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2022 ◽  
Author(s):  
Abderrahim Ed-Daoui ◽  
M’hammed Benelmostafa ◽  
Mohammed Dahmani ◽  
Abdelghani Chahlal

LWT ◽  
2022 ◽  
pp. 113093
Author(s):  
Zeineb Nhouchi ◽  
Eliot Patrick Botosoa ◽  
Christine Chene ◽  
Romdhane Karoui

2021 ◽  
Vol 12 ◽  
Author(s):  
Ying Wang ◽  
Xiao Xiao ◽  
Shipeng Chen ◽  
Chenjun Huang ◽  
Jun Zhou ◽  
...  

BackgroundThis study aimed to explore the molecular mechanism of the coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) serological pattern via intensive characterization of HBV s gene in both chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) patients.MethodA total of 73 HBsAg+/HBsAb+ patients (CHB = 36, HCC = 37) and 96 HBsAg+/HBsAb− patients (CHB = 47, HCC = 49) were enrolled from 13 medical centers in China. The sequence features were elaborated based on the combination of next-generation sequencing (NGS) and multidimensional bioinformatics analysis.ResultsThe 16 high-frequency missense mutations, changes of stop codon mutation, clustering, and random forest models based on quasispecies features demonstrated the significant discrepancy power between HBsAg+/HBsAb+ and HBsAg+/HBsAb− in CHB and HCC, respectively. The immunogenicity for cytotoxic T lymphocyte (CTL) epitope Se and antigenicity for the major hydrophilic region (MHR) were both reduced in HBsAg+/HBsAb+ patients (CTL Se: p < 0.0001; MHR: p = 0.0216). Different mutation patterns were observed between HBsAg+/HBsAb+ patients with CHB and with HCC. Especially, mutations in antigenic epitopes, such as I126S in CHB and I126T in HCC, could impact the conformational structure and alter the antigenicity/immunogenicity of HBsAg.ConclusionBased on NGS and bioinformatics analysis, this study indicates for the first time that point mutations and quasispecies diversities of HBV s gene could alter the MHR antigenicity and CTL Se immunogenicity and could contribute to the concurrent HBsAg+/HBsAb+ with different features in HCC and CHB. Our findings might renew the understanding of this special serological profile and benefit the clinical management in HBV-related diseases.


2021 ◽  
Vol 8 ◽  
Author(s):  
Maria Carmina Scala ◽  
Simone Di Micco ◽  
Delia Lanzillotta ◽  
Simona Musella ◽  
Veronica Di Sarno ◽  
...  

The fragile histidine triad (FHIT) protein is a member of the large and ubiquitous histidine triad (HIT) family of proteins. On the basis of genetic evidence, it has been postulated that the FHIT protein may function as tumor suppressor, implying a role for the FHIT protein in carcinogenesis. Recently, Gaudio et al. reported that FHIT binds and delocalizes annexin A4 (ANXA4) from plasma membrane to cytosol in paclitaxel-resistant lung cancer cells, thus restoring their chemosensitivity to the drug. They also identified the smallest protein sequence of the FHIT still interacting with ANXA4, ranging from position 7 to 13: QHLIKPS. This short sequence of FHIT protein was not only able to bind ANXA4 but also to hold its target in the cytosol during paclitaxel treatment, thus avoiding ANXA4 translocation to the inner side of the cell membrane. Starting from these results, to obtain much information about structure requirements involved in the interaction of the peptide mentioned above, we synthetized a panel of seven peptides through an Ala-scan approach. In detail, to study the binding of FHIT derived peptides with ANXA4, we applied a combination of different biophysical techniques such as differential scanning fluorimetry (DSF), surface plasmon resonance (SPR), and microscale thermophoresis (MST). Circular dichroism (CD) and nuclear magnetic resonance (NMR) were used to determine the conformational structure of the lead peptide (7–13) and peptides generated from ala-scan technique. The application of different biophysical and structural techniques, integrated by a preliminary biological evaluation, allowed us to build a solid structure activity relationship on the synthesized peptides.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sabrina Mariotti ◽  
Antonio Capocefalo ◽  
Maria Vincenza Chiantore ◽  
Angelo Iacobino ◽  
Raffaela Teloni ◽  
...  

Antibodies targeting Receptor Binding Domain (RBD) of SARS-CoV-2 have been suggested to account for the majority of neutralizing activity in COVID-19 convalescent sera and several neutralizing antibodies (nAbs) have been isolated, characterized and proposed as emergency therapeutics in the form of monoclonal antibodies (mAbs). However, SARS-CoV-2 variants are rapidly spreading worldwide from the sites of initial identification. The variants of concern (VOC) B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.167.2 (Delta) showed mutations in the SARS-CoV-2 spike protein potentially able to cause escape from nAb responses with a consequent reduction of efficacy of vaccines and mAbs-based therapy. We produced the recombinant RBD (rRBD) of SARS-CoV-2 spike glycoprotein from the Wuhan-Hu 1 reference sequence in a mammalian system, for mice immunization to isolate new mAbs with neutralizing activity. Here we describe four mAbs that were able to bind the rRBD in Enzyme-Linked Immunosorbent Assay and the transmembrane full-length spike protein expressed in HEK293T cells by flow cytometry assay. Moreover, the mAbs recognized the RBD in supernatants of SARS-CoV-2 infected VERO E6 cells by Western Blot under non-reducing condition or in supernatants of cells infected with lentivirus pseudotyped for spike protein, by immunoprecipitation assay. Three out of four mAbs lost their binding efficiency to completely N-deglycosylated rRBD and none was able to bind the same recombinant protein expressed in Escherichia coli, suggesting that the epitopes recognized by three mAbs are generated by the conformational structure of the glycosylated native protein. Of particular relevance, three mAbs were able to inhibit Wuhan SARS-CoV-2 infection of VERO E6 cells in a plaque-reduction neutralization test and the Wuhan SARS-CoV-2 as well as the Alpha, Beta, Gamma and Delta VOC in a pseudoviruses-based neutralization test. These mAbs represent important additional tools for diagnosis and therapy of COVID-19 and may contribute to the understanding of the functional structure of SARS-CoV-2 RBD.


