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Keywords = body weight regulation

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48 pages, 3026 KB  
Review
Lifestyle Medicine as Co-Therapy During Incretin-Based Anti-Obesity Pharmacotherapy: Integrating Physical Activity, Nutrition, and Behavioral Strategies for Long-Term Success
by Marta Mallardo, Antonietta Messina, Vincenzo Monda, Marco La Marra, Antonietta Monda, Salvatore Allocca, Maria Casillo, Girolamo Di Maio, Pasquale Perrone, Aurora Daniele, Marcellino Monda, Giovanni Messina, Fiorenzo Moscatelli and Rita Polito
Nutrients 2026, 18(17), 2748; https://doi.org/10.3390/nu18172748 (registering DOI) - 22 Aug 2026
Abstract
Background/Objectives: Obesity is a chronic, progressive, and relapsing disease that requires long-term, multidisciplinary management rather than episodic weight-loss treatment. Although novel incretin-based anti-obesity pharmacotherapies, including GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, have markedly improved the clinical management of obesity, weight reduction [...] Read more.
Background/Objectives: Obesity is a chronic, progressive, and relapsing disease that requires long-term, multidisciplinary management rather than episodic weight-loss treatment. Although novel incretin-based anti-obesity pharmacotherapies, including GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, have markedly improved the clinical management of obesity, weight reduction alone does not fully capture treatment success. Body composition, lean mass preservation, physical function, nutritional adequacy, psychological well-being, adherence, and long-term weight-loss maintenance are increasingly recognized as essential therapeutic outcomes. This narrative review critically examines the role of lifestyle medicine as a co-therapeutic strategy during modern anti-obesity pharmacotherapy, with particular attention to physical activity, nutrition, behavioral support, and individualized monitoring. Methods: A narrative literature search was conducted in PubMed up to June 2026. The review included studies addressing adults with overweight or obesity and evidence related to anti-obesity pharmacotherapy, physical activity, nutrition, body composition, functional outcomes, eating behavior, quality of life, treatment tolerability, adherence, weight regain, and long-term maintenance. Results: Current evidence indicates that incretin-based therapies produce substantial and clinically meaningful weight loss, but pharmacological efficacy may be limited by reductions in lean mass, gastrointestinal adverse events, inadequate nutritional intake, treatment discontinuation, and weight regain after drug withdrawal. Physical activity should be considered a therapeutic component rather than only a tool for increasing energy expenditure, as aerobic exercise supports cardiometabolic health and cardiorespiratory fitness, while resistance training helps preserve muscle strength, bone health, and functional capacity. Nutritional strategies are equally important, particularly during appetite suppression, to maintain adequate protein, fiber, fluids, micronutrients, and diet quality. Behavioral factors, including sleep, stress, mood, stigma, self-regulation, and the food environment, may influence adherence and long-term outcomes. Conclusions: Novel anti-obesity drugs should not be viewed as replacements for lifestyle medicine but as powerful tools within an integrated chronic-care model. The goal of treatment should move beyond maximal body-weight reduction to durable improvements in body composition, metabolic health, physical function, nutritional status, quality of life, and weight-loss maintenance. Full article
(This article belongs to the Section Nutrition and Obesity)
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16 pages, 1542 KB  
Article
Identification of Growth-Related Single-Nucleotide Polymorphisms in the cAMP-Dependent Protein Kinase Type I Regulatory Subunit-like Gene of the Oriental River Prawn, Macrobrachium nipponense
by Yuefan Zhang, Hao Dong, Xiaofan Fang, Hui Qiao, Wenyi Zhang, Yiwei Xiong, Sufei Jiang and Shubo Jin
Int. J. Mol. Sci. 2026, 27(16), 7500; https://doi.org/10.3390/ijms27167500 - 21 Aug 2026
Abstract
Macrobrachium nipponense is an economically important freshwater crustacean in China, and growth-related traits are major determinants of its commercial value. Identifying single nucleotide polymorphisms (SNPs) associated with growth-related traits may provide useful molecular markers for the genetic improvement of growth performance. Previous studies [...] Read more.
