Search Results (140)

White-Nose Syndrome (WNS) has devastated insectivorous bat populations, particularly in North America, leading to severe ecological and economic consequences. Despite extensive research, many aspects of the evolutionary history, mitochondrial genome organization, and metabolic adaptations of its etiological agent, Pseudogymnoascus destructans, remain unexplored. Here, we present a multi-scale genomic analysis integrating pangenome reconstruction, phylogenetic inference, Bayesian divergence dating, comparative mitochondrial genomics, and refined functional annotation. We show that P. destructans exhibits extensive mitochondrial genome rearrangements absent in its nonpathogenic relatives from the Leotiomycetes class, suggesting a potential link between mitochondrial evolution and pathogenic adaptation. Our divergence dating analysis reveals that P. destructans separated from its Antarctic relatives approximately 141 million years ago, before adapting to bat hibernacula in the Northern Hemisphere. Additionally, our refined functional annotation significantly expands the known functional landscape of P. destructans, revealing an extensive repertoire of previously uncharacterized proteins involved in carbohydrate metabolism and secondary metabolite biosynthesis—key processes that likely contribute to its pathogenic success. By providing new insights into the genomic basis of P. destructans adaptation and pathogenicity, our study refines the evolutionary framework of this fungal pathogen and creates the foundation for future research on WNS mitigation strategies. Full article

Traditionally studied in isolation, the oral and gut microbiota are now being recognized as interconnected through anatomical and physiological pathways forming a dynamic “oral–gut microbiota axis”. Both oral and gut microbiota undergo changes with aging, characterized by a decline in microbial diversity and a shift toward potentially harmful species. The aim of this review is, therefore, to provide an overview of oral–gut communications in mediating frailty and sarcopenia. PubMed, EMBASE and Scopus databases were searched for relevant articles. We limited our search to manuscripts published in the English language. Interactions between oral and gut microbiota occur mainly through three pathways namely the enteral, the bloodstream and the fecal-oral routes. Alterations in the oral–gut microbiota axis contribute to chronic low-grade inflammation (i.e., “inflamm-ageing”) and mitochondrial dysfunction, key mechanisms underlying frailty and sarcopenia. Microbial metabolites, such as short-chain fatty acids and modified bile acids, appear to play an emerging role in influencing microbial homeostasis and muscle metabolism. Furthermore, poor oral health associated with microbial dysbiosis may contribute to altered eating patterns that negatively impact gut microbiota eubiosis, further exacerbating muscle decline and the degree of frailty. Strategies aimed at modulating the microbiota, such as healthy dietary patterns with reduced consumption of ultra-processed foods, refined carbohydrates and alcohol, ensuring an adequate protein intake combined with physical exercise, as well as supplementation with prebiotics, probiotics, and omega-3 polyunsaturated fatty acids, are increasingly recognized as promising interventions to improve both oral and gut microbiota health, with beneficial effects on frailty and sarcopenia. A better understanding of the oral–gut microbiota axis offers promising insights into nutritional interventions and therapeutic strategies for the age-related muscle decline, frailty and systemic health maintenance. Full article

Background/Objectives: The consumption of refined carbohydrates has increased globally. It is associated with inflammation and oxidative stress, both recognized as risk factors for cardiovascular disease. This study investigated the effects of a refined carbohydrate-rich diet on the vascular reactivity of rat aorta. Methods: We acclimatized adult male Wistar rats for two weeks and then randomly assigned them to two experimental groups: a control (CT) group and a high-carbohydrate diet (HCD) group. The CT group received standard laboratory chow for 15 days, while the HCD group received a diet composed of 45% sweetened condensed milk, 10% refined sugar, and 45% standard chow. After the dietary exposure period, we evaluated the vascular reactivity of aortic rings, gene expression related to inflammation, superoxide dismutase activity, and biochemical parameters, including cholesterol, triglycerides, fasting glucose, and glucose and insulin tolerance. Results: The results demonstrate a reduction in vascular reactivity caused by endothelial alterations, including increased NO production, which was observed as higher vasoconstriction in the presence of L-NAME and aminoguanidine and upregulation of iNOS gene expression. In addition, increased production of free radicals, such as O₂^-, was observed, as well as immune markers like MCP-1 and CD86 in the HCD group. Additionally, the HCD group showed an increase in the TyG index, suggesting early metabolic impairment. GTT and ITT results revealed higher glycemic levels, indicating early signs of insulin resistance. Conclusions: These findings indicate that short-term consumption of a refined carbohydrate-rich diet may trigger oxidative stress and endothelial dysfunction, thereby increasing the risk of cardiovascular complications. Full article

