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International Journal of Molecular... Aug 2023The development of new neurotherapeutics depends on appropriate animal models being chosen in preclinical studies. The cuprizone model is an effective tool for studying...
The development of new neurotherapeutics depends on appropriate animal models being chosen in preclinical studies. The cuprizone model is an effective tool for studying demyelination and remyelination processes in the brain, but blood-brain barrier (BBB) integrity in the cuprizone model is still a topic for debate. Several publications claim that the BBB remains intact during cuprizone-induced demyelination; others demonstrate results that could explain the increased BBB permeability. In this study, we aim to analyze the permeability of the BBB for different macromolecules, particularly antibody conjugates, in a cuprizone-induced model of demyelination. We compared the traditional approach using Evans blue injection with subsequent dye extraction and detection of antibody conjugates using magnetic resonance imaging (MRI) and confocal microscopy to analyze BBB permeability in the cuprizone model. First, we validated our model of demyelination by performing T2-weighted MRI, diffusion tensor imaging, quantitative rt-PCR to detect changes in mRNA expression of myelin basic protein and proteolipid protein, and Luxol fast blue histological staining of myelin. Intraperitoneal injection of Evans blue did not result in any differences between the fluorescent signal in the brain of healthy and cuprizone-treated mice (IVIS analysis with subsequent dye extraction). In contrast, intravenous injection of antibody conjugates (anti-GFAP or non-specific IgG) after 4 weeks of a cuprizone diet demonstrated accumulation in the corpus callosum of cuprizone-treated mice both by contrast-enhanced MRI (for gadolinium-labeled antibodies) and by fluorescence microscopy (for Alexa488-labeled antibodies). Our results suggest that the methods with better sensitivity could detect the accumulation of macromolecules (such as fluorescent-labeled or gadolinium-labeled antibody conjugates) in the brain, suggesting a local BBB disruption in the demyelinating area. These findings support previous investigations that questioned BBB integrity in the cuprizone model and demonstrate the possibility of delivering antibody conjugates to the corpus callosum of cuprizone-treated mice.
Topics: Animals; Mice; Cuprizone; Blood-Brain Barrier; Diffusion Tensor Imaging; Evans Blue; Gadolinium; Antibodies; Immunoconjugates; Coloring Agents; Demyelinating Diseases
PubMed: 37628867
DOI: 10.3390/ijms241612688 -
Combined disposal of methyl orange and corn straw via stepwise adsorption-biomethanation-composting.Journal of Environmental Management Oct 2023Agriculture wastes have been proved to be the potential adsorbents to remove azo dye from textile wastewater, but the post-treatment of azo dye loaded agriculture waste...
Agriculture wastes have been proved to be the potential adsorbents to remove azo dye from textile wastewater, but the post-treatment of azo dye loaded agriculture waste is generally ignored. A three-step strategy including sequential adsorption-biomethanation-composting was developed to realize the co-processing of azo dye and corn straw (CS). Results showed that CS represented a potential adsorbent to remove methyl orange (MO) from textile wastewater, with the maximum MO adsorption capacity of 10.00 ± 0.46 mg/g, deriving from the Langmuir model. During the biomethanation, CS could serve as electron donor for MO decolorization and substrate for biogas production simultaneously. Though the cumulative methane yield of CS loaded with MO was 11.7 ± 2.28% lower than that of blank CS, almost complete de-colorization of MO could be achieved within 72 h. Composting could achieve the further degradation of aromatic amines (intermediates during the degradation of MO) and decomposition of digestate. After 5 days' composting, 4-aminobenzenesulfonic acid (4-ABA) was not detectable. The germination index (GI) also indicated that the toxicity of aromatic amine was eliminated. The overall utilization strategy gives novel light on the management of agriculture waste and textile wastewater.
Topics: Wastewater; Zea mays; Adsorption; Composting; Water Pollutants, Chemical; Azo Compounds; Coloring Agents; Kinetics
PubMed: 37329578
DOI: 10.1016/j.jenvman.2023.118358 -
Naunyn-Schmiedeberg's Archives of... Nov 2023Vascular cognitive impairment (VCI) has been one of the major types of cognitive impairment. Blood-brain barrier damage plays an essential part in the pathogenesis of...
