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Aberrant metabolism is the root cause of several serious health issues, creating a huge burden to health and leading to diminished life expectancy. A dysregulated metabolism induces the secretion of several molecules which in turn trigger the inflammatory pathway. Inflammation is the natural reaction of the immune system to a variety of stimuli, such as pathogens, damaged cells, and harmful substances. Metabolically triggered inflammation, also called metaflammation or low-grade chronic inflammation, is the consequence of a synergic interaction between the host and the exposome—a combination of environmental drivers, including diet, lifestyle, pollutants and other factors throughout the life span of an individual. Various levels of chronic inflammation are associated with several lifestyle-related diseases such as diabetes, obesity, metabolic associated fatty liver disease (MAFLD), cancers, cardiovascular disorders (CVDs), autoimmune diseases, and chronic lung diseases. Chronic diseases are a growing concern worldwide, placing a heavy burden on individuals, families, governments, and health-care systems. New strategies are needed to empower communities worldwide to prevent and treat these diseases. Precision medicine provides a model for the next generation of lifestyle modification. This will capitalize on the dynamic interaction between an individual’s biology, lifestyle, behavior, and environment. The aim of precision medicine is to design and improve diagnosis, therapeutics and prognostication through the use of large complex datasets that incorporate individual gene, function, and environmental variations. The implementation of high-performance computing (HPC) and artificial intelligence (AI) can predict risks with greater accuracy based on available multidimensional clinical and biological datasets. AI-powered precision medicine provides clinicians with an opportunity to specifically tailor early interventions to each individual. In this article, we discuss the strengths and limitations of existing and evolving recent, data-driven technologies, such as AI, in preventing, treating and reversing lifestyle-related diseases.

Metastasis is the leading cause of cancer-related mortality, representing a highly coordinated, multistep process in which malignant cells gain the ability to invade, survive in the circulation, and establish secondary tumors at distant sites. While genetic mutations initiate oncogenesis, accumulating evidence shows that epigenetic and epitranscriptomic regulators, encompassing DNA methylation, RNA modifications, and noncoding RNAs (ncRNAs), reshape metastatic phenotypes. This review integrates current insights into these mechanisms and their crosstalk, with a primary focus on their methylation modification. Given their plasticity and potential reversibility, these regulators are attractive targets for therapeutic intervention. Defining the dynamic interplay between DNA and RNA modifications and ncRNAs provides a coherent framework for controlling metastasis and guides the development of precision epigenetic strategies and biomarkers. Future research that integrates multi-omics approaches and spatial transcriptomics will be essential for revealing the epigenetic and epitranscriptomic layers of the metastatic landscape.

Qatar's cancer care strategy is shaped by the National Cancer Strategy (2011) and subsequent frameworks 2017–22, leading to the Qatar Cancer Plan 2023–2026. These initiatives emphasise prevention, early detection, and evidence-based management to reduce the effects of cancer on patients and the health-care system. Investments in advanced medical infrastructure, cutting-edge technology, and specialised professionals have considerably strengthened cancer care. However, challenges remain, including late-stage diagnoses and gaps in public awareness, which underscores the need for enhanced education and global collaboration. Precision medicine, public health initiatives, and research-driven policies position Qatar as a regional leader in oncology. By leveraging its robust health-care and research ecosystem, Qatar aims to advance cancer prevention, diagnosis, and treatment. Aligned with WHO Eastern Mediterranean region goals, the country strives to establish a model of excellence in oncological services.

Disparities in the genetic risk of cancer among various ancestry groups and populations remain poorly defined. This challenge is even more acute for Middle Eastern populations, where the paucity of genomic data could affect the clinical potential of cancer genetic risk profiling. We used data from the phase 1 cohort of the Qatar Genome Programme to investigate genetic variation in cancer-susceptibility genes in the Qatari population. The Qatar Genome Programme generated high-coverage genome sequencing on DNA samples collected from 6142 native Qataris, stratified into six distinct ancestry groups: general Arab, Persian, Arabian Peninsula, Admixture Arab, African, and South Asian. In this population-based, cohort study, we evaluated the performance of polygenic risk scores for the most common cancers in Qatar (breast, prostate, and colorectal cancers). Polygenic risk scores were trained in The Cancer Genome Atlas (TCGA) dataset, and their distributions were subsequently applied to the six different genetic ancestry groups of the Qatari population. Rare deleterious variants within 1218 cancer susceptibility genes were analysed, and their clinical pathogenicity was assessed by ClinVar and the CharGer computational tools. The cohort included in this study was recruited by the Qatar Biobank between Dec 11, 2012, and June 9, 2016. The initial dataset comprised 6218 cohort participants, and whole genome sequencing quality control filtering led to a final dataset of 6142 samples. Polygenic risk score analyses of the most common cancers in Qatar showed significant differences between the six ancestry groups (p<0·0001). Qataris with Arabian Peninsula ancestry showed the lowest polygenic risk score mean for colorectal cancer (−0·41), and those of African ancestry showed the highest average for prostate cancer (0·85). Cancer-gene rare variant analysis identified 76 Qataris (1·2% of 6142 individuals in the Qatar Genome Programme cohort) carrying ClinVar pathogenic or likely pathogenic variants in clinically actionable cancer genes. Variant analysis using CharGer identified 195 individuals carriers (3·17% of the cohort). Breast cancer pathogenic variants were over-represented in Qataris of Persian origin (22 [56·4%] of 39 BRCA1/BRCA2 variant carriers) and completely absent in those of Arabian Peninsula origin. We observed a high degree of heterogeneity for cancer predisposition genes and polygenic risk scores across ancestries in this population from Qatar. Stratification systems could be considered for the implementation of national cancer preventive medicine programmes. Qatar Foundation.

