Experimental Model For Study Research Articles

A comprehensive experimental and kinetic modeling study of di-isobutylene isomers: Part 1

Di-isobutylene has received significant attention as a promising fuel blendstock, as it can be synthesized via biological routes and is a short-listed molecule from the Co-Optima initiative. Di-isobutylene is also popularly used as an alkene representative in multi-component surrogate models for engine studies of gasoline fuels. However, there is limited experimental data available in the literature for neat di-isobutylene under engine-like conditions. Hence, most existing di-isobutylene models have not been extensively validated, particularly at lower temperatures (< 1000 K). Most gasoline surrogate models include the di-isobutylene sub-mechanism published by Metcalfe et al. [1] with little or no modification. The current study is undertaken to develop a detailed kinetic model for di-isobutylene and validate the model using a wide range of relevant experimental data. Part 1 of this study exclusively focuses on the low- to intermediate temperature kinetics of di-isobutylene. An upcoming part 2 discusses the high-temperature model development and validation of the relevant experimental targets. Ignition delay time measurements for the di-isobutylene isomers were performed at pressures ranging from 15 – 30 bar at equivalence ratios of 0.5, 1.0, and 2.0 diluted in air and in the temperature range 650 – 900 K using two independent rapid compression machine facilities. In addition, measurements of species identified during the oxidation of these isomers were performed in a jet-stirred reactor and in a rapid compression machine. A detailed kinetic model for the di-isobutylene isomers is developed to capture the wide range of new experimental targets. For the first time, a comprehensive low-temperature chemistry submodel is included. The differences in the important reaction pathways for the accurate prediction of the oxidation of the two DIB isomers are compared using reaction path analysis. The most sensitive reactions controlling the ignition delay times of the DIB isomers under the pressure and temperature conditions necessary for autoignition in engines are identified.

An experimental and detailed kinetic modeling study of the pyrolysis and oxidation of DMF over a wide range of conditions

A new chemical kinetic mechanism of DMF (N, N-dimethylformamide) is proposed. To assess the reliability of the mechanism, high pressure shock tube, single pulse shock tube and constant volume reactor were used to experimentally evaluate ignition delay times, high temperature pyrolysis, and laminar flame speeds of DMF, respectively. Ignition delay times of DMF/ “air” were measured for equivalence ratios of 0.5, 1.0, and 2.0, pressures of 2.0 and 10.0 bar, and temperature ranging from 900 to 1430 K. Additionally, ignition delay times of DMF/acetone/air were measured for equivalence ratios of 0.5 and 1.0, pressures of 2.0 and 10.0 bar, and temperature ranging from 900 to 1430 K. High temperature pyrolysis products of DMF/acetone mixtures, diluted in argon, were studied at 5.0 bar, temperatures between 1000 and 1600 K. Flame speed measurements of DMF/air were obtained for pressures of 100 and 200 kPa, temperatures of 398, 423, and 448 K, and equivalence ratios from 0.7 to 1.4. Simultaneously, a chemical kinetics mechanism was developed to simulate the experimental results using ChemKin Pro, with sensitivity and flux analysis being carried out to elucidate limitations and possible refinements.

Experimental and Kinetic Modeling Study on High-Temperature Autoignition of Cyclohexene.

Cyclohexene is an important intermediate during the oxidation of cycloalkanes, which comprise a significant portion of real fuels. Thus, experimental data sets and kinetic models of cyclohexene play an important role in the understanding of the combustion of cycloalkanes and real fuels. In this work, an experimental and kinetic modeling study of the high-temperature ignition of cyclohexene is performed. Ignition delay time (IDT) measurements are carried out in a high-pressure shock tube (HPST). The studied pressures are 5, 10, and 20 bar; the equivalence ratios are 0.5, 1.0, and 2.0; and the temperatures range from 980 to 1400 K for IDT in HPST. It is shown that the IDTs of cyclohexene exhibit Arrhenius behaviors as a function of temperature, and the IDTs decrease as the equivalence ratio and pressure increase. The experimental results are simulated using three previous detailed kinetic mechanisms and an updated detailed mechanism in this work. The updated detailed kinetic mechanism exhibits good agreement with experimental results. Reaction path analysis and sensitivity analysis are performed to provide insights into the chemical kinetics controlling the ignition of cyclohexene. The results demonstrate that different detailed kinetic mechanisms are significantly different, and there are still no unified conclusions about the major reaction path for cyclohexene oxidation. However, it is worth noting that the abstraction reaction by oxygen at the allylic site and the submechanism of cyclopentene are of significant importance for the accurate prediction of IDTs of cyclohexene. The present experimental data set and kinetic model should be valuable to improve our understanding of the combustion chemistry of cycloalkanes.

