Galectin-8 counteracts folic acid-induced acute kidney injury and prevents its transition to fibrosis.

Acute kidney injury (AKI), characterized by a sudden decline in kidney function involving tubular damage and epithelial cell death, can lead to progressive tissue fibrosis and chronic kidney disease due to interstitial fibroblast activation and tissue repair failures that lack direct treatments. After an AKI episode, surviving renal tubular cells undergo cycles of dedifferentiation, proliferation and redifferentiation while fibroblast activity increases and then declines to avoid an exaggerated extracellular matrix deposition. Appropriate tissue recovery versus pathogenic fibrotic progression depends on fine-tuning all these processes. Identifying endogenous factors able to affect any of them may offer new therapeutic opportunities to improve AKI outcomes. Galectin-8 (Gal-8) is an endogenous carbohydrate-binding protein that is secreted through an unconventional mechanism, binds to glycosylated proteins at the cell surface and modifies various cellular activities, including cell proliferation and survival against stress conditions. Here, using a mouse model of AKI induced by folic acid, we show that pre-treatment with Gal-8 protects against cell death, promotes epithelial cell redifferentiation and improves renal function. In addition, Gal-8 decreases fibroblast activation, resulting in less expression of fibrotic genes. Gal-8 added after AKI induction is also effective in maintaining renal function against damage, improving epithelial cell survival. The ability to protect kidneys from injury during both pre- and post-treatments, coupled with its anti-fibrotic effect, highlights Gal-8 as an endogenous factor to be considered in therapeutic strategies aimed at improving renal function and mitigating chronic pathogenic progression.

Genome sequencing and analysis of black flounder (Paralichthys orbignyanus) reveals new insights into Pleuronectiformes genomic size and structure.

Black flounder (Paralichthys orbignyanus, Pleuronectiformes) is a commercially significant marine fish with promising aquaculture potential in Argentina. Despite extensive studies on Black flounder aquaculture, its limited genetic information available hampers the crucial role genetics plays in the development of this activity. In this study, we first employed Illumina sequencing technology to sequence the entire genome of Black flounder. Utilizing two independent libraries-one from a female and another from a male-with 150 bp paired-end reads, a mean insert length of 350 bp, and over 35 X-fold coverage, we achieved assemblies resulting in a genome size of ~ 538 Mbp. Analysis of the assemblies revealed that more than 98% of the core genes were present, with more than 78% of them having more than 50% coverage. This indicates a somehow complete and accurate genome at the coding sequence level. This genome contains 25,231 protein-coding genes, 445 tRNAs, 3 rRNAs, and more than 1,500 non-coding RNAs of other types. Black flounder, along with pufferfishes, seahorses, pipefishes, and anabantid fish, displays a smaller genome compared to most other teleost groups. In vertebrates, the number of transposable elements (TEs) is often correlated with genome size. However, it remains unclear whether the sizes of introns and exons also play a role in determining genome size. Hence, to elucidate the potential factors contributing to this reduced genome size, we conducted a comparative genomic analysis between Black flounder and other teleost orders to determine if the small genomic size could be explained by repetitive elements or gene features, including the whole genome genes and introns sizes. We show that the smaller genome size of flounders can be attributed to several factors, including changes in the number of repetitive elements, and decreased gene size, particularly due to lower amount of very large and small introns. Thus, these components appear to be involved in the genome reduction in Black flounder. Despite these insights, the full implications and potential benefits of genome reduction in Black flounder for reproduction and aquaculture remain incompletely understood, necessitating further research.

Biological role of fructose in the male reproductive system: Potential implications for prostate cancer.

