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Abstract Background Lanthanide-based nanomaterials offer a promising alternative for cancer therapy because of their selectivity and effectiveness, which can be modified and predicted by leveraging the improved accuracy and enhanced decision-making of machine learning (ML) modeling. Methods In this study, erbium (Er3+) and ytterbium (Yb3+) were used to dope zinc oxide (ZnO) nanoparticles (NPs). Various characterization techniques and biological assays were employed to investigate the physicochemical and optical properties of the (Er, Yb)-doped ZnO NPs, revealing the influence of the lanthanide elements. Results The (Er, Yb)-doped ZnO NPs exhibited laminar-type morphologies, negative surface charges, and optical bandgaps that vary with the presence of Er3+ and Yb3+. The incorporation of lanthanide ions reduced the cytotoxicity activity of ZnO against HEPG-2, CACO-2, and U87 cell lines. Conversely, doping with Er3+ and Yb3+ enhanced the antioxidant activity of the ZnO against DPPH, ABTS, and H2O2 radicals. The extra tree (ET) and random forest (RF) models predicted the relevance of the characterization results vis-à-vis the cytotoxic properties of the synthesized NPs. Conclusion This study demonstrates, for the first time, the synthesis of ZnO NPs doped with Er and Yb via a solution polymerization route. According to characterization results, it was unveiled that the effect of optical bandgap variations influenced the cytotoxic performance of the developed lanthanide-doped ZnO NPs, being the undoped ZnO NPs the most cytotoxic ones. The presence alone or in combination of Er and Yb enhanced their scavenging capacity. ML models such as ET and RF efficiently demonstrated that the concentration and cell line type are key parameters that influence the cytotoxicity of (Er, Yb)-doped ZnO NPs achieving high accuracy rates of 98.96% and 98.67%, respectively. This study expands the knowledge of lanthanides as dopants of nanomaterials for biological and medical applications and supports their potential in cancer therapy by integrating robust ML approaches. Graphical abstract

This study evaluated the health benefits of carrots (Daucus carota) subjected to post-harvest wounding stress, emphasizing their anti-obesogenic, anti-inflammatory, and antioxidant properties. Carrots were shredded and stored at 15 ± 2 °C for 48 h to induce wounding stress, leading to a significant increase in chlorogenic acid content, by over 112.5 % compared to control. The study utilized 3T3-L1 cell differentiation assays to evaluate the anti-obesogenic potential, monitoring changes in lipid accumulation and adipogenesis-related gene expression. The anti-inflammatory activity was determined in LPS-stimulated RAW 264.7 macrophages by measuring nitrite production, while the antioxidant capacity was assessed using the DCFH-DA assay in Caco-2 cells. Key findings include a notable reduction in lipid accumulation in 3T3-L1 cells with stressed carrot extracts, particularly at 166 μg/mL concentration, showing an 18 % decrease compared to the control. Furthermore, there was a significant alteration in the expression of adipogenesis-related genes, with a 73 % decrease in FAS expression and a 160 % increase in ATGL expression. The stressed carrot extracts at 125 μg/mL also exhibited enhanced anti-inflammatory activity, inhibiting nitrite production by 44.60 %, a 153.26 % increase over the lower concentration. Additionally, antioxidant activity in stressed carrot extracts increased by 77.15 % at 125 μg/mL. These results indicate that wounding stress significantly boosts the health-promoting properties of carrots, suggesting their potential as functional foods for combating obesity and metabolic syndrome-related diseases. The study highlights the value of post-harvest treatments in enhancing the nutraceutical quality of vegetables.

BackgroundCognition and brain function is critical through childhood and should be improved with balanced diets. Incorporating bioactive ingredients such as omega-3 polyunsaturated fatty acids (ω3 PUFAs) and probiotics into food formulations could be used as an approach to improve cognitive function. This study evaluated the effects on cognitive capacity of complementing rodent diets with chocolate, by itself and in combination with ω3 PUFAs from fish oil and probiotics.MethodsSpatial learning and memory in the rats were determined by the Barnes maze test in short- and long-term memory. Samples from the cecum were obtained to assess microbial counts (Lactobacillus, Bifidobacterium, Enterobacteriaceae, and total bacteria), and brains were recovered to analyze the neural morphology of the tissues. Also, glucose, brain weights, and epididymal tissue were analyzed.ResultsThe combination of chocolate with fish oil and probiotics improved the memory of rats compared to the result of each bioactive compound when evaluated separately. Treatments did not affect sugar level, epididymal adipose tissue, or brain weight. On the other hand, consuming probiotics alone or in combination with chocolate decreased Enterobacteria counts, while Lactobacillus and Bifidobacteria counts were not affected. Neural morphological analysis showed that combining chocolate with probiotics and ω3 PUFAs increased the number of neurons in the hippocampal CA1 and CA3 regions.ConclusionChocolate added with probiotics and ω3 PUFAs improved spatial memory and learning in the studied model.

