Increase In Fluidity Research Articles

Shear-thinning hydrogels containing reactive oxygen species-responsive nanoparticles for salvianolic acid B delivery to rescue oxidative damaged HUVECs

Reactive oxygen species (ROS)-induced oxidative stress plays a key role in the peripheral arterial disease (PAD). Salvianolic acid B (SAB) is a natural phenolic compound and possesses antioxidant properties. However, the poor bioavailability of hydrophilic SAB may limit its applications. Boronic ester-based nanoparticles (NPs) as ROS‐responsive carriers can release drug rapidly and selectively at damaged tissue. Dextran, a polysaccharide, has been used to decrease the platelet aggregation in PAD patients. Laponite, a synthetic nanoclay, has been widely used in biomedical applications. In the study, the laponite hydrogels containing ROS-responsive dextran-based NPs was developed as a carrier for SAB delivery. The synthesis processes of boronic ester modified dextran (PHB-DEX) were characterized by Fourier transform infrared spectrophotometer and thermogravimetry analyzer. The PHB-DEX NP was ∼195.3 nm with spherical structure and could be hydrolyzed completely within 9 min under oxidative stress. Optimal concentration of SAB to treat HUVECs was ∼100 μM. The results of scanning electron microscopy demonstrated that SAB-loaded NPs (SAB-NPs) were well dispersed in laponite hydrogels matrix. The rheological behaviors of laponite containing SAB-NPs (LNPs) showed the shear-thinning properties and increase of fluidity when removing shear stress. The LNPs with sustained drug release properties could scavenge ROS and rescue human umbilical vein endothelial cells from oxidative damage via decrease of the inflammatory level (TNF, IL-1α, IL-1β, IL-6, and MMP-9) and apoptosis. The biocompatibility of the developed hydrogels has been demonstrated in-vivo. The results suggested that the developed LNPs might have potentials for PAD treatment.

Influence of modification with highly dispersed silicon carbide on the casting properties of the secondary alloy of the Al-Si system

One of the main areas of application of aluminum is the aerospace and transport industries, which are constantly increasing the requirements for the properties of cast products. The use of aluminum as the main material for the manufacture of various parts of vehicles can significantly reduce their weight, which leads to a decrease in fuel consumption. In order to meet the requirements of the modern world, the work considers studies to improve the quality and increase the properties of products from the secondary aluminum alloy AlSi12. Modern technologies for processing liquid aluminum alloy are analyzed. According to the results of an analytical review, it was found that modifiers that affect the size of the primary grain and the shape of inclusions of eutectic silicon are of the greatest interest. It was found that the modification processes do not change the chemical composition of the alloy, but rather contribute to a change in the size and shape of the structural components of the alloy. The paper considers the influence of an ultradispersed SiC modifier with a particle size of up to 200 nm on the casting properties of secondary aluminum alloys: fluidity, linear and volumetric shrinkage. The fluidity was studied in green sand and metal mould. It was found that the addition of 0.1 % SiC improves the fluidity of the secondary alloy from 560 to 630 mm for green sand mould and from 230 to 295 mm for a metal mould due to cleaning from non-metallic inclusions. A further increase in the SiC content to 0.2 % does not lead to an obvious increase in fluidity. The study of linear shrinkage found that increasing the content of the modifier to 0.2 % contributes to its decrease. At the same time, an increase in the pouring temperature of the alloy promotes an increase in the total linear shrinkage, which is associated with the long residence time of the metal in the liquid state. As a result of the rapid crystallization of the melt with additional nucleation centers in the role of which are particles of the ultradispersed modifier, the coefficient of volumetric shrinkage decreases from 28 to 20 %. The proposed technical solutions for the modification of alloys of the secondary alloy AlSi12 can be used in processes that will improve the quality of cast metal products with the economical use of energy resources and materials for its production.