Macrobrachium nipponense is an economically important freshwater crustacean in China, and growth-related traits are major determinants of its commercial value. Identifying single nucleotide polymorphisms (SNPs) associated with growth-related traits may provide useful molecular markers for the genetic improvement of growth performance. Previous studies have suggested that the cAMP-dependent protein kinase type I regulatory subunit-like gene (Mn-PKA-R1) is involved in the regulation of growth and molting in M. nipponense. In the present study, a cultured full-sib family comprising 120 females and 120 males was used to screen SNPs within the coding region of Mn-PKA-R1, and evaluate their associations with body weight, body length, full length, and abdominal width. Seven SNPs were identified in exon 12, including five nonsynonymous missense variants and two synonymous variants, whereas no SNPs were detected in the other exons examined. The mean effective number of alleles (Ne), observed heterozygosity (Ho), expected heterozygosity (He), Nei’s gene diversity (Nei), and polymorphic information content (PIC) were 1.3561, 0.3048, 0.2350, 0.2340, and 0.1962, respectively, in females, compared with 1.3118, 0.2714, 0.1868, 0.1861, and 0.1512, respectively, in males. Four SNPs were significantly associated with growth-related traits in females: C+82748G and A+82750G were associated with body weight and abdominal width, T+82810G was associated with abdominal width, and A+83324G was associated with body weight, full length, and abdominal width (p < 0.05). No significant genotype–trait associations were detected among the SNP loci that could be statistically evaluated in males. Pairwise r2 values ranged from 0.001 to 0.693 in females and from 0.000 to 0.351 in males, with generally higher values observed in females within the investigated full-sib family. Females also showed slightly higher mean genetic polymorphism parameters than males, while significant SNP–trait associations were detected only in females within this family. These findings provide candidate SNPs for further validation of their potential utility in marker-assisted selection in M. nipponense. Full article
(This article belongs to the Special Issue Molecular Genetics and Genomics of Aquatic Crustaceans)
27 pages, 6629 KB  
Article
Effects of Fermented Ginseng By-Product Supplementation on Growth Performance, Meat Quality, Flavor, and Fatty Acid Metabolism in Hongyu Roosters
by Hongxi Chen, Yuhao Liu, Shuo Zhang, Yi Jin, Wanfeng Liang, Xijiu Jin and Junzhe Min
Vet. Sci. 2026, 13(8), 844; https://doi.org/10.3390/vetsci13080844 - 21 Aug 2026
Abstract
Agricultural by-products and Chinese medicine crop residues, as non-traditional animal feed, have great potential to alleviate the scarcity of traditional feed and reduce the environmental burden. In this study, the effects of adding fermented ginseng by-products to the diet on growth performance, meat [...] Read more.
Agricultural by-products and Chinese medicine crop residues, as non-traditional animal feed, have great potential to alleviate the scarcity of traditional feed and reduce the environmental burden. In this study, the effects of adding fermented ginseng by-products to the diet on growth performance, meat quality, flavor characteristics and metabolism of Hongyu roosters were evaluated. A total of 100 Hongyu roosters were randomly assigned to either a control (Con) group fed a basal diet or a fermented ginseng by-products (Fe) group fed a basal diet supplemented with 3% fermented ginseng by-products, with five replicates per group, for 100 days. The results demonstrated that the fermented diet significantly enhanced final body weight and average daily gain (ADG) while reducing the feed conversion ratio (FCR) (p < 0.05). The percentages of breast and thigh muscles and breast muscle fiber diameter were significantly increased. The results also exhibited enhanced water-holding capacity, coupled with significantly decreased shear force and drip loss (p < 0.05). Electronic nose and tongue analyses confirmed enriched meat aroma and optimized taste profiles, which aligned with elevated levels of flavor-precursor amino acids and essential polyunsaturated fatty acids. Serum metabolomics found purine metabolism and the biosynthesis of unsaturated fatty acids to be pivotal pathways. Metabolites related to nucleotide and lipid metabolism were regulated. In conclusion, fermented ginseng by-products serve as an effective functional feed to improve poultry growth performance and meat quality. Full article
15 pages, 4018 KB  
Article
Diagnostic Performance of Serum Xenopsin-Related Peptide-1 in Gestational Diabetes Mellitus: A Prospective Observational Study
by Yasin Karadag, Ozgur Ozdemır, Gulseren İpek Karadag and Erinçe Tekin
Metabolites 2026, 16(8), 595; https://doi.org/10.3390/metabo16080595 - 21 Aug 2026
Abstract
Background/Objectives: Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders during pregnancy and is associated with adverse maternal and neonatal outcomes. Xenopsin-Related Peptide-1 (XRP-1) has recently emerged as a potential regulator of glucose metabolism and insulin homeostasis. This study [...] Read more.
Background/Objectives: Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders during pregnancy and is associated with adverse maternal and neonatal outcomes. Xenopsin-Related Peptide-1 (XRP-1) has recently emerged as a potential regulator of glucose metabolism and insulin homeostasis. This study evaluated serum XRP-1 levels and assessed their diagnostic performance in women with GDM. Methods: In this prospective observational study, 120 pregnant women between 24 and 28 weeks of gestation were enrolled, including 60 women with GDM and 60 healthy controls. Serum XRP-1 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Clinical, biochemical, and obstetric characteristics were compared between groups. Receiver operating characteristic (ROC) curve analysis and multivariable logistic regression were performed to evaluate the diagnostic performance and independent association of XRP-1 with GDM. Results: Serum XRP-1 levels were significantly higher in women with GDM than in healthy controls (3.45 ± 0.47 vs. 2.87 ± 0.46 ng/mL, p = 0.003). ROC analysis demonstrated moderate discriminatory performance for XRP-1 in identifying GDM (AUC = 0.658, 95% CI: 0.560–0.750), with an optimal cut-off value of 3.12 ng/mL, corresponding to 63.3% sensitivity and 61.7% specificity. Multivariable logistic regression demonstrated that serum XRP-1 remained independently associated with GDM after adjustment for maternal age, pre-pregnancy body mass index, gestational weight gain, and parity (adjusted OR 2.74, 95% CI 1.31–5.73; p = 0.007). HbA1c and C-reactive protein levels were also significantly higher in the GDM group. Conclusions: Serum XRP-1 concentrations were independently associated with GDM and demonstrated moderate diagnostic accuracy. Although XRP-1 cannot replace established diagnostic methods, it may represent a complementary biomarker for identifying gestational dysglycemia. Larger multicenter studies are required to validate its clinical utility. Full article
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25 pages, 4821 KB  
Article
Mechanism of Silybin in Alleviating Liver Damage Induced by Heat Stress of Peking Ducks
by Ziyue Zhang, Shihao Xuan, Junfeng Lv, Zhaofei Xia, Dong Zhang, Jing Chen, Zouran Lan, Guisheng Wang and Yanhan Liu
Animals 2026, 16(16), 2615; https://doi.org/10.3390/ani16162615 - 20 Aug 2026
Abstract
This study aimed to explore the protective mechanism of silybin against heat stress-induced liver injury in Peking ducks as a result of oxidative stress, inflammation, and lipid metabolism. One hundred and ninety-five 1-day-old healthy male Peking ducks with similar body weights were randomly [...] Read more.