Controlling axonal regeneration with acellular nerve allograft limits neuroma formation in peripheral nerve transection: An experimental study in a swine model.

Symptomatic neuromata are a common indication for revision surgery following amputation. Previously described treatments, including traction neurectomy, nerve transposition, targeted muscle re-innervation, and nerve capping, have provided inconsistent results or are technically challenging. Prior research using acellular nerve allografts (ANA) has shown controlled termination of axonal regrowth in long grafts. The purpose of this study was to determine the ability of a long ANA to prevent neuroma formation following transection of a peripheral nerve in a swine model. Twenty-two adult female Yucatan miniature swine (Sus scrofa; 4-6months, 15-25 kg) were assigned to control (ulnar nerve transection only, n= 10), treatment (ulnar transection and coaptation of 50 mm ANA, n= 10), or donor (n= 2) groups. Nerves harvested from donor group animals were treated to create the ANA. After 20 weeks, the transected nerves including any neuroma or graft were harvested. Both qualitative (nerve architecture, axonal sprouting) and quantitative histologic analyses (myelinated axon number, cross sectional area of nerve tissue) were performed. Qualitative histologic analysis of control specimens revealed robust axon growth into dense scar tissue. In contrast, the treatment group revealed dwindling axons in the terminal tissue, consistent with attenuated neuroma formation. Quantitative analysis revealed a significantly decreased number of myelinated axons in the treatment group (1232 ± 540) compared to the control group (44,380 ± 7204) (p< .0001). Cross sectional area of nerve tissue was significantly smaller in treatment group (2.83 ± 1.53 mm2 ) compared to the control group (9.14 ± 1.19 mm2 ) (p= .0012). Aberrant axonal growth is controlled to termination with coaptation of a 50 mm ANA in a swine model of nerve injury. These early results suggest further investigation of this technique to prevent and/or treat neuroma formation.

Efficacy of Tui-na for Treatment of Osteoarthritis: A Systematic Review and Meta-analysis

Osteoarthritis (OA) is one of the most common causes for chronic joint pain in canine patients. The objective of this systematic review and meta-analysis study was to determine whether Tui-na can be an effective treatment for osteoarthritis when performed alone or part of a multi-modal approach. All studies using Tui-na as a treatment for OA published in peer-reviewed journals were considered in initial search results. To be included in the meta-analysis, the study must have reported statistical results associated with one of the following endpoints: 1) relief of pain; 2) improvement of mobility; 3) improved quality of life. There were 10 articles in experimental OA animal models and 18 in human clinical studies that met inclusion criteria. Overall p-value on experimental OA animal model studies was 4.47×10-11, suggesting that Tui-na treatments were significantly effective when compared to model control animals not receiving treatments. Overall p-value on human studies was 6.74×10-13, also suggesting that Tui-na treatments can be effective for treating OA-related diseases in human patients. With treatment effective rate available in 14 human studies, meta-analysis performed with effect size model revealed a significant overall group effect (p = 6.72×10-10), suggesting patients treated with Tui-na can have a higher effective rate than those treated without receiving Tui-na. The positive results on experimental model and human clinical studies indicate that Tui-na treatments have potential to be an effective treatment option for veterinary patients with OA conditions.

Metabolic Injury of Hepatocytes Promotes Progression of NAFLD and AALD.

