Computational Mutagenesis of GPx7 and GPx8: Structural and Stability Insights into Rare Genetic and Somatic Missense Mutations and Their Implications for Cancer Development.

Somatic and genetic mutations in glutathione peroxidases (GPxs), including GPx7 and GPx8, have been linked to intellectual disability, microcephaly, and various tumors. GPx7 and GPx8 evolved the latest among the GPx enzymes and are present in the endoplasmic reticulum. Although lacking a glutathione binding domain, GPx7 and GPx8 possess peroxidase activity that helps the body respond to cellular stress.

DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways.

Hepatoblastoma (HBL) and fibrolamellar hepatocellular carcinoma (FLC) are the most common liver malignancies in children and young adults. FLC oncogenesis is associated with the generation of the fusion kinase, DNAJB1-PKAc (J-PKAc). J-PKAc has been found in 90% of FLC patients' tumors but not in other liver cancers.

miR-217-5p NanomiRs Inhibit Glioblastoma Growth and Enhance Effects of Ionizing Radiation via EZH2 Inhibition and Epigenetic Reprogramming.

: CSCs are critical drivers of the tumor and stem cell phenotypes of glioblastoma (GBM) cells. Chromatin modifications play a fundamental role in driving a GBM CSC phenotype. The goal of this study is to further our understanding of how stem cell-driving events control changes in chromatin architecture that contribute to the tumor-propagating phenotype of GBM.

Molecular Basis of Oncogenic PI3K Proteins.

The dysregulation of phosphatidylinositol 3-kinase (PI3K) signaling plays a pivotal role in driving neoplastic transformation by promoting uncontrolled cell survival and proliferation. This oncogenic activity is primarily caused by mutations that are frequently found in PI3K genes and constitutively activate the PI3K signaling pathway. However, tumorigenesis can also arise from nonmutated PI3K proteins adopting unique active conformations, further complicating the understanding of PI3K-driven cancers.

Predicting Postoperative Lung Cancer Recurrence and Survival Using Cox Proportional Hazards Regression and Machine Learning.

Background: Surgical resection remains the standard treatment for early-stage lung cancer. However, the recurrence rate after surgery is unacceptably high, ranging from 30% to 50%. Despite extensive efforts, accurately predicting the likelihood and timing of recurrence remains a significant challenge.

Preclinical Models for Functional Precision Lung Cancer Research.

Patient-centered precision oncology strives to deliver individualized cancer care. In lung cancer, preclinical models and technological innovations have become critical in advancing this approach. Preclinical models enable deeper insights into tumor biology and enhance the selection of appropriate systemic therapies across chemotherapy, targeted therapies, immunotherapies, antibody-drug conjugates, and emerging investigational treatments.

The RAGE Inhibitor TTP488 (Azeliragon) Demonstrates Anti-Tumor Activity and Enhances the Efficacy of Radiation Therapy in Pancreatic Cancer Cell Lines.

Pancreatic cancer is the third leading cause of cancer-related mortality in the United States, with rising incidence and mortality. The receptor for advanced glycation end products (RAGE) and its ligands significantly contribute to pancreatic cancer progression by enhancing cell proliferation, fostering treatment resistance, and promoting a pro-tumor microenvironment via activation of the nuclear factor-kappa B (NF-κB) signaling pathways. This study validated pathway activation in human pancreatic cancer and evaluated the therapeutic efficacy of TTP488 (Azeliragon), a small-molecule RAGE inhibitor, alone and in combination with radiation therapy (RT) in preclinical models of pancreatic cancer.

Exploring the Role of Glycine Metabolism in Coronary Artery Disease: Insights from Human Genetics and Mouse Models.

Circulating glycine levels have been associated with reduced risk of coronary artery disease (CAD) in humans but these associations have not been observed in all studies. We evaluated whether the relationship between glycine levels and atherosclerosis was causal using genetic analyses in humans and feeding studies in mice. Serum glycine levels were evaluated for association with risk of CAD in the UK Biobank.

A Randomized Pilot Study of Time-Restricted Eating Shows Minimal Microbiome Changes.

Objective: TRE is an emerging approach in obesity treatment, yet there is limited data on how it influences gut microbiome composition in humans. Our objective was to characterize the gut microbiome of human participants before and after a TRE intervention. This is a secondary analysis of a previously published clinical trial examining the effects of time-restricted eating (TRE).

