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Search Results (4,079)

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Keywords = severe obesity

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18 pages, 1056 KiB  
Article
Biomarkers of Metabolism and Inflammation in Individuals with Obesity and Normal Weight: A Comparative Analysis Exploring Sex Differences
by Eveline Gart, Jessica Snabel, Jelle C. B. C. de Jong, Lars Verschuren, Anita M. van den Hoek, Martine C. Morrison and Robert Kleemann
Int. J. Mol. Sci. 2025, 26(15), 7576; https://doi.org/10.3390/ijms26157576 - 5 Aug 2025
Abstract
Blood-based biomarkers allow monitoring of an individual’s health status and provide insights into metabolic and inflammatory processes in conditions like obesity, cardiovascular, and liver diseases. However, selecting suitable biomarkers and optimizing analytical assays presents challenges, is time-consuming and laborious. Moreover, knowledge of potential [...] Read more.
Blood-based biomarkers allow monitoring of an individual’s health status and provide insights into metabolic and inflammatory processes in conditions like obesity, cardiovascular, and liver diseases. However, selecting suitable biomarkers and optimizing analytical assays presents challenges, is time-consuming and laborious. Moreover, knowledge of potential sex differences remains incomplete as research is often carried out in men. This study aims at enabling researchers to make informed choices on the type of biomarkers, analytical assays, and dilutions being used. More specifically, we analyzed plasma concentrations of >90 biomarkers using commonly available ELISA or electrochemiluminescence-based multiplex methods, comparing normal weight (BMI < 25; n = 40) with obese (BMI > 30; n = 40) adult blood donors of comparable age. To help choose optimal biomarker sets, we grouped frequently employed biomarkers into biological categories (e.g., adipokines, acute-phase proteins, complement factors, cytokines, myokines, iron metabolism, vascular inflammation), first comparing normal-weight with obese persons, and thereafter exploratively comparing women and men within each BMI group. Many biomarkers linked to chronic inflammation and dysmetabolism were elevated in persons with obesity, including several adipokines, interleukins, chemokines, acute-phase proteins, complement factors, and oxidized LDL. Further exploration suggests sex disparities in biomarker levels within both normal-weight and obese groups. This comprehensive dataset of biomarkers across diverse biological domains constitutes a reference resource that may provide valuable guidance for researchers in selecting appropriate biomarkers and analytical assays for own studies. Moreover, the dataset highlights the importance of taking possible sex differences into account. Full article
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11 pages, 261 KiB  
Article
Investigation of the P1104A/TYK2 Genetic Variant in a COVID-19 Patient Cohort from Southern Brazil
by Giulianna Sonnenstrahl, Eduarda Sgarioni, Mayara Jorgens Prado, Marilea Furtado Feira, Renan Cezar Sbruzzi, Bibiana S. O. Fam, Alessandra Helena Da Silva Hellwig, Nathan Araujo Cadore, Osvaldo Artigalás, Alexandre da Costa Pereira, Lygia V. Pereira, Tábita Hünemeier and Fernanda Sales Luiz Vianna
COVID 2025, 5(8), 126; https://doi.org/10.3390/covid5080126 - 5 Aug 2025
Viewed by 38
Abstract
The P1104A variant in the TYK2 gene is recognized as the first common monogenic cause of tuberculosis, and recent studies also suggest a potential role in COVID-19 severity. However, its frequency and impact in admixed Latin American populations remain underexplored. Therefore, we investigated [...] Read more.