Nonalcoholic liver disease is a component of metabolic syndrome associated with obesity, insulin resistance, and hyperlipidemia. Excessive alcohol consumption may accelerate the progression of steatosis, steatohepatitis, and fibrosis. While simple steatosis is considered a benign condition, nonalcoholic steatohepatitis with inflammation and fibrosis may progress to cirrhosis, liver failure, and hepatocellular cancer. Studies in rodent experimental models and primary cell cultures have demonstrated several common cellular and molecular mechanisms in the pathogenesis and regression of liver fibrosis. Chronic injury and death of hepatocytes cause the recruitment of myeloid cells, secretion of inflammatory and fibrogenic cytokines, and activation of myofibroblasts, resulting in liver fibrosis. In this review, we discuss the role of metabolically injured hepatocytes in the pathogenesis of nonalcoholic steatohepatitis and alcohol-associated liver disease. Specifically, the role of chemokine production and de novo lipogenesis in the development of steatotic hepatocytes and the pathways of steatosis regulation are discussed.

Toward the cholinesterase inhibition potential of TADDOL derivatives: Seminal biological and computational studies

Alzheimer's disease (AD) is a degenerative neurological disease characterized by gradual loss of cognitive skills and memory. The exact pathogenesis involved still remains unrevealed, but several studies indicate the involvement of an array of different enzymes, underlining the multifactorial character of the disease. Inhibition of these enzymes is therefore a powerful approach in the development of AD treatments, with promising candidates, including acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase. Interestingly, AChE is the target of a major pesticide family (organophosphates), with several reports indicating an intersection between the pesticide's activity and AD. In this study, various TADDOL derivatives were synthesized and their in vitro activities as AChE/BuChE inhibitors as well as their antioxidant activities were studied. Molecular modeling studies revealed the capability of TADDOL derivatives to bind to AChE and induce inhibition, especially compounds 2b and 3c furnishing IC50 values of 36.78 ± 8.97 and 59.23 ± 5.31 µM, respectively. Experimental biological activities and molecular modeling studies clearly demonstrate that TADDOL derivatives with specific stereochemistry have an interesting potential for the design of potent AChE inhibitors. The encouraging results for compounds 2b and 3c indicate them as promising scaffolds for selective and potent AChE inhibitors.

Experimental and kinetic modeling study of laminar burning velocity enhancement by ozone additive in NH3+O2+N2 and NH3+CH4/C2H6/C3H8+air flames

Ammonia (NH3) is regarded as a promising future carbon-free fuel but needs to overcome drawbacks including extremely low burning velocity in practical combustion apparatus. In this study, ozone (O3) additive is used to elucidate one of the mechanisms of potential flame enhancement method based on plasma-assisted combustion. The effects of ozone addition on the laminar burning velocity of premixed NH3/(35%O2/65%N2) and NH3+ CH4/C2H6/C3H8+air flames over a wide range of equivalence ratios were investigated experimentally and numerically. Blending NH3 with hydrocarbons can decrease the ignition energy and increase the burning velocities of the whole mixture, which may contribute to developing ammonia co-fired mechanisms with varied complex fuels and validating the feasibility of NH3 using strategies in real applications. Measurements were conducted at atmospheric conditions using the Heat Flux method. For NH3/(35%O2/65%N2) flames, a significant increase was found on the fuel-lean side. Experimental data showed that maximum enhancement reaches 15.34% at ϕ=0.6 with 5000 ppm O3 additive. For NH3+CH4/C2H6/C3H8+air blended flames, the enhancement effect was much more profound under off-stoichiometric conditions, being 1.5–4 times higher than that under near-stoichiometric conditions. A 28-step O3 related kinetic sub-mechanism was integrated with five selected NH3-oxidation mechanisms to simulate the burning velocities of NH3/(35%O2/65%N2) flames and CEU-Mech for NH3+CH4/C2H6/C3H8+air flames. Simulation results show improved agreement with the experimental data, especially for fuel-rich conditions as NH3 blending ratio xNH3 increases from 0 to 0.9. Each of the NH3/CH4/air, NH3/C2H6/air and NH3/C3H8/air cases fits well between experimental data and numerical results with varied NH3-fuel blending ratios. Detailed kinetic analyses adopting the CEU-NH3−Mech integrated with O3 sub-mechanism were carried out and revealed that active radicals such as HNO, which are rapidly produced due to high O concentration from O3 decomposing in the pre-heating zone, interfered with the ammonia-fuel chemistry and thus evidently promoted the overall combustion process.

