LAS L-1 did not significantly affect the COD removal efficiency (74-88%) from the medium. These values are commonly obtained in full-scale anaerobic systems used to treat domestic sewage.


Assuntos
Ácidos Alcanossulfônicos , Reatores Biológicos , Ácidos Alcanossulfônicos/metabolismo , Anaerobiose , Biodegradação Ambiental , Esgotos/química , Tensoativos/metabolismo
5.
J Oleo Sci ; 71(9): 1421-1426, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35965089

RESUMO

The basidiomycetous yeast Pseudozyma tsukubaensis produces a mannosylerythritol lipid (MEL) homologue, a diastereomer type of MEL-B, from olive oil. In a previous study, MEL-B production was increased by the overexpression of lipase PaLIPAp in P. tsukubaensis 1E5, through the enhancement of oil consumption. In the present study, RNA sequence analysis was used to identify a promoter able to induce high-level PaLIPA expression. The recombinant strain, expressing PaLIPA via the translation elongation factor 1 alpha/Tu promoter, showed higher lipase activity, rates of oil degradation, and MEL-B production than the strain which generated in our previous study.


Assuntos
Ustilaginales , Basidiomycota , Glicolipídeos , Lipase/genética , Lipase/metabolismo , Fator 1 de Elongação de Peptídeos/genética , Fator 1 de Elongação de Peptídeos/metabolismo , Tensoativos/metabolismo , Ustilaginales/genética
6.
Int J Chron Obstruct Pulmon Dis ; 17: 1247-1260, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35651829

RESUMO

Background: Secretoglobin (SCGB) 3A2 is a novel bioactive molecule with anti-inflammatory and anti-fibrotic activities. SCGB3A2 also promotes the maturation of bronchial divergence and the lungs during embryonic development. However, much remains unknown concerning the roles of SCGB3A2 in diseases associated with aging. Methods: The lungs of Scgb3a2-knockout (KO) mice and their wild-type (WT) littermates were subjected to histological analysis, Victoria blue staining to evaluate of elastic fibers, and lung morphometric analysis during the postnatal period (birth to 8 weeks) and during aging (8 weeks to 2 years). Their spleens were also histologically evaluated. The expression of lung surfactant protein (SP) mRNAs was examined by quantitative reverse transcriptase-polymerase chain reaction. RNA sequencing (RNAseq) analysis was performed on 3-month-old KO and WT mouse lungs. Results: The alveolar spaces of KO mice continuously expanded between 0.5 and 2 years of age, accompanied by increases of the mean linear intercept and destructive index. KO mouse lungs displayed inflammation associated with lymphocyte aggregate starting at 1 year of age, and the inflammation was worse than that of WT mouse lungs. A high number of lymphoma-like cells were presented in 2-year-old KO mouse lungs. White pulp fusion was detected in the spleens of both WT and KO mice older than 0.5 years; however, the fusion was more severe in KO mice than in WT mice. The expression of surfactant protein (SP)-A, SP-B, SP-C, and SP-D mRNAs in KO mouse lungs decreased with age, and after 1 year of age, the expression of most SPs was significantly lower in KO mice than in WT mice. RNAseq demonstrated that the expression of immune system-related genes was highly altered in KO mouse lungs. Conclusion: SCGB3A2 may be required for maintaining homeostasis and immune activity in the lungs during aging. SCGB3A2 deficiency might increase the risk of emphysema of the lung.