The P1104A variant in the TYK2 gene is recognized as the first common monogenic cause of tuberculosis, and recent studies also suggest a potential role in COVID-19 severity. However, its frequency and impact in admixed Latin American populations remain underexplored. Therefore, we investigated the P1104A/TYK2 variant in a cohort comprising 1826 RT-PCR-confirmed COVID-19 patients from Southern Brazil. Cases were stratified by severity into non-severe (n = 1190) and severe (n = 636). Three homozygous individuals were identified—one non-severe and two severe cases—although no statistically significant association with disease severity was observed. The frequency of the C allele in the COVID-19 cohort (2.85%) was significantly higher than in Brazilian population databases, including “DNA do Brasil” (1.81%, p < 0.001) and ABraOM (2.34%, p = 0.03), but lower than in the multi-ancestry gnomAD database (3.71%, p = 0.01), possibly reflecting ancestry bias. We also observed associations between COVID-19 severity and sex (p = 0.003), age (p < 0.001), obesity (p < 0.001), diabetes (p < 0.001), and hypertension (p < 0.001). Future studies in larger and more diverse cohorts are needed to characterize the prevalence of the variant in admixed populations and assess its contribution to COVID-19 susceptibility. Full article
(This article belongs to the Section Host Genetics and Susceptibility/Resistance)
19 pages, 940 KiB  
Review
An Exploration of U.S. Nutritional Diet Policies: A Narrative Review for Transformation Toward Sustainable Food Systems
by Ana Daniela Gonzalez-Alvarez, Asma Tahir Awan and Manoj Sharma
Encyclopedia 2025, 5(3), 114; https://doi.org/10.3390/encyclopedia5030114 - 4 Aug 2025
Viewed by 230
Abstract
Background: Current food systems contribute significantly to poor public health and environmental degradation. With increasing rates of chronic disease and undernutrition globally and in the United States of America (U.S.), transforming food systems toward sustainability is a critical public health priority. Objectives: This [...] Read more.
Background: Current food systems contribute significantly to poor public health and environmental degradation. With increasing rates of chronic disease and undernutrition globally and in the United States of America (U.S.), transforming food systems toward sustainability is a critical public health priority. Objectives: This narrative review aimed to summarize U.S. policies from the past decade relevant to sustainable food systems, focusing on four domains—availability, accessibility, affordability, and desirability—proposed by the 22nd Annual Harvard Nutrition Obesity Symposium. Methods: Systematic searches were conducted using MEDLINE (PubMed), Scopus, U.S. Congress websites, and Google searches. Studies and policies published between 2013 and 2023 that addressed at least one of the four domains were included. Policies were reviewed according to their alignment with the policy lifecycle framework, encompassing formulation through implementation. Results: A review of the final 632 articles explained that, despite growing interest in sustainable food systems, there is a lack of comprehensive U.S. policies that address the four domains in an integrated manner. Most initiatives were limited in scope, often school-based, and not explicitly sustainability-focused. Food availability and accessibility policies exist but remain fragmented, while affordability and desirability domains are severely underrepresented. Few laws or bills have been enacted or evaluated for population-level or environmental outcomes. Conclusions: Transforming U.S. food systems requires more robust evidence-based policy development and evaluation. There is an urgent need for integrated multisectoral policy frameworks to ensure health, equity, and sustainability across all food system domains. Full article
(This article belongs to the Collection Food and Food Culture)
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11 pages, 229 KiB  
Article
The Impact of Obesity on Clostridioides difficile Infection Outcomes: A Retrospective Cohort Study
by Alaa Atamna, Manar Khalaila, Tanya Babich, Anan Zriek, Haim Ben Zvi, Gida Ayada, Avishay Elis, Jihad Bishara and Amir Nutman
J. Clin. Med. 2025, 14(15), 5459; https://doi.org/10.3390/jcm14155459 - 3 Aug 2025
Viewed by 175
Abstract
Background: Studies have demonstrated a positive correlation between high body mass index (BMI) and an increased risk of Clostridioides difficile infection (CDI), independent of antibiotic usage or healthcare exposures. Aim: To compare the outcomes of obese (BMI ≥ 30 kg/m2) and [...] Read more.