2021 ◽  
Author(s):  
Hussein Elganzory

Abstract Novel complexes of Cu(I,II), Zn(II) and Cd(II) of thiosemicarbazide ligand (H2LB) have been prepared and characterized. The results confirmed that gamma ray enhanced the stability of irradiated compounds as compared to non-irradiated . XRD patterns proved that increasing the crystallinity of particles in nano range after gamma irradiation. Data obtained indicated that the Cu(I) and Cd(II) ions coordinated to the ligand through the (C=O), N(2)H and (C=S), (neutral tridentate ligand). While, Cu(II) and Zn(II) complexes the ligand behaves as neutral tetradentate and coordination take place via (C=O) and two N(2)H . These studies revealed that, two kinds of stereochemical geometries; Cu(II) and Zn(II) complexes were predicted to be octahedral, Cu(I) and Cd(II) complexes were found to be tetrahedral. The theoretical conformational structure analyses were performed using DFT at B3LYP functional with 6‐31G(++)d,p basis set for ligand and LANL2DZ basis set for complexes. The inhibitory effect on the growth against gram-positive and gram-negative bacteria of prepared complexes have been tested. Results suggested that 1μg/ml and 5µg/ml for Cu(II) and Zn(II) complexes have higher activity than other complexes. The chelation could facilitate the ability to cross the cell membrane of E. coli. Molecular docking investigation proved that; the Zn(II) complex has interesting interactions with active site amino acids of topoisomerase II DNA gyrase enzymes (code: 2XCT).


2021 ◽  
Author(s):  
Hussein Elganzory

Abstract New complexes of Cu(I,II), Zn(II) and Cd(II) of thiosemicarbazide ligand 1-(p-(methylanilinocetyl-4-phenyl-thiosemicarbazide)(H2LB) have been prepared and characterized by 1HNMR, Mass spectra, FT-IR, elemental analyses, molar conductance, UV-visible spectra, magnetic susceptibility measurements, thermogravimetric analysis (TGA/DTG) and X-ray diffraction pattern before and after irradiation. The results confirmed that gamma ray enhanced the stability of irradiated compounds as compared to non-irradiated compounds. XRD patterns proved that increasing the crystallinity of the samples and the particles in nano range after gamma irradiation. The obtained data indicated that the Cu(I) and Cd(II) ions coordinated to the ligand through the (C = O), N(2)H and (C = S), the ligand behaves as neutral tridentate. While in complexes Cu(II) and Zn(II)complexes (B2 and B3) the ligand behave as neutral tetradentate and coordination take place via (C = O) and two N(2)H. These studies revealed that, two kinds of stereochemical geometries; Cu(II) and Zn(II) complexes were predicted to be octahedral, Cu(I) and Cd(II)complexes were found to be tetrahedral. The theoretical conformational structure analyses were performed using density functional theory for ligand and complexes at B3LYP functional with 6-31G(++)d,p basis set for ligand and LANL2DZ basis set for complexes. The ligand and its metal complexes have been tested for their inhibitory effect on the growth of bacteria against gram-positive (Streptococcus pyogenes) and gram-negative (Escherichia coli). Results suggested that in case of 1µg/ml and 5µg/ml for Cu(II) and Zn(II) complexes have higher activity than other complexes. The chelation could facilitate the ability to cross the cell membrane of E. coli and can be explained by Tweedy’s chelation theory. Molecular docking investigation proved that; the Zn(II) complex had interesting interactions with active site amino acids of topoisomerase II DNA gyrase enzymes (code: 2XCT).


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuxing Xia ◽  
Brach M. Bell ◽  
Benoit I. Giasson

AbstractAlzheimer’s disease is the leading cause of dementia and a defining hallmark is the progressive brain deposition of tau aggregates. The insidious accumulation of brain tau inclusions is also involved in a group of neurodegenerative diseases termed frontotemporal dementias. In all of these disorders, tau aggregates are enriched in post-translational modifications including acetylation, which has recently been identified at multiple sites. While most evidence suggest that tau acetylation is detrimental and promotes tau aggregation, a few studies support that tau acetylation within the KXGS motif can be protective and inhibit tau aggregation. To model site-specific acetylation at K259, K290, K321, and K353, acetylmimetics were created by mutating lysine to glutamine residues, which approximates size and charge of acetylation. HEK293T cells were transfected to express wild type tau, tau pathogenic mutations (P301L and P301L/S320F) or tau acetylmimetics and assessed by cell-based assays for microtubule binding and tau aggregation. Acetylmimetics within the KXGS motif (K259Q, K290Q, K321Q, K353Q) leads to significant decreased tau–microtubule interactions. Acetylmimetics K321Q and K353Q within the context of the pathogenic P301L tau mutation strongly inhibited prion-like seeded aggregation. This protective effect was confirmed to decrease intrinsic aggregation of P301L/S320F tau double mutation. Surprisingly, K321Q and K353Q acetylmimetics altered the conformational structure of P301L/S320F tau to extensively impair Thioflavin S binding. Site-specific acetylation of tau at K321 and K353 could represent a natural protective mechanism against tau aggregation and could be a potential therapeutic target.


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