The Impacts of Programs and Policies to Address Food Insecurity: An Analysis of Change in Income.

Background/objectives: This paper examines hunger over time to analyze how food insecurity is impacted by reduced income, including household funding from the government. Federal policies and community-based programs have the ability to prevent increases in food insecurity, particularly for populations that have risk factors, such as households with children; single-parent households; low-income households, especially those in rural areas; Black and Hispanic households; and, households experiencing economic hardships.

Methods: This study is bas ed on a cross-sectional survey that was administered in 2018 and 2019 to food pantry clients, an already food insecure population accessing resources, in Eastern Massachusetts.

The Bifidogenic Effect of 2'Fucosyllactose Is Driven by Age-Specific Species, Demonstrating Age as an Important Factor for Gut Microbiome Targeted Precision Medicine.

Background: The human gut microbiota develops in concordance with its host over a lifetime, resulting in age-related shifts in community structure and metabolic function. Little is known about whether these changes impact the community's response to microbiome-targeted therapeutics. Providing critical information on this subject, faecal microbiomes of subjects from six age groups, spanning from infancy to 70-year-old adults (n = six per age group) were harvested.

Cell Membrane Fatty Acids and PIPs Modulate the Etiology of Pancreatic Cancer by Regulating AKT.

Pancreatic ductal adenocarcinoma (PDAC) is one of the worst solid malignancies in regard to outcomes and metabolic dysfunction leading to cachexia. It is alarming that PDAC incidence rates continue to increase and warrant the need for innovative approaches to combat this disease. Due to its relatively slow progression (10-20 years), prevention strategies represent an effective means to improve outcomes.

The Etiology of Reduced Muscle Mass with Surgical and Pharmacological Weight Loss and the Identification of Potential Countermeasures.

Obesity represents a major health crisis in the United States, significantly increasing risks for chronic diseases and generating substantial economic costs. While bariatric surgery and pharmacological interventions such as GLP-1 receptor agonists have been proven effective in achieving substantial weight loss and improving comorbid conditions, they also raise concerns about the unintended loss of fat-free mass, particularly muscle. This loss of muscle mass compromises physical functionality, quality of life, and long-term metabolic health, particularly in individuals with sarcopenic obesity or those at risk of frailty.

Individual and Joint Associations Between Animal and Plant Protein Intakes with Impaired Fasting Glucose and Type 2 Diabetes in the Framingham Offspring Study.

Objectives: Given the considerable discrepancy in the literature regarding dietary protein and glucose homeostasis, we examined the prospective association between protein intake (total, animal, plant) and risk of type 2 diabetes mellitus or impaired fasting glucose (IFG). We also examined whether these associations differed by sex, body weight, or other risk factors.

Methods: We included 1423 subjects, aged ≥ 30 years, in the Framingham Offspring Study cohort.

Metabolic Adaptation and Its Determinants in Adolescents Two Years After Sleeve Gastrectomy.

Weight loss is associated with reductions in resting energy expenditure (REE), which are impacted by changes in body composition following sleeve gastrectomy (SG). Current data regarding changes in measured REE (mREE) and metabolic adaptation in adolescents after SG are limited. We evaluated changes in mREE, metabolic adaptation, and body composition in youths after SG vs.

Educational Intervention Boosts Dietitians' Knowledge of the Safety and Approval of Low- and No-Calorie Sweeteners.

Background/objectives: Low- and no-calorie sweeteners (LNCSs) provide sweetness in food applications that are suggested to support consumers' reduced consumption of caloric sweeteners and added sugar intake. Consumers seek guidance and advice on using LNCSs from healthcare providers, including dietitians and nutritionists. However, prior research suggests there may be inconsistent guidance on the use of LNCSs.

Balancing Nutritional and Environmental Sustainability Through the Evaluation of the Water Footprint of the Recommended Italian, Spanish, and American Diets.