Assuntos
Enfisema , Linfoma , Doença Pulmonar Obstrutiva Crônica , Envelhecimento , Animais , Feminino , Humanos , Inflamação/metabolismo , Pulmão/metabolismo , Linfoma/metabolismo , Linfoma/patologia , Camundongos , Camundongos Knockout , Gravidez , Doença Pulmonar Obstrutiva Crônica/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Secretoglobinas/genética , Secretoglobinas/metabolismo , Tensoativos/metabolismo
7.
Adv Colloid Interface Sci ; 306: 102718, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35714572

RESUMO

This review discusses the classification, characteristics, and applications of biosurfactants. The biosynthesis pathways for different classes of biosurfactants are reviewed. An in-depth analysis of reported research is carried out emphasizing the synthetic pathways, culture media compositions, and influencing factors on production yield of biosurfactants. The environmental, pharmaceutical, industrial, and other applications of biosurfactants are discussed in detail. A special attention is given to the biosurfactants application in combating the pandemic COVID-19. It is found that biosurfactant production from waste materials can play a significant role in enhancing circular bioeconomy and environmental sustainability. This review also details the life cycle assessment methodologies for the production and applications of biosurfactants. Finally, the current status and limitations of biosurfactant research are discussed and the potential areas are highlighted for future research and development. This review will be helpful in selecting the best available technology for biosynthesis and application of particular biosurfactant under specific conditions.


Assuntos
COVID-19 , Tensoativos , Humanos , Tensoativos/metabolismo
8.
Proc Natl Acad Sci U S A ; 119(25): e2123564119, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35696565

RESUMO

In the context of the rapid increase of antibiotic-resistant infections, in particular of pneumonia, antimicrobial photodynamic therapy (aPDT), the microbiological application of photodynamic therapy (PDT), comes in as a promising treatment alternative since the induced damage and resultant death are not dependent on a specific biomolecule or cellular pathway. The applicability of aPDT using the photosensitizer indocyanine green with infrared light has been successfully demonstrated for different bacterial agents in vitro, and the combination of pulmonary delivery using nebulization and external light activation has been shown to be feasible. However, there has been little progress in obtaining sufficient in vivo efficacy results. This study reports the lung surfactant as a significant suppressor of aPDT in the lungs. In vitro, the clinical surfactant Survanta® reduced the aPDT effect of indocyanine green, Photodithazine®, bacteriochlorin-trizma, and protoporphyrin IX against Streptococcus pneumoniae. The absorbance and fluorescence spectra, as well as the photobleaching profile, suggested that the decrease in efficacy is not a result of singlet oxygen quenching, while a molecular dynamics simulation showed an affinity for the polar head groups of the surfactant phospholipids that likely impacts uptake of the photosensitizers by the bacteria. Methylene blue is the exception, likely because its high water solubility confers a higher mobility when interacting with the surfactant layer. We propose that the interaction between lung surfactant and photosensitizer must be taken into account when developing pulmonary aPDT protocols.


Assuntos
Antibacterianos , Bactérias , Fotoquimioterapia , Fármacos Fotossensibilizantes , Tensoativos , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Verde de Indocianina/farmacologia , Pulmão/microbiologia , Simulação de Dinâmica Molecular , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Tensoativos/metabolismo
9.
Tissue Eng Regen Med ; 19(5): 1033-1050, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35670910

RESUMO

BACKGROUND: The progenitors to lung airway epithelium that are capable of long-term propagation may represent an attractive source of cells for cell-based therapies, disease modeling, toxicity testing, and others. Principally, there are two main options for obtaining lung epithelial progenitors: (i) direct isolation of endogenous progenitors from human lungs and (ii) in vitro differentiation from some other cell type. The prime candidates for the second approach are pluripotent stem cells, which may provide autologous and/or allogeneic cell resource in clinically relevant quality and quantity. METHODS: By exploiting the differentiation potential of human embryonic stem cells (hESC), here we derived expandable lung epithelium (ELEP) and established culture conditions for their long-term propagation (more than 6 months) in a monolayer culture without a need of 3D culture conditions and/or cell sorting steps, which minimizes potential variability of the outcome. RESULTS: These hESC-derived ELEP express NK2 Homeobox 1 (NKX2.1), a marker of early lung epithelial lineage, display properties of cells in early stages of surfactant production and are able to differentiate to cells exhibitting molecular and morphological characteristics of both respiratory epithelium of airway and alveolar regions. CONCLUSION: Expandable lung epithelium thus offer a stable, convenient, easily scalable and high-yielding cell source for applications in biomedicine.