BACKGROUND: Over the last 20 years, fructose has gradually emerged as a potential metabolic substrate capable of promoting the growth and progression of various cancers, including prostate cancer (PCa). The biological and molecular mechanisms that underlie the effects of fructose on cancer are beginning to be elucidated. METHODS: This review summarizes the biological function of fructose as a potential carbon source for PCa cells and its role in the functionality of the male reproductive tract under normal conditions. RESULTS: The most recent biological advances related to fructose transport and metabolism as well as their implications in PCa growth and progression suggest that fructose represent a potential carbon source for PCa cells. Consequently, fructose derivatives may represent efficient radiotracers for obtaining PCa images via positron emission tomography and fructose transporters/fructose-metabolizing enzymes could be utilized as potential diagnostic and/or predictive biomarkers for PCa. CONCLUSION: The existing data suggest that restriction of fructose from the diet could be a useful therapeutic strategy for patients with PCa.

New Plastic Crack-Tip Opening Displacement Tool Based on Digital Image Correlation for Estimating the Fatigue-Crack-Growth Law on 316L Stainless Steel.

This work presents a new approach for studying crack growth resulting from fatigue, which utilizes the plastic contribution of crack-tip opening displacement (CTODp). CTODp is used to predict austenitic stainless-steel crack propagation. Unlike linear elastic fracture mechanics analysis, the method presented here is also helpful for tasks other than small-scale yielding. The approach was based on correlating full-field displacement information with post-processing digital images. This work describes a detailed post-processing protocol that can be used to calculate CTODp. The results for steel compact-tension specimens were especially promising. Of note, there was a linear relationship between the propagation rate of fatigue cracks and the CTODp range.

Antifungal Activity of Selenium Nanoparticles Obtained by Plant-Mediated Synthesis.

The continuous need to satisfy world food demand has led to the search for new alternatives to combat economic losses in agriculture caused by phytopathogenic fungi. These organisms cause plant diseases, reducing their productivity and decreasing fruit quality. Among the new tools being explored is nanotechnology. Nanoparticles with antimicrobial properties could be an excellent alternative to address this problem. In this work, selenium nanoparticles (SeNPs) were obtained using plant extracts of Amphipterygium glaucum leaves (SeNPs-AGL) and Calendula officinalis flowers (SeNPs-COF). Characterization of the SeNPs was performed and their ability as antifungal agents against two commercially relevant plant pathogenic fungi, Fusarium oxysporum and Colletotrichum gloeosporioides, was evaluated. Assays were performed with different concentrations of SeNPs (0, 0.25, 0.5, 1.0, and 1.7 mg/mL). It was observed that both SeNPs had antifungal activity against both plant pathogens at concentrations of 0.25 mg/mL and above. SeNPs-AGL demonstrated better antifungal activity and smaller size (around 8.0 nm) than SeNPs-COF (134.0 nm). FTIR analysis evidenced the existence of different functional groups that constitute both types of SeNPs. There are factors that have to be considered in the antimicrobial activity of SeNPs such as nanoparticle size and phytochemical composition of the plant extracts used, as these may affect their bioavailability.

Active Surveillance in Prostate Cancer: Current and Potentially Emerging Biomarkers for Patient Selection Criteria.

BACKGROUND: Prostate cancer (PCa) represents one of the most frequent malignancies and the fifth leading cause of cancer death in adult men worldwide. PCa mortality rates have been declining in several Western countries; one of the possible reasons may be related to the application of prostate-specific antigen early detection policies. These early detection protocols increase PCa-specific patient survival; however, a high percentage of these cases corresponds to low-risk PCa that grows very slowly and is unlikely to metastasize to threaten survival. Many low-risk PCa patients receive aggressive therapies, such as radical prostatectomy and radiotherapy, that are costly for patients and/or health systems and generate side effects that affect the quality of life. An alternative to surgery and radiotherapy treatments for low-risk PCa is active surveillance (AS), a strategy based on close disease monitoring and intervention only if the disease progresses. However, proper identification of low-risk PCa patients at the time of diagnosis is essential for the effectiveness AS. The selection of AS candidates remains challenging; thus, effective prognostic biomarkers are needed. SUMMARY: This review article addresses the characteristics of the current and emerging PCa prognostic biomarkers, including tests available for tissue, blood, and urine analyses, for the appropriate selection of PCa patients for AS. In addition, and based on published literature, we performed a selection of potential new biomarkers that can distinguish low-risk PCa. KEY MESSAGES: The literature search yielded four tissue-based tests, two blood-based tests, and six urine-based tests that can be used to determine PCa risk classification. However, most available tests are expensive; thus, cost-effective analyses are needed in order to obtain the approval of government agencies and to be financed by the health systems. Available prognostic urine tests have shown great progress over the last years, and they have the advantage of being minimally invasive; therefore, they may become a routine disease progression test for patients under AS. In addition, new research conducted in the last decade has shown promising biomarkers, including mRNA, miRNA, long noncoding RNA, and metabolites, that could improve existing tests or allow the development of new tools for AS patient selection.