Background/Objectives: To assess the association between early pregnancy carbohydrate quality, as measured by the Carbohydrate Quality Index (CQI), and the risk of delivering a large-for-gestational-age (LGA) infant in a Mediterranean pregnant cohort of northern Greece. Methods: We analyzed singleton pregnancies from the BORN 2020 prospective cohort in Greece. Dietary intake was assessed via a validated food frequency questionnaire, and CQI was computed from glycemic index, fiber density, whole-to-refined grain ratio, and solid-to-liquid carbohydrate ratio. Multivariable logistic regression was used to estimate the association between CQI (in tertiles) and LGA risk, defined as birthweight >90th percentile. Results: Among the 797 participants, 152 (19.1%) delivered LGA infants, and 117 (14.7%) were diagnosed with GDM. Of those with GDM, 23 (19.7%) delivered LGA infants. In the total population, higher maternal weight (p < 0.001), height (p = 0.006), and pre-pregnancy BMI (p = 0.004) were significantly associated with LGA. A greater proportion of women with LGA had a BMI > 25 (p = 0.007). In the GDM subgroup, maternal height remained significantly higher in those who delivered LGA infants (p = 0.017). In multivariable models, moderate CQI was consistently associated with increased odds of LGA across all models (Model 1: aOR = 1.60 (95% CI: 1.03–2.50), p = 0.037, Model 2: aOR = 1.57 (95% CI: 1.01–2.46), p = 0.046, Model 3: aOR = 1.58 (95% CI: 1.01–2.47), p = 0.044, Model 4 aOR: 1.70; 95% CI: 1.08–2.72; p = 0.023), whereas high CQI was not. In the GDM subgroup, a significant association between high CQI and increased LGA risk was observed in less adjusted models (Model 1 aOR: 6.74; 95% CI: 1.32–56.66; p = 0.039, Model 2 aOR: 6.64; 95% CI: 1.27–57.48; p = 0.044), but this was attenuated and became non-significant in the fully adjusted model (aOR: 3.05; 95% CI: 0.47–30.22; p = 0.28). When examining CQI components individually, no consistent associations were observed. Notably, a higher intake of low-quality carbohydrates (≥50% of energy intake) was significantly associated with increased LGA risk in the total population (aOR: 4.25; 95% CI: 1.53–11.67; p = 0.005). Conclusions: Higher early pregnancy intake of low-quality carbohydrates was associated with an elevated risk of LGA in the general population. However, CQI itself showed a non-linear and inconsistent relationship with LGA, with moderate, but not high, CQI linked to increased risk, particularly in GDM pregnancies, where associations were lost after adjustment. Both carbohydrate quality and quantity evaluations are essential, particularly in high-risk groups, to inform dietary guidance in pregnancy. Full article