Experimental and kinetic modeling study of the CH4+H2S+air laminar burning velocities at atmospheric pressure

With the increasing demand for natural gas and depletion of many sweet gas fields, direct usage of sour gas, usually containing a large percentage of hydrogen sulfide (H2S), becomes a more economical choice in recent years. However, the laminar burning velocity (SL) of CH4+H2S flames have seldom been investigated due to the corrosivity and toxicity of H2S, and no available experimental data can be found for these mixtures burnt in the air. In this work, the laminar burning velocities of CH4+H2S+air flames were measured using the heat flux method at 1 atm and 298 K. The experimental data were obtained at various equivalence ratios and xH2S = 0–0.25, where xH2S refers to the mole fraction of H2S in the fuel. Simulations using a detailed mechanism of Mulvihill et al. (2019) were carried out, showing good agreement with the present experimental results. Kinetic analyses of A-factor SL reaction sensitivities, reaction pathways, and dominant intermediate species pointed out the importance of the C- and S-containing species interactions. To overcome the convergence problem of the Mulvihill mechanism, an examination of the unphysical reactions and species was carried out, which could be alleviated by making several reactions that violate the collision limit irreversible, accompanied by updating the heat capacity data. It's also found that substituting the hydrocarbon subset of the Mulvihill mechanism with mechanisms from FFCM-1, Konnov, San Diego, as well as Aramco noticeably deteriorates the simulation results due to the selection of different reaction rate constants.

Emerging accessibility patterns in long telomeric overhangs

We present single-molecule experimental and computational modeling studies investigating the accessibility of human telomeric overhangs of physiologically relevant lengths. We studied 25 different overhangs that contain 4-28 repeats of GGGTTA (G-Tract) sequence and accommodate one to seven tandem G-quadruplex (GQ) structures. Using the FRET-PAINT method, we probed the distribution of accessible sites via a short imager strand, which is complementary to a G-Tract and transiently binds to available sites. We report accessibility patterns that periodically change with overhang length and interpret these patterns in terms of the underlying folding landscape and folding frustration. Overhangs that have [4n]G-Tracts, (12, 16, 20…) demonstrate the broadest accessibility patterns where the peptide nucleic acid probe accesses G-Tracts throughout the overhang. On the other hand, constructs with [4n+2]G-Tracts, (14, 18, 22…) have narrower patterns where the neighborhood of the junction between single- and double-stranded telomeres is most accessible. We interpret these results as the folding frustration being higher in [4n]G-Tract constructs compared to [4n+2]G-Tract constructs. We also developed a computational model that tests the consistency of different folding stabilities and cooperativities between neighboring GQs with the observed accessibility patterns. Our experimental and computational studies suggest the neighborhood of the junction between single- and double-stranded telomeres is least stable and most accessible, which is significant as this is a potential site where the connection between POT1/TPP1 (bound to single-stranded telomere) and other shelterin proteins (localized on double-stranded telomere) is established.

Analysis of Peripheral Blood Basophils in Pediatric Systemic Lupus Erythematosus.

Basophils are the least abundant circulating leukocytes, and their immunological role has not yet been completely elucidated. There is evidence supporting their immunomodulatory role in several pathological settings; recently, studies in both experimental models and humans suggested that basophil homeostasis may be altered in systemic lupus erythematosus (SLE). Here, we first assessed circulating basophils in children affected with pediatric SLE (pSLE). In this cross-sectional study, circulating basophils were enumerated by fluorescence-based flow cytometry analysis in children affected with pSLE, in addition to children suffering from juvenile idiopathic arthritis (JIA) or non-inflammatory/non-rheumatic conditions. This study included 52 pediatric patients distributed in these three groups. We observed a statistically significant reduction of peripherally circulating basophils in children with pSLE compared to the other two groups of patients. This preliminary study is consistent with the available studies in adult patients with SLE showing a reduced number of circulating basophils. However, further research is needed to draw final conclusions on basophils’ homeostasis in pSLE, in addition to their correlation with the disease activity and concomitant therapies.