Cancer is a major cause of mortality and morbidity in the Middle East. Saudi Arabia, Qatar, and Jordan are home to more than 45 million people, and all three countries have had an upward trend in cancer incidence over the past three decades. In this Series paper, we analysed evidence from three publications in the Lancet Oncology on the current cancer burden, advancements in care, and remaining challenges. We also highlight future shared opportunities for collaboration between the three countries in the cancer control agenda. Notable progress has also been made in cancer care and research in all three countries. However, challenges persist in sustaining financial support for cancer care and addressing the high prevalence of established risk factors alongside a projected rise in incidence due to demographic changes. Our analysis indicates that this collaboration can harness many opportunities to both improve cancer care and reduce cancer incidence due to the similarities and shared goals among countries. These include collaboration on harmonised cancer registries, cross-border clinical trials, and regional leadership on clinical guidelines, prevention measures, and awareness.

Targeting of messenger RNAs (mRNAs) in neuron processes relies on cis ‐acting regulatory elements, the nature of which is poorly understood. Here, we report that approximately 30% of the best‐known dendritic mRNAs contain a guanine (G)–quadruplex consensus in their 3′‐untranslated region. Among these mRNAs, we show by using RNA structure probing that a G–quadruplex is present in the mRNAs of two key postsynaptic proteins: PSD‐95 and CaMKIIa. The G–quadruplex structure is necessary and sufficient for the potent and fast localization of mRNAs in cortical neurites and this occurs in a metabotropic glutamate receptor‐responsive manner. Thus, G–quadruplex seems to be a common neurite localization signal. Guanine‐quadruplex structures in the 3'‐UTR of neuronal mRNAs are shown to function as a neurite mRNA localization signal in mouse cortical neurons in a metabotrobic glutamate receptor‐responsive manner.

Thousands of long noncoding RNAs (lncRNAs) have been discovered, yet the function of the vast majority remains unclear. Here, we show that a p53-regulated lncRNA which we named PINCR (p53-induced noncoding RNA), is induced ~100-fold after DNA damage and exerts a prosurvival function in human colorectal cancer cells (CRC) in vitro and tumor growth in vivo. Targeted deletion of PINCR in CRC cells significantly impaired G1 arrest and induced hypersensitivity to chemotherapeutic drugs. PINCR regulates the induction of a subset of p53 targets involved in G1 arrest and apoptosis, including BTG2, RRM2B and GPX1. Using a novel RNA pulldown approach that utilized endogenous S1-tagged PINCR, we show that PINCR associates with the enhancer region of these genes by binding to RNA-binding protein Matrin 3 that, in turn, associates with p53. Our findings uncover a critical prosurvival function of a p53/PINCR/Matrin 3 axis in response to DNA damage in CRC cells. Though DNA contains the information needed to build the proteins that keep cells alive, only 2% of the DNA in a human cell codes for proteins. The remaining 98% is referred to as non-coding DNA. The information in some of these non-coding regions can still be copied into molecules of RNA, including long molecules called lncRNAs. Little is known about what lncRNAs actually do, but growing evidence suggests that these molecules are important for a number of vital processes including cell growth and survival. When the DNA in an animal cell gets damaged, the cell needs to decide whether to pause growth and repair the damage, or to kill itself if the harm is too great. One of the best-studied proteins guiding this decision is the p53 protein, which increases the number of protein-coding genes needed to carry out either option in this decision. That is to say that, p53 regulates the genes needed to kill the cell and the genes needed to temporarily pause its growth and repair the damage, which instead keeps the cell alive. So, how does the p53 protein guide the decision, and are lncRNA molecules involved? Using human colon cancer cells, Chaudhary et al. now report that when DNA is damaged, the levels of a specific lncRNA increase 100-fold. Further experiments showed that this lncRNA – named PINCR, which refers to p53-induced noncoding RNA – promotes the survival of cells. Chaudhary et al. showed that PINCR molecules do this by recruiting a protein called Matrin 3 to a certain region in the DNA called an enhancer and then links it to promoter region in the DNA of specific genes that temporarily pause cell growth but keep the cell alive. This in turn activates these ‘pro-survival genes’. In further experiments, when the PINCR molecules were essentially deleted, p53 was not able to fully activate these genes and as a result more of the cells died. Together these findings increase our knowledge of how lncRNAs can work, especially in the context of DNA damage in cancer cells. A next important step will be to uncover other roles for the PINCR molecule in both cancer and healthy cells.

