-
ACS Omega May 2023Two Schiff bases, ()-4-((2-chlorobenzylidene)amino)-1,5-dimethyl-2-phenyl-1,2-dihydro-3-pyrazol-3-one (4AAPOCB) and...
Two Schiff bases, ()-4-((2-chlorobenzylidene)amino)-1,5-dimethyl-2-phenyl-1,2-dihydro-3-pyrazol-3-one (4AAPOCB) and ()-4-((4-chlorobenzylidene)amino)-1,5-dimethyl-2-phenyl-1,2-dihydro-3-pyrazol-3-one (4AAPPCB), have been synthesized and grown as single crystals. Single-crystal X-ray diffraction analysis was employed to determine the crystal structure of the compounds, and the results suggest that the compounds crystallized into an orthorhombic crystal system having 222 and space groups, respectively. Further, the crystallinity of the compounds was analyzed by the PXRD technique. The UV-vis-NIR spectra of the compounds demonstrate excellent transmittance in the entire visible region. The lower cutoff wavelengths of the compounds were determined to be 338 and 333 nm, respectively; additionally, optical band gaps of the compounds found were 4.60 and 4.35 eV. FTIR and NMR (H and C) spectral techniques were utilized to analyze the molecular structure of the compounds. The compounds emit photoluminescence with broad emission bands with centers at 401 and 418 nm. The thermal stability and phase transitions were assessed through thermogravimetric methods. The phase transition prior to melting was indicated by the endothermic event at around 190 °C in the DTA curves of both crystals, and the same was observed in the DSC curves. The second harmonic efficiencies of the powdered compounds I and II were found to be 3.52 and 1.13 times better than that of the standard reference KDP. The 4AAPOCB and 4AAPPCB compounds showed isotropic polarizability amplitudes of 46.02 × 10 and 46.52 × 10 esu, respectively. The calculation of linear polarizability and NLO second-order polarizability (β) along with other optical parameters was performed for optimized geometries. The nonzero amplitudes of the average β values for compounds 4AAPOCB and 4AAPPCB were found to be 14.74 × 10 and 8.10 × 10 esu, respectively, which show a decent potential of the synthesized molecules for NLO applications. The calculated β amplitudes were further explained based on calculated electronic parameters like molecular electrostatic potentials, frontier molecular orbitals, molecular orbital energies, transition energies, oscillator strengths, and unit spherical representation of NLO polarizability. The current analysis emphasizes the significance of synthesized compounds as prospective candidates for optical and NLO applications through the use of experiments and quantum computations.
PubMed: 37151560
DOI: 10.1021/acsomega.2c08305 -
Frontiers in Bioengineering and... 2023Accurate blood glucose determination is essential to the clinical diagnosis and management of diabetes. This work establishes an inner filter effect (IFE) strategy...
Accurate blood glucose determination is essential to the clinical diagnosis and management of diabetes. This work establishes an inner filter effect (IFE) strategy between upconversion nanoparticles (UCNPs) and quinone-imine complex for glucose monitoring in human serum simply and efficiently. In this system, the enzyme glucose oxidase (GOx) catalyzes the reaction of glucose into hydrogen peroxide (HO) and gluconic acid when compulsion by oxygen. In the presence of horseradish peroxidase (HRP), the produced HO can catalytically oxidize phenol and 4-amino antipyrine (4-AAP) to generate quinone-imine products. The purple-colored quinone-imine complex effectively absorbed the fluorescence of NaYF:Yb, Er UCNPs, leading to the strong fluorescence quenching of UCNPs through IFE. Thus, a new approach was established for glucose monitoring by determining the fluorescence intensity. Under the optimal condition, this approach shows better linearity to glucose from 2-240 μmol/L with a low detection limit at 1.0 μmol/L. Owing to the excellent fluorescence property and background-free interference of the UCNPs, the biosensor was applied for glucose measurements in human serum and got a satisfactory result. Furthermore, this sensitive and selective biosensor revealed great potential for the quantitative analysis of blood glucose or different kinds of HO-involved biomolecules for the application of clinical diagnosis.
PubMed: 37101750
DOI: 10.3389/fbioe.2023.1168086 -
Disease Markers 2023To investigate the efficacy of butylphthalide combined with edaravone in the treatment of acute ischemic stroke and the effect on serum inflammatory factors.
OBJECTIVE
To investigate the efficacy of butylphthalide combined with edaravone in the treatment of acute ischemic stroke and the effect on serum inflammatory factors.