Bending and torsional vibration attenuation of multi-panel deployable solar array using reaction wheel actuators

PurposeThis paper aims to present a multi-axis actuating approach to attenuate the bending and torsional vibration of the solar array through the reaction wheel (RW) actuators.Design/methodology/approachThe motion equation of the solar array with the RW actuators is derived in modal coordinates for controller design. The reaction torques, induced by the speed change of the RW actuators, are controlled for vibration attenuation through the constraints on the actuators’ rotating speed. The proposed control approach is firstly verified with numerical simulation on the finite element model of a full-scale solar array. Experimental study of a simplified elastic plate model is subsequently performed for feasibility and validity investigation.FindingsBoth the numerical and experimental studies demonstrated the success of adopting RW as the actuator. Results from numerical simulation reveal that the vibration response peak can be reduced by 80% with 2% of mass increase by using the RW actuators.Practical implicationsIt is demonstrated that the multi-axis actuating method using RW actuators has a great potential in vibration attenuation of the multi-panel deployable solar array.Originality/valueAn approach to reduce bending and torsional vibration of solar array based on RW actuators is investigated. Theoretical analysis, numerical simulation and experimental study are conducted to demonstrate the validity of the proposed vibration attenuation approach and its potential application in the spacecraft design.

Experimental and kinetic model studies on the pyrolysis of 2-furfuryl alcohol at two reactors: Flow reactor and jet-stirred reactor

2-Furfuryl alcohol, derived from non-edible biomass, is the significant component of bio-oil in the pyrolysis of lignocellulose biomass and a potential alternative fuel or fuel additive. To better optimize the pyrolysis model of lignocellulose to improve the properties of pyrolysis bio-oil and further understand the combustion characteristics of 2-furfuryl alcohol, the pyrolysis experiments were performed in a flow reactor at 30 Torr for T = 1006 – 1339 K and 760 Torr for T = 850 – 1131 K, and in a jet-stirred reactor at 760 Torr for T = 750 – 1050 K. The pyrolysis products, including radicals (methyl, propargyl, allyl, and cyclopentadienyl), isomers (furfural/2-ethyl furan, furan/vinyl ketene, and allene/propyne), and aromatics (benzene, toluene, indene, etc.) were identified and measured using synchrotron vacuum ultraviolet photoionization mass spectrometry. A comprehensive kinetic model for 2-furfuryl alcohol pyrolysis was developed and was validated against the experimental data in the present and previous work. Rate of production analysis indicated that the C–O bond dissociation reaction, H-abstraction reactions on the hydroxymethyl group, and the H-addition reactions on the furan-ring controlled the consumption of 2-furfuryl alcohol and the formation of primary pyrolysis products like 2-methyl furan, 2-ethyl furan, furfural, and furan. In addition, the OH-addition reaction on the furan-ring had a certain contribution to the consumption of 2-furfuryl alcohol, while the contribution of H-shift reactions was negligible. The present work systematically compared the effects of methyl, ethyl, and hydroxymethyl groups on the decomposition of furanic fuels and the formation of major products. The results showed that the substituent groups can reduce the decomposition temperature of the fuels, especially the ethyl and hydroxymethyl groups. The alkyl substituent group can promote the formation of small hydrocarbons, of which the mole fraction increased with the length of the carbon chain increasing. The hydroxymethyl group facilitated the formation of oxygenated products.

Review on the Therapeutic Potential of Curcumin and its Derivatives on Glioma Biology.