In Ukrainian

Based on the analysis of the spectra, it has been found that compounds of flavonoid nature, binding to cell membranes, change not in all cases the fluidity of membrane lipids depending on the cell type. Obviously, vascular tissue cells are a kind of "target cells" for these substances, i.e. there is a selectivity of flavonoids to certain tissues of organs. A particularly noticeable increase in the lipid fluidity of membranes was observed due to the addition of flavonoid glycosides - hyperoside, stachanoaceside and liquiritin to segments of venous tissue, which correlated with the high affinity of these substances to liposomes. The addition to the vessels of the metabolite quercetin - chalcone also led to a sharp increase in the lipid fluidity of cells of arterial and venous tissue, what suggests the presence of biological activity in flavonoid metabolites. One of the mechanisms of increasing the resistance of arterial and venous vessels under the action of flavonoid substances is an increase in the lipid fluidity of cell membranes of these vessels, which reduces the fragility of blood vessels and increases their flexibility and elasticity. The apparent contradiction between the rapid metabolism of many flavonoids in animals and the prolonged pharmacological action can be explained by the capability of their metabolites, such as chalcone, to increase the lipid fluidity of vascular cell membranes, changing their resistance to external influences. Reducing the fragility of the pulmonary vessels and increasing their flexibility and elasticity can have a positive effect on a human body in the fight against coronavirus.

Effect of the natural polymethoxylated flavone artemetin on lipid oxidation and its impact on cancer cell viability and lipids

The biochemical class of the polymethoxylated flavonoids represents uncommon phenolic compounds in plants presenting a more marked lipophilic behavior due to the alkylation of its hydroxylic groups. As a polymethoxylated flavone, which concerns a different bioavailability, artemetin (ART) has been examined in vitro against lipid oxidation and its impact on cancer cells has been explored. Despite this flavone only exerted a slight protection against in vitro fatty acid and cholesterol oxidative degradation, ART significantly reduced viability and modulated lipid profile in cancer Hela cells at the dose range 10–50 μM after 72 h of incubation. It induced marked changes in the monounsaturated/saturated phospholipid class, significant decreased the levels of palmitic, oleic and palmitoleic acids, maybe involving an inhibitory effect on de novo lipogenesis and desaturation in cancer cells. Moreover, ART compromised normal mitochondrial function, inducing a noteworthy mitochondrial membrane polarization in cancer cells. A dose-dependent absorption of ART was evidenced in HeLa cell pellets (15.2% of the applied amount at 50 μM), coupled to a marked increase in membrane fluidity, as indicate by the dose-dependent fluorescent Nile Red staining (red emissions). Our results validate the ART role as modulatory agent on cancer cell physiology, especially impacting viability, lipid metabolism, cell fluidity, and mitochondrial potential.

Bicarbonate-Stimulated Membrane Reorganization in Stallion Spermatozoa.

Classical in vitro fertilization (IVF) is still poorly successful in horses. This lack of success is thought to be due primarily to inadequate capacitation of stallion spermatozoa under in vitro conditions. In species in which IVF is successful, bicarbonate, calcium, and albumin are considered the key components that enable a gradual reorganization of the sperm plasma membrane that allows the spermatozoa to undergo an acrosome reaction and fertilize the oocyte. The aim of this work was to comprehensively examine contributors to stallion sperm capacitation by investigating bicarbonate-induced membrane remodelling steps, and elucidating the contribution of cAMP signalling to these events. In the presence of capacitating media containing bicarbonate, a significant increase in plasma membrane fluidity was readily detected using merocyanine 540 staining in the majority of viable spermatozoa within 15 min of bicarbonate exposure. Specific inhibition of soluble adenylyl cyclase (sAC) in the presence of bicarbonate by LRE1 significantly reduced the number of viable sperm with high membrane fluidity. This suggests a vital role for sAC-mediated cAMP production in the regulation of membrane fluidity. Cryo-electron tomography of viable cells with high membrane fluidity revealed a range of membrane remodelling intermediates, including destabilized membranes and zones with close apposition of the plasma membrane and the outer acrosomal membrane. However, lipidomic analysis of equivalent viable spermatozoa with high membrane fluidity demonstrated that this phenomenon was neither accompanied by a gross change in the phospholipid composition of stallion sperm membranes nor detectable sterol efflux (p > 0.05). After an early increase in membrane fluidity, a significant and cAMP-dependent increase in viable sperm with phosphatidylserine (PS), but not phosphatidylethanolamine (PE) exposure was noted. While the events observed partly resemble findings from the in vitro capacitation of sperm from other mammalian species, the lack of cholesterol removal appears to be an equine-specific phenomenon. This research will assist in the development of a defined medium for the capacitation of stallion sperm and will facilitate progress toward a functional IVF protocol for horse gametes.