This study aimed to explore the protective mechanism of silybin against heat stress-induced liver injury in Peking ducks as a result of oxidative stress, inflammation, and lipid metabolism. One hundred and ninety-five 1-day-old healthy male Peking ducks with similar body weights were randomly divided into a control group, a heat-stress group, and three intervention groups treated with 400, 800, and 1600 mg/kg silybin under heat-stress from 21 d to 35 d for two weeks. The function indices, oxidative stress, inflammatory factor levels, histopathological changes and non-targeted lipidomic profiling in liver as well as growth performance were evaluated. Results showed that silybin supplementation partially alleviated the heat-stress-induced decreases in average daily feed intake and body weight gain (p > 0.05). Silybin supplementation at 400 and 800 mg/kg significantly reduced the heat-stress-induced increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (γ-GGT) (p < 0.05), whereas the effect of 1600 mg/kg silybin was not significant. Albumin (ALB) and globulin (GLB) levels were mainly improved in the 800 mg/kg group, and GLB was also increased in the 400 mg/kg group (p < 0.05). Silybin supplementation significantly improved hepatic antioxidant capacity, especially in the 400 and 800 mg/kg groups, as indicated by increased superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC), and decreased malondialdehyde (MDA) and reactive oxygen species (ROS) levels (p < 0.05). In addition, the 400 and 800 mg/kg groups showed more significant reductions in the pro-inflammatory factors IL-6 and TNF-α, while IL-10 was increased in silybin-supplemented groups (p < 0.05). Lipid metabolism disorders were improved through regulation of the sphingolipid and glycerophospholipid metabolism pathways, while it alleviated heat stress damage by reducing the expression of heat shock proteins. In conclusion, silybin holds promise as an effective feed additive to alleviate heat stress in poultry. This study provides a theoretical basis and practical approach for improving the health and productive performance of Peking ducks under heat-stress conditions. Full article
(This article belongs to the Special Issue Heat Stress Management in Poultry)
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26 pages, 6268 KB  
Article
Physiological and Molecular Effects of Zn–Fe Biofortified Alfalfa in Guinea Pigs Under Oxidative Stress
by Jorge Zegarra Flores, Ainer Condori Ramos, Franklin O. Areche, Froy Engelbert Coloma-Dongo, Fredy Grimaldo Calizaya Llatasi, Carmen Gisela Mindani Cáceres, Walver Keiser Lázaro Rodríguez, Hugo Vilcanqui Mamani and Livia Puma Mamani
Stresses 2026, 6(3), 58; https://doi.org/10.3390/stresses6030058 - 20 Aug 2026
Abstract
Oxidative stress is a major constraint limiting animal health and productive performance by disrupting redox homeostasis, mitochondrial function, intestinal integrity, and mineral metabolism. Agronomic biofortification of forage with essential trace minerals represents a promising nutritional strategy; however, its physiological and molecular mechanisms remain [...] Read more.