Background: Studies have demonstrated a positive correlation between high body mass index (BMI) and an increased risk of Clostridioides difficile infection (CDI), independent of antibiotic usage or healthcare exposures. Aim: To compare the outcomes of obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2) hospitalized patients with CDI. Methods: This retrospective cohort study included patients with CDI hospitalized in Beilinson hospital between January 2013 and January 2020. The primary outcome was 90-day all-cause mortality. Secondary outcomes included 30-day mortality, colectomy, intensive care unit (ICU) admission and length of hospital stay (LOS). Multivariate analysis was performed to identify the risk factors independently associated with 90-day mortality. Results: The study included 889 patients: 131 (15%) obese and 758 (85%) non-obese. The obese group was younger (median age 65 years vs. 73 years (p < 0.01)) and with a higher rate of diabetes mellitus (57/131 (44%) vs. 180/758 (24%) (p < 0.01)). The 90-day mortality was lower in the obese group: 19/131 (15%) vs. 170/752 (23%) (p = 0.04). The 30-day mortality was 8/131 (6%) vs. 96/757 (13%) (p = 0.03). ICU admission was 9/131 (7%) vs. 23/758 (3%) (p = 0.03), and median LOS was 19 vs. 12 days (p < 0.01) in obese and non-obese groups, respectively. In the multivariable analysis, after adjustment for age, Charlson’s comorbidity index ≥3, assistance in activities of daily living, treatment with proton pump inhibitors and severity of illness, obesity was not a significant risk factor for 90-day mortality (OR = 0.65, 95% CI: 0.38–1.01; p = 0.1). Conclusions: In this study, obesity was not significantly associated with 90-day mortality after adjustment for other risk factors; however, ICU admission was higher and LOS longer in this group. Full article
11 pages, 301 KiB  
Article
Impact of Maternal Overweight and Obesity on Pregnancy Outcomes Following Cesarean Delivery: A Retrospective Cohort Study
by Zlatina Nikolova, Milena Sandeva, Ekaterina Uchikova, Angelina Kirkova-Bogdanova, Daniela Taneva, Marieta Vladimirova and Lyubomira Georgieva
Healthcare 2025, 13(15), 1893; https://doi.org/10.3390/healthcare13151893 - 2 Aug 2025
Viewed by 238
Abstract
Background/Objectives: Maternal overweight and obesity are critical factors increasing the risk of various pregnancy complications. Maternal obesity can lead to fetal macrosomia and a heightened risk of intrauterine death, with long-term implications for the child’s health. This study aimed to analyze the [...] Read more.
Background/Objectives: Maternal overweight and obesity are critical factors increasing the risk of various pregnancy complications. Maternal obesity can lead to fetal macrosomia and a heightened risk of intrauterine death, with long-term implications for the child’s health. This study aimed to analyze the incidence of obesity and its impact on pregnancy outcomes in women who delivered by cesarean section at the University Hospital “St. George”, Plovdiv. Methods: A single-center retrospective cohort study was conducted. The documentary method was used for gathering data. Records were randomly selected. The statistical methods used included mean values, confidence intervals (of mean), frequency, and the Kolmogorov–Smirnov test for normality of distribution. Data comparisons were performed using the Mann–Whitney test. Mean values of numerical variables were compared using the independent samples t-test. Results: In total, 46.36% of women in this study were affected by obesity to varying degrees, and the proportion of women who were overweight at the end of their pregnancy was 37.85%. In the studied cohort, 15.99% of women were affected by hypertensive complications. This significant prevalence of obesity highlights concerns regarding body weight among women of reproductive age. This study emphasized a strong correlation between maternal obesity, particularly severe obesity, and the occurrence of preeclampsia. Conclusions: In this study among women who delivered by cesarean section, a significant proportion of them were affected by overweight and obesity. Data for our country are insufficient, and a more in-depth study of this problem is needed. Future research should explore the long-term impacts of maternal obesity on the health of the mother and the newborn. Full article
(This article belongs to the Special Issue Focus on Maternal, Pregnancy and Child Health)
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11 pages, 398 KiB  
Perspective
Implications of Metabolic Bariatric Surgery on Reproductive Health
by Amihai Rottenstreich and Yitka Graham
J. Clin. Med. 2025, 14(15), 5446; https://doi.org/10.3390/jcm14155446 - 2 Aug 2025
Viewed by 224
Abstract
In the last two decades, metabolic and bariatric surgery (MBS) has become the mainstay of treatment for severe and complex obesity. The majority of patients undergoing MBS are women of childbearing age. Coupled with the dramatic increase in the utilization of MBS, caregivers [...] Read more.
In the last two decades, metabolic and bariatric surgery (MBS) has become the mainstay of treatment for severe and complex obesity. The majority of patients undergoing MBS are women of childbearing age. Coupled with the dramatic increase in the utilization of MBS, caregivers are likely to encounter patients who have undergone MBS in routine practice. From this perspective, we highlight the different reproductive health challenges and issues encountered throughout the pre-operative, peri-operative, and postoperative phases. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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19 pages, 2656 KiB  
Article
Circulating Lipid Profiles Indicate Incomplete Metabolic Recovery After Weight Loss, Suggesting the Need for Additional Interventions in Severe Obesity
by Alina-Iuliana Onoiu, Vicente Cambra-Cortés, Andrea Jiménez-Franco, Anna Hernández-Aguilera, David Parada, Francesc Riu, Antonio Zorzano, Jordi Camps and Jorge Joven
Biomolecules 2025, 15(8), 1112; https://doi.org/10.3390/biom15081112 - 1 Aug 2025
Viewed by 143
Abstract
The effects of long-term adjustments in body weight on the lipid balance in patients with severe obesity are not well understood. This study aimed to evaluate a non-invasive lipidomic approach to identifying biomarkers that could help predict which patients may require additional therapies [...] Read more.