Assuntos
Células-Tronco Embrionárias Humanas , Diferenciação Celular , Epitélio , Humanos , Pulmão/metabolismo , Tensoativos/metabolismo
10.
Adv Biochem Eng Biotechnol ; 181: 73-122, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35526186

RESUMO

Wide ranges of microorganisms produce glycosylated lipids (GL), which are characterized by their tensio-active properties. Therefore, they can be used in different industrial applications as biosurfactants, such as food, agriculture, cosmetics, and health products among others. Two GL biosurfactants, rhamnolipids (RL) and sophorolipids (SL), are now commercially available and share a significant part of the biosurfactant market that in 2017 represented about 2.5% of the total surfactants market, estimated at 15 million tons globally.In this chapter, we present a general overview of GL biosurfactants in terms of their diversity and the microorganisms that produce them. Additionally, we focus on the more detailed description of RL, SL, mannosylerythritol lipids (MEL), and cellobiose lipids (CL).Pseudomonas aeruginosa, the ubiquitous opportunistic pathogenic bacterium, is the best RL producer, but other non-pathogenic bacteria like Burkholderia thailandensis and Pseudomonas chlororaphis NRRL B-30761 are also capable of producing them naturally. In addition, Pseudomonas putida has been used as heterologous host to produce RL with good yields. Here we describe the biosynthetic pathway for RL production, the genes involved in its synthesis, and some of the challenges for producing a homogeneous RL product in high quantities that is suitable for specific applications.SL, MEL, and CL are some of the GL biosurfactants produced in high quantities by fungi, like Starmerella bombicola, Moesziomyces aphidis, or Ustilago maydis. We provide an overview of some of their characteristics, insights on the metabolic pathways involved in their synthesis and genetic modifications performed to increase their production, as well as fermentation and purification strategies and some of their applications.


Assuntos
Celobiose , Pseudomonas putida , Celobiose/metabolismo , Fungos/genética , Fungos/metabolismo , Pseudomonas putida/genética , Tensoativos/metabolismo
11.
Chemosphere ; 302: 134870, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35537625

RESUMO

Fracturing flowback fluids (FFFs), which is generated from the process of oil and gas exploitation, is one of the major environmental concerns. In this study, a bacterial strain, Bacillus sp. SS15, capable of producing both bioflocculant (BF) and biosurfactant (BS), was isolated from oil-contaminated mudflat sediment. The BS produced by SS15 was identified as lipopeptide, which could reduce the surface tension of water from 74.2 mN/m to 36.6 mN/m with a critical micelle concentration of 44.4 mg/L. It also exhibited strong tolerance against a wide range of pH (2-12), temperature (4-60 °C), and salinity (0-100 g/L). Meanwhile, the BF produced by SS15 exhibited high flocculating activity (84.9%) for kaolin suspension, and was confirmed to be thermostable, salt-tolerant, and alkaliphilic. The combined treatment of bioremediation (introducing SS15 and BS) followed by flocculation (introducing BF) greatly promoted the removal of chroma (85.7% reduction), suspended solids (94.4% reduction), chemical oxygen demand (84.9% reduction), n-alkanes (50.0% reduction), and polycyclic aromatic hydrocarbons (66.5% reduction), respectively. The genome analysis showed that strain SS15 possessed abundant genes related to the synthesis of carbohydrate, protein, and lipid, which might play an important role in BF and BS synthesis. The findings in this study demonstrated that Bacillus sp. SS15 has promising prospect in the remediation of FFFs.