The studies on the membrane activity of triester of phosphatidylcholine in artificial membrane systems.

Due to the increasing number of infections together with the appearance of bacteria exhibiting multi-drug resistance, new antibiotics are being sought. In this context the interest of the cationic lipoids increases because of their amphiphilic structure and positive charge that can stimulates the antibacterial action of these compounds. Thus, in this work we have performed the studies on the effect of one selected triesters of phosphatidylcholine, namely 1,2-dipalmitoyl-sn-glycero-3-ethylphosphocholine (EDPPC), on the model lipid membranes. The investigations included the analysis of the impact of EDPPC on multicomponent monolayers and bilayers consisting of the lipids naturally occurring in bacterial membranes (phosphatidylethanolamines (PE), phosphatidylglycerols (PG) and cardiolipin (CL)), mixed in proportions reflecting the lipid composition of these biomembranes. In the study, the Langmuir monolayers (registered on water and PBS buffer) and liposomes as model bacterial biomembranes were applied. The obtained results demonstrate that the presence of cationic lipoid in PE/PG and PE/PG/CL systems significantly modifies their properties and molecular organization. The incorporation of EDPPC into model bacterial membranes primarily impact on the intermolecular interactions. It was shown that the strength of the interaction between the cationic lipid and the components of the model membranes depends both on the composition of the membrane as well as on the type of subphase. Furthermore, the investigated cationic lipoid leads to the decrease of the ordering of acyl chains and thus to the increase of fluidity of membranes. The obtained results allow one to propose that EDPPC may behave as antibiotic active at the level of membrane.

Number of Times Recycled and Its Effect on the Recyclability, Fluidity and Tensile Properties of Polypropylene Injection Molded Parts

The ease with which modern plastics can be injection molded makes them very suitable for the production of many different products and, today, plastics are often used as substitutes for metal. Polypropylene (PP) is one of the most widely used thermoplastics globally since it is very useful, cost-effective and flexible for molding. However, the amount of harm to the environment caused by plastic waste has become phenomenal and the recycling of plastics has become a serious aspect of environmental protection. PP, as the most commonly used plastic material, was selected for use in this study. It has a melt flow index of 15 g/min and its recyclability, fluidity, and physical properties, as well as manufacturing conditions, were explored in relation to the number of times the material could be recycled (TR). A cavity pressure sensor was used to measure the viscosity index of the recycled plastic after multiple cycles of plasticizing and injection, part molding, scrap-recycling, and crushing. A paperclip-shaped test specimen was used to determine PP fluidity and crystallinity of specimens with different TRs. Tensile tests were used to detect differences in the tensile strength between specimens made from Raw-PP and recycled PP. The results showed that PP that had been recycled several times had a higher melt flow index, material fluidity, melting peak area, crystallinity, crystallization rate, and crystallization temperature. Repeated injection and recycling of the material had reduced the length of the molecular chains and broadened the molecular weight distribution. This improved the fluidity and increased crystallinity. The increase in fluidity made cavity filling easier, reducing the cavity pressure as well as the viscosity index. The results of this study showed that the recycling of the PP could improve the physical properties of the products to a degree and also went some way to further the benefits of a circular economy. The recycling of injection-molded PP material can be added to renewable energy technologies and used in environmental impact assessment.

