Computational study of SENP1 in cancer by novel natural compounds and ZINC database screening

Introduction: Sentrin-specific protease 1 (SENP1) is a protein whose main function is deSUMOylation. SENP1 inhibits apoptosis, and increases angiogenesis, estrogen and androgen receptor transcription and c-Jun transcription factor, proliferation, growth, cell migration, and invasion of cancer. The in vivo and in vitro studies also demonstrated which natural compounds, especially phytochemicals, minerals, and vitamins, prevent cancer. More than 3,000 plant species have been reported in modern medicine. Natural compounds have many anti-cancerous andanti-turmeric properties such as antioxidative, antiangiogenic, antiproliferative, and pro-apoptotic properties.Methods: In this study, we investigated the interaction of some natural compounds with SENP1 to inhibit its activity. We also screened the ZINC database including natural compounds. Molecular docking was performed, and toxicity of compounds was determined; then, molecular dynamics simulation (MDS) and essential dynamics (ED) were performed on natural compounds with higher free binding energies and minimal side effects. By searching in a large library, virtual screening of the ZINC database was performed using LibDock and CDOCKER, and the final top 20 compounds were allowed for docking against SENP1. According to the docking study, the top three leading molecules were selected and further analyzed by MDS and ED.Results: The results suggest that resveratrol (from the selected compounds) and ZINC33916875 (from the ZINC database) could be more promising SENP1 inhibitory ligands.Discussion: Because these compounds can inhibit SENP1 activity, then they can be novel candidates for cancer treatment. However, wet laboratory experiments are needed to validate their efficacy as SENP1 inhibitors

Gastric cancer biomarkers; A systems biology approach

Gastric cancer is one of the most fatal cancers in the world. Many efforts in recent years have attempted to find effective proteins in gastric cancer. By using a comprehensive list of proteins involved in gastric cancer, scientists were able to retrieve interaction information. The study of protein-protein interaction networks through systems biology based analysis provides appropriate strategies to discover candidate proteins and key biological pathways.In this study, we investigated dominant functional themes and centrality parameters including betweenness as well as the degree of each topological clusters and expressionally active sub-networks in the resulted network. The results of functional analysis on gene sets showed that neurotrophin signaling pathway, cell cycle and nucleotide excision possess the strongest enrichment signals. According to the computed centrality parameters, HNF4A, TAF1 and TP53 manifested as the most significant nodes in the interaction network of the engaged proteins in gastric cancer. This study also demonstrates pathways and proteins that are applicable as diagnostic markers and therapeutic targets for future attempts to overcome gastric cancer. Keywords: Gastric cancer, Systems biology, Neurotrophin signaling pathway, HNF4A, TAF1, TP5

Monte carlo simulation of siemens oncor linear accelerator with beamnrc and dosxyznrc code

The Monte Carlo method is the most accurate method for simulation of radiation therapy equipment. The linear accelerators (linac) are currently the most widely used machines in radiation therapy centers. In this work, a Monte Carlo modeling of the Siemens ONCOR linear accelerator in 6 MV and 18 MV beams was performed. The results of simulation were validated by measurements in water by ionization chamber and extended dose range (EDR2) film in solid water. The linac′s X-ray particular are so sensitive to the properties of primary electron beam. Square field size of 10 cm Χ 10 cm produced by the jaws was compared with ionization chamber and film measurements. Head simulation was performed with BEAMnrc and dose calculation with DOSXYZnrc for film measurements and 3ddose file produced by DOSXYZnrc analyzed used homemade MATLAB program. At 6 MV, the agreement between dose calculated by Monte Carlo modeling and direct measurement was obtained to the least restrictive of 1%, even in the build-up region. At 18 MV, the agreement was obtained 1%, except for in the build-up region. In the build-up region, the difference was 1% at 6 MV and 2% at 18 MV. The mean difference between measurements and Monte Carlo simulation is very small in both of ONCOR X-ray energy. The results are highly accurate and can be used for many applications such as patient dose calculation in treatment planning and in studies that model this linac with small field size like intensity-modulated radiation therapy technique

