Drug/bioactive eluting chitosan composite foams for osteochondral tissue engineering

Joint defects associated with a variety of etiologies often extend deep into the subchondral bone leading to functional impairment and joint immobility, and it is a very challenging task to regenerate the bone-cartilage interface offering significant opportunities for biomaterial-based interventions to improve the quality of life of patients. Herein drug-/bioactive-loaded porous tissue scaffolds incorporating nano-hydroxyapatite (nHAp), chitosan (CS) and either hydroxypropyl methylcellulose (HPMC) or Bombyx mori silk fibroin (SF) are fabricated through freeze drying method as subchondral bone substitute. A combination of spectroscopy and microscopy (Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive X-ray (EDX), and X-ray fluorescence (XRF) were used to analyze the structure of the porous biomaterials. The compressive mechanical properties of these scaffolds are biomimetic of cancellous bone tissues and capable of releasing drugs/bioactives (exemplified with triamcinolone acetonide, TA, or transforming growth factor-β1, TGF-β1, respectively) over a period of days. Mouse preosteoblast MC3T3-E1 cells were observed to adhere and proliferate on the tissue scaffolds as confirmed by the cell attachment, live-dead assay and alamarBlue™ assay. Interestingly, RT-qPCR analysis showed that the TA downregulated inflammatory biomarkers and upregulated the bone-specific biomarkers, suggesting such tissue scaffolds have long-term potential for clinical application

Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins, and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Utilizing exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with YnMyr chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), with ages ranging from 1 to 50 years old, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%), and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%), and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%), and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each), as well as hypertrophy of the clava (24%) were common neuroimaging findings. acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism, and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localisation and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-Myristoylation was similarly affected in acbd6-deficient zebrafish and Xenopus tropicalis models, including Fus, Marcks, and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders

The Efficient Removal of Methylene Blue Dye Using CuO/PET Nanocomposite in Aqueous Solutions

The present research investigates the application of the green method to produce nanocomposites. The CuO/PET fiber nanocomposite can be prepared in two ways. The first way involves the application of the electrospinning technique by which waste plastic cups of polyethylene terephthalate (PET) are converted into nanofibers. In the second way, the copper nanoparticle (CuONPs) is synthesized with the natural capped plant extract of sumac (Rhus Coriaria L., family Anacardiaceae) and the CuONPs are then combined as a filler with the PET nanofiber using a cross-linked solvent. The X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), energy dispersion spectroscopy (EDS), and map elements distribution can be applied to investigate the surface modification and alteration of the composite nanofiber morphology. The collected data show that the produced CuO/PET nanocomposites have a high surface area, well distribution of elements, magnificent shape, and stable dispersion state. Furthermore, the CuO/PET nanocomposites are considered as an efficient photocatalytic removal of the toxic methylene blue dye (MB) in aqueous solutions. The results of the present study demonstrate that the photocatalytic efficiency for removing MB dye is achieved in a short time using a low-intensity irradiation ultraviolet light

The Efficient Removal of Methylene Blue Dye Using CuO/PET Nanocomposite in Aqueous Solutions

The present research investigates the application of the green method to produce nanocomposites. The CuO/PET fiber nanocomposite can be prepared in two ways. The first way involves the application of the electrospinning technique by which waste plastic cups of polyethylene terephthalate (PET) are converted into nanofibers. In the second way, the copper nanoparticle (CuONPs) is synthesized with the natural capped plant extract of sumac (Rhus Coriaria L., family Anacardiaceae) and the CuONPs are then combined as a filler with the PET nanofiber using a cross-linked solvent. The X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), energy dispersion spectroscopy (EDS), and map elements distribution can be applied to investigate the surface modification and alteration of the composite nanofiber morphology. The collected data show that the produced CuO/PET nanocomposites have a high surface area, well distribution of elements, magnificent shape, and stable dispersion state. Furthermore, the CuO/PET nanocomposites are considered as an efficient photocatalytic removal of the toxic methylene blue dye (MB) in aqueous solutions. The results of the present study demonstrate that the photocatalytic efficiency for removing MB dye is achieved in a short time using a low-intensity irradiation ultraviolet light