The effects of long-term adjustments in body weight on the lipid balance in patients with severe obesity are not well understood. This study aimed to evaluate a non-invasive lipidomic approach to identifying biomarkers that could help predict which patients may require additional therapies before and after weight loss. Using mass spectrometry, 275 lipid species were analysed in non-obese controls, patients with severe obesity, and patients one year after bariatric surgery. The results showed that severe obesity disrupts lipid pathways, contributing to lipotoxicity, inflammation, mitochondrial stress, and abnormal lipid metabolism. Although weight loss improved these disturbances, surgery did not fully normalise the lipid profiles of all patients. Outcomes varied depending on their baseline liver health and genetic differences. Persistent alterations in cholesterol handling, membrane composition, and mitochondrial function were observed in partial responders. Elevated levels of sterol lipids, glycerophospholipids, and sphingolipids emerged as markers of complete metabolic recovery, identifying candidates for targeted post-surgical interventions. These findings support the use of lipidomics to personalise obesity treatment and follow-up. Full article
(This article belongs to the Section Molecular Biomarkers)
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9 pages, 408 KiB  
Article
Less Time, Same Insight? Evaluating Short Functional Tests as Substitutes for the Six-Minute Walk Test and the Reliability and Validity of the 2MWT, 3MWT, and 1MSTS in Bariatric Surgery Candidates with Obesity
by Hamdiye Turan, Zeynal Yasaci and Hasan Elkan
Healthcare 2025, 13(15), 1883; https://doi.org/10.3390/healthcare13151883 - 1 Aug 2025
Viewed by 165
Abstract
Background and Objectives: Functional capacity assessment is essential in bariatric surgery candidates, but the Six-Minute Walk Test (6MWT) may be limited by fatigue, joint pain, and spatial constraints in individuals with severe obesity. Shorter tests such as the Two-Minute Walk Test (2MWT), Three-Minute [...] Read more.
Background and Objectives: Functional capacity assessment is essential in bariatric surgery candidates, but the Six-Minute Walk Test (6MWT) may be limited by fatigue, joint pain, and spatial constraints in individuals with severe obesity. Shorter tests such as the Two-Minute Walk Test (2MWT), Three-Minute Walk Test (3MWT), and One-Minute Sit-to-Stand Test (1MSTS) have been proposed as alternatives, yet comparative data in this population remain scarce. We aimed to evaluate the validity, reliability, and clinical utility of the 2MWT, 3MWT, and 1MSTS as substitutes for the 6MWT in patients preparing for bariatric surgery. Materials and Methods: In this cross-sectional study, 142 obese adults (BMI ≥ 30 kg/m2) underwent standardized 2MWT, 3MWT, 6MWT, and 1MSTS protocols. Correlation, linear regression, test–retest reliability (ICC), and ROC analyses were used to determine each test’s correlation and discriminative accuracy for impaired exercise tolerance (6MWT < 450 m). Results: The 3MWT showed the strongest correlation with the 6MWT (r = 0.930) and the highest explained variance (R2 = 0.865), especially in individuals with BMI > 50. It also exhibited excellent reliability (ICC > 0.9) and a strong ROC profile (AUC = 0.931; 212 m cut-off). The 2MWT demonstrated acceptable concurrent validity but slightly lower agreement. The 1MSTS showed weak and inconsistent associations with 6MWT performance, suggesting limited value in assessing aerobic capacity in this population. Conclusions: The 3MWT appears to be a valid, reliable, and clinically practical alternative to the 6MWT in individuals with severe obesity. The 2MWT may be used when time or patient tolerance is limited. The 1MSTS, while safe and simple, may reflect strength and coordination more than aerobic capacity, limiting its utility in this context. Full article
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20 pages, 576 KiB  
Article
Effectiveness of a Physiotherapy Stress-Management Protocol on Cardiorespiratory, Metabolic and Psychological Indicators of Children and Adolescents with Morbid Obesity
by Pelagia Tsakona, Alexandra Hristara-Papadopoulou, Thomas Apostolou, Ourania Papadopoulou, Ioannis Kitsatis, Eleni G. Paschalidou, Christos Tzimos, Maria G. Grammatikopoulou and Kyriaki Tsiroukidou
Children 2025, 12(8), 1010; https://doi.org/10.3390/children12081010 - 31 Jul 2025
Viewed by 223
Abstract
Background: Chronic stress in childhood and adolescence leads to excessive cortisol secretion, adipokines production and obesity with all the negative mental and physical effects on the health of individuals and adulthood. Objectives: The aim of the present non-randomized controlled trial was to investigate [...] Read more.