METHODS
One hundred and sixty patients with acute ischemic stroke who attended the neurovascular intervention department of our hospital from May 2020 to June 2022 were enrolled as study subjects for prospective analysis and were equally divided into a control group and an experimental group using the random number table method, with 80 cases in each group. The control group was treated with edaravone injection, while the experimental group was treated with butylphthalide combined with edaravone. The disease was recorded to compare the efficacy, erythrocyte sedimentation rate, homocysteine, serum inflammatory factors including tumor necrosis factor-, C-reactive protein and interleukin-6 levels, and the incidence of adverse reactions between the two groups.
RESULTS
The total effective rate of treatment in the experimental group was 90.0% (72/80), while that of the control group was 62.5% (50/80), the total effective rate of the experimental group was significantly higher than that of the control group, and the difference was statistically significant ( < 0.05). After treatment, the erythrocyte sedimentation rate, homocysteine level, and serum TNF-, CRP, and IL-6 levels of patients in the experimental group improved compared with those before treatment, and the degree of improvement was better than that of the control group, and the difference was statistically significant ( < 0.05). After 3 months of treatment, a comparison of the incidence of adverse reactions in the two groups showed no statistically significant difference between the two groups ( > 0.05).
CONCLUSION
The treatment of acute ischemic stroke with butylphthalide combined with edaravone has positive significance in improving blood circulation regulation and serum inflammatory factor levels and is reliable and worthy of clinical promotion.
Topics: Humans; Edaravone; Ischemic Stroke; Benzofurans; Inflammation; Interleukin-6; Stroke
PubMed: 37082457
DOI: 10.1155/2023/9969437 -
Frontiers in Pharmacology 2023Safe medications for mild mental diseases in pregnancy are needed. Phytomedicines from St. John's wort and valerian are valid candidates, but safety data in pregnancy...
Safe medications for mild mental diseases in pregnancy are needed. Phytomedicines from St. John's wort and valerian are valid candidates, but safety data in pregnancy are lacking. The transplacental transport of hyperforin and hypericin (from St. John's wort), and valerenic acid (from valerian) was evaluated using the cotyledon perfusion model (4 h perfusions, term placentae) and, in part, the Transwell assay with BeWo b30 cells. Antipyrine was used for comparison in both models. U(H)PLC-MS/MS bioanalytical methods were developed to quantify the compounds. Perfusion data obtained with term placentae showed that only minor amounts of hyperforin passed into the fetal circuit, while hypericin did not cross the placental barrier and valerenic acid equilibrated between the maternal and fetal compartments. None of the investigated compounds affected metabolic, functional, and histopathological parameters of the placenta during the perfusion experiments. Data from the Transwell model suggested that valerenic acid does not cross the placental cell layer. Taken together, our data suggest that throughout the pregnancy the potential fetal exposure to hypericin and hyperforin - but not to valerenic acid - is likely to be minimal.
PubMed: 37063288
DOI: 10.3389/fphar.2023.1123194 -
International Wound Journal Oct 2023Random skin flap transplantation is a commonly used technique. However, ischemia and ischemia-reperfusion injury always impair its therapeutic effectiveness through...
Random skin flap transplantation is a commonly used technique. However, ischemia and ischemia-reperfusion injury always impair its therapeutic effectiveness through acclerating oxidative stress, apoptosis and suppressing angiogenesis. To survive, cells rely on mediating autophagy, DNA repair, immunoregulation to resist these cellular injuries. Thus, mediating autophagy may affect the survival of random skin flaps. The edaravone (EDA), a oxygen radicals scavenger, also possesses autophagy mediator potential, we investigated the effects of EDA on skin flap survival and its autophagy-related mechanisms. In vivo, mice were administered EDA or saline intraperitoneally for 7 days postoperatively. We found that EDA ameliorated the viability of random skin flaps, promoted autophagy and angiogenesis, attenuated apoptosis and oxidative stress. In vitro, mouse umbilical vascular endothelial cells (MUVECs) were administered EDA or 3-methyladenine (3-MA, an autophagy inhibitor) or rapacymin (Rapa, an autophagy activator) at the beginning of oxygen glucose deprivation (OGD). We found that EDA promoted cell viability, activated autophagy, enhanced angiogenesis, alleviated apoptosis and oxidative stress. On one hand, 3-MA reversed the effects of EDA on cell viability, oxidative stress and apoptosis via inhibiting autophagy. On the other hand, Rapa had the similar effects of EDA. Furthermore, EDA-induced autophagy was mediated through downregulating PI3K/Akt/mTOR signalling pathway. The findings showed that EDA ameliorated viability of random skin flaps by promoting angiogenesis, suppressing oxidative stress and apoptosis, which may be mediated by autophagic activation through downregulating PI3K/AKT/mTOR signalling pathway.