Vascular cognitive impairment (VCI) has been one of the major types of cognitive impairment. Blood-brain barrier damage plays an essential part in the pathogenesis of VCI. At present, the treatment of VCI is mainly focused on prevention, with no drug clinically approved for the treatment of VCI. This study aimed to investigate the effects of DL-3-n-butylphthalide (NBP) on VCI rats. A modified bilateral common carotid artery occlusion (mBCCAO) model was applied to mimic VCI. The feasibility of the mBCCAO model was verified by laser Doppler, N-Ammonia-Positron Emission Computed Tomography (PET), and Morris Water Maze. Subsequently, the Morris water maze experiment, Evans blue staining, and western blot of tight junction protein were performed to evaluate the effect of different doses of NBP (40 mg/kg, 80 mg/kg) on the improvement of cognitive impairment and BBB disruption induced by mBCCAO. Immunofluorescence was employed to examine the changes in pericyte coverage in the mBCCAO model and the effect of NBP on pericyte coverage was preliminarily explored. mBCCAO surgery led to obvious cognitive impairment and the decrease of whole cerebral blood flow, among which the blood flow in the cortex, hippocampus and thalamus brain regions decreased more significantly. High-dose NBP (80 mg/kg) improved long-term cognitive function in mBCCAO rats, alleviated Evans blue leakage and reduced the loss of tight junction proteins (ZO-1, Claudin-5) in the early course of the disease, thereby exerting a protective effect on the blood-brain barrier. No significant changes in pericyte coverage were observed after mBCCAO. High-dose NBP improved cognitive function in mBCCAO rats. High-dose NBP protected the integrity of BBB by upregulating TJ protein expression, rather than regulating pericyte coverage ratio. NBP could be a potential drug for the treatment of VCI.
Topics: Rats; Animals; Blood-Brain Barrier; Evans Blue; Brain Ischemia; Cognition; Cognitive Dysfunction; Benzofurans
PubMed: 37243759
DOI: 10.1007/s00210-023-02530-5 -
Molecules (Basel, Switzerland) Jun 2024A highly sensitive, selective and recyclable histidine detection method based on magnetic FeO@mTiO (M-TiO) nanocomposites with SERRS was developed. Mesoporous M-TiO...
A highly sensitive, selective and recyclable histidine detection method based on magnetic FeO@mTiO (M-TiO) nanocomposites with SERRS was developed. Mesoporous M-TiO nanoparticles were functionalized with 4-aminothiophenol and then coupled with histidine through an azo coupling reaction in 5 min, producing the corresponding azo compound. The strong and specific SERRS response of the azo product allowed for ultrasensitive and selective detection for histidine with an M-TiO device loaded with Ag NPs due to the molecular resonance effect and plasmonic effect of Ag NPs under a 532 nm excitation laser. The sensitivity was further enhanced with the magnetic enrichment of M-TiO. The limit of detection (LOD) was as low as 8.00 × 10 mol/L. The M-TiO demonstrated applicability towards histidine determination in human urine without any sample pretreatment. Additionally, the M-TiO device can be recycled for 3 cycles with the photodegradation of the azo product under UV irradiation due to TiO-assisted and plasmon-enhanced photocatalysis. In summary, a multifunctional and recyclable M-TiO device was synthesized based on azo coupling and SERRS spectroscopy for ultra-sensitive and specific histidine sensing. In addition, the proposed system demonstrated the potential for the multiplex determination of toxic compounds in the fields of food safety, industrial production and environmental protection, which benefit from the fingerprint property and universality of SERRS.
Topics: Titanium; Histidine; Nanocomposites; Limit of Detection; Humans; Metal Nanoparticles; Silver; Azo Compounds
PubMed: 38930970
DOI: 10.3390/molecules29122906 -
Chemosphere May 2024Azo dyes are largely used in many industries and discharged in large volumes of their effluents into the aquatic environment giving rise to non-esthetic pollution and... (Review)
Review
Azo dyes are largely used in many industries and discharged in large volumes of their effluents into the aquatic environment giving rise to non-esthetic pollution and health-risk problems. Due to the high stability of azo dyes in ambient conditions, they cannot be abated in conventional wastewater treatment plants. Over the last fifteen years, the decontamination of dyeing effluents by persulfate (PS)-based advanced oxidation processes (AOPs) has received a great attention. In these methods, PS is activated to be decomposed into sulfate radical anion (SO), which is further partially hydrolyzed to hydroxyl radical (OH). Superoxide ion (O) and singlet oxygen (O) can also be produced as oxidants. This review summarizes the results reported for the discoloration and mineralization of synthetic and real waters contaminated with azo dyes covering up to November 2023. PS activation with iron, non-iron transition metals, and carbonaceous materials catalysts, heat, UVC light, photocatalysis, photodegradation with iron, electrochemical and related processes, microwaves, ozonation, ultrasounds, and other processes is detailed and analyzed. The principles and characteristics of each method are explained with special attention to the operating variables, the different oxidizing species generated yielding radical and non-radical mechanisms, the addition of inorganic anions and natural organic matter, the aqueous matrix, and the by-products identified. Finally, the overall loss of toxicity or partial detoxification of treated azo dye solutions during the PS-based AOPs is discussed.