Background: Melanoma, one of the most aggressive forms of skin cancer, has seen significant therapeutic advances with immune checkpoint inhibitors (ICIs). However, many patients fail to respond or develop resistance, creating the need for adjunct strategies. Objective: The objective of this study is to critically evaluate how specific dietary patterns and nutrient-derived metabolites modulate melanoma metabolism and immunotherapy outcomes, emphasizing translational implications. Methods: We performed an integrative review of preclinical and clinical studies investigating dietary interventions in melanoma models and ICI-treated patients. Mechanistic insights were extracted from studies on nutrient transport, immunometabolism, and microbiome–immune interactions, including data from ongoing nutritional clinical trials. Results: Diets rich in fermentable fibers, plant polyphenols, and unsaturated lipids, such as Mediterranean and ketogenic diets, seem to contribute to the reprogramming of tumor metabolism and enhance CD8+ T-cell activity. Fasting-mimicking and methionine-restricted diets modulate T-cell fitness and tumor vulnerability via nutrient stress sensors (e.g., UPR, mTOR). High fiber intake correlates with favorable gut microbiota and improved ICI efficacy, while excess protein, methionine, or refined carbohydrates impair immune surveillance via lactate accumulation and immunosuppressive myeloid recruitment. Several dietary molecules act as network-level modulators of host and microbial proteins, with parallels to known drug scaffolds. Conclusions: Integrating dietary interventions into melanoma immunotherapy can significantly influence metabolic reprogramming by targeting metabolic vulnerabilities and reshaping the tumor–immune–microbiome axis. When combined with AI-driven nutrient–protein interaction mapping, this approach offers a precision nutrition paradigm that supports both physicians and patients, emerging as a novel layer to enhance and consolidate existing therapeutic strategies. Full article

Circulating tumor cells (CTCs) are multifaceted biomarkers with significant potential for precision oncology, offering opportunities to refine diagnoses and personalize treatments across various cancer types, including colorectal and breast cancer. CTC assays serve as reliable prognostic indicators, even during chemotherapy and/or molecularly targeted therapies. Notably, CTCs exhibit heterogeneity that gradually develops during carcinogenesis and becomes more pronounced in advanced disease stages. These intra- and intertumoral heterogeneities pose challenges, particularly when drug-resistant clones emerge following therapy. The dynamic behavior of CTCs provides valuable insights into treatment response and prognosis. Extensive efforts have led to the development of technologies for effective CTC isolation, accelerating their clinical implementation. While both CTC and circulating tumor DNA (ctDNA) tests offer prognostic value, they reflect different aspects of tumor biology: CTC counts indicate tumor progression, while ctDNA levels correlate with tumor burden. The combined analysis is expected to yield complementary insights. CTC tests are feasible in general hospitals and may serve as tumor markers comparable to, or even superior to, conventional markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) for colorectal cancer, and CA15-3 for breast cancer. Early incorporation of CTC tests into routine blood panels appears to be a rational and promising approach. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is a major pregnancy complication with rising global prevalence. The Mediterranean Diet (MD) has shown metabolic benefits, but total adherence scores may obscure meaningful variation in dietary quality. This study aimed to investigate whether specific dietary patterns, identified within the MD framework, and their glycemic load (GL) are associated with GDM risk. Methods: This prospective cohort is part of the BORN2020 longitudinal study on pregnant women in Greece; dietary intake was assessed using a validated food frequency questionnaire (FFQ) at two time points (pre-pregnancy and during pregnancy). MD adherence was categorized by Trichopoulou score tertiles. GL was calculated for food groups using glycemic index (GI) reference values and carbohydrate content. Dietary patterns were identified using factor analysis. Logistic regression models estimated adjusted odds ratios (aORs) for GDM risk, stratified by MD adherence and time period, controlling for maternal, lifestyle, and clinical confounders. Results: In total, 797 pregnant women were included. Total MD adherence was not significantly associated with GDM risk. However, both food-specific GLs and dietary patterns with distinct dominant foods were predictive. GL from boiled greens/salads was consistently protective (aOR range: 0.09–0.19, p < 0.05). Patterns high in tea, coffee, and herbal infusions before pregnancy were linked to increased GDM risk (aOR = 1.96, 95% CI: 1.31–3.02, p = 0.001), as were patterns rich in fresh juice, vegetables, fruits, legumes, and olive oil during pregnancy (aOR = 2.91, 95% CI: 1.50–6.24, p = 0.003). A pattern dominated by sugary sweets, cold cuts, animal fats, and refined products was inversely associated with GDM (aOR = 0.34, 95% CI: 0.17–0.64, p = 0.001). A pattern characterized by sugar alternatives was associated with higher risk for GDM (aOR = 4.94, 95% CI: 1.48–19.36, p = 0.014). These associations were supported by high statistical power (power = 1). Conclusions: Within the context of the MD, evaluating both the glycemic impact of specific food groups and identifying risk-associated dietary patterns provides greater insight into GDM risk than overall MD adherence scores alone. Full article

