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Respiratory Research Oct 2023The standard therapy for bronchial asthma consists of combinations of acute (short-acting ß-sympathomimetics) and, depending on the severity of disease, additional...
INTRODUCTION
The standard therapy for bronchial asthma consists of combinations of acute (short-acting ß-sympathomimetics) and, depending on the severity of disease, additional long-term treatment (including inhaled glucocorticoids, long-acting ß-sympathomimetics, anticholinergics, anti-IL-4R antibodies). The antidepressant amitriptyline has been identified as a relevant down-regulator of immunological T2-phenotype in asthma, acting-at least partially-through inhibition of acid sphingomyelinase (ASM), an enzyme involved in sphingolipid metabolism. Here, we investigated the non-immunological role of amitriptyline on acute bronchoconstriction, a main feature of airway hyperresponsiveness in asthmatic disease.
METHODS
After stimulation of precision cut lung slices (PCLS) from mice (wildtype and ASM-knockout), rats, guinea pigs and human lungs with mediators of bronchoconstriction (endogenous and exogenous acetylcholine, methacholine, serotonin, endothelin, histamine, thromboxane-receptor agonist U46619 and leukotriene LTD4, airway area was monitored in the absence of or with rising concentrations of amitriptyline. Airway dilatation was also investigated in rat PCLS by prior contraction induced by methacholine. As bronchodilators for maximal relaxation, we used IBMX (PDE inhibitor) and salbutamol (ß-adrenergic agonist) and compared these effects with the impact of amitriptyline treatment. Isolated perfused lungs (IPL) of wildtype mice were treated with amitriptyline, administered via the vascular system (perfusate) or intratracheally as an inhalation. To this end, amitriptyline was nebulized via pariboy in-vivo and mice were ventilated with the flexiVent setup immediately after inhalation of amitriptyline with monitoring of lung function.
RESULTS
Our results show amitriptyline to be a potential inhibitor of bronchoconstriction, induced by exogenous or endogenous (EFS) acetylcholine, serotonin and histamine, in PCLS from various species. The effects of endothelin, thromboxane and leukotrienes could not be blocked. In acute bronchoconstriction, amitriptyline seems to act ASM-independent, because ASM-deficiency (Smdp1) did not change the effect of acetylcholine on airway contraction. Systemic as well as inhaled amitriptyline ameliorated the resistance of IPL after acetylcholine provocation. With the flexiVent setup, we demonstrated that the acetylcholine-induced rise in central and tissue resistance was much more marked in untreated animals than in amitriptyline-treated ones. Additionally, we provide clear evidence that amitriptyline dilatates pre-contracted airways as effectively as a combination of typical bronchodilators such as IBMX and salbutamol.
CONCLUSION
Amitriptyline is a drug of high potential, which inhibits acute bronchoconstriction and induces bronchodilatation in pre-contracted airways. It could be one of the first therapeutic agents in asthmatic disease to have powerful effects on the T2-allergic phenotype and on acute airway hyperresponsiveness with bronchoconstriction, especially when inhaled.
Topics: Mice; Rats; Humans; Animals; Guinea Pigs; Bronchoconstriction; Methacholine Chloride; Amitriptyline; Histamine; Bronchodilator Agents; Serotonin; Acetylcholine; Sympathomimetics; 1-Methyl-3-isobutylxanthine; Dilatation; Lung; Asthma; Albuterol; Endothelins; Thromboxanes
PubMed: 37907918
DOI: 10.1186/s12931-023-02580-6 -
Frontiers in Bioscience (Landmark... Aug 2023A previously unstudied medicinal plant, (Berland.) I.M. Johnst. (Scrophulariaceae) was investigated to evaluate its potential in preventing and treating...
Neuroprotection against Aluminum Chloride-Induced Hippocampus Damage in Albino Wistar Rats by (Berl.) I.M. Johnst. Leaf Extracts: A Detailed Insight into Phytochemical Analysis and Antioxidant and Enzyme Inhibition Assays.
BACKGROUND
A previously unstudied medicinal plant, (Berland.) I.M. Johnst. (Scrophulariaceae) was investigated to evaluate its potential in preventing and treating neurodegenerative diseases, including Alzheimer's disease.
