Investigating the mortality trend of gastrointestinal cancers in Babol, North Iran (2013-2021).

BACKGROUND AND AIM: This study aims to examine the mortality rate and trend of gastrointestinal cancers, particularly gastric cancer, as the leading cause of death among cancers in northern Iran over a 9-year period. In light of the changing incidence and mortality rates of cancer in Iran and around the world, the importance of these diseases in people's lives, and the necessity of updating and monitoring the trend of cancer mortality, we have decided to report on the mortality trend of gastrointestinal cancers, based on crude and age-standardized rates. METHOD: This study is a cross-sectional examination of deaths caused by gastrointestinal cancers in Babol city, Iran, between 2013 and 2021. Data was collected from the cause of death registration and classification system of Babol University of Medical Sciences. Population estimation was obtained from the latest census reports. The crude and age-standardized mortality rates and trends of the cancers were calculated. RESULTS: Overall, there were 1345 deaths from gastrointestinal cancers with an average age of 69.11 ± 14.25 years. The crude and age-standardized rates of these cancers rose from 24.1 to 20.1 per hundred thousand people in 2012 to 29.5 and 25.5 per hundred thousand people, respectively. This trend became more prevalent significantly with the increase of each decade of age for both men (P-value Trend = 0.002) and women (P-value Trend = 0.012). An analysis of gastrointestinal cancers revealed a decreasing trend for cancers of the small intestine, an increasing trend for cancers of the colon, pancreas, and gallbladder, and a stable trend for the remaining cancers over the study period. CONCLUSION: The age-standardized rate and the number of gastrointestinal cancers is rising, highlighting the importance of preventative measures such as screening, increasing public awareness, and appropriate diagnostic methods.

AI-driven covalent drug design strategies targeting main protease (mpro) against SARS-CoV-2: structural insights and molecular mechanisms.

The emergence of new SARS-CoV-2 variants has raised concerns about the effectiveness of COVID-19 vaccines. To address this challenge, small-molecule antivirals have been proposed as a crucial therapeutic option. Among potential targets for anti-COVID-19 therapy, the main protease (Mpro) of SARS-CoV-2 is important due to its essential role in the virus's life cycle and high conservation. The substrate-binding region of the core proteases of various coronaviruses, including SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV), could be used for the generation of new protease inhibitors. Various drug discovery methods have employed a diverse range of strategies, targeting both monomeric and dimeric forms, including drug repurposing, integrating virtual screening with high-throughput screening (HTS), and structure-based drug design, each demonstrating varying levels of efficiency. Covalent inhibitors, such as Nirmatrelvir and MG-101, showcase robust and high-affinity binding to Mpro, exhibiting stable interactions confirmed by molecular docking studies. Development of effective antiviral drugs is imperative to address potential pandemic situations. This review explores recent advances in the search for Mpro inhibitors and the application of artificial intelligence (AI) in drug design. AI leverages vast datasets and advanced algorithms to streamline the design and identification of promising Mpro inhibitors. AI-driven drug discovery methods, including molecular docking, predictive modeling, and structure-based drug repurposing, are at the forefront of identifying potential candidates for effective antiviral therapy. In a time when COVID-19 potentially threat global health, the quest for potent antiviral solutions targeting Mpro could be critical for inhibiting the virus.Communicated by Ramaswamy H. Sarma.

An overview of the vaccine platforms to combat COVID-19 with a focus on the subunit vaccines.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that has caused the recent coronavirus disease (COVID-19) global pandemic. The current approved COVID-19 vaccines have shown considerable efficiency against hospitalization and death. However, the continuation of the pandemic for more than two years and the likelihood of new strain emergence despite the global rollout of vaccination highlight the immediate need for the development and improvement of vaccines. mRNA, viral vector, and inactivated virus vaccine platforms were the first members of the worldwide approved vaccine list. Subunit vaccines. which are vaccines based on synthetic peptides or recombinant proteins, have been used in lower numbers and limited countries. The unavoidable advantages of this platform, including safety and precise immune targeting, make it a promising vaccine with wider global use in the near future. This review article summarizes the current knowledge on different vaccine platforms, focusing on the subunit vaccines and their clinical trial advancements against COVID-19.

In silico design of a multi-epitope vaccine against the spike and the nucleocapsid proteins of the Omicron variant of SARS-CoV-2.

Computational studies can comprise an effective approach to treating and preventing viral infections. Since 2019, the world has been dealing with the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The most important achievement in this short period of time in the effort to reduce morbidity and mortality was the production of vaccines and effective antiviral drugs. Although the virus has been significantly suppressed, it continues to evolve, spread, and evade the host's immune system. Recently, researchers have turned to immunoinformatics tools to reduce side effects and save the time and cost of traditional vaccine production methods. In the present study, an attempt has been made to design a multi-epitope vaccine with humoral and cellular immune response stimulation against the Omicron variant of SARS-CoV-2 by investigating new mutations in spike (S) and nucleocapsid (N) proteins. The population coverage of the vaccine was evaluated as appropriate compared to other studies. The results of molecular dynamics simulation and molecular mechanics/generalized Born surface area (MM/GBSA) calculations predict the stability and proper interaction of the vaccine with Toll-like receptor 4 (TLR-4) as an innate immune receptor. The results of the immune simulation show a significant increase in the coordinated response of IgM and IgG after the third injection of the vaccine. Also, in the continuation of the research, spike proteins from BA.4 and BA.5 lineages were screened by immunoinformatics filters and effective epitopes were suggested for vaccine design. Despite the high precision of computational studies, in-vivo and in-vitro research is needed for final confirmation.Communicated by Ramaswamy H. Sarma.