The Differential Paracrine Role of the Endothelium in Prostate Cancer Cells.

The survival of patients with solid tumors, such as prostate cancer (PCa), has been limited and fleeting with anti-angiogenic therapies. It was previously thought that the mechanism by which the vasculature regulates tumor growth was driven by a passive movement of oxygen and nutrients to the tumor tissue. However, previous evidence suggests that endothelial cells have an alternative role in changing the behavior of tumor cells and contributing to cancer progression. Determining the impact of molecular signals/growth factors released by endothelial cells (ECs) on established PCa cell lines in vitro and in vivo could help to explain the mechanism by which ECs regulate tumor growth. Using cell-conditioned media collected from HUVEC (HUVEC-CM), our data show the stimulated proliferation of all the PCa cell lines tested. However, in more aggressive PCa cell lines, HUVEC-CM selectively promoted migration and invasion in vitro and in vivo. Using a PCa-cell-line-derived xenograft model co-injected with HUVEC or preincubated with HUVEC-CM, our results are consistent with the in vitro data, showing enhanced tumor growth, increased tumor microvasculature and promoted metastasis. Gene set enrichment analyses from RNA-Seq gene expression profiles showed that HUVEC-CM induced a differential effect on gene expression when comparing low versus highly aggressive PCa cell lines, demonstrating epigenetic and migratory pathway enrichments in highly aggressive PCa cells. In summary, paracrine stimulation by HUVEC increased PCa cell proliferation and tumor growth and selectively promoted migration and metastatic potential in more aggressive PCa cell lines.

Pharmacological targets for the induction of ferroptosis: Focus on Neuroblastoma and Glioblastoma.

Neuroblastomas are the main extracranial tumors that affect children, while glioblastomas are the most lethal brain tumors, with a median survival time of less than 12 months, and the prognosis of these tumors is poor due to multidrug resistance. Thus, the development of new therapies for the treatment of these types of tumors is urgently needed. In this context, a new type of cell death with strong antitumor potential, called ferroptosis, has recently been described. Ferroptosis is molecularly, morphologically and biochemically different from the other types of cell death described to date because it continues in the absence of classical effectors of apoptosis and does not require the necroptotic machinery. In contrast, ferroptosis has been defined as an iron-dependent form of cell death that is inhibited by glutathione peroxidase 4 (GPX4) activity. Interestingly, ferroptosis can be induced pharmacologically, with potential antitumor activity in vivo and eventual application prospects in translational medicine. Here, we summarize the main pathways of pharmacological ferroptosis induction in tumor cells known to date, along with the limitations of, perspectives on and possible applications of this in the treatment of these tumors.

Contenido de proteínas en suplementos proteicos y disconformidad con el etiquetado / Protein content in protein supplements and labelling non-compliance