Gliomas are common and aggressive brain tumors that carry a poor prognosis. The current multimodal therapeutic option for glioma includes surgery subsequently temozolomide chemotherapy and/or radiation; but gliomas are often associated with multidrug resistance, intensive adverse events, and tumor relapse. Thus, novel interventions that can enhance successful chemo-prevention and overcome therapeutic resistance are urgently needed. Phytochemicals have several biological properties with multi-target sites and relatively limited degrees of toxicity. Curcumin is a natural polyphenolic compound with several anti-tumor effects which potentially inhibit tumor growth, development, proliferation, invasion, dissemination, and angiogenesis in different human malignancies. Experimental model studies have demonstrated that curcumin attenuates glioma cell viability by G2/M cell cycle arrest, apoptosis, induction of autophagy, gene expression alteration, and disruption of multi-molecular pathways. Moreover, curcumin has been reported to re-sensitize cancer to chemotherapeutics as well as augment the effect of radiotherapy on glioma cells. In this review, we have provided an update on the in vitro and in vivo effects of curcumin-based therapy on gliomas. We have also discussed the use of curcumin in combination therapies, its effectiveness on drug-resistant cells, and new formulations of curcumin in the treatment of gliomas.

Hypothalamic Control of Forelimb Motor Adaptation.

The ability to perform skilled arm movements is central to everyday life, as limb impairments in common neurologic disorders such as stroke demonstrate. Skilled arm movements require adaptation of motor commands based on discrepancies between desired and actual movements, called sensory errors. Studies in humans show that this involves predictive and reactive movement adaptations to the errors, and also requires a general motivation to move. How these distinct aspects map onto defined neural signals remains unclear, because of a shortage of equivalent studies in experimental animal models that permit neural-level insights. Therefore, we adapted robotic technology used in human studies to mice, enabling insights into the neural underpinnings of motivational, reactive, and predictive aspects of motor adaptation. Here, we show that forelimb motor adaptation is regulated by neurons previously implicated in motivation and arousal, but not in forelimb motor control: the hypothalamic orexin/hypocretin neurons (HONs). By studying goal-oriented mouse-robot interactions in male mice, we found distinct HON signals occur during forelimb movements and motor adaptation. Temporally-delimited optosilencing of these movement-associated HON signals impaired sensory error-based motor adaptation. Unexpectedly, optosilencing affected neither task reward or execution rates, nor motor performance in tasks that did not require adaptation, indicating that the temporally-defined HON signals studied here were distinct from signals governing general task engagement or sensorimotor control. Collectively, these results reveal a hypothalamic neural substrate regulating forelimb motor adaptation.SIGNIFICANCE STATEMENT The ability to perform skilled, adaptable movements is a fundamental part of daily life, and is impaired in common neurologic diseases such as stroke. Maintaining motor adaptation is thus of great interest, but the necessary brain components remain incompletely identified. We found that impaired motor adaptation results from disruption of cells not previously implicated in this pathology: hypothalamic orexin/hypocretin neurons (HONs). We show that temporally confined HON signals are associated with skilled movements. Without these newly-identified signals, a resistance to movement that is normally rapidly overcome leads to prolonged movement impairment. These results identify natural brain signals that enable rapid and effective motor adaptation.

Intermittent fasting: a strategy to counteract aging linked to oxidative stress

Aging is a multifactorial deterioration process that occurs in the life of an organism, which seems to be linked to oxidative stress. Intermittent fasting (IF) consists of food restriction with intermediate periods of regular food intake repeatedly. Various studies in human beings and experimental animal models have shown that intermittent fasting counteracts various alterations associated with age and weight loss, a decrease in the concentration of insulin, glucose, and serum lipids, and oxidative stress, improving antioxidant defense. This review summarizes the evidence available to date in PubMed to analyze the effects of IF on the aging process and its link with oxidative stress. The results suggested that food restriction on alternate days and with a time restriction improves aging processes by decreasing oxidative stress markers and increasing autophagy related to longevity. IF represents a promising non-pharmacological alternative to improve health in the adult population. However, more studies are required to know the chronic effect of fasting and recognize its effects as a therapy in diseases associated with aging.

The effect of perichondrium on cartilage graft properties.

