Ascorbic Acid Reduces the Adverse Effects of Delayed Administration of Tissue Plasminogen Activator in a Rat Stroke Model

Delayed treatment of stroke with recombinant tissue plasminogen activator (r‐tPA) induces overexpression of matrix metalloproteinase 9 (MMP‐9) which leads to breakdown of the blood–brain barrier (BBB) and causes more injuries to the brain parenchyma. In this study, the effect of ascorbic acid (AA), an antioxidant agent, on the delayed administration of r‐tPA in a rat model of permanent middle cerebral artery occlusion (MCAO) was investigated. Forty male rats were randomly divided into four groups: untreated control rats (ischaemic animals), AA‐treated (500 mg/kg; 5 hr after stroke) rats, r‐tPA‐treated (5 hr after stroke 1 mg/kg) rats and rats treated with the combination of AA and r‐tPA. Middle cerebral artery occlusion was induced by occluding the right middle cerebral artery (MCA). Infarct size, BBB, brain oedema and the levels of MMP‐9 were measured at the end of study. Neurological deficits were evaluated at 24 and 48 hr after stroke. Compared to the control or r‐tPA‐treated animals, AA alone (p < 0.001) or in combination with r‐tPA (p < 0.05) significantly decreased infarct volume. Ascorbic acid alone or r‐tPA + AA significantly reduced BBB permeability (p < 0.05), levels of MMP‐9 (p < 0.05 versus control; p < 0.01 versus r‐tPA) and brain oedema (p < 0.001) when compared to either the control or the r‐tPA‐treated animals. Latency to the removal of sticky labels from the forepaw was also significantly decreased after the administration of AA + r‐tPA (p < 0.05) at 24 or 48 hr after stroke. Based on our data, acute treatment with AA may be considered as a useful candidate to reduce the side effects of delayed application of r‐tPA in stroke therapy.     

Cationic Albumin‐Conjugated Chelating Agent as a Novel Brain Drug Delivery System in Neurodegeneration

The critical role of metal ions and in particular iron in oxidative stress and protein aggregation offers chelation therapy as a sensible pharmaceutical strategy in oxidative stress‐induced neuronal damages. In this research, we conjugated an iron‐chelating agent, deferasirox, to cationized human serum albumin molecules in order to develop a novel brain delivery system for the management of neurodegenerative disorders due to the significant role of oxidative stress‐induced neuronal injury in such diseases. Cationized albumin is known to be able to transport to brain tissue via adsorptive‐mediated transcytosis. The developed structures were molecularly characterized, and their conjugation ratio was determined. PC12 cell line was utilized to evaluate the neuroprotective features of these newly developed molecules in the presence of hydrogen peroxide neuronal damage and to identify the mechanisms behind the observed neuronal protection including apoptotic and autophagic pathways. Furthermore, a rat model of Alzheimer's disease was utilized to evaluate the impact of conjugated structures in vivo. Data analysis revealed that the conjugated species were able to hinder apoptotic cell death while enhancing autophagic process. The developed conjugated species were also able to attenuate amyloid beta‐induced learning deficits when administered peripherally.     

Monocarboxylate Transporter 1 Inhibitors as Potential Anticancer Agents

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Electrodegradation of 2,4-dichlorophenoxyacetic acid herbicide from aqueous solution using three-dimensional electrode reactor with G/β-PbO2 anode: Taguchi optimization and degradation mechanism determination

This study aimed to investigate the electro-degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) from aqueous solution using two and three-dimensional electrode (2D and 3D) reactors with graphite(G)/β-PbO₂ anode. To increase the degradation efficiency, affecting parameters on the electro-degradation process were investigated and optimized by adopting the Taguchi design of experiments approach. The structure, morphology and electrochemical properties of the electrodes were studied by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), linear sweep voltammetry and cyclic voltammograms. The controllable factors, i.e., electrolysis time, 2,4-D initial concentration, solution pH and current density (j) were optimized. Under optimum conditions, the 2,4-D degradation efficiency was 75.6% using 2D and 93.5% using 3D electrode processes. The percentage contribution of each controllable factor was also determined. The pH of the solution was identified as the most influential factor, and its percentage contribution value was up to 39.9% and 40.4% for 2D and 3D electrode processes, respectively. Considering the parameters of the kinetics, it was found that the degradation of 2,4-D and removal of COD using the G/β-PbO₂ electrode obey the pseudo-first order kinetics. In addition, the mineralization pathway of 2,4-D at G/β-PbO₂ electrode was proposed. The results also demonstrated that the 3D electrode process with G/β-PbO₂ anode can be considered as a useful method for degradation and mineralization of 2,4-D herbicides from aqueous solution.

Optimization of process parameters using the Taguchi method, electrochemical degradation and electrochemical degradation mechanism of 2,4-D herbicide using 2D and 3D reactors with G/β-PbO₂ anode were investigated.     