JUSTIFICACIÓN: el ejercicio físico y el deporte se acompaña, especialmente si la actividad física se orienta a la ganancia de masa muscular, del consumo de suplementos proteicos. A nivel global se observa un incremento y diversificación en la comercialización y el consumo de suplementos proteicos que invita a evaluar su calidad y la conformidad de su etiquetado e información al consumidor.OBJETIVOS: determinar el contenido de proteínas en suplementos proteicos y verificar su conformidad con los valores declarados por el fabricante en el etiquetado.MATERIAL Y MÉTODOS: el contenido proteico de 19 muestras de suplementos proteicos (47,4 % adquiridas en tiendas de deporte. 31,6 % en gimnasios, 10,5 % en herbolarios y 10,5 % en tiendas online) de 11 marcas diferentes y de 4 tipo de proteína (suero 73,7 %, suero y huevo 10,5 %, guisante 5,3 %, guisante y arroz 10,5 %) y con origen europeo (89 %) y extracomunitario (UK 11 %) fue analizado mediante el método Kjeldahl.RESULTADOS/DISCUSIÓN: el contenido medio de proteínas en los complementos proteicos analizados oscila entre 19,47 - 91,57 g/100 g producto. 3 muestras (16%), todas ellas de origen animal extraídas del suero, cumplían o incluso superaban la cantidad de proteínas indicada en la etiqueta del producto. 4 muestras (21 %) presentaron una conformidad superior al 90 % entre el contenido real y declarado de proteínas. 12 muestras (63 %) registraron una diferencia por defecto de más de 10 g de proteína respecto al etiquetado lo que supone un porcentaje de conformidad entre la concentración proteica real y la declarada en el etiquetado por el fabricante del 40 – 88 % lo que revela la variabilidad y cuestiona la calidad de estos productos. Además, la falta de conformidad en el contenido proteico puede derivar en una ingesta de proteínas inferior a la prevista por el consumidor. (AU)

Los suplementos proteicos como fuente de Na, Mg, K, Ca, Fe y Zn / Protein supplementation as a source of Na, Mg, K, Ca, Fe and Zn

JUSTIFICACIÓN: además de proteínas, los suplementos proteicos contienen otros elementos de interés nutricional (Na, Mg, K, Ca, Fe y Zn) que disponen de ingestas diarias recomendadas (IDR). Sin embargo, su creciente autoconsumo invita a evaluar su calidad y la seguridad de su uso.OBJETIVOS: determinar el contenido de Na, Mg, K, Ca, Fe y Zn en suplementos proteicos y evaluar la exposición dietética en población adulta (20 - 49 años) en base a la pauta media de consumo y las IDR establecidas.MATERIAL Y MÉTODOS: Na, Mg, K, Ca, Fe y Zn fueron cuantificados mediante espectrometría de emisión óptica con plasma acoplado inductivamente y detector óptico (ICP-OES) en 27 muestras de suplementos proteicos (92,6 % de origen europeo) de 17 marcas y de 5 tipos según la fuente de proteína (suero (81,5 %), guisante y arroz (7,4 %), soja (3,7 %), guisante, garbanzo, cáñamo, calabaza (3,7 %), cacahuete (3,7 %). La evaluación dietética para la población española adulta se ejecutó considerando un consumo de 25 g/día y las IDR (mg/día) fijadas: Na (1500); Mg (350 hombres y 300 mujeres); K (3100); Ca (900); Fe (9 hombres y 18 mujeres) y Zn (9,5 hombres y 7 mujeres) (FESNAD, 2010).RESULTADOS/DISCUSIÓN: los suplementos proteicos deben ser considerados, en consumidores crónicos, como fuentes dietéticas adicionales de Na, Mg, K, Ca, Fe y Zn pues sus contenidos medios (mg/kg) son: 3537 (434-9891), 673 (202-2686), 4460 (726- 7491), 3044 (305-7764), 36,6 (3,1-282,8), 14,7 (1,7-65,4), respectivamente. La gran variabilidad en el contenido entre los distintos complementos, posiblemente debida a la fuente de la proteína, condiciona la variable contribución a las IDR derivada del consumo de estos productos. (AU)

Ingesta de Fluoruro a partir de zumos y néctares de frutas. Evaluación del riesgo en población infantil y adolescente / Fluoride intake from fruit juices and nectars. Risk assessment in children and adolescents