Oxidative stress is a major constraint limiting animal health and productive performance by disrupting redox homeostasis, mitochondrial function, intestinal integrity, and mineral metabolism. Agronomic biofortification of forage with essential trace minerals represents a promising nutritional strategy; however, its physiological and molecular mechanisms remain poorly understood. This study evaluated the effects of dietary zinc–iron (Zn–Fe) biofortified alfalfa on oxidative stress, antioxidant defense, mineral transport, mitochondrial bioenergetics, intestinal barrier integrity, inflammatory responses, tissue mineral deposition, and growth performance in guinea pigs. Forty-eight male guinea pigs were allocated to six experimental groups according to dietary treatment (control, Zn-biofortified alfalfa, or Zn–Fe biofortified alfalfa) and oxidative stress status. Oxidative biomarkers, antioxidant enzyme activities, inflammatory mediators, mineral concentrations, targeted RT–qPCR, mitochondrial function, intestinal histomorphology, and multivariate physiological analyses were performed. Zn–Fe biofortified alfalfa markedly reduced reactive oxygen species, malondialdehyde, protein carbonyls, 8-hydroxy-2′-deoxyguanosine, advanced oxidation protein products, and the oxidative stress index while significantly increasing superoxide dismutase, catalase, glutathione peroxidase, total antioxidant capacity, and the glutathione redox ratio. Targeted gene-expression analysis demonstrated coordinated upregulation of intestinal mineral transporters (ZIP4, DMT1, and MT1), activation of the Nrf2 antioxidant pathway, increased expression of mitochondrial regulatory genes, and suppression of inflammatory mediators. These molecular responses were accompanied by improved ATP production, mitochondrial membrane potential, respiratory-chain activity, preservation of intestinal villus architecture, enhanced expression of tight-junction proteins, increased tissue Zn and Fe deposition, superior feed efficiency, and greater body weight gain. Integrated physiological analyses consistently identified the Zn–Fe biofortified treatment as the highest-performing physiological phenotype, indicating coordinated adaptation across multiple biological systems. These findings demonstrate that Zn–Fe biofortified alfalfa enhances oxidative stress resilience through simultaneous regulation of mineral transport, antioxidant defense, mitochondrial bioenergetics, intestinal barrier integrity, and systemic physiological performance. Agronomic biofortification of forage therefore represents a promising nutritional strategy for improving animal health, mineral utilization, and productive efficiency under oxidative stress. Full article
(This article belongs to the Section Animal and Human Stresses)
17 pages, 18606 KB  
Article
Combined Exposure to Deoxynivalenol and Patulin Aggravates Liver Injury in Mice via Triggering Inflammation, Apoptosis, and Oxidative Stress
by Qingqing Zhao, Zenghao Xu, Xianglong Dai, Xingyu Zhang, Maolong Li, Juan Chang, Qingqiang Yin, Guoyu Yang and Chaoqi Liu
Toxins 2026, 18(8), 355; https://doi.org/10.3390/toxins18080355 - 20 Aug 2026
Abstract
Deoxynivalenol (DON) and patulin (PAT) are common mycotoxins in cereals and fruits, posing health risks for animals and human beings. In order to study their liver toxicity, 24 mice were randomly assigned to four groups, with six replicates in each group (one mouse [...] Read more.
Deoxynivalenol (DON) and patulin (PAT) are common mycotoxins in cereals and fruits, posing health risks for animals and human beings. In order to study their liver toxicity, 24 mice were randomly assigned to four groups, with six replicates in each group (one mouse per cage). The mice were intragastrically administered with DON, PAT, DON + PAT (DP), or without DON and PAT (the control group) for 28 days, respectively. The results showed that body weight gain was significantly reduced by all toxin treatments, compared with the control group, and the lowest body weight gain was observed in the DP group. Histopathology revealed that hepatocyte damage and inflammatory infiltration were more serious in the DP group, exhibiting the highest mRNA abundances of MyD88, IFN-γ, and JAK2. The severity of hepatocyte apoptosis induced in each group followed the order: DON > DP > PAT; the severity of oxidative stress was ranked as DP > DON > PAT. Transcriptomic analysis revealed that numerous differentially expressed genes were regulated by DP treatment, which were mainly enriched in the MAPK, JAK-STAT, and transforming growth factor (TGF)-β signaling pathways. In conclusion, individual exposure to DON or PAT triggered hepatic injury, and their co-exposure further exacerbated liver damage. Full article
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22 pages, 7749 KB  
Article
Genomic Dissection of Growth Traits and Spatial Independence from Breed-Defining Loci in Jining Grey Goats
by Yongbo Chen, Tianxu Liu, Aowu Wu, Jingchao Cao, Di Lian and Zhengxing Lian
Animals 2026, 16(16), 2593; https://doi.org/10.3390/ani16162593 - 19 Aug 2026
Viewed by 137
Abstract
Improving growth while preserving breed-defining characteristics is a central challenge in indigenous livestock breeding. We addressed this issue in Jining Grey goats using low-depth whole-genome sequencing and a conservative multi-evidence marker-prioritization framework. The discovery cohort included 70 performance-graded goats at 3 months ( [...] Read more.
Improving growth while preserving breed-defining characteristics is a central challenge in indigenous livestock breeding. We addressed this issue in Jining Grey goats using low-depth whole-genome sequencing and a conservative multi-evidence marker-prioritization framework. The discovery cohort included 70 performance-graded goats at 3 months (n = 37) and 6 months (n = 33; mean depth, 2.07×), and 47 seven-day-old goats from the same project were used for exploratory early-life trend analysis (mean depth, 2.10×). After site-level filtering, phasing, and within-cohort imputation, masking-based assessment of 120,000 genotype cells yielded 94.38% exact genotype concordance and a hard-dosage correlation of 0.919. Performance grading captured consistent differences in body weight and body-size traits, but the small 3-month Conventional group required conservative interpretation. Selective-sweep analyses highlighted breed-background regions, including signals near KIT, whereas GWAS and superior-genotype comparisons prioritized candidate growth loci, including chr10:78518687 for six-month chest girth and literature-supported genes involved in muscle growth and developmental regulation. Overlap and permutation analyses indicated limited physical overlap between growth-prioritized loci and major selective-sweep regions. A 99-SNP candidate panel showed exploratory prediction potential (maximum cross-validated r ≈ 0.47), whereas seven-day analyses showed only nominal trends without FDR significance. These findings provide a preliminary marker resource for future Jining Grey goat breeding and conservation, pending external validation, denser genotyping, and functional confirmation. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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25 pages, 5447 KB  
Article
Blood-Based Characterization of Hypoxia-Tolerant and Hypoxia-Susceptible Atlantic Salmon (Salmo salar) Under Acute Hypoxic Stress
by Salinas-Parra Nicolás, Caballero Paz, Romero Alfonso, Martínez Karin, Soto Carlos and Gallardo-Matus José
Animals 2026, 16(16), 2582; https://doi.org/10.3390/ani16162582 - 18 Aug 2026
Viewed by 212
Abstract
Hypoxia is a significant environmental and production-related stressor in Atlantic salmon aquaculture, yet the blood-based mechanisms underlying differential hypoxia tolerance remain poorly characterized. In this study, we examined hematological, biochemical, and transcriptional responses in Atlantic salmon parr classified as hypoxia-tolerant or hypoxia-susceptible following [...] Read more.