The transcription factor caudal-type homeobox 1 (CDX1) is a key regulator of differentiation in the normal colon and in colorectal cancer (CRC). CDX1 activates the expression of enterocyte genes, but it is not clear how the concomitant silencing of stem cell genes is achieved. MicroRNAs (miRNAs) are important mediators of gene repression and have been implicated in tumor suppression and carcinogenesis, but the roles of miRNAs in differentiation, particularly in CRC, remain poorly understood. Here, we identified microRNA-215 (miR-215) as a direct transcriptional target of CDX1 by using high-throughput small RNA sequencing to profile miRNA expression in two pairs of CRC cell lines: CDX1-low HCT116 and HCT116 with stable CDX1 overexpression, and CDX1-high LS174T and LS174T with stable CDX1 knockdown. Validation of candidate miRNAs identified by RNA-seq in a larger cell-line panel revealed miR-215 to be most significantly correlated with CDX1 expression. Quantitative ChIP–PCR and promoter luciferase assays confirmed that CDX1 directly activates miR-215 transcription. miR-215 expression is depleted in FACS-enriched cancer stem cells compared with unsorted samples. Overexpression of miR-215 in poorly differentiated cell lines causes a decrease in clonogenicity, whereas miR-215 knockdown increases clonogenicity and impairs differentiation in CDX1-high cell lines. We identified the genome-wide targets of miR-215 and found that miR-215 mediates the repression of cell cycle and stemness genes downstream of CDX1. In particular, the miR-215 target gene BMI1 has been shown to promote stemness and self-renewal and to vary inversely with CDX1. Our work situates miR-215 as a link between CDX1 expression and BMI1 repression that governs differentiation in CRC. Significance In the colon, stem cell self-renewal and multipotency is regulated by the polycomb complex protein BMI1, among other genes. Differentiation is regulated by the transcription factor caudal-type homeobox 1 (CDX1), expression of which coincides with repression of BMI1. Colorectal cancer stem cells (CSCs) express BMI1 but not CDX1. Tumors that silence CDX1 have a higher proportion of CSCs and an undifferentiated histology, whereas aberrant CDX1 expression is associated with intestinal metaplasias such as Barrett's esophagus. We have identified microRNA-215 (miR-215) as a target of CDX1 in colon cancer that mediates repression of BMI1. MiR-215 operates downstream of CDX1 to promote differentiation and inhibit stemness. In combination with recent advances in the therapeutic uses of small RNAs, miR-215 could offer a novel method to specifically target CSCs.

Allium sativum (garlic) is widely known and is consumed as a natural prophylactic worldwide. It produces more than 200 identified chemical compounds, with more than 20 different kinds of sulfide compounds. The sulfide compounds particularly are proven to contribute to its various biological roles and pharmacological properties such as antimicrobial, antithrombotic, hypoglycemic, antitumour, and hypolipidemic. Therefore, it is often referred as disease-preventive food. Sulphur-containing compounds from A. sativum are derivatives of S-alkenyl-l-cysteine sulfoxides, ajoene molecules, thiosulfinates, sulfides, and S-allylcysteine. This review presents an overview of the water-soluble and oil-soluble sulphur based phytochemical compounds present in garlic, highlighting their mechanism of action in treating various health conditions. However, its role as a therapeutic agent should be extensively studied as it depends on factors such as the effective dosage and the suitable method of preparation.

Eighty one percent of adolescents aged 11–17 years are inadequately physically active worldwide. Physical activity (PA) recommendations for high school children have not been studied previously in schools in the Qatar region. The objectives of the study were: (i) to assess the level of compliance of the recommended PA and to assess if there are any gender differences; and (ii) to analyze the recommended step count compliance during school and non-school days. An observational cross-sectional study was conducted. Twenty-nine children (12 boys and 17 girls) aged 13–17 years (15.24 ± 1.46) took part in this study. Participants wore Fitbit Charge 5 wrist bands for three weeks to collect various digital biomarkers including moderate-to-vigorous physical activity (MVPA) and step counts (tracking during out-of-school time and school time). Based on this study, high school children in the two Qatar region schools did not meet the MVPA and steps/day recommendation by the established agencies: 38% of the total study group met the recommended 60 min/day of activity (50% boys, 29% girls). Gender differences were also observed in PA levels and steps per day: for non-school days, 17% met the recommended 10,000 steps/day (25% boys, 12% girls). There was a pattern of greater PA performance and steps during the weekdays as opposed to the weekend, but these values showed no robust evidence in favor of H1 or statistical significance for step counts. However, the evidence was robust in favor of H1 (difference between weekend and weekday) due to a statistically significant difference for meeting the 60 min/day activity. While further studies are required to establish if this is a general trend in Qatari schools, this pilot study does highlight the need to design more effective programs and messaging strategies to improve PA levels in the high school population.