JUSTIFICACIÓN: el fluoruro es una hormetina (beneficioso a dosis bajas y tóxica a dosis altas) a la cual el hombre se expone por vía dietética. La European Food Safety Authority (EFSA) no ha estimado un Torerable Upper Level pero ha establecido una Adequate Intake (AI) de 0.05 (mg/día kg p.c.). Los zumos/néctares, consumidos mayoritariamente por niños, han sido identificados como fuentes dietéticas de F-. y su estudio se alinea con la recomendación de EFSA de ampliar el registro de niveles de F- en alimentos.OBJETIVOS: determinar el contenido de fluoruro en zumos y néctares y evaluar, en diferentes patrones de consumo, la exposición dietética a F- derivada de su consumo en distintos subgrupos de población infantil.MATERIAL Y MÉTODOS: 60 muestras de diferentes marcas y sabores fueron analizadas por determinación potenciométrica de ion selectivo de F-. La estimación de la exposición y la evaluación del riesgo se realizó para dos escenarios de consumo; 1 y 2 envases/día (0.2 y 0.4 L/día).RESULTADOS/DISCUSIÓN: la concentración media de F- fue de 0.42 ± 0.31 (mg/L) y por sabores: melocotón 0.33±0.24 (0.06-0.72), manzana 0.46±0.36 (0.12-1.14) y piña 0.48±0.31 (0.2-1.1) mg/L. (AU)

Overview and New Insights Into the Diversity, Evolution, Role, and Regulation of Kisspeptins and Their Receptors in Teleost Fish.

In the last two decades, kisspeptin (Kiss) has been identified as an important player in the regulation of reproduction and other physiological functions in vertebrates, including several fish species. To date, two ligands (Kiss1, Kiss2) and three kisspeptin receptors (Kissr1, Kissr2, Kissr3) have been identified in teleosts, likely due to whole-genome duplication and loss of genes that occurred early in teleost evolution. Recent results in zebrafish and medaka mutants have challenged the notion that the kisspeptin system is essential for reproduction in fish, in marked contrast to the situation in mammals. In this context, this review focuses on the role of kisspeptins at three levels of the reproductive, brain-pituitary-gonadal (BPG) axis in fish. In addition, this review compiled information on factors controlling the Kiss/Kissr system, such as photoperiod, temperature, nutritional status, sex steroids, neuropeptides, and others. In this article, we summarize the available information on the molecular diversity and evolution, tissue expression and neuroanatomical distribution, functional significance, signaling pathways, and gene regulation of Kiss and Kissr in teleost fishes. Of particular note are recent advances in understanding flatfish kisspeptin systems, which require further study to reveal their structural and functional diversity.

Critically Ill Patients Treated for Chimeric Antigen Receptor-Related Toxicity: A Multicenter Study.

OBJECTIVES: To report the epidemiology, treatments, and outcomes of adult patients admitted to the ICU after cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. DESIGN: Retrospective cohort study. SETTING: Nine centers across the U.S. part of the chimeric antigen receptor-ICU initiative. PATIENTS: Adult patients treated with chimeric antigen receptor T-cell therapy who required ICU admission between November 2017 and May 2019. INTERVENTIONS: Demographics, toxicities, specific interventions, and outcomes were collected. RESULTS: One-hundred five patients treated with axicabtagene ciloleucel required ICU admission for cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome during the study period. At the time of ICU admission, the majority of patients had grade 3-4 toxicities (66.7%); 15.2% had grade 3-4 cytokine release syndrome and 64% grade 3-4 immune effector cell-associated neurotoxicity syndrome. During ICU stay, cytokine release syndrome was observed in 77.1% patients and immune effector cell-associated neurotoxicity syndrome in 84.8% of patients; 61.9% patients experienced both toxicities. Seventy-nine percent of patients developed greater than or equal to grade 3 toxicities during ICU stay, however, need for vasopressors (18.1%), mechanical ventilation (10.5%), and dialysis (2.9%) was uncommon. Immune Effector Cell-Associated Encephalopathy score less than 3 (69.7%), seizures (20.2%), status epilepticus (5.7%), motor deficits (12.4%), and cerebral edema (7.9%) were more prevalent. ICU mortality was 8.6%, with only three deaths related to cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Median overall survival time was 10.4 months (95% CI, 6.64-not available mo). Toxicity grade or organ support had no impact on overall survival; higher cumulative corticosteroid doses were associated to decreased overall and progression-free survival. CONCLUSIONS: This is the first study to describe a multicenter cohort of patients requiring ICU admission with cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy. Despite severe toxicities, organ support and in-hospital mortality were low in this patient population.