Prognostic correlation of NOTCH1 and SF3B1 mutations with chromosomal abnormalities in chronic lymphocytic leukemia patients

Abstract Background and Aim Chronic lymphocytic leukemia (CLL) is a monoclonal malignancy of B lymphocytes. Since common mutations in NOTCH1 and SF3B1, along with other possible chromosomal alterations, change disease severity and survival of patients with CLL, we aimed to evaluate the correlation of common mutations in NOTCH1 and SF3B1 as the poor prognostic markers with chromosomal abnormalities and clinical hematology. Method This retrospective study was performed on the peripheral blood of 51 patients diagnosed before chemotherapy with CLL. G‐banding karyotype and FISH were performed. For NOTCH1, exon 34 and for SF3B1, exons 14,15,16 were assessed using Sanger sequencing. Results The mutation frequency of NOTCH1 and SF3B1 with the pathogenic clinical status was 6:51 (11.76%), and variants obtained from both genes were 9:51 (17.64%). The frequency of SF3B1 mutation (K666E) was higher than in previous studies (p‐value <.05). There was a significant correlation between NOTCH1 mutations and del17p13 (p‐value = .068), also SF3B1 mutations with del11q22 (p‐value = .095) and del13q14 (p‐value = .066). Up to 90% of the specific stimuli used for the G‐banding karyotype successfully identified the malignant clone. There was a significant relationship between the cluster of differentiation 38 (CD38) expression level and NOTCH1 mutations (p‐value = .019) and a significant correlation between Binet classification and the SF3B1 (p‐value = .096). Conclusion The correlation of NOTCH1 and SF3B1 mutations with chromosomal abnormalities and CD38 expression may reveal the overall patient's survival rate. The mutations may be effective in the clonal expansion and progression of CLL, particularly in the diagnosis stage, as well as the control and management of the treatment

Outcomes and Their State-level Variation in Patients Undergoing Surgery With Perioperative SARS-CoV-2 Infection in the USA. A Prospective Multicenter Study

Objective: To report the 30-day outcomes of patients with perioperative SARS-CoV-2 infection undergoing surgery in the USA. Background: Uncertainty regarding the postoperative risks of patients with SARS-CoV-2 exists. Methods: As part of the COVIDSurg multicenter study, all patients aged ≥17 years undergoing surgery between January 1 and June 30, 2020 with perioperative SARS-CoV-2 infection in 70 hospitals across 27 states were included. The primary outcomes were 30-day mortality and pulmonary complications. Multivariable analyses (adjusting for demographics, comorbidities, and procedure characteristics) were performed to identify predictors of mortality. Results: A total of 1581 patients were included; more than half of them were males (n = 822, 52.0%) and older than 50 years (n = 835, 52.8%). Most procedures (n = 1261, 79.8%) were emergent, and laparotomies (n = 538, 34.1%). The mortality and pulmonary complication rates were 11.0 and 39.5%, respectively. Independent predictors of mortality included age ≥70 years (odds ratio 2.46, 95% confidence interval [1.65-3.69]), male sex (2.26 [1.53-3.35]), ASA grades 3-5 (3.08 [1.60-5.95]), emergent surgery (2.44 [1.31-4.54]), malignancy (2.97 [1.58-5.57]), respiratory comorbidities (2.08 [1.30-3.32]), and higher Revised Cardiac Risk Index (1.20 [1.02-1.41]). While statewide elective cancelation orders were not associated with a lower mortality, a sub-analysis showed it to be associated with lower mortality in those who underwent elective surgery (0.14 [0.03-0.61]). Conclusions: Patients with perioperative SARS-CoV-2 infection have a significantly high risk for postoperative complications, especially elderly males. Postponing elective surgery and adopting non-operative management, when reasonable, should be considered in the USA during the pandemic peaks