The role of perichondrium in cartilage graft survival has been long debated. Although the innate function of perichondrium in providing mechanical and regenerative support to cartilage in its native position is relatively undisputed, studies continue to vacillate over how the perichondrium effects cartilage grafts once transplanted. This review evaluates historical and recent experiments showing how perichondrium may or may not impact graft survival. Experimental studies in animal models have more recently evaluated macroscopic and microscopic properties of diced cartilage grafts with and without perichondrium, finding that in general grafted cartilage with perichondrial components retains greater weight and mechanical strength compared with cartilage without perichondrial components. However, these findings have not been replicated in humans. Solid pieces of rib cartilage have most recently been used without perichondrium to prevent warping, though no studies have evaluated whether retaining perichondrium with oblique and concentric cutting techniques may effect overall resorption. Although historical opinions and more recent animal studies suggest a role of perichondrium in cartilage graft survival, randomized controlled human studies are still lacking on whether retaining perichondrium truly effects graft survival and ultimate surgical outcomes.

The results of the application of a new technique of open implantation of self-opening transcatheter aortic valves in an experiment

Background. In recent years, transcatheter implantation of the aortic valve has become increasingly performed as an alternative to "open" prosthetics. The undoubted advantage of this technology is its minimally invasive nature, which in most cases provides a favorable clinical outcome of the intervention. The transcatheter method of aortic valve prosthetics does not require sternotomy and connection of an artificial circulation device, which significantly reduces the risk of postoperative mortality and complications. However, despite all the advantages of the existing models, they are not without drawbacks that force researchers to develop and test new transcatheter valves. The problem of experimental studies of new models of self-opening transcatheter aortic valves is mainly determined by the anatomical features of the aortic root of animals. In this regard, the development of a reliable method of implantation of valve prostheses in the experiment is an urgent problem of preclinical testing.Aim. Development of a protocol for open implantation of a transcatheter aortic valve in experiment and evaluation of long-term results.Methods. To develop an experimental model, pigs of the "Landras" breed, females weighing 129.83 ± 9 kg were used. Transcatheter aortic valve implantation was performed under conditions of artificial circulation and moderate hypothermia (33-34°C) through a transverse aortotomy under the control of vision. During the experiment, invasive monitoring of blood pressure, central venous pressure, heart rhythm, body temperature, blood gas composition, activated clotting time was performed. The correct positioning and hemodynamic parameters after implantation were evaluated using transesophageal echocardiography.Results. In a series of chronic experiments, 18 open implantations of self-opening transcatheter aortic valves were performed. Successful positioning was achieved in 100% of cases. The developed protocol of open implantation made it possible to achieve reliable fixation of the prosthesis in the orthotopic position, as well as to prevent the migration of the prosthesis, the development of mitral regurgitation, paraaortic fistulas and coronary circulation disorders.Conclusion. In the course of the study, a simple and effective method of open implantation of a transcatheter aortic heart valve prosthesis was developed in an experiment. Received 1 October 2021. Revised 1 November 2021. Accepted 12 November 2021. Funding: This work was carried out within the framework of the state task of Ministry of Health of Russian Federation No. 121032300337-5. Conflict of interest: Authors declare no conflict of interest. Contribution of the authorsConception and study design: M.O. Zhulkov, D.A. Sirota, K.V. Kozyr, D.S. SergeevichevData collection and analysis: M.O. ZhulkovDrafting the article: M.O. ZhulkovCritical revision of the article: D.A. Sirota, A.M. ChernyavskiyExperimental part: M.O. Zhulkov, H.A. Agaeva, A.K. Sabetov, I.S. Zykov, A.R. TarkovaFinal approval of the version to be published: M.O. Zhulkov, K.V. Kozyr, I.S. Zykov, A.R. Tarkova, H.A. Agaeva, A.K. Sabetov, D.A. Sirota, D.S. Sergeevichev, A.M. Chernyavski

Intravenous As2O3 as a promising treatment for psoriasis — an experimental study in psoriasis-like mouse model

