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Abstract In this work, the binding mechanism between donepezil (DNP) and bovine serum albumin (BSA) was established using several techniques, including fluorimetry, UV- spectrophotometry, synchronous fluorimetry (SF), fourier transform infrared (FTIR), fluorescence resonance energy transfer (FRET) besides molecular docking study. The fluorescence quenching mechanism of DNP-BSA binding was a combined dynamic and static quenching. The thermodynamic parameters, binding forces, binding constant, and the number of binding sites were determined using a different range of temperature settings. Van't Hoff's equation was used to calculate the reaction parameters, including enthalpy change (ΔHο) and entropy change (ΔSο). The results pointed out that the DNP-BSA binding was endothermic. It was shown that the stability of the drug-protein system was predominantly due to the intermolecular hydrophobic forces. Additionally, the site probing method revealed that subdomain IIA (Site I) is where DNP and BSA's binding occurs. This was validated using a molecular docking study with the most stable DNP configuration. This study might help to understand DNP's pharmacokinetics profile and toxicity as well as provides crucial information for its safe use and avoiding its toxicity.

Introduction Pulmonary arterial hypertension (PH) is commonly found in patients with mitral valve diseases. Most of the drugs used for PH treatment are nonselective pulmonary vasodilators that may cause a modest decrease in pulmonary arterial pressure, but they may cause a marked decrease in systemic vascular resistance as well, which leads to hypotension and a decrease in perfusion of vital organs. Inhaled drugs such as milrinone and nitroglycerine may be safer as a large dose of the drug can selectively target the pulmonary circulation, which leads to a reduction of their systemic adverse effects. Aim This double-blind, randomized study compared milrinone inhalation versus nitroglycerin inhalation on pulmonary artery pressure and other hemodynamics in postoperative patients immediately after mitral valve replacement surgery. Patients and methods A total of 40 participants with isolated mitral stenosis or isolated mitral incompetence or their combination plus PH [mean pulmonary artery pressure (mPAP) >40 mmHg] scheduled for mitral valve replacement were interviewed. Immediately postoperatively in the ICU, we randomized the patients into two groups, with 20 patients each. Group A consisted of 20 patients who received milrinone inhalation, whereas group B consisted of 20 patients who received nitroglycerine inhalation. Hemodynamic parameters (heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure, central venous pressure, pulmonary artery systolic pressure, pulmonary diastolic pressure, mPAP, fractional shortening, ejection fraction, and pressure of oxygen/fraction of inspired oxygen ratio) were recorded in both groups at three time points: T1, before drug delivery; T2, just after drug delivery; and T3, just before extubation. Results The study showed that both milrinone and nitroglycerin inhalation caused a marked reduction in systolic, diastolic, and mPAPs without causing any hemodynamic deterioration effects on systolic, diastolic, or mean arterial pressures. Conclusion Although both milrinone and nitroglycerin inhalation proved to be effective pulmonary artery vasodilators that avoided systemic adverse effects, nitroglycerin inhalation is a less expensive, easily obtained drug that can serve as an inhaled pulmonary vasodilator in patients with mitral valve diseases and PH following mitral valve replacement surgeries.

Anaerobic digestion (AD) from organic waste has gained worldwide attention because it offers significant environmental and economic benefits. It can reduce the local waste through recycling which will conserve resources, reduce greenhouse gas emissions, and build economic resilience in the face of an uncertain future for energy production and waste disposal. The productive use of local waste through recycling conserves resources by reducing landfill space, the whole of life impacts of landfilling, and post-closure maintenance of landfills. Turning waste into a renewable energy source will assist the decarbonisation of the economy by reducing harmful emissions and pollutants. Therefore, this mini-review aims to summarise key factors and present valuable evidence for an efficient AD process. It also presents the pros and cons of different AD process to convert organic waste along with the reactor technologies. Besides, this paper highlights the challenges and the future perspective of the AD process. However, it is highlighted that for an effective and efficient AD process, appropriate temperature, pH, a strong inoculum to substrate ratio, good mixing and small particle sizes are important factors. The selection of suitable AD process and reactor is important because not all types of processes and reactors are not effective for processing organic waste. This study is of great importance for ongoing work on renewable energy generation from waste and provides important knowledge of innovative waste processing. Finally, it is recommended that the government should increase their support towards the AD technology and consider the unutilized significant potential of gaseous biofuel production. [ABSTRACT FROM AUTHOR]