Topics: Mice; Animals; Edaravone; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Endothelial Cells; TOR Serine-Threonine Kinases; Autophagy
PubMed: 37042039
DOI: 10.1111/iwj.14184 -
Cellulose (London, England) 2023In this work, new chitosan derivative nanofibers that exhibit antibacterial properties were successfully fabricated. The two CS Schiff base derivatives (CS-APC and...
In this work, new chitosan derivative nanofibers that exhibit antibacterial properties were successfully fabricated. The two CS Schiff base derivatives (CS-APC and CS-2APC) were prepared by incorporating 4-amino antipyrine moiety in two different ratios, followed by a reductive amination to obtain the corresponding derivatives CS-APCR and CS-2APCR. Spectral analyses were used to confirm the chemical structure. The molecular docking evaluation of CS-APC, CS-APCR, and CS was conducted on DNA topoisomerase IV, thymidylate kinase and SARS-CoV-2 main protease (3CL) active sites. CS-APCR showed a well-fitting into the three enzyme active sites with docking score values of - 32.76, - 35.43 and - 30.12 kcal/mol, respectively. The nanocomposites of CS derivatives were obtained by electrospinning the blends of CS-2APC and CS-2APCR with polyvinyl pyrrolidone (PVP) at 20 kV. The morphology of the nanofibers was investigated by scanning electron microscopy (SEM). It was found that fiber diameters were significantly decreased when CS-2APC and CS-2APCR were incorporated into pure PVP to reach 206-296 nm and 146-170 nm, respectively, compared to 224-332 nm for pure PVP. The derivatives of CS and their nanofibers with PVP were found to have antibacterial activities against two strains of and Data revealed that CS-2APC nanofibers showed antibacterial activity to the two strains of less than CS-2APCR nanofibers.
PubMed: 36994234
DOI: 10.1007/s10570-023-05124-9 -
CNS Neuroscience & Therapeutics Sep 2023Previous research has suggested that vanishing white matter disease (VWMD) astrocytes fail to fully differentiate and respond differently to cellular stresses compared...
INTRODUCTION
Previous research has suggested that vanishing white matter disease (VWMD) astrocytes fail to fully differentiate and respond differently to cellular stresses compared to healthy astrocytes. However, few studies have investigated potential VWMD therapeutics in monoculture patient-derived cell-based models.
METHODS
To investigate the impact of alterations in astrocyte expression and function in VWMD, astrocytes were differentiated from patient and control induced pluripotent stem cells and analyzed by proteomics, pathway analysis, and functional assays, in the absence and presence of stressors or potential therapeutics.
RESULTS
Vanishing white matter disease astrocytes demonstrated significantly reduced expression of astrocyte markers and markers of inflammatory activation or cellular stress relative to control astrocytes. These alterations were identified both in the presence and absence of polyinosinic:polycytidylic acid stimuli, which is used to simulate viral infections. Pathway analysis highlighted differential signaling in multiple pathways in VWMD astrocytes, including eukaryotic initiation factor 2 (EIF2) signaling, oxidative stress, oxidative phosphorylation (OXPHOS), mitochondrial function, the unfolded protein response (UPR), phagosome regulation, autophagy, ER stress, tricarboxylic acid cycle (TCA) cycle, glycolysis, tRNA signaling, and senescence pathways. Since oxidative stress and mitochondrial function were two of the key pathways affected, we investigated whether two independent therapeutic strategies could ameliorate astrocyte dysfunction: edaravone treatment and mitochondrial transfer. Edaravone treatment reduced differential VWMD protein expression of the UPR, phagosome regulation, ubiquitination, autophagy, ER stress, senescence, and TCA cycle pathways. Meanwhile, mitochondrial transfer decreased VWMD differential expression of the UPR, glycolysis, calcium transport, phagosome formation, and ER stress pathways, while further modulating EIF2 signaling, tRNA signaling, TCA cycle, and OXPHOS pathways. Mitochondrial transfer also increased the gene and protein expression of the astrocyte marker, glial fibrillary acidic protein (GFAP) in VWMD astrocytes.
CONCLUSION
This study provides further insight into the etiology of VWMD astrocytic failure and suggests edaravone and mitochondrial transfer as potential candidate VWMD therapeutics that can ameliorate disease pathways in astrocytes related to oxidative stress, mitochondrial dysfunction, and proteostasis.
Topics: Humans; Astrocytes; Edaravone; Eukaryotic Initiation Factor-2; Leukoencephalopathies; Mitochondria; White Matter
PubMed: 36971196
DOI: 10.1111/cns.14190 -
Brain Stimulation 2023Although amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease and unfortunately incurable yet, incremental attention has been drawn to...