Study on characteristics of temperature field in cargo tank during heating of cargo oil

In order to avoid the difficulties of unloading due to natural cooling and solidification of cargo oil in the process of shipping, the cargo oil is heated and insulated. In this paper, based on the heat transfer theory, and the fluid dynamics software FLUENT was used to establish a three-dimensional scale model to simulate the actual heating process of the cargo oil in the oil tank, and the change law of the temperature field of the cargo oil in the oil tank was calculated and analyzed.The results show that the temperature of cargo oil is approximately proportional to the heating time. During the heating process of the cargo oil, the rise of the temperature of the cargo oil leads to the increase of oil fluidity, and the oil above the heat source flows upward along the bulkhead, resulting in vortexes of different sizes. In the same heating time, the external temperature difference is 40 K, the oil temperature rise difference is 1.5 K. The variation of temperature field in the heating process of cargo oil is of engineering significance to improve heating efficiency, reduce operating cost and reduce environmental pollution.

Using the negative hydration of inorganic salt ions to improve the properties of Alkali-activated slag cement in plastic stage

Alkali-activated slag (AAS) cement is a low-carbon environmentally friendly cementitious material. Water glass (WG) activated slag cement has excellent physical and mechanical properties, but it is not conducive to the construction due to its rapid setting and hardening, easy loss of fluidity. Negative hydration ions can reduce the viscosity of aqueous solution. So, in the present paper, inorganic salt composed of negative hydration ions were used to adjust the fluidity and setting time of AAS paste. The results show that with the increase of NaCl, KCl, KBr and KNO3, the initial fluidity of AAS paste increases slightly, and the 30 min fluidity increases a lot, while the fluidity at 60 min is greatly affected by the amount of inorganic salt. KNO3 shows the greatest initial fluidity increase. When 0.2% Ba(NO3)2 is added with other four inorganic salts, the fluidity retention is significantly improved, especially the fluidity of 60 min. When 5% NaCl, KCl, KBr and KNO3 respectively mixed with 0.2% Ba(NO3)2 are added, the fluidity retention of AAS paste at 60 min are 97.4%, 92.7%, 100%, 82.5% respectively. Compared with the AAS paste without inorganic salt, when 5% NaCl, KCl, KBr and KNO3 respectively blended with 0.2% Ba(NO3)2 are added, the initial setting time increase by 228.6%, 285.7% 307.1% and 239.3%, while the final setting time increase by 175.6%, 222.0%, 231.7% and 178.0% respectively. With the inorganic salt, the ζ-potential of the originally negative AAS cement suspension become more negative, both yield stress and plastic viscosity coefficient decease, especially the plastic viscosity coefficient greatly reduces. This may be the reason for the change of fluidity and setting time of AAS paste.

Molecular dynamics simulation of waxy deposition in crude oil system

Understanding the phase transition and deposition behavior of crude oil system with waxy is of great significance to ensure the safe production and transportation of oil. In this paper, molecular dynamics simulation is employed to explore the deposition process of crude oil system with heterogeneous waxy on the solid surface. The results show that in a multiphase system, the morphology of paraffin wax crystals will change correspondingly at different system temperatures. At low-temperature, the paraffin molecules are arranged in an orderly manner, which are easier to form wax crystals, resulting in the density of the system that changes greatly. As the temperature increases, the aggregation of the wax molecules decreases, which makes the fluidity increase, and it is not easy to form wax crystals.

A selective Nile Red based solvatochromic probe: A study of fluorescence in LUVs and GUVs model membranes

In this work, a membrane probe (NR18) with a Nile Red-based chromophore, a long tail of 18 carbon atoms and a zwitterionic head was synthesized. The probe is optimized to remain anchored to the phospholipid bilayer without internalizing. NR18 was fully characterized chemically and optically and showed marked solvatochromism. Incorporation into model membranes of LUVs and GUVs having different compositions, demonstrated that the probe could be used to discriminate the lipid order in membranes, based on the fluorescent radiation emitted. Spectrophotometric and fluorimetric measurements on LUVs showed that the emission wavelength increases with temperature, confirming the increase in fluidity and hydration in membranes at higher temperatures. DFT simulations helped us to clarify the impact of NR18 on the membrane thickness and the order parameter showing that NR18 does not cause substantial perturbation in the bilayer. Moreover, we demonstrated that the presence of an enaminic terminal group is mainly responsible for the ability of NR18 to have a different fluorescence in Ld and Lo membranes.