Topics: Azo Compounds; Water Pollutants, Chemical; Iron; Oxidation-Reduction; Oxidants; Water
PubMed: 38527631
DOI: 10.1016/j.chemosphere.2024.141766 -
Diseases of Aquatic Organisms Sep 2023The emerging fungal pathogen Batrachochytrium dendrobatidis (Bd) threatens hundreds of amphibian species globally. During laboratory-based experiments it is often...
The emerging fungal pathogen Batrachochytrium dendrobatidis (Bd) threatens hundreds of amphibian species globally. During laboratory-based experiments it is often essential to quantify live Bd cells, but a comparison of the effectiveness of methods for counting and assessing the viability of the infectious zoospore life stage has not been done. A direct comparison of staining methods that assess viability will ensure that the most accurate and efficient method is used. Here, we compared the use of 2 relatively cheap common stains, trypan blue and methylene blue, and assessed their accuracy and precision for estimating the viability of Bd zoospores during both manual counting and colorimetric assays. We stained known proportions of killed Bd zoospores (0, 0.25, 0.50, 0.75, and 1.00) with each stain and estimated the proportion of stained (dead) and unstained (viable) cells in each sample using both manual counting and colorimetric assays. Trypan blue was found to be a much more effective stain than methylene blue for both microscopy and colorimetric assays. Additionally, counting zoospores via microscopy was both a more accurate and precise technique. We recommend using manual counts via microscopy using the trypan blue stain for assessing Bd zoospore viability.
Topics: Animals; Batrachochytrium; Methylene Blue; Trypan Blue; Biological Assay
PubMed: 37706644
DOI: 10.3354/dao03749 -
Journal of Neuromuscular Diseases 2024Spinal muscular atrophy (SMA) is a progressive neuromuscular disease caused by mutations in Survival motor neuron 1 (SMN1) gene, leading to reduction in survival motor...
BACKGROUND
Spinal muscular atrophy (SMA) is a progressive neuromuscular disease caused by mutations in Survival motor neuron 1 (SMN1) gene, leading to reduction in survival motor neuron protein (SMN), key for motor neuron survival and function in the brainstem and spinal cord. Risdiplam is an orally administered SMN2-splicing modifier which increases production of functional SMN protein. Risdiplam was offered in the UK under early access to medicines scheme (EAMS) to SMA type 1 and 2 patients aged 2 months and older, not suitable for authorised treatments from September 2020 to December 2021.
OBJECTIVE
To describe the largest paediatric European real-world set of data on patients' characteristics and short-term safety for risdiplam in Great Britain through EAMS.
METHODS
We collated data from SMA REACH UK a national clinical and research network for all patients enrolled onto EAMS and assessed all submitted adverse events.
RESULTS
Of the 92 patients; 78% were Type 2 SMA, mean age 10.9 years, range 0-17 years. 56 were treatment naïve, 33 previously treated; of these 25 had received nusinersen, 3 previous treatment unknown. Sixty adverse events (AEs) were reported occurring in 34 patients. The commonest were respiratory tract infections and gastrointestinal disturbance. Four life-threatening events were reported with 2 deaths and permanent cessation of risdiplam in 3 patients.Overall, 38/60 AEs were considered unrelated to risdiplam, 10/60 related to risdiplam and for 12/60 causality not specified.
CONCLUSIONS
This study found a safety profile similar to clinical trials with no new safety concerns identified. With the restricted eligibility of onasemnogene abeparvovec and complications of nusinersen administration, EAMS allowed access or continued treatment to naïve patients or patients no longer suitable for approved medications. Collection of longitudinal data for this complex population is needed, to provide greater insights into risdiplam's role in addressing patients' needs into the future.
Topics: Humans; Child; Infant, Newborn; Infant; Child, Preschool; Adolescent; United Kingdom; Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood; Pyrimidines; Azo Compounds
PubMed: 38189761
DOI: 10.3233/JND-230162 -
Journal of Bioscience and Bioengineering Aug 2023The effective results of the enzymatic decolorization of industrial azo dyes found in wastewater, which cause serious health and environmental problems, with peroxidases...
Enzymatic degradation of azo dyes methylene blue and congo red with peroxidase purified from cauliflower using affinity chromatography technique: Kinetic study, optimization and metal binding activity.
