Background Metabolic profiling of blood metabolites, particularly in plasma and serum, is vital for studying human diseases, human conditions, drug interventions and toxicology. The clinical significance of blood arises from its close ties to all human cells and facile accessibility. However, patient-specific variables such as age, sex, diet, lifestyle and health status, along with pre-analytical conditions (sample handling, storage, etc.), can significantly affect metabolomic measurements in whole blood, plasma, or serum studies. These factors, referred to as confounders, must be mitigated to reveal genuine metabolic changes due to illness or intervention onset. Review objective This review aims to aid metabolomics researchers in collecting reliable, standardized datasets for NMR-based blood (whole/serum/plasma) metabolomics. The goal is to reduce the impact of confounding factors and enhance inter-laboratory comparability, enabling more meaningful outcomes in metabolomics studies. Key concepts This review outlines the main factors affecting blood metabolite levels and offers practical suggestions for what to measure and expect, how to mitigate confounding factors, how to properly prepare, handle and store blood, plasma and serum biosamples and how to report data in targeted NMR-based metabolomics studies of blood, plasma and serum.

Conformational diseases are caused by the aggregation of misfolded proteins. The risk for such pathologies develops years before clinical symptoms appear, and is higher in people with alpha-1 antitrypsin (AAT) polymorphisms. Thousands of people with alpha-1 antitrypsin deficiency (AATD) are underdiagnosed. Enemy-aggregating proteins may reside in these underdiagnosed AATD patients for many years before a pathology for AATD fully develops. In this perspective review, we hypothesize that the AAT protein could exert a new and previously unconsidered biological effect as an endogenous metal ion chelator that plays a significant role in essential metal ion homeostasis. In this respect, AAT polymorphism may cause an imbalance of metal ions, which could be correlated with the aggregation of amylin, tau, amyloid beta, and alpha synuclein proteins in type 2 diabetes mellitus (T2DM), Alzheimer's and Parkinson's diseases, respectively.

Background: The incidence of early‐onset colorectal cancer (EO‐CRC) has been consistently rising leading to a significant cancer burden among younger adults in Asian and Middle Eastern high‐income countries. The study aims to investigate the survival outcomes of EO‐CRC among high‐income Asian and Middle Eastern populations from 1990 to 2019 using the mortality‐to‐incidence ratio, with a focus on examining the differences in gender.Methods: This is a systematic analysis of the Global Burden of Disease (GBD) 2019 study. We include individuals aged 15 to 49 years old in high‐income Asian and the Middle Eastern countries. The colorectal cancer mortality‐to‐incidence ratio (MIR) was calculated for both genders by dividing the age‐specific mortality rate per 100,000 for colorectal cancer by the age‐specific incidence rate per 100,000 for each nation in the sample for a given year.Results: An overall decline in male and female MIR was observed from 1990 to 2019 in Asian and Middle Eastern countries. Ten out of thirteen Asian and Middle Eastern countries had a higher female MIR compared to their male counterparts. The global male MIR was found to be significantly higher than that of female (p‐value 0.008, coefficient estimate: 1.51). In Middle Eastern countries, Saudi Arabia had a significantly higher female MIR compared to their male counterparts (p < 0.0001, coefficient estimate: 12.65).Conclusion: This research addresses the knowledge gap concerning gender‐based differences in EO‐CRC survival outcomes in high‐income Asian and Middle Eastern countries, providing insights into the factors influencing these disparities in these regions. Policymakers should focus on developing targeted prevention and treatment programs for women, and addressing cultural and social barriers that may prevent women from seeking timely medical care.

Early-onset colorectal cancer (EO-CRC) incidence and prevalence trends in the rise in high income countries, such as the Gulf Cooperation Council (GCC) countries. The study aimed to offer an up-to-date assessment of the overall burden of CRC, and EO-CRC in GCC countries and project its incidence and mortality in 2030. The prevalence, incidence, mortality, years of life lived with disability (YLDs), and disability-adjusted life years (DALYs) of CRC were obtained from the Global Burden of Disease (GBD) Study 2019. The incidence and mortality of CRC, and EO-CRC up to 2030 were predicted. All GCC countries showed a higher annual average percentage changes (AAPC) AAPC incidence rate for EO-CRC compared to CRC. In Saudi Arabia the number of CRC cases has increased from 1990 1484.57; (95 % UI 1987.98,1083.86) 11.4-fold-increase to 16991.83; (95 % UI 21754.79,12892.12) in 2019. In 2030, the total incidence cases of CRC for the six Gulf countries are expected to reach 13,339 thousand, primarily driven by Saudi Arabia with 7,910.19 cases. In 2030, the CRC mortality rate is projected to be 7,647 cases, with nearly 57 % of CRC mortality cases anticipated in Saudi Arabia. This study sheds light on the alarming rise in CRC and EO-CRC across Gulf countries from 1990 to 2019, emphasizing Saudi Arabia's significant burden. It projects a concerning increase in CRC incidence and mortality by 2030, primarily in Saudi Arabia, and highlights the need for immediate public health interventions.

Prion diseases are a group of rare neurodegenerative disorders that develop as a result of the conformational conversion of normal prion protein (PrP^C) to the disease-associated isoform (PrP^Sc). The mechanism that actually causes disease remains unclear. However, the mechanism underlying the conformational transformation of prion protein is partially understood—in particular, there is strong evidence that copper ions play a significant functional role in prion proteins and in their conformational conversion. Various models of the interaction of copper ions with prion proteins have been proposedfor theCu (II)-binding, cell-surfaceglycoprotein known as prion protein(PrP).Changes in the concentration of copper ions in the brain have been associated with prion diseases and there is strong evidence that copper plays a significant functional role in the conformational conversion of PrP. Nevertheless, because copper ions have been shown to have both a positive and negative effect on prion disease onset, the role played by Cu (II) ions in these diseases remains a topic of debate. Because of the unique properties of paramagnetic Cu (II) ions in the magnetic field, their interactions with PrP can be tracked even at single atom resolution using nuclear magnetic resonance (NMR) spectroscopy. Various NMR approaches have been utilized to study the kinetic, thermodynamic, and structural properties of Cu (II)-PrP interactions. Here, we highlight the different models of copper interactions with PrP with particular focus on studies that use NMR spectroscopy to investigate the role played by copper ions in prion diseases.

The MCPH1 gene, also known as BRCT-repeat inhibitor of hTERT expression (BRIT1), has three BRCA1 carboxyl-terminal domains which is an important regulator of DNA repair, cell cycle checkpoints and chromosome condensation. MCPH1/BRIT1 is also known as a tumour suppressor in different types of human cancer. The expression level of the MCPH1/BRIT1 gene is decreased at the DNA, RNA or protein level in a number of types of cancers including breast cancer, lung cancer, cervical cancer, prostate cancer and ovarian cancer compared to normal tissue. This review also showed that deregulation of MCPH1/BRIT1 is significantly associated with reduced overall survival in 57% (12/21) and relapsed free survival in 33% (7/21) of cancer types especially in oesophageal squamous cell carcinoma and renal clear cell carcinoma. A common finding of this study is that the loss of MCPH1/BRIT1 gene expression plays a key role in promoting genome instability and mutations supporting its function as a tumour suppressor gene.