Intergenerational Class Mobility of Labour Market Entrants in Germany and the UK since the 1950s

Abstract This study examines over-time trends in intergenerational class mobility based on cohorts of labour market entrants in Germany and the UK since the 1950s. We calculate absolute and relative mobility rates, separately for men and women, using the German Socio-Economic Panel (1984–2016), the UK Household Longitudinal Study (2009–2016), and the UK Labour Force Survey (2014–2017). Regarding absolute mobility, we find marked country differences in upward and downward rates. In Germany, downward mobility decreased, while upward mobility rose. In the UK, downward mobility increased, while upward mobility declined. We provide evidence that these differences can be linked to contrasting changes in the distribution of origin and destination classes. Regarding relative mobility, striking country similarities appear. For both countries, we observe increases in social fluidity for respondents entering the labour market during the 1950s and 1960s that cease to continue for cohorts thereafter. Comparisons between adjacent cohorts do not provide evidence that social fluidity follows cyclical developments of the economy or shorter-term volatilities in the labour market.

Synthesis of Alkyl Aliphatic Hydrazine and Application in Crude Oil as Flow Improvers

In this paper, alkyl aliphatic hydrazine, which is different from traditional polymer fluidity improver, was synthesized from aliphatic hydrazine and cetane bromide, and evaluated as a pour point and viscosity-reducer depressant for crude oil. The evaluation results showed that alkyl aliphatic hydrazone fully reduced the pour point and viscosity of crude oil with the increase of crude oil fluidity. The viscosity reduction rate of crude oil in Jinghe oilfield was 79.6%, and the pour point was reduced by about 11.3 °C. The viscosity reduction rate of crude oil in Xinjiang Oilfield was 74.7%, and the pour point was reduced by 8.0 °C. The long alkyl chain is beneficial to the eutectic of wax in crude oil, and the polar group inhibits the crystal growth, resulting in the decrease of pour point and viscosity. The waste oil is fully recycled into oilfield chemicals.

Social fluidity mobilizes contagion in human and animal populations.

Humans and other group-living animals tend to distribute their social effort disproportionately. Individuals predominantly interact with a small number of close companions while maintaining weaker social bonds with less familiar group members. By incorporating this behavior into a mathematical model, we find that a single parameter, which we refer to as social fluidity, controls the rate of social mixing within the group. Large values of social fluidity correspond to gregarious behavior, whereas small values signify the existence of persistent bonds between individuals. We compare the social fluidity of 13 species by applying the model to empirical human and animal social interaction data. To investigate how social behavior influences the likelihood of an epidemic outbreak, we derive an analytical expression of the relationship between social fluidity and the basic reproductive number of an infectious disease. For species that form more stable social bonds, the model describes frequency-dependent transmission that is sensitive to changes in social fluidity. As social fluidity increases, animal-disease systems become increasingly density-dependent. Finally, we demonstrate that social fluidity is a stronger predictor of disease outcomes than both group size and connectivity, and it provides an integrated framework for both density-dependent and frequency-dependent transmission.

Pharmacological Alteration of Cellular Mechanical Properties in Pulmonary Arterial Smooth Muscle Cells of Idiopathic Pulmonary Arterial Hypertension.