METHODS
Methanolic leaf extract (MELE) and its fractions (HELE, CHLE, and BULE) were evaluated for their polyphenolic content and antioxidant activity by five different methods, including enzyme inhibition assays, which are clinically linked to neurodegenerative diseases. The potentially active -butanol fraction (BULE) was further evaluated for its neuroprotective effects using an albino rat animal model and phytoconstituents profiling using Liquid chromatography with tandem mass spectrometry (LC-MS/MS), and molecular docking by Maestro® Schrödinger.
RESULTS
The -butanol fraction (BULE) in the hydroalcoholic leaf extract exhibited the highest total phenolic content (230.435 ± 1.575 mg gallic acid equivalent gm-1± SD). The chloroform leaf extract exhibited the highest total flavonoid content (293.343 ± 3.756 mg quercetin equivalent gm-1± SD) as well as the highest antioxidant content, which was equivalent to Trolox, with five assay methods. Similarly, the chloroform and n-butanol fractions from the hydroalcoholic leaf extract significantly inhibited human acetylcholinesterase and butyrylcholinesterase with their IC50 values of 12.14 ± 0.85 and 129.73 ± 1.14 µg∙mL-1, respectively. The study revealed that BULE exhibited a significant neuroprotective effect at doses of 200 and 400 mg/kg/day in an aluminum chloride-induced neurodegenerative albino rat model. The LC-MS/MS analysis of BULE tentatively confirmed the presence of biologically active secondary metabolites, such as theobromine, propyl gallate, quercetin-3-O-glucoside, myricetin-3-acetylrhamnoside, isoquercitrin-6'-O-malonate, diosmetin-7-O-glucuronide-3'-O-pentose, pinoresinol diglucoside, asarinin, eridictoyl, epigallocatechin, methyl gallate derivative, and eudesmin. The results from the computational molecular docking of the identified secondary metabolites revealed that diosmetin-7-O-glucuronide-3'-O-pentose had the highest binding affinity to human butyrylcholinesterase, while isoquercetin-6'-O-malonate had the highest to human acetylcholinesterase, and pinoresinol diglucoside to human salivary alpha-amylase.
CONCLUSIONS
The present study concluded a need for further exploration into this medicinal plant, including the isolation of the bioactive compounds responsible for its neuroprotective effects.
Topics: Rats; Animals; Humans; Antioxidants; Neuroprotection; Neuroprotective Agents; Acetylcholinesterase; Aluminum Chloride; Butyrylcholinesterase; 1-Butanol; Chloroform; Chromatography, Liquid; Glucuronides; Molecular Docking Simulation; Tandem Mass Spectrometry; Hippocampus; Scrophulariaceae; Plant Extracts
PubMed: 37664939
DOI: 10.31083/j.fbl2808184 -
ACS Omega Sep 2023Methylene blue (MB) dye or methyl thioninium chloride is one of the hazardous cationic dyes that are discharged into the textile effluent causing a highly negative...
Methylene blue (MB) dye or methyl thioninium chloride is one of the hazardous cationic dyes that are discharged into the textile effluent causing a highly negative environmental impact. The present work targets the investigation of the adsorption performance of some chitosan-modified products toward the MB dye from simulated solutions. The claimed chitosan derivatives were prepared, characterized, and applied for the removal of lead and copper cations from an aqueous medium in a previous work. These include: ,-carboxymethyl chitosan (,-CM/Cs), chitosan grafted with glutaraldehyde (Cs/GA), chitosan cross-linked with GA/epichlorohydrin (Cs/GA/ECH), and chitosan cross-linked with glutaraldehyde/methylene bis(acrylamide) (Cs/GA/MBA). The modified chitosan derivatives in this study displayed outstanding mechanical qualities, exceptional reusability, and a significant amount of adsorption capacity. The ability of prepared Cs derivatives to eradicate MB was as follows: ,-CM/Cs (95.1 mg/g) < Cs/GA (120.1 mg/g) < Cs/GA/ECH (220.1 mg/g) < Cs/GA/MBA (270.0 mg/g). The swelling performance of the prepared sorbents was verified under different experimental conditions, and the data revealed that the maximum swelling was attained at pH = 9, temperature 55 °C, and after 24 h. The produced Cs derivatives showed exceptional reusability by maintaining higher adsorption effectiveness throughout five cycles. The MB dye was adsorbed onto the modified derivatives according to pseudo-second-order kinetics and the Langmuir model. Moreover, the adsorption process was monitored via atomic force microscopy to verify the differences between the dye-free and dye-loaded adsorbents.