Assuntos
Bacillus , Bacillus/genética , Bacillus/metabolismo , Biodegradação Ambiental , Floculação , Lipopeptídeos , Tensão Superficial , Tensoativos/metabolismo
12.
Int J Pharm ; 621: 121780, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35504427

RESUMO

Treatment for CNS related diseases are limited by the difficulty of the drugs to cross the blood-brain barrier (BBB). The functionalization of polymeric nanoparticles (NPs) coated with the surfactants polysorbate 80 (PS80) and poloxamer 188 (P188), have shown promising results as drugs carriers are able to cross the BBB on animal models. In this study, poly(lactide-co-glycolide) (PLGA) NPs coated with PS80 and P188, labelled with a fluorescent dye were tested on human pre-clinical in vitro model to evaluate and compare their uptake profiles, mechanisms of transport and crossing over human brain-like endothelial cells (BLECs) mimicking the human BBB. In addition, these NPs were produced using a method facilitating their reproducible production at high scale, the MicroJet reactor® technology. Results showed that both formulations were biocompatible and able to be internalized within the BLECs in different uptake profiles depending on their coating: P188 NP showed higher internalization capacity than PS80 NP. Both NPs uptakes were ATP-dependent, following more than one endocytosis pathway with colocalization in the early endosomes, ending with a NPs release in the brain compartment. Thus, both surfactant-coated PLGA NPs are interesting formulations for delivery to the brain through the BBB, presenting different uptake profiles.


Assuntos
Nanopartículas , Surfactantes Pulmonares , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Portadores de Fármacos/metabolismo , Células Endoteliais/metabolismo , Excipientes/metabolismo , Humanos , Poloxâmero/metabolismo , Polissorbatos , Surfactantes Pulmonares/metabolismo , Tensoativos/metabolismo
13.
Molecules ; 27(10)2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35630660

RESUMO

In the present study, chitosan-decorated multiple nanoemulsion (MNE) was formulated using a two-step emulsification process. The formulated multiple nanoemuslion was evaluated physiochemically for its size and zeta potential, surface morphology, creaming and cracking, viscosity and pH. A Franz diffusion cell apparatus was used to carry out in vitro drug-release and permeation studies. The formulated nanoemulsion showed uniform droplet size and zeta potential. The pH and viscosity of the formulated emulsion were in the range of and suitable for topical delivery. The drug contents of the simple nanoemulsion (SNE), the chitosan-decorated nanoemulsion (CNE) and the MNE were 71 ± 2%, 82 ± 2% and 90 ± 2%, respectively. The formulated MNE showed controlled release of itraconazole as compared with that of the SNE and CNE. This was attributed to the chitosan decoration as well as to formulating multiple emulsions. The significant permeation and skin drug retention profile of the MNE were attributed to using the surfactants tween 80 and span 20 and the co-surfactant PEG 400. ATR-FTIR analysis confirmed that the MNE mainly affects the lipids and proteins of the skin, particularly the stratum corneum, which results in significantly higher permeation and retention of the drug. It was concluded that the proposed MNE formulation delivers drug to the target site of the skin and can be therapeutically used for various cutaneous fungal infections.


Assuntos
Quitosana , Administração Cutânea , Quitosana/química , Emulsões/química , Pele/metabolismo , Absorção Cutânea , Tensoativos/metabolismo
14.
J Appl Microbiol ; 133(3): 1229-1244, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35598183

RESUMO

The use of surfactants in households and industries is inevitable and so is their discharge into the environment, especially into the water bodies as effluents. Being surface-active agents, their utilization is mostly seen in soaps, detergents, personal care products, emulsifiers, wetting agents, etc. Anionic surfactants are the most used class. These surfactants are responsible for the foam and froth in the water bodies and cause potential adverse effects to both biotic and abiotic components of the ecosystem. Surfactants are capable of penetrating the cell membrane and thus cause toxicity to living organisms. Accumulation of these compounds has been known to cause significant gill damage and loss of sight in fish. Alteration of physiological and biochemical parameters of water decreases the amount of dissolved oxygen and thus affecting the entire ecosystem. Microbes utilizing surfactants as substrates for energy form the basis of the biodegradation of these compounds. The main organisms for surfactant biodegradation, both in sewage and natural waters, are bacteria. Several Pseudomonas and Bacillus spp. have shown efficient degradation of anionic surfactants namely: sodium dodecyl sulphate (SDS), linear alkylbenzene sulphonate (LAS), sodium dodecylbenzenesulphonate (SDBS). Also, several microbial consortia constituting Alcaligenes spp., Citrobacter spp., etc. have shown efficacy in the degradation of surfactants. The biodegradation efficiency studies of these microbes/microbial consortia would be of immense help in formulating better solutions for the bioremediation of surfactants and help to reduce their potential environmental hazards.