BACKGROUND
Although amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease and unfortunately incurable yet, incremental attention has been drawn to targeting the health of corticospinal motor neurons. Focused ultrasound combined with systemically circulating microbubbles (FUS/MB) is an emerging modality capable of site-specific molecular delivery temporarily and noninvasively within a range of appropriate parameters.
OBJECTIVE
To investigate the effect of FUS/MB-enhanced delivery of therapeutics to the motor cortex on the disease progression by using a transgenic mouse model of ALS.
METHODS
Multiple FUS/MB-enhanced deliveries of Edaravone (Eda) to the motor cortex were performed on the SOD1 mouse model of ALS. The motor function of the animals was evaluated by gait analysis, grip strength and wire hanging tests. Corticospinal and spinal motor neuronal health, misfolded SOD1 protein and neuroinflammation after treatments were evaluated by histological examination.
RESULTS
Ultrasound-enhanced delivery of Eda in the targeted motor cortex was achieved by a two-fold increase without gross tissue damage. Compared with the ALS mice administered Eda treatments only, the animals given additionally FUS/MB-enhanced brain delivery of Eda (FUS/MB + Eda) exhibited further improvements in neuromuscular functions characterized by gait patterns, muscular strength, and motor coordination along with rescued muscle atrophy. FUS/MB + Eda treatments conferred remarkable neuroprotection to both upper and lower motor neurons revealed by normalized neuronal morphology with increasing cell body size and profoundly alleviated neuroinflammation and misfolded SOD1 protein in the brains and lumbar spinal cords.
CONCLUSION
We report a pilot study that non-invasive ultrasound-enhanced brain delivery of Eda provides additive amelioration on disease progression of ALS and suggest that broadening the target from spinal to cortical network functions using the FUS/MB-enhanced delivery can be a rational therapeutic strategy of this debilitating disorder.
Topics: Mice; Animals; Amyotrophic Lateral Sclerosis; Superoxide Dismutase-1; Edaravone; Neuroinflammatory Diseases; Neurodegenerative Diseases; Pilot Projects; Superoxide Dismutase; Motor Neurons; Mice, Transgenic; Brain; Disease Progression; Disease Models, Animal
PubMed: 36931463
DOI: 10.1016/j.brs.2023.03.006 -
Chinese Medical Journal Mar 2023
Topics: Humans; Aged; Edaravone; Neurocognitive Disorders; Cognition Disorders; Arthroplasty, Replacement, Hip
PubMed: 36914959
DOI: 10.1097/CM9.0000000000001973 -
Oxidative Medicine and Cellular... 2023Ischemic stroke is the most common among various stroke types and the second leading cause of death, worldwide. Edaravone (EDV) is one of the cardinal antioxidants that...
Enhancing the Neuroprotection Potential of Edaravone in Transient Global Ischemia Treatment with Glutathione- (GSH-) Conjugated Poly(methacrylic acid) Nanogel as a Promising Carrier for Targeted Brain Drug Delivery.
Ischemic stroke is the most common among various stroke types and the second leading cause of death, worldwide. Edaravone (EDV) is one of the cardinal antioxidants that is capable of scavenging reactive oxygen species, especially hydroxyl molecules, and has been already used for ischemic stroke treatment. However, poor water solubility, low stability, and bioavailability in aqueous media are major EDV drawbacks. Thus, to overcome the aforementioned drawbacks, nanogel was exploited as a drug carrier of EDV. Furthermore, decorating the nanogel surface with glutathione as targeting ligands would potentiate the therapeutic efficacy. Nanovehicle characterization was assessed with various analytical techniques. Size (199 nm, hydrodynamic diameter) and zeta potential (-25 mV) of optimum formulation were assessed. The outcome demonstrated a diameter of around 100 nm, sphere shape, and homogenous morphology. Encapsulation efficiency and drug loading were determined to be 99.9% and 37.5%, respectively. drug release profile depicted a sustained release process. EDV and glutathione presence in one vehicle simultaneously made the possibility of antioxidant effects on the brain in specific doses, which resulted in elevated spatial memory and learning along with cognitive function in Wistar rats. In addition, significantly lower MDA and PCO and higher levels of neural GSH and antioxidant levels were observed, while histopathological improvement was approved. The developed nanogel can be a suited vehicle for drug delivery of EDV to the brain and improve ischemia-induced oxidative stress cell damage.
Topics: Rats; Animals; Rats, Wistar; Edaravone; Nanogels; Neuroprotection; Brain; Glutathione; Ischemia; Ischemic Stroke; Antioxidants; Acute Disease
PubMed: 36865347
DOI: 10.1155/2023/7643280