Hypoxia is a significant environmental and production-related stressor in Atlantic salmon aquaculture, yet the blood-based mechanisms underlying differential hypoxia tolerance remain poorly characterized. In this study, we examined hematological, biochemical, and transcriptional responses in Atlantic salmon parr classified as hypoxia-tolerant or hypoxia-susceptible following an acute progressive hypoxia challenge. Time to loss of equilibrium and dissolved oxygen concentration at loss of equilibrium were recorded. Blood samples were analyzed for hematological parameters, serum metabolites, and the expression of genes related to hypoxia signaling, glycolysis, oxidative stress, and immune regulation. Hypoxia-tolerant fish maintained equilibrium significantly longer than susceptible fish (Tolerant: 224 ± 18 min; Susceptible: 115 ± 24 min) and tolerated lower dissolved oxygen concentrations (Tolerant: 1.89 ± 0.09 mg L−1; Susceptible: 2.55 ± 0.34 mg L−1) before losing their ability to maintain equilibrium. Tolerance varied among families, while body weight was not significantly associated with time to loss of equilibrium. Acute hypoxia altered erythrocyte-related parameters, increased serum lactate (p < 0.0001), and reduced total protein (p = 0.0148) in both phenotypes. At the transcriptional level, tolerant fish exhibited higher expression of hif1α (p = 0.0012), k6pp (p = 0.0045) and il15 (p = 0.0159), along with reduced phd3 (p = 0.0317) expression, whereas susceptible fish showed increased anx1 expression. Taken together, our results showed that hypoxia tolerance in Atlantic salmon is associated with a coordinated blood response involving metabolic compensation and hypoxia-responsive signaling, supporting the use of blood as a practical tool for identifying resilient fish. Full article
(This article belongs to the Section Aquatic Animals)
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36 pages, 889 KB  
Review
Metabolic Syndrome and Pancreatic Cancer: Linking Insulin Resistance, Inflammation, and Carcinogenesis
by Rahela Borbei, Vlad Dumitru Brata, Ioana Dobrotă, Ligia-Maria Ceteraș, Mihai Clim, Teodora-Gabriela Alexescu, Mircea-Vasile Milaciu, Mirela-Georgiana Perne, Cezara-Andreea Gerdanovics, Lucia Maria Procopciuc, Angela Cozma and Olga-Hilda Orășan
Diagnostics 2026, 16(16), 2616; https://doi.org/10.3390/diagnostics16162616 - 18 Aug 2026
Viewed by 273
Abstract
Metabolic syndrome (MetS) is a composite classification defined by heterogeneous combinations of cardiometabolic abnormalities. Several components have been associated with pancreatic cancer (PC), but studies often conflate long-term metabolic exposure, tumor-related prediagnostic metabolic change, and prognosis after diagnosis. This review critically evaluates these [...] Read more.
Metabolic syndrome (MetS) is a composite classification defined by heterogeneous combinations of cardiometabolic abnormalities. Several components have been associated with pancreatic cancer (PC), but studies often conflate long-term metabolic exposure, tumor-related prediagnostic metabolic change, and prognosis after diagnosis. This review critically evaluates these three settings. This narrative review searched PubMed, Scopus, and Web of Science through April 2026, prioritizing meta-analyses, prospective cohorts, Mendelian randomization studies, clinical studies, preclinical mechanistic evidence, and guidelines. Evidence was interpreted with attention to reverse causation, residual confounding, outcome definitions, and validation. Meta-analyses report a 25–34% higher PC risk among individuals with MetS, with a stepwise gradient across the number of metabolic components; hyperglycemia showed the strongest association among individual components (RR 1.55, 95% CI 1.42–1.70). However, MetS represents multiple versions of exposure, and the epidemiological and clinical evidence remains predominantly observational. Proposed mechanisms involving insulin signaling, adipokines, oxidative stress, epigenetic regulation, and the microbiome are largely preclinical and are not pancreas-specific. New-onset diabetes, rising HbA1c, and involuntary weight loss may mark occult pancreatic ductal adenocarcinoma, but available risk-enrichment models and biomarkers are insufficiently validated for routine screening. After diagnosis, metabolic status and body-composition measures have been associated with survival and perioperative outcomes, although confounding and cancer-related cachexia complicate interpretation. MetS is consistently associated with PC risk but is neither a single causal exposure nor an established target for PC prevention. MetS alone does not justify pancreatic imaging or biomarker testing. Lifestyle and pharmacologic treatment should follow established cardiometabolic indications; their effects on PC incidence remain unproven. Priorities include component-specific causal studies and prospective validation of risk-enrichment strategies. Full article
(This article belongs to the Special Issue Diagnostic Innovations in Metabolic Diseases Management)
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28 pages, 3337 KB  
Article
Preclinical Evaluation of Combined Polo-like Kinase 1 Inhibition and Navitoclax in Experimental Models of Lung Cancer
by Bárbara Pinto, Mateus Prates-Rodrigues, Daniel Augusto Barnabe Nobre, Mariana de Oliveira Silva, Bárbara M. de Amorim-Santos, João P. N. Silva, Patrícia M. A. Silva, Bruno Sarmento, Marisa Salvi, Geovanni Dantas Cassali, Elaine Maria de Souza-Fagundes, Hassan Bousbaa and Juliana Carvalho-Tavares
Int. J. Mol. Sci. 2026, 27(16), 7359; https://doi.org/10.3390/ijms27167359 - 17 Aug 2026
Viewed by 260
Abstract
Targeted therapies have substantially advanced cancer treatment; however, therapeutic resistance remains a major challenge, particularly in lung cancer. Polo-like kinase 1 (PLK-1), a key regulator of mitosis, is frequently overexpressed in lung tumors and has emerged as an attractive anticancer target. Although PLK-1 [...] Read more.