Assuntos
Ecossistema , Tensoativos , Animais , Bactérias/metabolismo , Biodegradação Ambiental , Tensoativos/metabolismo , Água/metabolismo
15.
J Assist Reprod Genet ; 39(7): 1531-1544, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35538257

RESUMO

PURPOSE: This study aims to investigate whether indomethacin (IND) delays preterm birth by regulating the Notch pathway, Tlr receptors, and Sp-A in the placenta in lipopolysaccharide (LPS)-induced preterm labor (PTL) model. METHODS: CD-1 mice were distributed to the pregnant control (PC), Sham, PBS, IND (2 mg/kg; i.p.), LPS (25 µg/100 µl; intrauterine), and LPS + IND groups. The injections were performed on day 14.5 of pregnancy. Placentae were collected on day 15.5 of pregnancy, and immunohistochemical analyzes were performed. Differences in staining intensities between the Cox-1, Notch-1 (N1), Dll-1, Jagged-2 (Jag-2), Tlr-2, and Tlr-4 proteins were compared. RESULTS: Preterm labor rates were 100% and 66% (preterm delivery delayed 5 h) in the LPS and LPS + IND groups, respectively. In LPS-treated mice, a general morphological deterioration was observed in the placenta. Total placental mid-sagittal measurement was significantly reduced in the LPS-treated group, while it was similar to the PC group in the LPS + IND group. Cox-1 expression in the LZ increased, and Sp-A expression decreased after LPS injection, and IND administration diminished this increase. N1 expression increased in the labyrinth zone (LZ) and the junctional zone (JZ). Dll-1 and Jag-2 expression increased in the JZ after LPS injection (p < 0.0001). IND administration diminished Tlr-2 expression in the LZ and Tlr-4 expression in the JZ after LPS injection. CONCLUSION: In conclusion, PG (prostaglandin) inhibition may alter Notch signaling, Tlr, and Sp-A protein expression and may be associated with delayed labor in LPS-induced mice.


Assuntos
Trabalho de Parto Prematuro , Nascimento Prematuro , Animais , Feminino , Humanos , Recém-Nascido , Lipopolissacarídeos/toxicidade , Camundongos , Placenta/metabolismo , Gravidez , Prostaglandinas/efeitos adversos , Prostaglandinas/metabolismo , Tensoativos/efeitos adversos , Tensoativos/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Útero
16.
J Control Release ; 345: 734-743, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35367276

RESUMO

In the context of increased interest in permeability enhancement technologies to achieve mucosal delivery of drugs and biologics, we report our study on effects of the amphiphilic surfactant at cell membrane and cell population levels. Our results show that modulation in membrane order and fluidity initially occurs on insertion of individual surfactant molecules into the outer leaflet of membrane lipid bilayer; a process occurring at concentrations below surfactant's critical micellar concentration. The surfactant insertion, and consequent increase in membrane fluidity, are observed to be spatially heterogenous, i.e. manifested as 'patches' of increased membrane fluidity. At the cell population level, spatially heterogeneous activity of surfactant is also manifested, with certain cells displaying high permeability amongst a 'background' population. We propose that this heterogeneity is further manifested in a broad profile of intracellular and nuclear exposure levels to a model drug (doxorubicin) observed in cell population. The study points to heterogeneous nature of surfactant effects at cell membrane and cells in population levels.