Knee osteoarthritis (OA) is a common degenerative joint disease affecting global health. Its increasing prevalence, particularly among aging populations, remains a leading cause of disability. Besides conventional pharmacological and surgical treatments, dietary interventions are promising strategies to alleviate OA symptoms and progression. Unfortunately, scientific evidence does not support many commonly used, misleading ideas about nutrition in knee OA. Recent data highlight the detrimental effects of high-carbohydrate and high-fat diets, particularly those rich in refined sugars and saturated fats, which exacerbate systemic inflammation and contribute to cartilage degradation. Conversely, diets rich in omega-3 fatty acids, polyphenols, and dietary fiber have shown anti-inflammatory and chondroprotective properties. A Mediterranean diet rich in these nutrients effectively prevents the development of OA and its comorbidities, including obesity and cardiovascular disease. The role of supplements, such as glucosamine, chondroitin, and vitamin D, is questioned due to the lack of evidence supporting their efficacy in treating knee OA. Despite dietary recommendations published annually, there is still a need to debunk many myths that are not confirmed by current evidence. The significant research gaps require more extensive, controlled studies to establish evidence-based dietary recommendations (particularly carbohydrates, dietary fiber, and antioxidant intake). This comprehensive review provides insight into the various indications for the impact of nutrition on knee OA, focusing on key nutrients such as carbohydrates, fats, proteins, antioxidants, and selected micronutrients, providing the clinician with ready-to-implement nutritional modifications. Such an analysis may help clinicians and patients incorporate dietary strategies into treating knee OA, emphasizing the need for personalized, sustainable approaches. Full article

Pea and lentil flours are added to baked foods, pastas, and snacks to improve nutritional quality and functionality compared to products made solely with refined wheat flour. However, the effect of whole pulses versus their serving size equivalent of flour on blood glucose has not been investigated in persons with altered glycemic response. Health claims for whole pulses are based on a ½ cup amount whereas commercial pulse flour servings are typically a smaller size. The glycemic responses of four treatment meals containing 50 g available carbohydrate as ½ cup whole pulse or the dry weight equivalent of pulse flour were compared with a control beverage (Glucola^®). Eleven adults with type 2 diabetes mellitus (T2DM) and eight adults with metabolic syndrome (MetS) completed the study. Venous blood samples were collected at fasting and at 30 min intervals postprandial for three hours. Changes in net difference in plasma glucose over time from baseline and incremental area under the curve (iAUC) segments were analyzed. All four pulse meals attenuated the iAUC compared to the control from 0 to 120 min for T2DM participants and 0–180 min for MetS participants. Whole pulses produced a lower glycemic response than pulse flours in the early postprandial period for persons with T2DM and during the overall test period for those with MetS. Full article

Wastes resulting from the depulping of tropical fruits such as siriguela (Spondias purpurea), umbu (Spondias tuberosa), and juçara (Euterpe edulis) can be used as a source of bioactive compounds and nutrients. Therefore, the aim of this work was to chemically characterize the flours of siriguela seeds and peels (FSSs and FSPs), umbu seeds and peels (FUSs and FUPs), umbu pulp refine cake (FUC), and defatted juçara pulp refine cake (FJC) based on their proximate composition and mineral content, fatty acids, total phenolic content (TPC) and antioxidant capacity (ABTS^•+, DPPH^•, and FRAP). The results were expressed on a dry basis. The FJC had the highest lipid and protein percentage (10% and 31%, respectively), while for carbohydrates; FUS samples had the highest value (80%). FSSs presented the highest levels of Ca (239.7 mg 100 g⁻¹), Mg (183.3 mg 100 g⁻¹), and FSP of K (1403.9 mg 100 g⁻¹). Regarding the fatty acid profiles, palmitic acid (C16:0) was found as the main fatty acid in FSSs (28.87%), FSPs (69.31%), and FUC (45.68%), while oleic acid (C18:1) was found as the main fatty acid in FUSs (32.63%), FUPs (48.24%), and FJC (61.58%). The FUP sample exhibited the highest antioxidant potential (1852.81 mg GAE 100 g⁻¹, 130 µmol Trolox g⁻¹, 131 µmol Trolox g⁻¹, and 590 µmol Fe²⁺ g⁻¹ by TPC, ABTS^•+, DPPH^•, and FRAP, respectively). As the first comparative study of these specific fruits wastes, the results showed that their flours are promising sources of nutrients and bioactive compounds. In addition, their use can contribute to the circular economy and Sustainable Development Goals (SDGs) 2 and 12 of the 2030 Agenda. Full article

