In the ALDH2 rs671 variant, a guanine changes to an adenine, resulting in a dramatic decrease in the catalytic activity of the enzyme. Population-based data are contradictory about whether this ...variant increases the risk of Alzheimer's disease. In East Asian populations, the prevalence of the ALDH2 rs671 variant is 30-50%, making the National Human Brain Bank for Development and Function (the largest brain bank in East Asia) an important resource to explore the link between the ALDH2 rs671 polymorphism and Alzheimer's disease pathology. Here, using 469 postmortem brains, we find that while the ALDH2 rs671 variant is associated with increased plaque deposits and a higher Aβ40/42 ratio, it is not an independent risk factor for Alzheimer's disease. Mechanistically, we show that lower ALDH2 activity leads to 4-HNE accumulation in the brain. The (R)-4-HNE enantiomer adducts to residue Lys53 of C99, favoring Aβ40 generation in the Golgi apparatus. Decreased ALDH2 activity also lowers inflammatory factor secretion, as well as amyloid β phagocytosis and spread in brains of patients with Alzheimer's disease. We thus define the relationship between the ALDH2 rs671 polymorphism and amyloid β pathology, and find that ALDH2 rs671 is a key regulator of Aβ40 or Aβ42 generation.
Human ALX1 gene (ALX Homeobox 1) is a protein coding gene and gene ontology annotations related to this gene include DNA-binding transcription factor activity and protein heterdimerization activity. ...It is necessary for survival of forebrain mesenchyme and may be involved in development of cervix. However, the function of the gene has yet to be determined in humans. Here we generated an ALX1 homozygous human embryonic stem cell line (WAe001-A-060) by a CRISPR/Cas9 system. The WAe001-A-060 has a normal undifferentiated morphology and karyotype, pluripotency and three germ layers differentiation potential in vivo.
This research underlines the potential of alginate multilayered gel microspheres for the layered encapsulation and the simultaneous delivery of vitamin B2 (VB) and β-carotene (BC). Chitosan was used ...to improve the stability and controlled release ability of alginate-based gel microspheres. It was shown that a clear multilayered structure possessed the characteristics of pH response, and excellent thermal stability. The sodium alginate concentration and the number of layers had notable effects on mechanical properties and particle size of gel microspheres. Fourier-transform infrared spectroscopy and X-ray diffraction analyses further proved that VB and BC were encapsulated within the gel microspheres. Compared with the three-layer VB-loaded gel microspheres, the total release of VB from the three-layer VB and BC-loaded gel decreased from 93.23% to 85.58%. The total release of BC from the three-layer VB and BC-loaded gel increased from 66.11% to 69.24% compared with three-layer BC-loaded gel. The simultaneous encapsulation of VB and BC in multilayered gel microspheres can markedly improve their bioaccessibility and bioavailability. These results showed the multilayer gel microspheres synthesized herein have potential for applications in the layered encapsulation and simultaneous delivery of various bioactive substances to the intestinal tract.
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•The non-covalent interaction mechanism between SPI and catechin was studied.•The quenching of SPI by catechin was mainly static quenching.•The effect of catechin with different ...concentrations on SPI conformation was studied.•Hydrophobic interactions and hydrogen bonds were main forces of SPI-Catechin complex.
Understanding the molecular mechanism behind protein–polyphenol interactions is critical for the application of protein–polyphenol compounds in foods. The purpose of this research was to investigate the non-covalent interaction mechanism between soy protein isolate (SPI) and catechin and its effect on protein conformation. We observed that particle size, ζ-potential, and polyphenol bound equivalents of SPI increased significantly after non-covalent modification with catechin. These changes caused SPI to aggregate and form a network-like structure. Fourier transform infrared spectroscopy (FTIR) indicated that increased catechin concentrations caused SPI to become looser and more disordered as its α-helix and β-sheet transformed into β-turn and random coil. Furthermore, internal structure of SPI was opened and its hydrophobic groups were exposed to a polar environment, which was demonstrated by decreased surface hydrophobicity. Thermodynamic analysis and molecular docking results showed that the main forces present between SPI and catechin were hydrophobic interactions and hydrogen bonds.
Myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) causes major disability as a consequence of recurrent demyelinating events and neuronal loss. Biomarkers identifying different ...phenotypes of recurrence or tissue damage might be useful to guide individualized therapy. Herein, we evaluated serum neurofilament light chain (sNfL) as a potential biomarker in both adult and pediatric MOGAD patients. Forty‐nine patients with MOGAD (37 adults, 12 children) and 71 healthy controls (HCs) (56 adults, 15 children) were enrolled prospectively from September 2019 to April 2021 at the Third Affiliated Hospital of Sun Yat‐sen University and the Children's Hospital, Zhejiang University School of Medicine. sNfL levels were determined using ultrasensitive single‐molecule array assay and correlated with clinical parameters. The sNfL levels in MOGAD adults in a relapsed state (median: 31.0 pg/ml) were higher than those in a remission state (8.1 pg/ml, p = 0.001) and in HC adults (10.3 pg/ml, p = 0.004). Similar results were observed in children (relapse: 46.8 pg/ml vs. remission: 13.1 pg/ml, p = 0.001; and vs. HCs: 8.2 pg/ml, p = 0.007) sNfL levels were correlated with recent relapses within 60 days (multivariate: β = 2.02, p = 0.003), seizures (multivariate: β = 2.50, p = 0.021) and brain lesions on magnetic resonance imaging (MRI) of a recent relapse (multivariate: β = 1.72, p = 0.012). Our study showed that sNfL levels are beneficial for identifying recent relapses and seizures and suggest that adult and pediatric MOGAD patients had similar sNfL levels.