Targeted therapies have substantially advanced cancer treatment; however, therapeutic resistance remains a major challenge, particularly in lung cancer. Polo-like kinase 1 (PLK-1), a key regulator of mitosis, is frequently overexpressed in lung tumors and has emerged as an attractive anticancer target. Although PLK-1 inhibition induces robust antitumor effects in preclinical models, its translation into clinical benefit has been limited, particularly when used as monotherapy. Previous in vitro work from our group demonstrated that combining PLK-1 inhibition with the pro-apoptotic agent Navitoclax markedly enhanced cancer cell death by reducing mitotic slippage and promoting post-mitotic apoptosis. Here, we investigated whether this combinatorial strategy translates into therapeutic benefit in vivo. Using Lewis lung carcinoma (LLC1) cells, we evaluated the effects of BI2536 (a PLK-1 inhibitor) and Navitoclax, alone or in combination, in vitro and in male C57BL/6J mice using three lung cancer models: subcutaneous, intranasal, and intrapulmonary. The in vitro results corroborated the findings of our previous work, demonstrating synergistic effects. In the murine models, tumor progression, body weight, survival, and histopathological features were assessed to evaluate therapeutic efficacy and systemic toxicity. In the subcutaneous model, BI2536 monotherapy significantly reduced tumor volume compared with vehicle-treated controls, while Navitoclax alone and the combination therapy also produced tumor growth inhibition. In contrast, in the intranasal model, no significant differences were observed in body weight or survival among groups. Nonetheless, treatment with BI2536 alone or in combination with Navitoclax significantly reduced tumor cell proliferative activity. In the aggressive intrapulmonary (orthotopic) model, rapid disease progression and high mortality were observed across all groups. Notably, BI2536 treatment was associated with improved survival compared with Navitoclax monotherapy, whereas the combination therapy did not confer additional survival benefit. Histological analyses revealed highly proliferative tumors with pronounced cellular and nuclear atypia. Moreover, the BI2536 monotherapy group exhibited significantly greater necrosis/apoptosis than the other treatment groups, while diffuse and focal hepatic steatosis was observed exclusively in the combination group. Together, these findings indicate that while PLK-1 inhibition exerts antitumor effects in certain in vivo contexts, the therapeutic synergy observed in vitro with Navitoclax does not consistently translate to in vivo lung cancer models. This study highlights the challenges of translating combinatorial mitotic and apoptotic targeting strategies into effective in vivo therapies and underscores the importance of model selection and tumor microenvironment in preclinical drug evaluation. Full article
(This article belongs to the Special Issue Recent Trends in Experimental Models for Cancer Research)
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14 pages, 3081 KB  
Article
Seminal Vesicle Abnormalities and Exploratory miR-664-5p and FOXO Findings in Aged Mice Following Long-Term Butyl Benzyl Phthalate Exposure
by Seonhwa Hwang, Hyun Bon Kang, Dae Hyun Kim, Hyung Hoi Kim and Min Hi Park
Antioxidants 2026, 15(8), 1021; https://doi.org/10.3390/antiox15081021 - 17 Aug 2026
Viewed by 176
Abstract
Butyl benzyl phthalate (BBP), a widely used endocrine-disrupting chemical, has been associated with reproductive toxicity; however, its long-term effects during aging remain poorly understood. In the present study, we examined the effects of prolonged BBP exposure on the male reproductive system using naturally [...] Read more.