PubMed: 37744862
DOI: 10.1021/acsomega.3c03735 -
Organometallics Nov 2023Protolysis of AlMe or AlBu with 2-diisopropylphosphinopyrrole (1) yields molecules containing two flanking phosphines and a central Al-Me (2-Me), Al-Bu (2-Bu), or Al-H...
Protolysis of AlMe or AlBu with 2-diisopropylphosphinopyrrole (1) yields molecules containing two flanking phosphines and a central Al-Me (2-Me), Al-Bu (2-Bu), or Al-H (2-H) unit. The reactions of 2-Me with [LMCl] (L = cyclooctene or 1/2 1,5-cyclooctadiene and M = Rh or Ir) in the presence of pyridine produces PAlP pincer complexes (3-Rh and 3-Ir) with Al-Cl and M-Me bonds. The analogous reaction of a mixture of 2-Bu and 2-H with [LMCl] and pyridine resulted in the formation of analogous Rh-H (4-Rh) and Ir-H (4-Ir) complexes. Treatment of 3-Rh with NaBEtH produced compound 5-Rh with an Al-Me and a Rh-H bond; the analogous reaction of 3-Ir did not result in a clean product. 4-Ir accepted an equivalent of H to produce 6-Ir with two terminal Ir-H bonds and one bridging Al-H-Ir moiety, whereas 4-Rh did not react with H. The density functional theoretical treatment is in accord with this finding, highlights the likely mechanism for the H addition, and supports the bonding picture in 6-Ir arising from NMR and X-ray diffraction (XRD) observations. Spectroscopic data and XRD studies are consistent with distorted square-pyramidal structures (about Rh or Ir) for compounds 3-5, with an alane occupying the apical position. Complexes 3 and 4 possess some of the shortest known Rh-Al or Ir-Al distances.
PubMed: 38357656
DOI: 10.1021/acs.organomet.3c00359 -
RSC Advances Dec 2023Gas sensors are used to detect gas components in human breath to diagnose diseases, such as cancers. However, choosing suitable two-dimensional materials for gas sensors...
Gas sensors are used to detect gas components in human breath to diagnose diseases, such as cancers. However, choosing suitable two-dimensional materials for gas sensors is a challenge. Germanene can be a good candidate because of its outstanding electronic and structural properties. Based on the density functional theory calculations with various schemes, such as PBE + vdW-DF2, HSE06 + PBE, and HSE06 + vdW-DF2, we elucidated the structural and electronic properties of germanene substrates (perfect, vacancy-1, and vacancy-2) while adsorbing hepatocellular carcinoma-related volatile organic compounds (VOCs), , acetone, 1,4-pentadiene, methylene chloride, phenol, and allyl methyl sulfide. These gases have been selected for investigation because of their most frequent occurence in diagnosing the disease. We found that vacancy substrates enhanced the adsorption strength of the VOCs compared to the perfect one, where the phenol adsorbed most strongly and exhibited the most profound influence on the structural deformation of the substrates over the other VOCs. Besides, the adsorbed VOCs significantly modified the energy bandgap of the considered germanene substrates. In particular, the gases, except allyl methyl sulfide, vanished the bandgap of the vacancy-1 germanene and converted this substrate from a semiconductor to a metal, while they widened the bandgap of the vacancy-2 structure compared to the isolated case. Therefore, the perfect and vacancy-2 germanene sheets could maintain their semiconducting state upon gas adsorption, implying that these substrates may be suitable candidates for gas sensing applications. The nature of the interaction between the VOCs and the germanene substrates is a physical adsorption with a weak charge exchange, which mainly comes from the contribution of the p orbital of the VOCs and the p orbital of Ge.
PubMed: 38090092
DOI: 10.1039/d3ra05927h -
ACS Omega Oct 2023Eutectic solvent systems are versatile solvents that have found widespread use in numerous applications. Traditional solvents are homogeneous, having only one component,...