Assuntos
Surfactantes Pulmonares , Tensoativos , Membrana Celular/metabolismo , Excipientes , Humanos , Bicamadas Lipídicas/metabolismo , Micelas , Permeabilidade , Surfactantes Pulmonares/metabolismo , Tensoativos/metabolismo
17.
Adv Colloid Interface Sci ; 304: 102659, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35421637

RESUMO

The surface of pulmonary alveolar subphase is covered with a mixture of lipids and proteins. This lung surfactant plays a crucial role in lung functioning. It shows a complex phase behavior which can be altered by the interaction with third molecules such as drugs or pollutants. For studying multicomponent biological systems, it is of interest to couple experimental approach with computational modelling yielding atomic-scale information. Simple two, three, or four-component model systems showed to be useful for getting more insight in the interaction between lipids, lipids and proteins or lipids and proteins with drugs and impurities. These systems were studied theoretically using molecular dynamic simulations and experimentally by means of the Langmuir technique. A better understanding of the structure and behavior of lung surfactants obtained from this research is relevant for developing new synthetic surfactants for efficient therapies, and may contribute to public health protection.


Assuntos
Simulação de Dinâmica Molecular , Surfactantes Pulmonares , Lipídeos , Pulmão/metabolismo , Surfactantes Pulmonares/metabolismo , Tensoativos/metabolismo
18.
Cells ; 11(7)2022 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-35406686

RESUMO

NKX2.1 is a master regulator of lung morphogenesis and cell specification; however, interactions of NKX2.1 with various transcription factors to regulate cell-specific gene expression and cell fate in the distal lung remain incompletely understood. FOXO1 is a key regulator of stem/progenitor cell maintenance/differentiation in several tissues but its role in the regulation of lung alveolar epithelial progenitor homeostasis has not been evaluated. We identified a novel role for FOXO1 in alveolar epithelial cell (AEC) differentiation that results in the removal of NKX2.1 from surfactant gene promoters and the subsequent loss of surfactant expression in alveolar epithelial type I-like (AT1-like) cells. We found that the FOXO1 forkhead domain potentiates a loss of surfactant gene expression through an interaction with the NKX2.1 homeodomain, disrupting NKX2.1 binding to the SFTPC promoter. In addition, blocking PI-3K/AKT signaling reduces phosphorylated FOXO-1 (p-FOXO1), allowing accumulated nuclear FOXO1 to interact with NKX2.1 in differentiating AEC. Inhibiting AEC differentiation in vitro with keratinocyte growth factor (KGF) maintained an AT2 cell phenotype through increased PI3K/AKT-mediated FOXO1 phosphorylation, resulting in higher levels of surfactant expression. Together these results indicate that FOXO1 plays a central role in AEC differentiation by directly binding NKX2.1 and suggests an essential role for FOXO1 in mediating AEC homeostasis.


Assuntos
Células Epiteliais Alveolares , Surfactantes Pulmonares , Células Epiteliais Alveolares/metabolismo , Células Epiteliais/metabolismo , Fator 7 de Crescimento de Fibroblastos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Surfactantes Pulmonares/metabolismo , Tensoativos/metabolismo
19.
Environ Sci Technol ; 56(10): 6305-6314, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35467837

RESUMO

Bioconcentration factors (BCFs) in rainbow trout were measured for 10 anionic surfactants with a range of alkyl chain lengths and different polar head groups. The BCFs ranged from 0.04 L kg-1 ww (for C10SO3) to 1370 L kg-1 ww (C16SO3). There was a strong correlation between the log BCF and log membrane lipid-water distribution ratio (DMLW, r2 = 0.96), and biotransformation was identified as the dominant elimination mechanism. The strong positive influence of DMLW on BCF was attributed to two phenomena: (i) increased partitioning from water into the epithelial membrane of the gill, leading to more rapid diffusion across this barrier and more rapid uptake, and (ii) increased sequestration of the surfactant body burden into membranes and other body tissues, resulting in lower freely dissolved concentrations available for biotransformation. Estimated whole-body in vivo biotransformation rate constants kB-BCF are within a factor three of rate constants estimated from S9 in vitro assays for six of the eight test chemicals for which kB-BCF could be determined. A model-based assessment indicated that the hepatic clearance rate of freely dissolved chemicals was similar for the studied surfactants. The dataset will be useful for evaluation of in silico and in vitro methods to assess bioaccumulation.