This study investigated the effects of dietary carbohydrate levels (control 8.13%, HG1 12.03%, and HG2 14.15%) on growth performance and glutamate metabolism in Chinese perch (S. chuatsi) (initial weight: 39.12 ± 0.25 g) reared at 12–15 °C. Diets were isonitrogenous (49% protein). After 8 weeks, the HG1 group optimized weight gain rate (WGR), specific growth rate (SGR), and protein efficiency ratio (PER), while reducing feed conversion ratio (FCR). HG1 and HG2 groups reduced liver glutamate/glutamine levels while downregulating the expression of key ammonia-metabolizing genes (gs, gdh, and ampd), collectively suppressing glutamate-mediated ammonia excretion. HG1 and HG2 groups enhanced glycolysis (upregulated gk and pk) coupled with suppressed gluconeogenesis (decreased PEPCK and G6Pase activities) in the liver. Concurrent downregulation of proteolytic markers (mafbx and murf1) in the muscle indicated improved protein conservation efficiency in the HG1 and HG2 groups. The HG1 diet optimally enhances growth by promoting glycolysis, reducing ammonia excretion, and improving feed efficiency. The insights gained from this research will be used to refine the low-temperature culture feed for Chinese perch, aiming to decrease ammonia and nitrogen emissions, thereby advancing the practice of low-ammonia emission culture for this species. Full article

Congestion represents a defining hallmark of heart failure (HF) leading to increased morbidity and mortality in HF patients. While it was traditionally viewed as a simple and uniform state of volume overload, contemporary understanding has emphasized its complexity, distinguishing between intravascular, interstitial, and tissue congestion. Congestion contributes to overt clinical manifestation of HF. However, subclinical congestion often goes undetected, increasing the risk of adverse outcomes. Residual congestion, in particular, remains a frequent and challenging issue, with its persistence at discharge being strongly linked to rehospitalization and poor prognosis. Clinical evaluation often fails to reliably identify the resolution of congestion, highlighting the need for supplementary diagnostic methods. Improvement in imaging modalities, including lung ultrasound, venous Doppler, and echocardiography, have significantly enhanced the detection of congestion. Moreover, biomarkers such as natriuretic peptides, bioactive adrenomedullin, soluble CD146, and carbohydrate antigen 125 offer valuable, complementary insights into fluid distribution and the severity of HF congestion. Therefore, a comprehensive, multimodal strategy that integrates clinical evaluation with imaging and biomarker data is crucial for optimizing the management of congestion in HF. Future approaches should prioritize personalized decongestive therapy, addressing both intravascular and tissue congestion, while aiming to preserve renal function and limit neurohormonal activation. Refinement of these strategies holds promise for improving long-term outcomes, reducing rehospitalizations, and enhancing overall patient prognosis. Full article