Background: Chronic stress in childhood and adolescence leads to excessive cortisol secretion, adipokines production and obesity with all the negative mental and physical effects on the health of individuals and adulthood. Objectives: The aim of the present non-randomized controlled trial was to investigate the effect of a stress management protocol with diaphragmatic breathing (DB) and physiotherapy exercise on stress, body composition, cardiorespiratory and metabolic markers of children and adolescents with morbid obesity. Methods: The study included 31 children and adolescents (5–18 years old) with morbid obesity (22 in the intervention arm and 9 controls). All participants completed anxiety questionnaires and a self-perception scale. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), blood pressure (BP) and SpO2 were measured. Fasting glucose, uric acid, triglycerides, HbA1c, (AST/SGOT), (ALT/SGPT), HDL, LDL, insulin, ACTH, cortisol, HOMA-IR, 17-OH, S-DHEA, SHBG were assessed, and anthropometric measurements were also performed. Results: In the intervention group, 4 months after the treatment, an improvement was noted in the BMI, BMI z-score, waist-to-height ratio, FEV1, SpO2, pulse and systolic BP. HDL increased, ALT/SGPT and insulin resistance improved. Positive changes were observed in temporary and permanent stress and self-esteem of children in the intervention group, including anxiety, self-perception, physical appearance, etc. Conclusions: A combined exercise and DB protocol has a positive effect on stress, by improving body composition, reducing insulin resistance, and ameliorating physical and mental health and quality of life of pediatric patients with morbid obesity. Full article
(This article belongs to the Special Issue Childhood Obesity: Prevention, Intervention and Treatment)
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11 pages, 275 KiB  
Article
Polygenic Score for Body Mass Index Is Associated with Weight Loss and Lipid Outcomes After Metabolic and Bariatric Surgery
by Luana Aldegheri, Chiara Cipullo, Natalia Rosso, Eulalia Catamo, Biagio Casagranda, Pablo Giraudi, Nicolò de Manzini, Silvia Palmisano and Antonietta Robino
Int. J. Mol. Sci. 2025, 26(15), 7337; https://doi.org/10.3390/ijms26157337 - 29 Jul 2025
Viewed by 361
Abstract
Metabolic and bariatric surgery (MBS) is an effective treatment for severe obesity, though individual responses vary widely, partly due to genetic predisposition. This study investigates the association of a body mass index (BMI) polygenic score (PGS) with weight loss and metabolic outcomes following [...] Read more.
