Background: Targeted therapy is a novel, promising approach to anticancer treatment that endeavors to overcome drug resistance to traditional chemotherapies. Patients with the L858R mutation in epidermal growth factor receptor (EGFR) respond to the first generation tyrosine kinase inhibitors (TKIs); however, after one year of treatment, they may become resistant. The T790M mutation is the most probable cause for drug resistance. Third generation drugs, including Osimertinib (AZD9291), are more effective against T790M and other sensitive mutations. Osimertinib is effective against the L844V mutation, has conditional effectiveness for the L718Q mutation, and is ineffective for the Cys797Ser (C797S) mutation. Cells that have both the T790M and C797 mutations are more resistant to third generation drugs. Although research has shown that Osimertinib is an effective treatment for EGFR L844V cells, this has not been shown for cells that have the C797S mutation. This molecular mechanism has not been well-studied.Methods: In the present study, we used the GROMACS software for molecular dynamics simulation to identify interactions between Osimertinib and the kinase part of EGFR in L844V and C797S mutants.
Results:We evaluated native EGFR protein and the L844V and C797S mutations' docking and binding energy, kI, intermolecular, internal, and torsional energy parameters. Osimertinib was effective for the EGFR L844V mutation, but not for EGFR C797S. All simulations were validated by rootmean-square deviation (RMSD), root-mean square fluctuation (RMSF), and radius of gyration (ROG).
Background: Different studies have investigated the association between p53 codon 72 Arg>Pro polymorphism and cancer risk.
Because of the lack of consensus of the results in individual studies, we conducted this meta-analysis by pooling all currently available
case–control studies to estimate the effect of p53 codon 72 Arg/Pro polymorphism on cancer susceptibility in Iranian population.
Methods: A comprehensive search was undertaken and primary data from all peer-reviewed journals indexed in PubMed, Google
Scholar, Scopus, Magiran, Scientific Information Databank (SID), Iran Medex, and CAB abstract electronic were used to conduct this
meta-analysis. We considered some exclusion and inclusion criteria to select the articles. Statistical heterogeneity was explored using
the I-square. Publication bias was assessed graphically and statistically by Begg’s funnel plot and Egger test. All statistical analyses
were performed using StatsDirect software and a two- tailed test. P-value less than 0.05 was considered statistically significant for any
test.
Results: Our dataset, which included 35 case-control studies, consisted of 2426 cancer cases and 2928 controls. Pooled OR and
95%CI indicated that codon 72 Arg>Pro polymorphism was not associated with odds of developing cancer among Iranian population
in the dominant model (Pro/Pro+Arg/Pro vs. Arg/Arg: OR= 0.96, 95%CI= 0.74 to 1.24 chi2= 0.06, p= 0.8). Moreover, no significant
association was detected in variant allele (Pro vs Arg: OR= 1.075, 95%CI= 0.91 to 1.25), homozygous (Pro/Pro vs Arg/Arg:
OR=0.911 95%CI= 0.66 to 1.25), and heterozygous (Arg/Pro vs Arg/Arg: OR= 0.84, 95%CI= 0.7 to 1).
Conclusion: Our study revealed that p53 codon 72 Arg>Pro polymorphism was not associated with overall cancer odds in Iranian
population.
Since the ongoing pandemic of COVID-19, caused by SARS-CoV-2, has had a signifi cant impact on public health and, also the clinical benefi ts of the medications are so limited, preventive measures may be able to help control its spread. Because the petroleum jelly compound could alter the physicochemical properties that affect adhesion, we investigated the preventive role of Petroleum jelly on covid-19 infection. Forty people with no sign and no history of covid-19 infection, were included in this study. They use petroleum jelly (Vaseline) nasally twice a day for about two months. After that time, participants tested by RT-qPCR to determine any infection with SARS-CoV-2 virus. There was a signifi cant difference in terms of RT-qPCR results between the intervention and control groups. Petroleum jelly may be effective in preventing covid-19 infection (Tab. 2, Fig. 1, Ref. 13).
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