The work reported herein describes the synthesis of a new series of anti-inflammatory pyrazolyl thiazolones. In addition to COX-2/15-LOX inhibition, these hybrids exerted their anti-inflammatory actions through novel mechanisms. The most active compounds possessed COX-2 inhibitory activities comparable to celecoxib (IC50 values of 0.09–0.14 µM) with significant 15-LOX inhibitory activities (IC50s 1.96 to 3.52 µM). Upon investigation of their in vivo anti-inflammatory activities and ulcerogenic profiles, these compounds showed activity patterns equivalent or more superior to diclofenac and/or celecoxib. Intriguingly, the most active compounds were more effective than diclofenac in suppressing monocyte-to-macrophage differentiation and inflammatory cytokine production by activated macrophages, as well as their ability to induce macrophage apoptosis. The latter finding potentially adds a new dimension to the previously reported anti-inflammatory mechanisms of similar compounds. These compounds were effectively docked into COX-2 and 15-LOX active sites. Also, in silico predictions confirmed the appropriateness of these compounds as drug-like candidates.

In this study, the solution casting method was employed to prepare plasticized polymer electrolytes of chitosan (CS):LiCO2CH3:Glycerol with electrochemical stability (1.8 V). The electrolyte studied in this current work could be established as new materials in the fabrication of EDLC with high specific capacitance and energy density. The system with high dielectric constant was also associated with high DC conductivity (5.19 × 10−4 S/cm). The increase of the amorphous phase upon the addition of glycerol was observed from XRD results. The main charge carrier in the polymer electrolyte was ion as tel (0.044) < tion (0.956). Cyclic voltammetry presented an almost rectangular plot with the absence of a Faradaic peak. Specific capacitance was found to be dependent on the scan rate used. The efficiency of the EDLC was observed to remain constant at 98.8% to 99.5% up to 700 cycles, portraying an excellent cyclability. High values of specific capacitance, energy density, and power density were achieved, such as 132.8 F/g, 18.4 Wh/kg, and 2591 W/kg, respectively. The low equivalent series resistance (ESR) indicated that the EDLC possessed good electrolyte/electrode contact. It was discovered that the power density of the EDLC was affected by ESR.

Introduction Pulmonary arterial hypertension (PH) is commonly found in patients with mitral valve diseases. Most of the drugs used for PH treatment are nonselective pulmonary vasodilators that may cause a modest decrease in pulmonary arterial pressure, but they may cause a marked decrease in systemic vascular resistance as well, which leads to hypotension and a decrease in perfusion of vital organs. Inhaled drugs such as milrinone and nitroglycerine may be safer as a large dose of the drug can selectively target the pulmonary circulation, which leads to a reduction of their systemic adverse effects. Aim This double-blind, randomized study compared milrinone inhalation versus nitroglycerin inhalation on pulmonary artery pressure and other hemodynamics in postoperative patients immediately after mitral valve replacement surgery. Patients and methods A total of 40 participants with isolated mitral stenosis or isolated mitral incompetence or their combination plus PH [mean pulmonary artery pressure (mPAP) >40 mmHg] scheduled for mitral valve replacement were interviewed. Immediately postoperatively in the ICU, we randomized the patients into two groups, with 20 patients each. Group A consisted of 20 patients who received milrinone inhalation, whereas group B consisted of 20 patients who received nitroglycerine inhalation. Hemodynamic parameters (heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure, central venous pressure, pulmonary artery systolic pressure, pulmonary diastolic pressure, mPAP, fractional shortening, ejection fraction, and pressure of oxygen/fraction of inspired oxygen ratio) were recorded in both groups at three time points: T1, before drug delivery; T2, just after drug delivery; and T3, just before extubation. Results The study showed that both milrinone and nitroglycerin inhalation caused a marked reduction in systolic, diastolic, and mPAPs without causing any hemodynamic deterioration effects on systolic, diastolic, or mean arterial pressures. Conclusion Although both milrinone and nitroglycerin inhalation proved to be effective pulmonary artery vasodilators that avoided systemic adverse effects, nitroglycerin inhalation is a less expensive, easily obtained drug that can serve as an inhaled pulmonary vasodilator in patients with mitral valve diseases and PH following mitral valve replacement surgeries. [ABSTRACT FROM AUTHOR]