Nitric oxide functionalized molybdenum(0) pyrazolone Schiff base complexes: thermal and biochemical study

This work describes the synthesis and characterization of three molybdenum dinitrosyl Schiff base complexes of the general formula [Mo(NO)₂(L)(OH)], where L is N-(dehydroacetic acid)-4-aminoantipyrene (dha-aapH), N-(4-acetylidene-3-methyl-1-phenyl-2-pyrazolin-5-one)-4-aminoantipyrine (amphp-aapH) or N-(3-methyl-1-phenyl-4-propionylidene-2-pyrazolin-5-one)-4-aminoantipyrine (mphpp-aapH). The complexes were formulated on the basis of spectroscopic analyses, elemental composition, magnetic susceptibility measurements, molar conductance behaviour and determination of the respective decomposition temperatures. A comparative experimental-theoretical approach was followed to elucidate the structure of the complexes. Fourier transform infra-red (FT-IR) spectroscopy, thermo-gravimetry (TG) and electronic spectral insights were mainly focused on the confirmation of the formation of the complexes. The computational density functional theory (DFT) calculations evaluated in the study involve the molecular specification for the use of LANL2DZ/RB3LYP formalism for metal atoms and 6-311G/RB3LYP for the remaining non-metal atoms. The study reveals a suitable cis-octahedral geometry for the complexes. The TG curve of one of the representative complexes was evaluated to find the respective thermodynamic and kinetic parameters using various physical methods. The Freeman & Carroll (FC) differential method, the Horowitz and Metzger (HM) approximation method, the Coats–Redfern method and the Broido method were employed to present a comparative thermal analysis of the complex. The Broido method proved the best fit to the results for the compound under question. In addition to structural and thermal analyses, the study also deals with the in vitro antimicrobial and anticancer sensitivity of the complexes. The results revealed potent biological properties of the representative complex containing dha-aapH. Cell toxicity tests against COLO-205 human cancer cell line using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay showed an IC₅₀ value of 53.13 μgm mL⁻¹ for the Schiff base and 10.51 μgm L⁻¹ for the respective complex. Similarly the same complex proved to be an effective antimicrobial agent against Aspergillus, Pseudomonas, E. coli and Streptococcus. The results indicated a more pronounced activity against Pseudomonas and Streptococcus than the other two microbial species.

This work describes the thermal and biological implications of three pyrazolone-dinitrosylmolybdenum(0) complexes.     

Toxicity of fungicides to Pisum sativum: a study of oxidative damage,growth suppression,cellular death and morpho-anatomical changes

Considering the fungicidal threat to the sustainable agro-environment, the toxicological impacts of three fungicides, namely kitazin, hexaconazole and carbendazim, on the biological, chemical and morpho-anatomical changes of peas were assessed. Fungicide applications in general caused a slow but gradual reduction in growth, symbiosis and yields of peas, which, however, varied appreciably among species and concentrations of the three fungicides. Of the three fungicides, carbendazim had the most lethal effect, in which it delayed seed germination and also diminished the overall pea growth. Carbendazim at 3000 μg kg⁻¹ maximally reduced the germination, SVI, size of roots and shoots and total dry matter accumulation in roots, shoots and whole plants distinctly by 40%, 84%, 72%, 73%, 68%, 75% and 73% (p ≤ 0.05), respectively. Hexaconazole at 120 μg kg⁻¹ significantly (p ≤ 0.05) declined total chlorophyll, carotenoids, grain yields, grain protein, root P and shoot N by 19%, 28%, 46%, 69%, 48% and 51%, respectively, over the control. The synthesis of stress biomarkers and oxidative stress were increased with increasing dosage rates of fungicides. Proline content in roots, shoots, leaves and grains, MDA, electrolyte leakage and H₂O₂ of plants grown in soil treated with 288 μg kg⁻¹ kitazin were increased significantly (p ≤ 0.05) by 73%, 52%, 41%, 24%, 59%, 40% and 27%, respectively, relative to the control. Antioxidant defence enzymes were greater in pea foliage. The SEM and CLSM images revealed an obvious alteration in root tips, enhanced cellular damage and cell death when plants were raised under fungicide stress. Also, morpho-anatomical variations in fungicide-treated foliage were visible in the SEM images. Overall, the present study suggests that a careful and secure strategy should be adopted before fungicides are chosen for enhancing pulse production in different agro-climatic regions.

Considering the fungicidal threat to the sustainable agro-environment, the toxicological impacts of three fungicides, namely kitazin, hexaconazole and carbendazim, on the biological, chemical and morpho-anatomical changes of peas were assessed.     

Does prior immunization with measles,mumps, and rubella vaccines contribute to the antibody response to COVID-19 antigens?

Background: Incidence and severity of SARS-CoV2 infection are significantly lower in children and teenagers proposing that certain vaccines, routinely administered to neonates and children may provide cross-protection against this emerging infection. Objective: To assess the cross-protection induced by prior measles, mumps and rubella (MMR) vaccinations against COVID-19. Methods: The antibody responses to MMR and tetanus vaccines were determined in 53 patients affected with SARS-CoV2 infection and 52 age-matched healthy subjects. Serum levels of antibodies specific for NP and RBD of SARS-CoV2 were also determined in both groups of subjects with ELISA. Results: Our results revealed significant differences in anti-NP (p <0.0001) and anti-RBD (p <0.0001) IgG levels between patients and healthy controls. While the levels of rubella- and mumps specific IgG were not different in the two groups of subjects, measles-specific IgG was significantly higher in patients (p <0.01). The serum titer of anti-tetanus antibody, however, was significantly lower in patients compared to healthy individuals (p <0.01). Conclusion: Our findings suggest that measles vaccination triggers those B cells cross-reactive with SARS-CoV2 antigens leading to the production of increased levels of measles-specific antibody.