Estimation of the Plastic Zone in Fatigue via Micro-Indentation.

Accurate knowledge of the plastic zone of fatigue cracks is a very direct and effective way to quantify the damage of components subjected to cyclic loads. In this work, we propose an ultra-fine experimental characterisation of the plastic zone based on Vickers micro-indentations. The methodology is applied to different compact tension (CT) specimens made of aluminium alloy 2024-T351 subjected to increasing stress intensity factors. The experimental work and sensitivity analysis showed that polishing the surface to #3 µm surface finish and applying a 25 g-force load for 15 s produced the best results in terms of resolution and quality of the data. The methodology allowed the size and shape of both the cyclic and the monotonic plastic zones to be visualised through 2D contour maps. Comparison with Westergaard's analytical model indicates that the methodology, in general, overestimates the plastic zone. Comparison with S355 low carbon steel suggests that the methodology works best for alloys exhibiting a high strain hardening ratio.

Simultaneous Droplet Generation with In-Series Droplet T-Junctions Induced by Gravity-Induced Flow.

Droplet microfluidics offers a wide range of applications, including high-throughput drug screening and single-cell DNA amplification. However, these platforms are often limited to single-input conditions that prevent them from analyzing multiple input parameters (e.g., combined cellular treatments) in a single experiment. Droplet multiplexing will result in higher overall throughput, lowering cost of fabrication, and cutting down the hands-on time in number of applications such as single-cell analysis. Additionally, while lab-on-a-chip fabrication costs have decreased in recent years, the syringe pumps required for generating droplets of uniform shape and size remain cost-prohibitive for researchers interested in utilizing droplet microfluidics. This work investigates the potential of simultaneously generating droplets from a series of three in-line T-junctions utilizing gravity-driven flow to produce consistent, well-defined droplets. Implementing reservoirs with equal heights produced inconsistent flow rates that increased as a function of the distance between the aqueous inlets and the oil inlet. Optimizing the three reservoir heights identified that taller reservoirs were needed for aqueous inlets closer to the oil inlet. Studying the relationship between the ratio of oil-to-water flow rates (Φ) found that increasing Φ resulted in smaller droplets and an enhanced droplet generation rate. An ANOVA was performed on droplet diameter to confirm no significant difference in droplet size from the three different aqueous inlets. The work described here offers an alternative approach to multiplexed droplet microfluidic devices allowing for the high-throughput interrogation of three sample conditions in a single device. It also has provided an alternative method to induce droplet formation that does not require multiple syringe pumps.

Empirical Study of a Room-Level Localization System Based on Bluetooth Low Energy Beacons.

The ability to locate an object or a person at room-level inside a building or a house could have multiple applications. In this study, we adapt the fingerprint technique using Bluetooth Low Energy to locate the exact room of a person, seeking a simple and low-cost solution. The system is based on BLE beacons deployed at fixed positions and a person carrying a BLE scanner that generates fingerprints from the BLE beacons in coverage. We formulate it as a classification problem where each room is a class; the objective is to estimate the exact room, trying to maximize the area and number of rooms, but also trying to minimize the number of BLE beacons. The room estimation engine is based on a kNN (k-nearest neighbors) classifier. We evaluate the accuracy in two real scenarios and empirically measure the room estimation success related to the number of BLE beacons. As a proof-of-concept, a laptop and a Raspberry Pi are used as BLE scanners to test different hardware. We follow a measurement campaign for several days at different times to evaluate the stability and repeatability of the system. With just a few beacons an accuracy between 70 and 90% is achieved for house and university scenarios.