The study of trends in mortality of respiratory system cancers in Babol, North of Iran (2013-2021).

Background: In Iran, cancers are known as the second leading cause of death, among which respiratory system cancers are particularly important because lung cancer is the second most common cause of death in this country. This study aimed to estimate the crude and age-standardized mortality and its trends during 9 years in the Northern city of Iran, Babol. Methods: In this cross-sectional study, all the recorded deaths due to respiratory system cancers in Babol during the years 2013-2021 on the Classification of Causes of Deaths and Death Registration System of Babol University of Medical Sciences were taken into consideration, and the population estimate was based on the latest census. Finally, the crude and age-standardized rates of mortality and trends of cancer incidents were calculated. Results: In general, 393 deaths with an overall mean age of 67.8±3.9 years have happened due to respiratory system cancers. The crude and standardized rates of respiratory system cancers increased from 6.5 and 5.5 per hundred thousand people in 2013 to 9.1 and 7.8 per hundred thousand people in 2021, respectively. With each decade in age, their trends increased significantly in men (p=0.024) and remained constant in women (p=0.262). In examining the trend of respiratory system cancers, we found an increasing trend for lung cancer and a constant trend for larynx and oropharynx cancers. There was also a decreasing trend for hypopharyngeal cancer. Conclusions: The age-standardized rate and trend of respiratory system cancers are increasing. Therefore, it is important to prevent their prevalence by reducing the risk factors and increasing the general awareness of risks and timely diagnosis.

Insights into the structural peculiarities of the N-terminal and receptor binding domains of the spike protein from the SARS-CoV-2 Omicron variant.

Since the new variant of SARS-CoV-2, Omicron (BA.1) has raised serious concerns, it is important to investigate the effects of mutations in the NTD and RBD domains of the spike protein for the development of COVID-19 vaccines. In this study, computational analysis of the Wuhan and Omicron NTDs and RBDs in their unbound and bound states to mAb 4A8 and ACE2 were performed. In addition, the interaction of NTD with antibody and RBD with ACE2 were evaluated in the presence of long glycans. The results show that long glycans at the surface of NTDs can reduce the accessibility of protein epitopes, thereby reducing binding efficiency and neutralizing potency of specific antibodies. Also, our findings indicate that the existence of the long glycans result in increased stability and enhanced affinity of the RBD to ACE2 in the Wuhan and Omicron variant. Key residues that play an important role in increasing the structural stability of the protein were identified using RIN analysis and in the state of interaction with mAb 4A8 and ACE2 through per-residue decomposition analysis. Further, the results of the free energy binding calculation using MM/GBSA method show that the Omicron variant has a higher infectivity than the Wuhan. This study provides a better understanding of the structural changes in the spike protein and can be useful for the development of novel therapeutics.

The First Step of Health Policy-Making for Lifestyle Modifications at Middle Age: Problem Identification in 40- to 60-Year-Old Population, Northern Iran.

Background: The purpose of this study was to determine the current situation of lifestyle behaviors and related outcomes, as the first step to make proper local health policies for improvement of health lifestyle behaviors. Materials and Methods: This analytic research has been conducted as a cross-sectional study on the middle-aged (40-60 years old) population of Amirkola, Northern Iran. The Persian translation of the Health-Promoting Lifestyle Profile II questionnaire and the International Physical Activity Questionnaire were used for data collection. Also, anthropometric variables, blood pressure, fasting blood sugar, and serum lipids profile were examined. Results: Three hundred one individuals have been enrolled in the study. Results showed that 10.6% of the participants had unhealthy lifestyle behaviors in the subdomain of spiritual growth; 46.8% in the subdomain of health responsibility; and 48.2% in the subdomains of stress management, physical activity, and nutrition; men had more physical activity than women (p < 0.001). Totally, 189 persons (63.9%) had serum cholesterol greater than or equal to 200 mg/dL; seventy-five individuals (25%) had high blood pressure. One hundred twenty-six persons (81.8%) of women and 103 (70.1%) of men were overweight or obese. Conclusions: Health lifestyle behaviors in 40- to 60-year-old population need a proper intervention to improve the current situation.

Family Planning Practice by Patterns of Marriage in the North of Iran.

BACKGROUND: The fertility experience in Iran suggests that the family planning programs had an effective role in the fertility reduction. This study aimed to specify patterns of marriage in Iran and especially in a northern city of Iran and to investigate the association between patterns of marriage and contraceptive use before first pregnancy and current contraceptive use. METHODS: In this cross-sectional study, following the implementation of an expert panel in order to investigate marriage patterns, 880 women aged 15-49 yr old, were selected by multistage cluster sampling and completed the "reproductive practices" questionnaire in Babol City, northern Iran, in 2013. The data were analyzed using IBM SPSS ver.16 and descriptive and analytical parameters. RESULTS: There are three patterns of marriage in the northern part of Iran: Traditional, Mixed and Modern marriage and between different patterns there is no statistically significant difference in the contraceptive use. CONCLUSION: According to the lack of significant relationship between patterns of marriage and the contraceptives use, which is one of the proximate determinants of fertility, the policy makers should pay attention to other determinants of fertility in order to manage the problems and implications of population decline in the country.