: The water footprint (WF) provides information on the impact of individual foods on water consumption, but to better direct food production toward water saving, we need to understand how to reduce the WF of our diets while keeping it healthy. In this study, we compared the WF of healthy diets based on national food-based dietary guidelines with the aim of highlighting changes in dietary patterns that could reduce water requirements without compromising nutritional adequacy. : Three 2000 kcal/day dietary patterns were elaborated following the Italian, Spanish, and American dietary guidelines, and their total, green, blue, and grey WFs were calculated.

Comparative Investigation of Untargeted and Targeted Metabolomics in Turmeric Dietary Supplements and Rhizomes.

In the present study, we analyzed the bioactive curcuminoids content in eight capsules (DS-1-DS-7 and DS-9), one tablet (DS-8), three ground turmeric samples (DS-10-DS-12), and three ground turmeric rhizomes (TR-1, TR-2, and TR-3). Initial screening with infrared and ultraviolet-visible spectroscopy coupled with a principal component analysis (PCA) revealed distinct differences between the samples analyzed. Hence, targeted and untargeted analyses were performed using ultra-high-performance liquid chromatography and gas chromatography coupled with mass spectrometry detections.

Integrating Bacteriocins and Biofilm-Degrading Enzymes to Eliminate Persistence.

is a Gram-positive bacterium causing listeriosis, a severe infection responsible for significant morbidity and mortality globally. Its persistence on food processing surfaces via biofilm formation presents a major challenge, as conventional sanitizers and antimicrobials exhibit limited efficacy against biofilm-embedded cells. This study investigates a novel approach combining an engineered polysaccharide-degrading enzyme (CAase) with a bacteriocin (thermophilin 110) produced by .

ProBDNF as a Myokine in Skeletal Muscle Injury: Role in Inflammation and Potential for Therapeutic Modulation of p75.

Brain-derived neurotropic factor (BDNF) is expressed by skeletal muscle as a myokine. Our previous work showed that the active precursor, proBDNF, is the predominant form of BDNF expressed in skeletal muscle, and that following skeletal muscle injury, proBDNF levels are significantly increased. However, the function of the muscle-derived proBDNF in injury-induced inflammation has yet to be fully understood.

Regulation of Age-Related Lipid Metabolism in Ovarian Cancer.

The mortality rate of ovarian cancer (OC) remains the highest among female gynecological malignancies. Advanced age is the highest risk factor for OC development and progression, yet little is known about the role of the aged tumor microenvironment (TME). We conducted RNA sequencing and lipidomic analysis of young and aged gonadal adipose tissue from rat xenografts before and after OC formation.

Repurposing FDA-Approved Drugs for Eumycetoma Treatment: Homology Modeling and Computational Screening of CYP51 Inhibitors.

Eumycetoma, a chronic fungal infection caused by , is a neglected tropical disease characterized by tumor-like growths that can lead to permanent disability and deformities if untreated. Predominantly affecting regions in Africa, South America, and Asia, it imposes significant physical, social, and economic burdens. Current treatments, including antifungal drugs like itraconazole, often show variable efficacy, with severe cases necessitating surgical intervention or amputation.

Defining Mechanistic Links Between the Non-Coding Variant rs17673553 in and Lupus Susceptibility.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by widespread inflammation and autoantibody production. Its development and progression involve genetic, epigenetic, and environmental factors. Although genome-wide association studies (GWAS) have repeatedly identified a susceptibility signal at 16p13, its fine-scale source and its functional and mechanistic role in SLE remain unclear.

RiboTag RNA Sequencing Identifies Local Translation of HSP70 in Astrocyte Endfeet After Cerebral Ischemia.

Brain ischemia causes disruption in cerebral blood flow and blood-brain barrier integrity, which are normally maintained by astrocyte endfeet. Emerging evidence points to dysregulation of the astrocyte translatome during ischemia, but its effects on the endfoot translatome are unknown. In this study, we aimed to investigate the early effects of ischemia on the astrocyte endfoot translatome in a rodent cerebral ischemia and reperfusion model of stroke.

NAFLD and NAFLD Related HCC: Emerging Treatments and Clinical Trials.

Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated fatty liver disease (MAFLD), is the most prevalent liver disease worldwide. It is associated with an increased risk of developing hepatocellular carcinoma (HCC) in the background of cirrhosis or without cirrhosis. The prevalence of NAFLD-related HCC is increasing all over the globe, and HCC surveillance in NAFLD cases is not that common.