Metabolic and bariatric surgery (MBS) is an effective treatment for severe obesity, though individual responses vary widely, partly due to genetic predisposition. This study investigates the association of a body mass index (BMI) polygenic score (PGS) with weight loss and metabolic outcomes following surgery. A cohort of 225 patients undergoing MBS was analyzed at baseline (T0), six (T6), and twelve (T12) months, with anthropometric and biochemical parameters recorded at each time point. Total weight loss (TWL) and excess weight loss (EWL) percentages were calculated. PGS was computed using the LDpred-grid Bayesian method. The mean age was 45.9 ± 9.4 years. Males had a higher baseline prevalence of type 2 diabetes (T2D) and comorbidities (p < 0.001). Linear regression analysis confirmed an association between PGS and baseline BMI (p = 0.012). Moreover, mediation analysis revealed that baseline BMI mediated the effect of the PGS on %TWL at T12, with an indirect effect (p-value = 0.018). In contrast, high-density lipoprotein-cholesterol (HDL-C) at T6 and triglycerides (TG) at T12 showed direct associations with the PGS (p-value = 0.004 and p-value = 0.08, respectively), with no significant mediation by BMI. This study showed a BMI-mediated association of PGS with %TWL and a direct association with lipid changes, suggesting its potential integration into personalized obesity treatment. Full article
(This article belongs to the Special Issue Genetic and Molecular Mechanisms of Obesity)
19 pages, 5661 KiB  
Article
Impact of Obesity and Ageing on the Expression of Key Mediators of SARS-CoV-2 Infection in Human Adipose Tissue
by Maria Salazar, Mariana Ferreira, Sandra Marisa Oliveira, Francisca Saraiva, Carlos Pinho, Mariana Jarnalo, Inês Correia-Sá, Inês Falcão-Pires, Adelino Leite-Moreira, Delminda Neves, Henrique Almeida, Adriana R. Rodrigues and Alexandra M. Gouveia
Int. J. Mol. Sci. 2025, 26(15), 7313; https://doi.org/10.3390/ijms26157313 - 29 Jul 2025
Viewed by 296
Abstract
Increased body mass index (BMI) and age are associated with COVID-19 severity. SARS-CoV-2 infection occurs through ACE2 binding, with TMPRSS2, ADAM17, and NRP1 facilitating this process. This study describes how adipose tissue (AT) location, BMI, age, and obesity affect these proteins’ expression. AT [...] Read more.
Increased body mass index (BMI) and age are associated with COVID-19 severity. SARS-CoV-2 infection occurs through ACE2 binding, with TMPRSS2, ADAM17, and NRP1 facilitating this process. This study describes how adipose tissue (AT) location, BMI, age, and obesity affect these proteins’ expression. AT was collected from subcutaneous (abdominal superficial [AS], abdominal deep [AD], thigh [T]) and visceral (epiploon [E]) areas from middle-aged women without obesity (BMI 23.9 kg/m2, age 48.3 years). Subcutaneous AT was also obtained from middle-aged women with previous obesity (BMI 24.8 kg/m2, previously 41.7 kg/m2, age 46.9 years), older women with obesity (BMI 32.3 kg/m2, age 70.8 years), and older women without obesity (BMI 23.7 kg/m2, age 70.6 years). ACE2, TMPRSS2, ADAM17, and NRP1 expression was evaluated by qPCR and Western blotting. All proteins were more expressed in visceral AT. ACE2, TMPRSS2, and NRP1 positively correlated with BMI in AS and/or E, while NRP1 correlated with age in T. In subcutaneous AT, ACE2 and NRP1 were more influenced by obesity while TMPRSS2 was more age-dependent. In women with previous obesity, ACE2 and NRP1 levels decreased, while TMPRSS2 and ADAM17 remained unchanged. These findings highlight the differential influence of visceral AT, obesity, and age on the expression of SARS-CoV-2 cell entry mediators, potentially contributing to COVID-19 severity. Full article
(This article belongs to the Special Issue Adipose Tissue and Gene Expression)
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20 pages, 887 KiB  
Review
Epigenetics of Endometrial Cancer: The Role of Chromatin Modifications and Medicolegal Implications
by Roberto Piergentili, Enrico Marinelli, Lina De Paola, Gaspare Cucinella, Valentina Billone, Simona Zaami and Giuseppe Gullo
Int. J. Mol. Sci. 2025, 26(15), 7306; https://doi.org/10.3390/ijms26157306 - 29 Jul 2025
Viewed by 259
Abstract
Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Risk factors for EC include metabolic alterations (obesity, metabolic syndrome, insulin resistance), hormonal imbalance, age at menopause, reproductive factors, and inherited conditions, such as Lynch syndrome. For the inherited forms, several [...] Read more.
Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Risk factors for EC include metabolic alterations (obesity, metabolic syndrome, insulin resistance), hormonal imbalance, age at menopause, reproductive factors, and inherited conditions, such as Lynch syndrome. For the inherited forms, several genes had been implicated in EC occurrence and development, such as POLE, MLH1, TP53, PTEN, PIK3CA, PIK3R1, CTNNB1, ARID1A, PPP2R1A, and FBXW7, all mutated at high frequency in EC patients. However, gene function impairment is not necessarily caused by mutations in the coding sequence of these and other genes. Gene function alteration may also occur through post-transcriptional control of messenger RNA translation, frequently caused by microRNA action, but transcriptional impairment also has a profound impact. Here, we review how chromatin modifications change the expression of genes whose impaired function is directly related to EC etiopathogenesis. Chromatin modification plays a central role in EC. The modification of chromatin structure alters the accessibility of genes to transcription factors and other regulatory proteins, thus altering the intracellular protein amount. Thus, DNA structural alterations may impair gene function as profoundly as mutations in the coding sequences. Hence, its central importance is in the diagnostic and prognostic evaluation of EC patients, with the caveat that chromatin alteration is often difficult to identify and needs investigations that are specific and not broadly used in common clinical practice. The different phases of the healthy endometrium menstrual cycle are characterized by differential gene expression, which, in turn, is also regulated through epigenetic mechanisms involving DNA methylation, histone post-translational modifications, and non-coding RNA action. From a medicolegal and policy-making perspective, the implications of using epigenetics in cancer care are briefly explored as well. Epigenetics in endometrial cancer is not only a topic of biomedical interest but also a crossroads between science, ethics, law, and public health, requiring integrated approaches and careful regulation. Full article
(This article belongs to the Section Molecular Oncology)
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27 pages, 5430 KiB  
Article
Gene Monitoring in Obesity-Induced Metabolic Dysfunction in Rats: Preclinical Data on Breast Neoplasia Initiation
by Francisco Claro, Joseane Morari, Camila de Angelis, Emerielle Cristine Vanzela, Wandir Antonio Schiozer, Lício Velloso and Luis Otavio Zanatta Sarian
Int. J. Mol. Sci. 2025, 26(15), 7296; https://doi.org/10.3390/ijms26157296 - 28 Jul 2025
Viewed by 310
Abstract
Obesity and metabolic dysfunction are established risk factors for luminal breast cancer, yet current preclinical models inadequately recapitulate the complex metabolic and immune interactions driving tumorigenesis. To develop and characterize an immunocompetent rat model of luminal breast cancer induced by chronic exposure to [...] Read more.
Obesity and metabolic dysfunction are established risk factors for luminal breast cancer, yet current preclinical models inadequately recapitulate the complex metabolic and immune interactions driving tumorigenesis. To develop and characterize an immunocompetent rat model of luminal breast cancer induced by chronic exposure to a cafeteria diet mimicking Western obesogenic nutrition, female rats were fed a cafeteria diet or standard chow from weaning. Metabolic parameters, plasma biomarkers (including leptin, insulin, IGF-1, adiponectin, and estrone), mammary gland histology, tumor incidence, and gene expression profiles were longitudinally evaluated. Gene expression was assessed by PCR arrays and qPCR. A subgroup underwent dietary reversal to assess the reversibility of molecular alterations. Cafeteria diet induced significant obesity (mean weight 426.76 g vs. 263.09 g controls, p < 0.001) and increased leptin levels without altering insulin, IGF-1, or inflammatory markers. Histological analysis showed increased ductal ectasia and benign lesions, with earlier fibroadenoma and luminal carcinoma development in diet-fed rats. Tumors exhibited luminal phenotype, low Ki67, and elevated PAI-1 expression. Gene expression alterations were time point specific and revealed early downregulation of ID1 and COX2, followed by upregulation of MMP2, THBS1, TWIST1, and PAI-1. Short-term dietary reversal normalized several gene expression changes. Overall tumor incidence was modest (~12%), reflecting early tumor-promoting microenvironmental changes rather than aggressive carcinogenesis. This immunocompetent cafeteria diet rat model recapitulates key metabolic, histological, and molecular features of obesity-associated luminal breast cancer and offers a valuable platform for studying early tumorigenic mechanisms and prevention strategies without carcinogen-induced confounders. Full article
(This article belongs to the Special Issue Genomic Research in Carcinogenesis, Cancer Progression and Recurrence)
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12 pages, 653 KiB  
Article
Association of Lipoprotein Lipase (LPL) Variants rs8176337, rs303, and rs304 with Body Mass Index and Total Cholesterol
by Suzanne A. Al-Bustan, Ahmad E. Al-Serri, Amani M. Al-Adsani, Lavina Miranda, Babitha G. Annice, Hala Hamdan and Majed A. Alnaqeeb
Int. J. Mol. Sci. 2025, 26(15), 7282; https://doi.org/10.3390/ijms26157282 - 28 Jul 2025
Viewed by 234
Abstract
Several single-nucleotide polymorphisms (SNPs) across the lipoprotein lipase (LPL) gene have been found to be associated with dyslipidemia and obesity. Several InDels and SNPs in exon 1, intron 2, and intron 7 have been reported; however, their association with lipid parameters [...] Read more.