Objective To evaluate the efficacy and mechanistic bases of the intravenous injection of arsenic trioxide at clinical-relevant doses for treating an imiquimod-induced psoriasis-like mouse model. Methods After inducing psoriasis-like skin lesions on the back of mice with imiquimod, mice in each group were injected with a clinical dose of arsenic trioxide through the tail vein. The changes in the gene expression, protein expression and distribution of relevant inflammatory factors were evaluated in the inflicted skin area, for mechanisms underlying the efficacy of intravenous As2O3 intervention. HaCaT cells were used to establish an in vitro psoriasis model and pcDNA3.1-NF-κB overexpression plasmid was transfected into cells to overexpress P65, which further confirmed the role of the NF-κB signaling pathway in the effectiveness of As2O3. Results Clinical dose of As2O3 can significantly improve abnormal symptoms and pathological changes in psoriasis-like skin lesions induced by IMQ in mice. While IMQ induced abnormal expression and distribution of inflammatory factors in the RIG-I pathway and the microRNA-31 (miR-31) pathway in psoriatic skin tissues, intravenous As2O3 can effectively regulate and restore the normality. The leading role of NF-κB signaling was evidenced in vivo and validated in vitro using the NF-κB-overexpressed HaCaT cell model. Conclusion Clinical dosage of As2O3 may achieve effective treatment of IMQ-induced psoriatic skin lesions by modulating the NF-κB signaling pathway which regulates both the RIG-I and the miR-31 lines of action. Our data provided strong evidence supporting the claim that systemic As2O3 administration of clinical doses can be a promising treatment for psoriasis patients.

O-307 Cannabidiol as a potential novel treatment for endometriosis by its anti-inflammatory and anti-oxidative effects in an experimental rat model

Abstract Study question Can cannabidiol (CBD) - a nonpsychoactive constituent of the cannabis plant – be used in the treatment of endometriosis by its anti-inflammatory and anti-oxidative effects? Summary answer CBD appears to be a potential novel therapeutic agent in the treatment of endometriosis through inhibiting inflammation and decreasing oxidative stress in a dose-dependent manner. What is known already The endocannabinoid system (ECS) consists of various bioactive lipids that are produced endogenously which activate cannabinoid 1-2 receptors (CB1-2). Alterations in ECS are associated with many physiological and pathological conditions throughout the body including endometriosis. The events that play role in the development and growth of ectopic endometriotic implants are proliferation, angiogenesis, and inflammation. By their anti-inflammatory and anti-oxidative effects, phyto and synthetic cannabinoids had been investigated and started being used for diseases with similar mechanisms. CBD is a nonpsychoactive constituent of the cannabis plant which acts indirectly upon the CB-1 receptor and as an inverse agonist of CB-2 receptor. Study design, size, duration Endometrial implants were surgically induced in 36 female Wistar-Albino rats in the first surgery. After confirmation of endometriotic foci in the second surgery, the rats were randomized into four groups. Group 1 (leuprolide acetate group) was given a single 1 mg/kg subcutaneous injection of leuprolide acetate. Groups 2,3 and 4 were 5 mg/kg CBD, saline solution (control group), and 20 mg/kg CBD injected groups, respectively, and daily intra-peritoneal (i.p.) injections were applied for seven days. Participants/materials, setting, methods After 21 days from the second surgery, the rats were sacrificed and histopathological analysis of endometriotic lesions, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), interleukin 1 (IL-1), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-a) measurements in blood and peritoneal fluid samples, and immunohistochemical staining for TNF-a expression in endometriotic tissue were evaluated. Main results and the role of chance After treatment, significant reductions in TOS, OSI, IL-1, IL-6 and TNF-α levels in the blood and peritoneal fluid samples and TNF-α expression of endometriotic implants (p &amp;lt; 0.01) and increased TAS (p &amp;lt; 0.01) were found in the CBD 5mg/kg and leuprolide acetate groups. Limitations, reasons for caution The limitation is that this is an experimental rat model study. Wider implications of the findings This is the first study in the literature that evaluates the effects of a phytocannabinoid -CBD- on endometriosis in a rat model. With its anti-inflammatory and anti-oxidative effects and favorable safety and tolerability profile, it might be a candidate for a novel treatment in endometriosis. Trial registration number not applicable