BackgroundIdiopathic pulmonary arterial hypertension (IPAH) is a progressive disease caused by vascular remodeling of the pulmonary arteries with elevated pulmonary vascular resistance. Recently, various pulmonary vasodilator drugs have become available in the clinical field, and have dramatically ameliorated the prognosis of IPAH. However, little is known about how the mechanical properties of pulmonary arterial smooth muscle cells (PASMCs) are altered under drug supplementation.MethodsAtomic force microscopy (AFM) was used to investigate the mechanical properties of PASMCs derived from a patient with IPAH (PAH-PASMCs) and a healthy control (N-PASMCs) which received the supplementation of clinically used drugs for IPAH: sildenafil, macitentan, and riociguat.ResultsPASMCs derived from PAH-PASMCs were stiffer than those derived from N-PASMCs. With sildenafil treatment, the apparent Young’s modulus (E0) of cells significantly decreased in PAH-PASMCs but remained unchanged in N-PASMCs. The decrease in E0 of PAH-PASMCs was also observed in macitentan and riociguat treatment. The stress relaxation AFM revealed that the decrease in E0 of PAH-PASMCs resulted from a decrease in the cell elastic modulus and/or increase in cell fluidity. The combination treatment of macitentan and riociguat showed an additive effect on cell mechanical properties, implying that this clinically accepted combination therapy for IPAH influences the intracellular mechanical components.ConclusionsPulmonary vasodilator drugs affect the mechanical properties of PAH-PASMCs, and there exists a mechanical effect of combination treatment on PAH-PASMCs.

Biomolecular changes and subsequent time-dependent recovery in hippocampal tissue after experimental mild traumatic brain injury

Traumatic brain injury (TBI) is the main cause of disability and mortality in individuals under the age of 45 years. Elucidation of the molecular and structural alterations in brain tissue due to TBI is crucial to understand secondary and long-term effects after traumatic brain injury, and to develop and apply the correct therapies. In the current study, the molecular effects of TBI were investigated in rat brain at 24 h and 1 month after the injury to determine acute and chronic effects, respectively by Fourier transform infrared imaging. This study reports the time-dependent contextual and structural effects of TBI on hippocampal brain tissue. A mild form of TBI was induced in 11-week old male Sprague Dawley rats by weight drop. Band area and intensity ratios, band frequency and bandwidth values of specific spectral bands showed that TBI causes significant structural and contextual global changes including decrease in carbonyl content, unsaturated lipid content, lipid acyl chain length, membrane lipid order, total protein content, lipid/protein ratio, besides increase in membrane fluidity with an altered protein secondary structure and metabolic activity in hippocampus 24 h after injury. However, improvement and/or recovery effects in these parameters were observed at one month after TBI.

Molecular Mechanisms of Apoptosis Induction and Its Regulation by Fatty Acids in Pancreatic β-Cells

Pancreatic β-cell failure and death contribute significantly to the pathogenesis of type 2 diabetes. One of the main factors responsible for β-cell dysfunction and subsequent cell death is chronic exposure to increased concentrations of FAs (fatty acids). The effect of FAs seems to depend particularly on the degree of their saturation. Saturated FAs induce apoptosis in pancreatic β-cells, whereas unsaturated FAs are well tolerated and are even capable of inhibiting the pro-apoptotic effect of saturated FAs. Molecular mechanisms of apoptosis induction by saturated FAs in β-cells are not completely elucidated. Saturated FAs induce ER stress, which in turn leads to activation of all ER stress pathways. When ER stress is severe or prolonged, apoptosis is induced. The main mediator seems to be the CHOP transcription factor. Via regulation of expression/activity of pro- and anti-apoptotic Bcl-2 family members, and potentially also through the increase in ROS production, CHOP switches on the mitochondrial pathway of apoptosis induction. ER stress signalling also possibly leads to autophagy signalling, which may activate caspase-8. Saturated FAs activate or inhibit various signalling pathways, i.e., p38 MAPK signalling, ERK signalling, ceramide signalling, Akt signalling and PKCδ signalling. This may lead to the activation of the mitochondrial pathway of apoptosis, as well. Particularly, the inhibition of the pro-survival Akt signalling seems to play an important role. This inhibition may be mediated by multiple pathways (e.g., ER stress signalling, PKCδ and ceramide) and could also consequence in autophagy signalling. Experimental evidence indicates the involvement of certain miRNAs in mechanisms of FA-induced β-cell apoptosis, as well. In the rather rare situations when unsaturated FAs are also shown to be pro-apoptotic, the mechanisms mediating this effect in β-cells seem to be the same as for saturated FAs. To conclude, FA-induced apoptosis rather appears to be preceded by complex cross talks of multiple signalling pathways. Some of these pathways may be regulated by decreased membrane fluidity due to saturated FA incorporation. Few data are available concerning molecular mechanisms mediating the protective effect of unsaturated FAs on the effect of saturated FAs. It seems that the main possible mechanism represents a rather inhibitory intervention into saturated FA-induced pro-apoptotic signalling than activation of some pro-survival signalling pathway(s) or metabolic interference in β-cells. This inhibitory intervention may be due to an increase of membrane fluidity.

