Programmed cell death 1 (PDCD1) gene haplotypes and susceptibility of patients to basal cell carcinoma

Molecular Biology Reports - Programmed death-1 (PD-1), as an immunoinhibitory receptor encoded by programmed cell death-1 (PDCD1) gene, has a pivotal role in tolerance to self-antigens. Mutations...     

Design of a Multi-epitope Vaccine Against Acinetobacter baumannii Using Immunoinformatics Approach

International Journal of Peptide Research and Therapeutics - Acinetobacter baumannii is one of the most successful pathogens causing nosocomial infections and has significantly multidrug-resistant....     

Mutant p53 binds to estrogen receptor negative promoter via DNMT1 and HDAC1 in MDA-MB-468 breast cancer cells

DNA methylation and histone deacetylation are two epigenetic mechanisms involved in the lack of estrogen receptor (ER) expression. Our previous studies demonstrated that mutant p53 along with repression complex proteins including DNMT1, HDAC1 and MeCP2 is associated with ER-negative promoter in MDA-MB-468 cells. To elucidate the molecular mechanism of estrogen receptor 1 (ESR1) gene silencing in these cells, we down-regulated DNMT1 and HDAC1 expression using siRNAs and studied the ability of DNMT1, HDAC1, MeCP2 and p53 in binding to ESR1 promoter CpG island. Our results showed that DNMT1 or HDAC1 down-regulation disassembled the repression complex proteins and mutant p53 from ER-negative promoter. The partial demethylation of ESR1 promoter and ER re-expression in down-regulated cells supports these findings. In vivo binding studies demonstrated that mutation of p53 protein in this cell line did not affect its binding capacity to DNMT1, HDAC1 and MeCP2 proteins. Our observations suggest that not only histone deacetylase activity of HDAC1 contributes to inactivation of methylated ESR1 gene but also HDAC1 presence on ESR1 promoter is important for assembly of DNMT1 in repression complex. In addition, our data revealed that mutant p53 protein binds to the promoter of ESR1 through direct interaction with HDAC1 and indirect interaction with DNMT1, MeCP2 proteins in the ER-negative MDA-MB-468 cells.     

In vitro cytotoxicity studies of parent and nanoencapsulated Holmium-2,9-dimethyl-1,10-phenanthroline complex toward fish-salmon DNA-binding properties and antibacterial activity

Abstract

In this study, the interaction of Holmium (Ho) complex including 2, 9-dimethyl-1,10-phenanthroline, also called Neocuproine (Neo), [Ho(Neo)₂Cl₃.H₂O], as fluorescence probe with fish-salmon DNA (FS-DNA) is studied during experimental investigations. Multi-spectroscopic methods are utilized to determine the affinity binding constants (K_b) of complex–FS-DNA. It is found that fluorescence of Ho complex is strongly quenched by the FS-DNA through a static quenching procedure. Under optimal conditions in Tris(trishydroxymethyl-aminomethane)–HCl buffer at 25?°C with pH?≈?7.2, intrinsic binding constant K_b of Ho complex is 6.12?±?0.04?×?10⁵ M^?1. Also, the binding site number and Stern–Volmer quenching constant are calculated. There are different approaches, including iodide quenching assay, salt effect and thermodynamical assessment to determine the features of the binding mode between Ho complex and FS-DNA. Also, the parent and starch and lipid nanoencapsulated Ho complex, as potent antitumor candidates, were synthesized. The main structure of Ho complex is maintained after encapsulation using starch and lipid nanoparticles. 3-[4,5-Dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method was used to assess the anticancer properties of Ho complex and its encapsulated forms on human cancer cell lines of human lung carcinoma cell line and breast cancer cell line. In conclusion, these compounds could be considered as new antitumor candidates.

Communicated by Ramaswamy H. Sarma     

Lymphopenia in COVID‐19: Therapeutic opportunities

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is uncontrollably spread all over the world. The host immune responses strongly try to confront it with all the potential cells and cytokines. With chronically condition of SARS‐CoV‐2, natural killer cells and T cells become exhausted and decreasing their count leads to lymphopenia. Inability to eradicate the infected organ makes hyperinitiation of the immune system, which releases the excessive inflammatory cytokines to compensate the exhausted one as well as the low lymphocytes counts; it consequently leads to the cytokine storm syndrome. These mechanisms and the potential therapeutic targeting are discussed in this paper.     

Synthesis,Biological Evaluation and Molecular Docking of Deferasirox and Substituted 1,2,4‐Triazole Derivatives as Novel Potent Urease Inhibitors: Proposing Repositioning Candidate

A series of new deferasirox derivatives were synthesized through the reaction of monosubstituted hydrazides with 2‐(2‐hydroxyphenyl)‐4H‐benzo[e][1,3]oxazin‐4‐one. For the first time, deferasirox and some of its derivatives were evaluated for their in vitro inhibitory activity against Jack bean urease. The potencies of the members of this class of compounds are higher than that of acetohydroxamic acid. Two compounds, bearing tetrazole and hydrazine derivatives (bioisoester of carboxylate group), represented the most potent urease inhibitory activity with IC₅₀ values of 1.268 and 3.254 μm , respectively. In silico docking studies were performed to delineate possible binding modes of the compounds with the enzyme, urease. Docking analysis suggests that the synthesized compounds were anchored well in the catalytic site and extending to the entrance of binding pocket and thus restrict the mobility of the flap by interacting with its crucial amino acid residues, CME592 and His593. The overall results of urease inhibition have shown that these target compounds can be further optimized and developed as a lead skeleton for the discovery of novel urease inhibitors     

TWIST1 correlates with Notch signaling pathway to develop esophageal squamous cell carcinoma

Molecular and Cellular Biochemistry - Notch signaling pathway mediates different biological processes including stem cell self-renewal, progenitor cell fate decision, and terminal differentiation....     

Simultaneous and sensitive determination of a quaternary mixture of AA, DA, UA and Trp using a modified GCE by iron ion-doped natrolite zeolite-multiwall carbon nanotube

The evaluation of a novel modified glassy carbon electrode modified with iron ion-doped natrolite zeolite-multiwalled carbon nanotube for the simultaneous and sensitive determination of ascorbic acid (AA), dopamine (DA), uric acid (UA) and tryptophan (Trp) has been described. The measurements were carried out using cyclic voltammetry in buffer solution with pH 1. This modified electrode exhibits potent and persistent electroxidation behavior followed by well-separated oxidation peaks towards AA, DA, UA and Trp with increasing of the oxidation current. For the quaternary mixture containing AA, DA, UA and Trp, the 4 compounds can well separate from each other at the scan rate of 100 mVs(-1) with a potential difference of 270 mV, 150 mV and 260 mV for the oxidation peak potentials of AA-DA, DA-UA and UA-Trp, respectively, which was large enough to simultaneous determine AA, DA, UA and Trp. The catalytic peak current obtained, was linearly dependent on the AA, DA, UA and Trp concentrations in the range of 7.77-833 μM, 7.35-833 μM, 0.23-83.3 μM and 0.074-34.5 μM and the detection limits for AA, DA, UA and Trp were 1.11, 1.05, 0.033 and 0.011 μM, respectively. The analytical performance of this sensor has been evaluated for simultaneous detection of AA, DA, UA and Trp in human serum and urine samples.