Iron homeostasis plays an important role in maintaining cellular homeostasis; however, excessive iron can promote the production of reactive oxygen species (ROS). Ferroptosis is iron-dependent programmed cell death that is characterized by excessive iron accumulation, elevated lipid peroxides, and the overproduction of ROS. The maintenance of iron homeostasis is contingent upon the activity of the transferrin receptor (TfR), ferritin (Ft), and ferroportin (FPn). In the retina, iron accumulation and lipid peroxidation can contribute to the development of age-related macular degeneration (AMD). This phenomenon can be explained by the occurrence of the Fenton reaction, in which the interaction between divalent iron and hydrogen peroxide leads to the generation of highly reactive hydroxyl radicals. The hydroxyl radicals exhibit a propensity to attack proteins, lipids, nucleic acids, and carbohydrates, thereby instigating oxidative damage and promoting lipid peroxidation. Ultimately, these processes culminate in cell death and retinal degeneration. In this context, a comprehensive understanding of the exact mechanisms underlying ferroptosis may hold significant importance for developing therapeutic interventions. This review summarizes recent findings on iron metabolism, cellular ferroptosis, and lipid metabolism in the aging retina. We also introduce developments in the therapeutic strategies using iron chelating agents. Further refinements of these knowledges would deepen our comprehension of the pathophysiology of AMD and advance the clinical management of degenerative retinopathy. A comprehensive search strategy was employed to identify relevant studies on the role of ferroptosis in AMD. We performed systematic searches of the PubMed and Web of Science electronic databases from inception to the current date. The keywords used in the search included “ferroptosis”, “AMD”, “age-related macular degeneration”, “iron metabolism”, “oxidative stress”, and “ferroptosis pathways”. Peer-reviewed articles, including original research, reviews, meta-analyses, and clinical studies, were included in this paper, with a focus on the molecular mechanisms of ferroptosis in AMDs. Studies not directly related to ferroptosis, iron metabolism, or oxidative stress in the context of AMD were excluded. Furthermore, articles that lacked sufficient data or were not peer-reviewed (e.g., conference abstracts, editorials, or opinion pieces) were not considered. Full article

Endurance athletes frequently experience muscle damage and inflammation due to prolonged, high-intensity exercise, which can impair recovery and hinder performance. This review examines the role of branched-chain amino acid (BCAA) supplementation in muscle repair, inflammation modulation, and immune regulation. BCAAs—particularly leucine and isoleucine—activate key molecular pathways, including the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), to promote muscle protein synthesis and enhance energy metabolism. They also attenuate inflammatory responses by modulating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinase (MAPK), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways, reducing levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). In addition, BCAAs influence immune function via mechanistic target of rapamycin complex 1 (mTORC1) signaling, enhance autophagy, and mitigate exercise-induced apoptosis. These molecular effects result in reduced muscle soreness, lower muscle damage biomarker levels (e.g., creatine kinase, lactate dehydrogenase), and improved recovery. Practical considerations such as optimal dosage, timing, and co-supplementation with carbohydrates, proteins, or omega-3s are also addressed. While BCAAs show promise as a nutritional strategy for enhancing recovery and controlling inflammation in endurance athletes, further research is needed to refine personalized protocols and clarify long-term effects. Full article

The ketogenic diet (KD) is a dietary intervention comprising a high-fat, low-carbohydrate, and moderate-protein intake designed to induce a metabolic state known as ketosis, whereby ketone bodies are produced as an alternative source of energy. Initially established as a treatment for intractable epilepsy, the KD has subsequently gained significant attention for its potential to manage neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s disease. Ketone bodies, such as beta-hydroxybutyrate (BHB), have been demonstrated to possess neuroprotective properties. The increasing prevalence of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s disease, poses a significant public health challenge worldwide. With neurological disorders being the second-leading cause of death globally, the need for effective therapeutic interventions has never been more urgent. Recent evidence suggests that dietary interventions, particularly the ketogenic diet, offer promising potential in mitigating the progression of these diseases by influencing metabolic processes and providing neuroprotective benefits. The ketogenic diet, characterized by high-fat and low-carbohydrate intake, induces ketosis, leading to the production of ketone bodies like beta-hydroxybutyrate, which enhance mitochondrial efficiency, reduce oxidative stress, and modulate inflammatory pathways—mechanisms critical in neurodegenerative pathophysiology. This review explores the role of the ketogenic diet in managing neurological conditions, examining its mechanisms of action, historical context, and therapeutic efficacy. The paper also discusses emerging evidence linking the ketogenic diet to improved cognitive function, reduced motor symptoms, and enhanced mitochondrial activity in patients with neurodegenerative disorders. Additionally, the review highlights the need for further research to refine the therapeutic applications of the ketogenic diet, investigate its impact on various neurodegenerative diseases, and better understand its potential long-term effects. This study underscores the importance of nutrition as a vital aspect of the treatment strategy for neurological diseases, advocating for continued exploration of dietary interventions to improve brain health and function. Full article