This study determined the level of serum neurofilament light chain (sNfL) by ultrasensitive single‐molecule array assay. The authors found that the sNfL was significantly higher in relapse than in remission in both adult and pediatric patients with myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD). sNfL levels were significantly increased in the brain phenotype in MOGAD patients compared with healthy controls and were beneficial for identifying recent relapses and seizures. These findings are of great importance because sNfL is a promising biomarker for identifying phenotypes of recurrence in MOGAD, which might be useful to guide individualized therapy and reduce burdens on patients.
This research underlines the potential of alginate multilayered gel microspheres for the layered encapsulation and the simultaneous delivery of vitamin B
(VB) and β-carotene (BC). Chitosan was used ...to improve the stability and controlled release ability of alginate-based gel microspheres. It was shown that a clear multilayered structure possessed the characteristics of pH response, and excellent thermal stability. The sodium alginate concentration and the number of layers had notable effects on mechanical properties and particle size of gel microspheres. Fourier-transform infrared spectroscopy and X-ray diffraction analyses further proved that VB and BC were encapsulated within the gel microspheres. Compared with the three-layer VB-loaded gel microspheres, the total release of VB from the three-layer VB and BC-loaded gel decreased from 93.23% to 85.58%. The total release of BC from the three-layer VB and BC-loaded gel increased from 66.11% to 69.24% compared with three-layer BC-loaded gel. The simultaneous encapsulation of VB and BC in multilayered gel microspheres can markedly improve their bioaccessibility and bioavailability. These results showed the multilayer gel microspheres synthesized herein have potential for applications in the layered encapsulation and simultaneous delivery of various bioactive substances to the intestinal tract.
Objective To explore the pathogenic mechanism of myelin oligodendrocyte glycoprotein-IgG（MOG-IgG）associated disorders （MOGAD） and screen the treatment drugs by establishing the MOGAD in vitro ...demyelination model. Methods The patient-derived MOG-IgG was purified by using the affinity chromatography based on transfected cells. The MOGAD in vitro demyelination model was constructed by the interaction between MOG-IgG and complement based on rat organotypic cerebellar slice and neuron-oligodendrocyte co-culture model. The expression level of myelin basic protein （MBP） and its colocalization with neurofilament protein （NF） were used as indicators to evaluate the myelin formation and injury. The myelin repair effect of drugs that promote the remyelination for multiple sclerosis was evaluated in this demyelination model. Results Highly-specific MOG-IgG was purified by the affinity chromatography based on transfected cells. After the treatment of antibodies and complement, the expression level of MBP and the colocaliz
Molar concentration of gold nanoparticles is one of the most critical parameters of gold colloids in order to develop their applications in sensing, diagnostics and nanomedicine. Previous methods ...often stand just for gold nanoparticles with regular shape and narrow size distribution. In the present work, we proposed an absolute quantification method that determined the molar concentration of gold nanoparticles with arbitrary shapes and polydisperse sizes. This approach involved the real time monitoring and counting of individual nanoparticles collision events, from which the quantification of molar concentration was achieved using a theoretical model consisting of Fiek＇s laws of diffusion and Stokes-Einstein equation. The determination of spherical gold nanoparticles concentration resulted in excellent agreement with traditional spectrometry method. It was further demonstrated that the present approach can be expanded to determine the molar concentration of gold nanoparticles with arbitrary shapes and poly-diversed distributions.
Ubiquitin-like 3 (UBL3) is a well-conserved ubiquitin-like protein (UBL) in eukaryotes and regulates the ubiquitin cascade, but the significant roles of UBL3 in cellular processes remained unknown. ...Recently, UBL3 was elucidated to be a post-translational modification factor that promotes protein sorting to small extracellular vesicles (sEVs). Proteins sorted into sEVs have been studied as etiologies of sEV-related diseases. Also, there have been attempts to construct drug delivery systems (DDSs) by loading proteins into sEVs. In this review, we introduce the new concept that UBL3 has a critical role in the protein-sorting system and compare structure conservation between UBL3 and other UBLs from an evolutionary perspective. We conclude with future perspectives for the utility of UBL3 in sEV-related diseases and DDS.Key words: UBL3, small extracellular vesicles, protein sorting, ubiquitin-like protein, post-translational modification
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