The Fluidity of Aluminium Ductile Irons

The fluidity and the effective surface tension of Al-Ductile iron (Fe-3.2C-8.5Al-0.05Mg) were studied at different pouring temperatures. A fluidity test comprising strips 1, 2, 4-and 8-mm-thickness were molded in sodium silicate-bonded silica sand. Our results quantify the increase of melt fluidity with increasing casting modulus and pouring temperature and show that the effective surface tension of the alloy is about 1.8 N/m. Comparing this value with the surface tension of Si-ductile irons and Al-ductile irons of lower Al contents, we conclude that the high level of Al used in this study results in the formation of an alumina film on the advancing liquid front, which raises the effective surface tension, reduces fluidity by 100 mm and reduces the ability of the metal to enter narrow sections from 0.4 to 1.0 mm thickness.

Inhibition of Na+ /H+ exchanger isoform 3 improves gut fluidity and alkalinity in cystic fibrosis transmembrane conductance regulator-deficient and F508del mutant mice.

Constipation and intestinal obstructive episodes are major health problems in cystic fibrosis (CF) patients. Three FDA-approved drugs against constipation-prone irritable bowel syndrome were tested for their ability to increase luminal fluidity and alkalinity in cystic fibrosis transmembrane conductance regulator (CFTR) null (cftr-/- ) and F508del mutant (F508delmut/mut ) murine intestine. Guanylate cyclase C agonist linaclotide, PGE1 analogue lubiprostone and intestine-specific NHE3 inhibitor tenapanor were perfused through a ~3 cm jejunal, proximal or mid-distal colonic segment in anaesthetized cftr-/- , F508delmut/mut and WT mice. Net fluid balance was determined gravimetrically and alkaline output by pH-stat back titration. Basal jejunal fluid absorptive rates were significantly higher and basal HCO3- output was significantly lower in cftr-/- and F508delmut/mut compared to WT mice. In cftr-/- and F508delmut/mut mice, all three drugs significantly inhibited the fluid absorptive rate and increased alkaline output in the jejunum and tenapanor and lubiprostone, but not linaclotide, in the colon. After tenapanor pre-incubation, linaclotide elicited a robust fluid secretory response in WT jejunum, while no further change in absorptive rates was observed in cftr-/- and F508delmut/mut jejunum, suggesting that the increase in gut fluidity and alkalinity by linaclotide in CF gut is mediated via NHE3 inhibition. Lubiprostone also inhibited fluid absorption in cftr-/- and F508delmut/mut jejunum via NHE3 inhibition but had a residual NHE3-independent effect. Linaclotide, lubiprostone and tenapanor reduced fluid absorption and increased alkaline output in the CF gut. Their application may ameliorate constipation and reduce obstructive episodes in CF patients.

Preparation, characterization and release behavior of chitosan-coated nanoliposomes (chitosomes) containing olive leaf extract optimized by response surface methodology

The online version contains supplementary material available at (10.1007/s13197-021-04972-2).