Butyl benzyl phthalate (BBP), a widely used endocrine-disrupting chemical, has been associated with reproductive toxicity; however, its long-term effects during aging remain poorly understood. In the present study, we examined the effects of prolonged BBP exposure on the male reproductive system using naturally aged C57BL/6J mice. Mice received BBP at 169 μg/kg/day in drinking water for 10 or 22 months and were analyzed at 24 months of age. No significant differences in body weight, food intake, or water consumption were observed among the experimental groups. Representative gross images showed apparent distension and dark-red discoloration of the seminal vesicles in BBP-exposed aged mice. Compared with Young mice, the BBP-exposed aged groups showed higher expression of IL-1β, IL-6, TNFα, SOD1, and SOD2 and lower CAT expression in the seminal vesicle. H2DCFDA fluorescence showed a non-significant increasing trend. Because an untreated age-matched Old group was not included in the seminal vesicle analyses, the effects of aging and BBP could not be distinguished. In contrast, the testis showed limited changes in inflammatory cytokine-, antioxidant enzyme-, and steroidogenesis-related gene expression and in H2DCFDA fluorescence relative to the untreated Old group. Exploratory miRNA sequencing of pooled testicular RNA and comparison with a TM3 Leydig cell dataset identified miR-664-5p as a candidate showing higher relative abundance in both datasets. TargetScan analysis predicted binding sites for miR-664-5p in FOXO1 and FOXO3. In BBP-treated TM3 cells, FOXO3 protein expression was decreased, and FOXO6 expression was increased, whereas FOXO1 showed no consistent dose-dependent change. These molecular findings do not establish direct regulation of FOXO proteins by miR-664-5p or explain the seminal vesicle findings. Full article
(This article belongs to the Special Issue Oxidative Stress Induced by Environmental Pollutants)
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33 pages, 27737 KB  
Article
Integrated WGCNA, Network Pharmacology, and UPLC-MS/MS Profiling for Investigating the Antitumor Effects of the Kansui Radix Dichloromethane Fraction Against Renal Cell Carcinoma with Experimental Validation
by Zhuoyang Cheng, Xinyue Chen, Shiqi Wang, Yunuan Bai and Jiangtao Zhou
Int. J. Mol. Sci. 2026, 27(16), 7325; https://doi.org/10.3390/ijms27167325 - 16 Aug 2026
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Abstract
Kansui Radix, the root of Euphorbia kansui, was first described in Shen Nong Ben Cao Jing as a traditional Chinese medicine, known for its effects of expelling water, reducing edema, and dissipating masses. It is traditionally indicated for conditions such as “watery [...] Read more.
Kansui Radix, the root of Euphorbia kansui, was first described in Shen Nong Ben Cao Jing as a traditional Chinese medicine, known for its effects of expelling water, reducing edema, and dissipating masses. It is traditionally indicated for conditions such as “watery accumulation” and “abdominal masses (zheng-jia)”, which share certain similarities with the clinical manifestations of renal cell carcinoma (RCC), including renal masses, edema, and body cavity effusion. Despite the recognized antitumor effects of Kansui Radix, the pharmacological basis and specific molecular mechanisms underlying its inhibition of RCC progression remain unclear. The goal of this study was therefore to evaluate the antitumor efficacy of Kansui-DCM in RCC and to explore its potential mechanism. To this end, the chemical composition of the dichloromethane fraction of Kansui Radix (Kansui-DCM) was characterized by UPLC-MS. The antiproliferative effects of Kansui-DCM on 786-O and RENCA cells were evaluated using the CCK-8 assay. Apoptotic morphology, apoptosis rate, cell migration and invasion abilities were assessed. An RCC mouse model was established, and tumor growth and histopathological staining were evaluated after drug administration. Immunohistochemistry, transcriptomic analysis, WGCNA (weighted gene co-expression network analysis), network pharmacology, and immunofluorescence were employed to investigate the molecular pathway. Protein and gene expression were analyzed by Western blot and qRT-PCR, respectively. Finally, the interactions between the active components and key targets were substantiated through molecular docking and molecular dynamics simulations. A total of 1397 compounds were detected in Kansui-DCM by UPLC-MS. In vitro experiments demonstrated that Kansui-DCM inhibited the proliferation of 786-O and RENCA cells in a dose-dependent manner, induced apoptosis, and suppressed cell invasion and migration in RENCA cells. Treatment with Kansui-DCM markedly suppressed tumor growth in vivo, as reflected by a reduction in tumor volume. Immunohistochemical analysis indicated that the expression levels of CD31, COX-2, and Ki67 were markedly decreased, while the expression level of CD8 was significantly increased. Integrated analysis using WGCNA and network pharmacology predicted that Kansui-DCM may exert its effects through the regulation of the HIF/VEGF signaling pathway, which was further validated by immunofluorescence, Western blot, and qRT-PCR assays. Molecular docking and molecular dynamics simulations demonstrated stable interactions between multiple active components of Kansui-DCM and key targets such as VEGFR2 and HIF-2α. In conclusion, these findings suggested that Kansui-DCM exerts anti-RCC effects associated with regulation of the HIF/VEGF pathway. Full article
(This article belongs to the Special Issue Pharmacological Effects of Bioactive Compounds Derived from Plants)
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Article
Serum Chemerin Concentrations and Tissue Immunoreactivity in Colorectal Adenoma and Colorectal Cancer: An Exploratory Case–Control Study
by Piotr Szredzki, Aleksandra Szredzka, Anna Belina, Maria Marlicz, Mikołaj Podlasek, Paweł Guzik, Tomasz Góra, Anastasios Koulaouzidis, Wojciech Marlicz, Karolina Skonieczna-Żydecka and Michał Kukla
Diagnostics 2026, 16(16), 2589; https://doi.org/10.3390/diagnostics16162589 - 16 Aug 2026
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Abstract
Background/Objectives: Chemerin is an adipokine implicated in metabolic regulation, inflammation and cancer biology, but its value as a circulating biomarker in colorectal neoplasia remains uncertain. We investigated serum chemerin concentrations in patients with colorectal cancer (CRC), patients with colorectal polyps and colonoscopy-negative controls, [...] Read more.