Eutectic solvent systems are versatile solvents that have found widespread use in numerous applications. Traditional solvents are homogeneous, having only one component, and their chemistry is relatively simple, with some exceptions. On the other hand, deep eutectic solvents (DESs) comprise binary components, generally a donor and an acceptor in hydrogen bonding with varying ratios. The interaction chemistry among the donor and acceptor involved in hydrogen bonding in DESs is complicated. Although numerous research is focused on the synthesis and application of DESs, few studies are reported to elucidate the complex structure and dynamic and interaction behavior of DESs. In this study, we employed calorimetry, vibrational spectroscopy techniques including FTIR and Raman, and nuclear magnetic resonance to derive insight into the structural feature and noncovalent contact of choline chloride (ChCl) and citric acid (CA) while they formed DESs. The 1:1 ChCl/CA eutectic system showed phase transitions and melting peaks with the most pronounced peak at 156.22 °C, suggesting the DESs melting at a lower temperature than the melting temperatures of ChCl and CA. In addition to IR and Raman findings, H NMR investigations demonstrate hydrogen bonding intermolecular interactions between ChCl and CA, supporting the formation of 1:1 ChCl/CA DESs based on the deshielded chemical shifts of the proton for Ch. The interaction of the chloride anion with the methyl protons (H4) and methylene protons (H3) of ChCl as well as the strong hydrogen bonding interactions between the hydroxyl hydrogen (H1) of ChCl with one of CA's carbonyl oxygens both supported the formation of conformer E. In addition, molecular dynamics followed by the density functional theory (DFT) was employed to visualize the structure and interaction of DESs using the ωB97XD theory and 6-311++G (d,p) basis set. Both experimental and theoretical IR, Raman, and structural analyses provided evidence of the formation of DESs by possessing hydrogen bonds. These multifaceted experimental and computational investigations provide details of structural and intermolecular interactions of ChCl/CA DESs.
PubMed: 37867676
DOI: 10.1021/acsomega.3c04570 -
Molecules (Basel, Switzerland) Dec 2023Lily is one of the most important cut flowers in the world, with a rich floral fragrance. To further explore the fragrance emission mechanisms of lily cultivars,...
Lily is one of the most important cut flowers in the world, with a rich floral fragrance. To further explore the fragrance emission mechanisms of lily cultivars, headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and organic solvent extraction-gas chromatography-mass spectrometry (OSE-GC-MS) were used to unveil the volatile organic compounds (VOCs) and endogenous extracts of seven lily cultivars. Furthermore, real-time quantitative PCR (qRT-PCR) was used to determine the expression levels of two key genes ( and ) related to the biosynthesis of monoterpenoids and methyl benzoate. The results show that forty-five VOCs were detected in the petals of seven lily cultivars, and the main compounds were monoterpenoids and phenylpropanoids/benzenoids. Dichloromethane was the best solvent for extracting the endogenous extracts of 'Viviana' petals and eighteen endogenous extracts were detected using dichloromethane to extract the petals of seven lily cultivars. Each compound's emission ratio (natural logarithm of the ratio of VOC content to endogenous extract content) was calculated, and linear regression analyses between emission ratios and boiling points were conducted. Significant linear negative correlations existed between the emission ratios and boiling points of compounds, and the regression equations' coefficients of determination () were all greater than 0.7. was expressed highly in 'Viviana', 'Pink News', and 'Palazzo', and was expressed highly in 'Pink News' and 'Palazzo'. Correlation analyses between the gene expression levels and the monoterpenoids and methyl benzoate contents found that the expression levels have strong positive correlations with monoterpenoids content, while no correlations were found between the expression levels of and the contents of methyl benzoate. This study lays the foundation for research on the release patterns of VOCs in the flowers of , and the breeding of lilies for their floral fragrance.
Topics: Lilium; Volatile Organic Compounds; Methylene Chloride; Plant Breeding; Flowers; Solid Phase Microextraction; Solvents; Monoterpenes
PubMed: 38138428
DOI: 10.3390/molecules28247938 -
ACS Omega Oct 2023The effect of the ionic liquids (ILs) 1-methyl-3-tetradecylimidazolium chloride ([CMIM][Cl]), 1-dodecyl-3-methylimidazolium chloride ([CMIM][Cl]), and...
