Molecular Structural Analysis of Porcine CMAH-Native Ligand Complex and High Throughput Virtual Screening to Identify Novel Inhibitors

Porcine meat is the most consumed red meat worldwide. Pigs are also vital tools in biological and medical research. However, xenoreactivity between porcine's N-glycolylneuraminic acid (Neu5Gc) and human anti-Neu5Gc antibodies poses a significant challenge. On the one hand, dietary Neu5Gc intake has been connected to particular human disorders. On the other hand, some pathogens connected to pig diseases have a preference for Neu5Gc. The Cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) catalyses the conversion of N-acetylneuraminic acid (Neu5Ac) to Neu5Gc. In this study, we predicted the tertiary structure of CMAH, performed molecular docking, and analysed the protein-native ligand complex. We performed a virtual screening from a drug library of 5M compounds and selected the two top inhibitors with Vina scores of -9.9 kcal/mol for inhibitor 1 and -9.4 kcal/mol for inhibitor 2. We further analysed their pharmacokinetic and pharmacophoric properties. We conducted stability analyses of the complexes with molecular dynamic simulations of 200 ns and binding free energy calculations. The overall analyses revealed the inhibitors' stable binding, which was further validated by the MMGBSA studies. In conclusion, this result may pave the way for future studies to determine how to inhibit CMAH activities. Further in vitro studies can provide in-depth insight into these compounds' therapeutic potential

One more rep! The case for resistance training in young cancer survivors

Resistance training is now seen as a powerful tool to improve the health and functionality of cancer survivors. Literature shows that it can be implemented both during and after cancer treatment, with the intent of preserving muscle mass in the former and increasing muscle mass in the latter case. However, currently available data on this matter are predominantly derived from adult cancer survivors (ACS), and it is questionable whether the exact same raining regimen should be implemented in young cancer survivors (YCS) given the unique challenges they experience throughout their disease trajectory. Therefore, the goal of this work is to distill the existing evidence on resistance training (RT) interventions in ACS and facilitate discussion on whether the same patterns of RT can be applied in YCS

Choose the healthy way! Physical activity as a tool to improve mental health in young cancer survivors

N

Choose the healthy way! Physical activity as a tool to improve mental health in young cancer survivors

The progress in medical sciences has dramatically improved the survival probability of youth affected by cancer. Nevertheless, young cancer survivors continue experiencing side effects even months or years after therapy completion, both physical and psychological

An Overview of the Importance and Value of Porcine Species in Sialic Acid Research

Humans frequently interact with pigs, whose meat is also one of the primary sources of animal protein. They are one of the main species at the center of sialic acid (Sia) research. Sias are sugars at terminals of glycoconjugates, are expressed at the cell surfaces of mammals, and are important in cellular interactions. N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac) are notable Sias in mammals. Cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) encodes the CMAH enzyme that biosynthesizes Neu5Gc. Although humans cannot endogenously synthesize Neu5Gc due to the inactivation of this gene by a mutation, Neu5Gc can be metabolically incorporated into human tissues from red meat consumption. Interactions between Neu5Gc and human anti-Neu5Gc antibodies have been associated with certain diseases and disorders. In this review, we summarized the sialic acid metabolic pathway, its regulation and link to viral infections, as well as the importance of the pig as a model organism in Sia research, making it a possible source of Neu5Gc antigens affecting human health. Future research in solving the structures of crucial enzymes involved in Sia metabolism, as well as their regulation and interactions with other enzymes, especially CMAH, could help to understand their function and reduce the amount of Neu5Gc

An In Silico Functional Analysis of Non-Synonymous Single-Nucleotide Polymorphisms of Bovine <i>CMAH</i> Gene and Potential Implication in Pathogenesis

The sugar molecule N-glycolylneuraminic acid (Neu5Gc) is one of the most common sialic acids discovered in mammals. Cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) catalyses the conversion of N-acetylneuraminic acid (Neu5Ac) to Neu5Gc, and it is encoded by the CMAH gene. On the one hand, food metabolic incorporation of Neu5Gc has been linked to specific human diseases. On the other hand, Neu5Gc has been shown to be highly preferred by some pathogens linked to certain bovine diseases. We used various computational techniques to perform an in silico functional analysis of five non-synonymous single-nucleotide polymorphisms (nsSNPs) of the bovine CMAH (bCMAH) gene identified from the 1000 Bull Genomes sequence data. The c.1271C>T (P424L) nsSNP was predicted to be pathogenic based on the consensus result from different computational tools. The nsSNP was also predicted to be critical based on sequence conservation, stability, and post-translational modification site analysis. According to the molecular dynamic simulation and stability analysis, all variations promoted stability of the bCMAH protein, but mutation A210S significantly promoted CMAH stability. In conclusion, c.1271C>T (P424L) is expected to be the most harmful nsSNP among the five detected nsSNPs based on the overall studies. This research could pave the way for more research associating pathogenic nsSNPs in the bCMAH gene with diseases

Experiences, behaviours, and perspectives of young cancer survivors on physical activity

This narrative review aimed to identify young cancer survivors’ behaviours, experiences, and perspectives concerning physical activity, and identify useful strategies for promoting a healthy lifestyle. A manual search on the following databases was conducted: PubMed, Scopus, and Web of Science. The search was conducted between June 1, 2023, and April 12, 2024. Articles published from database inception up to April 12, 2024, were retrieved. Articles published in any language were considered. Perspectives including ideas, perceived barriers, and facilitators have been identified. Young cancer survivors seem to engage in physical activity as a useful coping strategy to regain normality and keep healthy after the cancer diagnosis. Although emotional and social support seems fundamental to increase participation, several other factors, including physical limitations, fatigue, sex, cancer type, and socio-economic status can influence physical activity participation. For those engaged in physical activity, the preferred activities are walking, biking, going to the gym, and exercising at home, while the least preferred are exercising at the hospital or boot camp-based exercises. Yoga is more frequently chosen by those still under treatment. Young cancer survivors appear to have unique needs different from those of adult cancer survivors. Mode of treatment delivery, increased awareness concerning the effects of physical activity, including families and friends, connecting survivors, and providing social support together with increasing motivation are key strategies for the promotion of physical activity in young cancer survivors. Fitness and healthcare professionals should consider these aspects to increase young cancer survivors' involvement in physical activities