The effective results of the enzymatic decolorization of industrial azo dyes found in wastewater, which cause serious health and environmental problems, with peroxidases have recently increased the interest in these enzyme sources. Redox-mediated decolorization of Methylene Blue and Congo Red azo dyes with cauliflower (Brassica oleracea var. botrytis L.) peroxidase (CPOD) purified in one step using 4-amino 3-bromo 2-methyl benzohydrazide molecule was investigated for the first time. The inhibition effect of this molecule, which is used as a ligand in affinity chromatography, on the CPOD enzyme was investigated. The K and IC values for this enzyme were calculated as 0.113 ± 0.012 mM and 0.196 ± 0.011 mM, respectively. With the affinity gel obtained by binding to the Sepharose-4B-l-tyrosine matrix of this molecule, which shows a reversible inhibition effect, the purification values of CPOD enzyme were determined as 562-fold with a specific activity of 50,250 U mg. The purity of the enzyme was checked by the SDS-PAGE technique and its molecular weight was determined. A single band at 44 kDa was observed for the CPOD enzyme. In dye decolorization studies, the effects of dye, enzyme, and hydrogen peroxide concentrations as well as time, pH, and temperature were investigated. The profiles of the optimum conditions for both dyes were similar, and the percentages of decolorization of Methylene Blue and Congo Red under these conditions were 89% and 83%, respectively, at the end of the 40 min reaction time. Again, when examining the effect of metal ions on enzyme activity, it was found that there was no significant negative change in CPOD.
Topics: Peroxidase; Congo Red; Methylene Blue; Brassica; Azo Compounds; Coloring Agents; Peroxidases; Metals; Chromatography, Affinity; Biodegradation, Environmental
PubMed: 37331844
DOI: 10.1016/j.jbiosc.2023.05.011 -
Environmental Pollution (Barking, Essex... Jul 2023Understanding the role of oxido-reductase enzymes followed by deciphering the functional genes and their corresponding proteins are crucial for the speculation of...
Understanding the role of oxido-reductase enzymes followed by deciphering the functional genes and their corresponding proteins are crucial for the speculation of molecular mechanism for azo dye degradation. In the present study, decolourization efficiency of developed microbial consortium was tested using 100 mgL reactive blue 13 (RB13) and the results showed ∼92.67% decolourization of RB13 at 48 h of incubation. The fourier-transform infrared spectroscopy (FTIR), high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analysis were performed to identify the metabolites formed during RB13 degradation, followed by hypothesizing the metabolic pathway. The GC-MS analysis showed formation of 1,4-dihydronaphthalen-1-ol and 1,3,5-triazin-2-amine as the final degraded compounds after enzymatic breakdown of RB13 dye. The activity of different oxido-reductase enzymes was determined, and the results showed that NADH DCIP reductase and azo reductase had higher activity than other enzymes. It clearly indicated the degradation was initiated with the enzymatic cleavage of azo bond of RB13. Further, the functional genes were annotated against the database of clusters of orthologous groups (COGs) and kyoto encyclopedia of genes and genomes (KEGG). It provided valuable information about the role of crucial functional genes and their corresponding proteins correlated with dominant bacterial species in degradation of RB13. Hence, the present research is the first systematic study that correlated the formation of degradation compounds with the functional genes/enzymes and their corresponding bacterial species responsible for RB13 degradation.
Topics: Coloring Agents; Biodegradation, Environmental; Microbial Consortia; Azo Compounds; Spectroscopy, Fourier Transform Infrared
PubMed: 37105464
DOI: 10.1016/j.envpol.2023.121718 -
Biomaterials Mar 2024Impaired angiogenesis, bacterial infection, persistent severe pain, exacerbated inflammation, and oxidative stress injury are intractable problems in the treatment of...
Impaired angiogenesis, bacterial infection, persistent severe pain, exacerbated inflammation, and oxidative stress injury are intractable problems in the treatment of chronic diabetic ulcer wounds. A strategy that effectively targets all these issues has proven challenging. Herein, an in-situ sprayable nanoparticle-gel composite comprising platinum clusters (Pt) loaded-mesoporous polydopamine (MPDA) nanoparticle and QX-314-loaded fibrin gel (Pt@MPDA/QX314@Fibrin) was developed for diabetic wound analgesia and therapy. The composite shows good local analgesic effect of QX-314 mediated by near-infrared light (NIR) activation of transient receptor potential vanilloid 1 (TRPV1) channel, as well as multifunctional therapeutic effects of rapid hemostasis, anti-inflammation, antioxidation, and antibacterial properties that benefit the fast-healing of diabetic wounds. Furthermore, it demonstrates that the composite, with good biodegradability and biosafety, significantly relieved wound pain by inhibiting the expression of c-Fos in the dorsal root ganglion and the activation of glial cells in the spinal cord dorsal horn. Consequently, our designed sprayable Pt@MPDA/QX314@Fibrin composite with good biocompatibility, NIR activation of TRPV1 channel-mediated QX-314 local wound analgesia and comprehensive treatments, is promising for chronic diabetic wound therapy.
Topics: Rats; Animals; Pain; Analgesics; Diabetes Mellitus; Nanocomposites; Fibrin; Anti-Bacterial Agents; Diazonium Compounds; Lidocaine; Pyridines
PubMed: 38224643
DOI: 10.1016/j.biomaterials.2024.122467