Several single-nucleotide polymorphisms (SNPs) across the lipoprotein lipase (LPL) gene have been found to be associated with dyslipidemia and obesity. Several InDels and SNPs in exon 1, intron 2, and intron 7 have been reported; however, their association with lipid parameters and body mass index (BMI) remains unclear. Here, we aimed to investigate the relationship among LPL variants, lipid levels, and BMI in a Kuwaiti population. Sanger sequencing was performed on three targeted regions of the LPL gene. Based on the minor allele frequency, Hardy–Weinberg equilibrium, and linkage disequilibrium, five SNPs were selected and genotyped in a cohort of 688 Kuwaiti samples to investigate their association with lipid levels and BMI. A total of 30 variants (6 InDels and 24 SNPs) were identified; of them, 5 SNPs (rs1800590, rs74377536, rs8176337, rs303, and rs304) were selected for their association with BMI and lipid levels. The G-allele of rs8176337 was found to be associated with increased BMI (β = 1.41; 95% confidence interval = 0.22–2.60; p = 0.02). In addition, an association was observed for rs303 and rs304 with both cholesterol and LDL (p < 0.05). Overall, our results demonstrate an association between LPL variants and lipid levels, and the observed association between rs8176337 and BMI was novel. Full article
(This article belongs to the Section Macromolecules)
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Article
Evaluation of Pre-Treatment Assessment of Semaglutide Users: Balancing the Benefits of Weight Loss vs. Potential Health Consequences
by Faten F. Bin Dayel, Rakan J. Alanazi, Miteb A. Alenazi, Sahar Alkhalifah, Mohammed Alfaifi, Sultan Alghadeer and Abdulrahman Alwhaibi
Healthcare 2025, 13(15), 1827; https://doi.org/10.3390/healthcare13151827 - 26 Jul 2025
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Abstract
Background: Although semaglutide (Ozempic®) is being prescribed off-label to individuals with obesity, some concerns have arisen regarding its use, particularly regarding the risk of thyroid and pancreatic disorders. Therefore, it is crucial to screen patients’ medical and family disease histories, as [...] Read more.
Background: Although semaglutide (Ozempic®) is being prescribed off-label to individuals with obesity, some concerns have arisen regarding its use, particularly regarding the risk of thyroid and pancreatic disorders. Therefore, it is crucial to screen patients’ medical and family disease histories, as well as certain clinical parameters, before initiating this treatment for obesity or weight management. However, there is limited research investigating whether pretreatment assessment is adopted in clinical practice. Method: This is a single-center retrospective study involving adults who were prescribed semaglutide for obesity or weight management. Demographic data, comorbid conditions, semaglutide-related lab work, and disease history assessments, including pancreatitis, thyroid abnormalities, oculopathy, neuropathy, and any family history of thyroid cancer, were evaluated and documented prior to treatment initiation. Results: In total, 715 patients were included in the study, with an average age of 40.2 ± 12.0 years, and 49.5% of participants were male. The average weight and BMI prior to using semaglutide were 99.8 ± 18.1 kg and 36.3 ± 8.3 kg/m2, respectively, with predominantly overweight and obese individuals (collectively 91.3%). Approximately 69% of patients had 3–5 complications, with a high prevalence of cardiovascular and metabolic diseases before using semaglutide. Although HbA1c, serum creatinine, TSH, T3, T4, triglycerides, HDL, LDL, total cholesterol, and total bilirubin were monitored prior to semaglutide use, none of the patients’ pancreatic lipase, amylase, or calcitonin levels were measured. Although it is important to investigate all personal and family disease histories, including thyroid abnormalities, thyroid cancer, pancreatitis, retinopathy, eye problems, and neuropathy prior to semaglutide initiation, checks were only conducted in 1.8% of patients, despite 98.6% having at least one of the diseases assessed pretreatment. Conclusions: The current pretreatment assessment approach for patients prescribed semaglutide for weight reduction is underdeveloped, particularly with regard to assessing the influence of disease history on semaglutide use. This predisposes patients to a risk of severe clinical outcomes, including thyroid cancer, pancreatitis, and retinopathy. Full article
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