The effect of the ionic liquids (ILs) 1-methyl-3-tetradecylimidazolium chloride ([CMIM][Cl]), 1-dodecyl-3-methylimidazolium chloride ([CMIM][Cl]), and 1-decyl-methylimidazolium chloride ([CMIM][Cl]) on the structure of bovine serum albumin (BSA) was investigated by fluorescence spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, small-angle X-ray scattering (SAXS), and molecular dynamics (MD) simulations. Concerning the fluorescence measurements, we observed a blue shift and a fluorescence quenching as the IL concentration increased in the solution. Such behavior was observed for all three studied imidazolium-based ILs, being larger as the number of methylene groups in the alkyl chain increased. UV-vis absorbance measurements indicate that even at relatively small IL/protein ratios, like 1:1 or 1:2, ([CMIM][Cl]) is able to change, at least partially, the sample turbidity. SAXS results agree with the spectroscopic techniques and suggest that the proteins underwent partial unfolding, evidenced by an increase in the radius of gyration () of the scattering particle. In the absence and presence of ([CMIM][Cl]) = 3 mM BSA increases from 29.1 to 45.1 Å, respectively. Together, these results indicate that the interaction of BSA with ILs is divided into three stages: the first stage is characterized by the protein in its native form. It takes place for protein/IL ≤ 1:2, and the interaction is predominantly due to the electrostatic forces provided by the negative charges on the surface of BSA and the cationic polar head of the ILs. In the second stage, higher IL concentrations induce the unfolding of the protein, most likely inducing the unfolding of domains I and III, in such a way that the protein's secondary structure is kept almost unaltered. In the last stage, IL micelles start to form, and therefore, the interaction with protein reaches a saturation point and free micelles may be formed. We believe that this work provides new information about the interaction of ILs with BSA.
PubMed: 37867681
DOI: 10.1021/acsomega.3c04188 -
Acta Crystallographica. Section E,... Sep 2023In the hydrated title salt, CHNS ·Cl·HO, the asymmetric unit comprises one 2-amino-5-{(1)-1-[(carbamo-thioyl-amino)-imino]-eth-yl}-4-methyl-1,3-thia-zol-3-ium cation,...
In the hydrated title salt, CHNS ·Cl·HO, the asymmetric unit comprises one 2-amino-5-{(1)-1-[(carbamo-thioyl-amino)-imino]-eth-yl}-4-methyl-1,3-thia-zol-3-ium cation, one chloride anion and one water mol-ecule of crystallization. The cation is nearly flat (r.m.s. deviation of non-H atoms is 0.0814 Å), with the largest deviation of 0.1484 (14) Å observed for one of the methyl C atoms. In the crystal, the cations are linked by O-H⋯Cl, N-H⋯Cl, N-H⋯O, N-H⋯S and C-H⋯S hydrogen bonds, forming a tri-periodic network. The most important contributions to the crystal packing are from H⋯H (35.4%), S⋯H/H⋯S (24.4%), N⋯H/H⋯N (8.7%), Cl⋯H/H⋯Cl (8.2%) and C⋯H/H⋯C (7.7%) inter-actions.
PubMed: 37693676
DOI: 10.1107/S2056989023007090 -
Polymers Sep 2023Excellent mechanical properties and self-healing properties are very important for the practical application of hydrogel flexible sensors. In this study, acrylic acid...
Excellent mechanical properties and self-healing properties are very important for the practical application of hydrogel flexible sensors. In this study, acrylic acid and stearyl methyl acrylate were selected as monomers to synthesize hydrophobic association hydrogels, and multi-physically cross-linked hydrogels were synthesized by adding ferric chloride and polyvinyl alcohol to introduce ion interaction and a hydrogen bond cross-linking network. The hydrogels were characterized by FTIR, XRD and SEM, and the mechanical properties and self-healing properties were tested using a universal testing machine. It was confirmed that the strength of the hydrogel was significantly improved with the addition of ferric chloride and polyvinyl alcohol, and the hydrogel still showed good self-healing properties. Further testing of its application as a conductive sensor has demonstrated sensitive and stable motion sensing capabilities. This provides an important reference for high-performance hydrogel sensors with both high strength and self-healing properties.
PubMed: 37765600
DOI: 10.3390/polym15183748