Lack of experience is a main cause of maternal death in placenta accreta spectrum patients.

INTRODUCTION: Placenta accreta spectrum (PAS) is a serious condition with a mortality as high as 7%. However, the factors associated with this type of death have not been adequately described, with an almost complete lack of publications analyzing the determining factors of death in this disease. The aim of our work is to describe the causes of death related to PAS and to analyze the associated diagnosis and treatment problems. MATERIAL AND METHODS: This is an inter-continental, multicenter, descriptive, retrospective study in low- and middle-income countries. Maternal deaths related to PAS between January 2015 and December 2020 were included. Crucial points in the management of PAS, including prenatal diagnosis and details of the surgical treatment and postoperative management, were evaluated. RESULTS: Eighty-two maternal deaths in 16 low- and middle-income countries, on three continents, were included. Almost all maternal deaths (81 cases, 98.8%) were preventable, with inexperience among surgeons being identified as the most relevant problem in the process that led to death among 87% (67 women) of the cases who had contact with health services. The main cause of death associated with PAS was hemorrhage (69 cases, 84.1%), and failures in the process leading to the diagnosis were detected among 64.6% of cases. Although the majority of cases received medical attention and 50 (60.9%) were treated at referral centers for severe obstetric disease, problems were identified during treatment in all cases. CONCLUSIONS: Lack of experience and inadequate surgical technique are the most frequent problems associated with maternal deaths in PAS. Continuous training of interdisciplinary teams is critical to modify this tendency.

Dietary Fructose Promotes Prostate Cancer Growth.

Clinical localization of primary tumors and sites of metastasis by PET is based on the enhanced cellular uptake of 2-deoxy-2-[18F]-fluoro-D-glucose (FDG). In prostate cancer, however, PET-FDG imaging has shown limited clinical applicability, suggesting that prostate cancer cells may utilize hexoses other than glucose, such as fructose, as the preferred energy source. Our previous studies suggested that prostate cancer cells overexpress fructose transporters, but not glucose transporters, compared with benign cells. Here, we focused on validating the functional expression of fructose transporters and determining whether fructose can modulate the biology of prostate cancer cells in vitro and in vivo. Fructose transporters, Glut5 and Glut9, were significantly upregulated in clinical specimens of prostate cancer when compared with their benign counterparts. Fructose levels in the serum of patients with prostate cancer were significantly higher than healthy subjects. Functional expression of fructose transporters was confirmed in prostate cancer cell lines. A detailed kinetic characterization indicated that Glut5 represents the main functional contributor in mediating fructose transport in prostate cancer cells. Fructose stimulated proliferation and invasion of prostate cancer cells in vitro. In addition, dietary fructose increased the growth of prostate cancer cell line-derived xenograft tumors and promoted prostate cancer cell proliferation in patient-derived xenografts. Gene set enrichment analysis confirmed that fructose stimulation enriched for proliferation-related pathways in prostate cancer cells. These results demonstrate that fructose promotes prostate cancer cell growth and aggressiveness in vitro and in vivo and may represent an alternative energy source for prostate cancer cells. SIGNIFICANCE: This study identifies increased expression of fructose transporters in prostate cancer and demonstrates a role for fructose as a key metabolic substrate supporting prostate cancer cells, revealing potential therapeutic targets and biomarkers.

Hexose Transporters in Cancer: From Multifunctionality to Diagnosis and Therapy.

Cancer cells increase their metabolic activity by enhancing glucose uptake through overexpression of hexose transporters (Gluts). Gluts also have the capacity to transport other molecules besides glucose, including fructose, mannose, and dehydroascorbic acid (DHA), the oxidized form of vitamin C. The majority of research studies in this field have focused on the role of glucose transport and metabolism in cancer, leaving a substantial gap in our knowledge of the contribution of other hexoses and DHA in cancer biology. Here, we summarize the most recent advances in understanding the role that the multifunctional transport capacity of Gluts plays in biological and clinical aspects of cancer, and how these characteristics can be exploited in the search for novel diagnostic and therapeutic strategies.