Background/Objectives: Chemerin is an adipokine implicated in metabolic regulation, inflammation and cancer biology, but its value as a circulating biomarker in colorectal neoplasia remains uncertain. We investigated serum chemerin concentrations in patients with colorectal cancer (CRC), patients with colorectal polyps and colonoscopy-negative controls, and explored chemerin immunoreactivity in available polyp and tumour tissue. Methods: This exploratory observational case–control study included 41 patients with CRC, 20 patients with colorectal polyps and 29 colonoscopy-negative controls. Serum chemerin was measured by ELISA. Tissue specimens underwent routine histopathology and qualitative immunohistochemical staining for chemerin. Between-group comparisons were performed using non-parametric tests; subgroup analyses were exploratory and unadjusted. Results: Serum chemerin concentrations did not differ significantly between CRC and controls (median 144.0 vs. 135.7 ng/mL; p = 0.41), CRC and polyp groups (144.0 vs. 97.4 ng/mL; p = 0.24), or polyp and control groups (97.4 vs. 135.7 ng/mL; p = 0.94). Chemerin immunostaining was absent in CRC tissue (0/41) and conventional adenomatous polyps (0/15), whereas all available hyperplastic/serrated lesions showed epithelial cytoplasmic and/or stromal immunoreactivity (5/5); in lesions containing dysplasia, dysplastic glands showed no detectable staining. In controls, higher chemerin concentrations were associated with hyperglycaemia, hypertension, body weight and bilirubin, but these exploratory findings were not adjusted for multiplicity or metabolic confounding. Conclusions: In this exploratory cohort, serum chemerin did not discriminate CRC or colorectal adenoma from colonoscopy-negative controls. Together with the absence of staining in CRC and conventional adenomas, the findings argue against chemerin as a standalone circulating or commonly expressed tissue biomarker for these lesions under the assay conditions used. Immunoreactivity in the non-dysplastic epithelial and/or stromal compartments of hyperplastic/serrated lesions remains preliminary and requires prospective confirmation with standardised pre-analytics, quantitative pathology scoring and adjustment for metabolic confounders. Full article
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15 pages, 1591 KB  
Article
Effects of Dietary Recombinant Irisin on Growth Performance, Serum Antioxidant and Immune Indices, and Cecal Microbiota of Broilers
by Pei Wen, Haiyang Wu, Feitao Dang, Jinbo Sun, Hongwei Shi, Yi Yan, Jiayin Lu, Xiaomao Luo, Yanjun Dong and Haidong Wang
Vet. Sci. 2026, 13(8), 811; https://doi.org/10.3390/vetsci13080811 - 15 Aug 2026
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Abstract
Irisin is a myokine derived from fibronectin type III domain-containing protein 5 (FNDC5) and is involved in energy metabolism, muscle development, and oxidative regulation. Although irisin has been extensively studied in mammals, its potential application in poultry production remains unclear. Enhancing growth performance [...] Read more.
Irisin is a myokine derived from fibronectin type III domain-containing protein 5 (FNDC5) and is involved in energy metabolism, muscle development, and oxidative regulation. Although irisin has been extensively studied in mammals, its potential application in poultry production remains unclear. Enhancing growth performance and physiological resilience is critical for male white-feathered broiler chickens under intensive production systems. This study investigated the effects of dietary irisin supplementation on growth performance and physiological responses in male white-feathered broiler chickens. A total of 180 broilers were randomly allocated to three treatments, with six replicate pens of ten birds per treatment: basal diet and basal diet supplemented with 5 and 10 mg/kg irisin for 42 days. At 42 days, one bird from each replicate pen was sampled for carcass, meat-quality, serum, immune, and microbiota analyses. Dietary irisin supplementation significantly increased final body weight and average daily gain compared with the control group. Feed conversion ratio decreased from 1.51 in the control group to 1.46 in the 5 and 10 mg/kg groups. Carcass evaluation showed higher slaughter yield and breast muscle yield in irisin-supplemented birds, and cooking loss was significantly reduced in both breast and thigh muscles. Serum superoxide dismutase (SOD) activity was elevated in irisin-treated groups. In addition, immunoglobulin Y (IgY) and immunoglobulin M (IgM) concentrations were significantly increased. No significant treatment effects were observed for total antioxidant capacity (T-AOC), catalase (CAT), malondialdehyde (MDA), inflammatory cytokines (IL-6, TNF-α), or immune organ indices (thymus, spleen and bursa of Fabricius). Gut microbiota analysis showed numerical differences in the relative abundance of several major bacterial taxa among treatments. In conclusion, dietary irisin supplementation was associated with improved growth performance and selected carcass, meat-quality, antioxidant, immunoglobulin, and cecal microbiota outcomes in male white-feathered broiler chickens, supporting further investigation of its potential as a functional feed additive in poultry nutrition. Full article
(This article belongs to the Section Nutritional and Metabolic Diseases in Veterinary Medicine)
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