Assuntos
Oncorhynchus mykiss , Poluentes Químicos da Água , Animais , Bioacumulação , Biotransformação , Oncorhynchus mykiss/metabolismo , Tensoativos/metabolismo , Água/metabolismo , Poluentes Químicos da Água/análise
20.
Comput Intell Neurosci ; 2022: 7205016, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463266

RESUMO

Objective: To study the mechanism of chronic obstructive pulmonary disease (COPD) in diagnosing alveolar factors and analyze the effect of miR-149-3p on alveolar inflammatory factors and the expression of surfactant protein D (SP-D) and SP-A on the lung surface mediated by Wnt pathway. Methods: Patients with stable COPD were taken as the research subjects, and healthy volunteers as the control group. Cardiac color Doppler ultrasound was adopted to measure the ventricular structure of patients. The ultrasound simulation method was introduced in the ultrasound imaging. The ultrasound image was processed based on the intelligent ultrasound simulation algorithm. The changes in the structure of the left and right ventricles were analyzed and compared in the two groups. The expression changes of miR-149-3p, Wnt1, ß-catenin, RhoA, and Wnt5a in lung tissues of mice in three groups were detected, as well as the content of tumor necrosis factor- (TNF-) α, IL-1ß, interleukin (IL-6), nuclear factor kB (NF-kB), and other inflammatory factors in bronchoalveolar tissues of mice in three groups. Results: The position where the attenuation ratio was less than 0.92 in the experiment under the ultrasonic simulation algorithm had a gray value of 50. Compared with the control group, the right ventricular mass index of patients with stable COPD was statistically considerable (P < 0.05). In patients with stable COPD, the overall right ventricular longitudinal strain, right ventricular diastolic longitudinal strain rate (RV DLSR), right ventricular diastolic circumferential strain rate, and right ventricular longitudinal displacement were significantly impaired (P < 0.05). The content of miR-149-3p in the lung tissue of the model group was dramatically inferior to that of the control group and the interference group (P < 0.05). The contents of Wnt1, ß-catenin, RhoA, and Wnt5a in the lung tissue of the model group were dramatically superior to those of the control group (P < 0.05). In addition, the expressions of TNF-α, IL-1ß, IL-6, and NF-kB in the alveolar lavage fluid of the model group were statistically different from those of control group (P < 0.05). The expression levels of SP-D and surfactant protein A (SP-A) in the COPD group were also statistically different from those of control group (P < 0.05). Conclusion: miR-149-3p regulated the expression of Wnt1, ß-catenin, RhoA, and Wnt5a, which also affected the signal transmission of the Wnt pathway, causing changes in the expression of alveolar inflammatory factors. Eventually, it affected the development of COPD.


Assuntos
MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Animais , Humanos , Interleucina-6/metabolismo , Interleucina-6/farmacologia , Pulmão , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , MicroRNAs/farmacologia , NF-kappa B/metabolismo , NF-kappa B/farmacologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Proteína A Associada a Surfactante Pulmonar/metabolismo , Proteína A Associada a Surfactante Pulmonar/farmacologia , Proteína D Associada a Surfactante Pulmonar/metabolismo , Proteína D Associada a Surfactante Pulmonar/farmacologia , Tensoativos/metabolismo , Tensoativos/farmacologia , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismo , beta Catenina/farmacologia
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