Using wounding stress to increase the bioactive phenolic content in fruits and vegetables offers a promising strategy to enhance their health benefits. When wounded, such phenolics accumulate in plants and can provide antioxidant, anti-inflammatory, and anti-obesogenic properties. This study investigates the potential of using wounding stress-treated carrots biofortified with phenolic compounds as a raw material to extract carrot juice with increased nutraceutical properties. Fresh carrots were subjected to wounding stress via slicing and then stored at 15 °C for 48 h to allow phenolic accumulation. These phenolic-enriched slices were blanched, juiced, and blended with orange juice (75:25 ratio) and 15% (w/v) broccoli sprouts before pasteurization. The pasteurized juice was characterized by its physicochemical attributes and bioactive compound content over 28 days of storage at 4 °C. Additionally, its antioxidant, anti-inflammatory, and anti-obesogenic potentials were assessed using in vitro assays, both pre- and post-storage. The results reveal that juice derived from stressed carrots (SJ) possessed 49%, 83%, and 168% elevated levels of total phenolics, chlorogenic acid, and glucosinolates, respectively, compared to the control juice (CJ) (p < 0.05). Both juices reduced lipid accumulation in 3T3-L1 cells and nitric oxide production in Raw 264.7 cells, without significant differences between them. SJ further displayed a 26.4% increase in cellular antioxidant activity. The juice’s bioactive characteristics remained stable throughout storage time. In conclusion, the utilization of juice obtained from stressed carrots in a blend with orange juice and broccoli sprouts offers a promising method to produce a beverage enriched in bioactive compounds and antioxidant potential.

Current efforts to find novel treatments that counteract multiple sclerosis (MS) have pointed toward immunomodulation and remyelination. Currently, cell therapy has shown promising potential to achieve this purpose. However, disadvantages such as poor survival, differentiation, and integration into the target tissue have limited its application. A series of recent studies have focused on the cell secretome, showing it to provide the most benefits of cell therapy. Exosomes are a key component of the cell secretome, participating in the transfer of bioactive molecules. These nano-sized vesicles offer many therapeutical advantages, such as the capacity to cross the blood-brain barrier, an enrichable cargo, and a customizable membrane. Moreover, integrating of biomaterials into exosome therapy could lead to new tissue-specific therapeutic strategies. In this work, the use of exosomes and their integration with biomaterials is presented as a novel strategy in the treatment of MS.

Alzheimer’s disease (AD) is a chronic brain disorder characterized by progressive intellectual decline and memory and neuronal loss, caused mainly by extracellular deposition of amyloid-β (Aβ) and intracellular accumulation of hyperphosphorylated tau protein, primarily in areas implicated in memory and learning as prefrontal cortex and hippocampus. There are two forms of AD, a late-onset form that affects people over 65 years old, and the early-onset form, which is hereditable and affect people at early ages ~45 years. To date, there is no cure for the disease; consequently, it is essential to develop new tools for the study of processes implicated in the disease. Currently, in vitro AD three-dimensional (3D) models using induced pluripotent stem cells (iPSC)-derived neurons have broadened the horizon for in vitro disease modeling and gained interest for mechanistic studies and preclinical drug discovery due to their potential advantages in providing a better physiologically relevant information and more predictive data for in vivo tests. Therefore, this study aimed to establish a 3D cell culture model of AD in vitro using iPSCs carrying the A246E mutation. We generated human iPSCs from fibroblasts from a patient with AD harboring the A246E mutation in the PSEN1 gene. Cell reprogramming was performed using lentiviral vectors with Yamanaka’s factors (OSKM: Oct4, Sox2, Klf4, and c-Myc). The resulting iPSCs expressed pluripotency genes (such as Nanog and Oct4), alkaline phosphatase activity, and pluripotency stem cell marker expression, such as OCT4, SOX2, TRA-1-60, and SSEA4. iPSCs exhibited the ability to differentiate into neuronal lineage in a 3D environment through dual SMAD inhibition as confirmed by Nestin, MAP2, and Tuj1 neural marker expression. These iPSC-derived neurons harbored Aβ oligomers confirmed by Western Blot (WB) and immunostaining. With human iPSC-derived neurons able to produce Aβ oligomers, we established a novel human hydrogel-based 3D cell culture model that recapitulates Aβ aggregation without the need for mutation induction or synthetic Aβ exposure. This model will allow the study of processes implicated in disease spread throughout the brain, the screening of molecules or compounds with therapeutic potential, and the development of personalized therapeutic strategies.

The consumption of vegetables is essential for reducing the risk of noncommunicable diseases, yet global intake falls short of recommended levels. Enhancing the nutraceutical content of vegetables through postharvest abiotic stress, such as ultraviolet B (UVB) radiation, offers a promising solution to increase health benefits. This study developed a user-friendly, at-home UVB device designed to increase the phytochemical content in common vegetables like carrots, lettuce, and broccoli. The device applies UVB radiation (305–315 nm) to fresh-cut vegetables, optimizing exposure time and intensity to maximize nutraceutical enrichment. The results demonstrated that UVB exposure increased the phenolic content by 44% in carrots, 58% in broccoli, and 10% in lettuce, with chlorogenic acid levels rising by 367% in lettuce, 547% in broccoli, and 43% in carrots after 48 h of storage. UVB treatment also enhanced antioxidant activity by up to 41% in broccoli and anti-inflammatory potential by 22% in carrots. In terms of gene expression, UVB treatment upregulated UCP-1 expression by 555% in carrots, enhanced thermogenesis, and increased SIRT-1 and ATGL expression by over 200%, promoting lipid metabolism. This process provides a convenient and efficient method for consumers to boost the health benefits of their vegetables. The study concludes that UVB-induced abiotic stress is an effective strategy to improve vegetable nutritional quality, offering a novel approach to increasing bioactive compound intake and aiding in the prevention of diet-related diseases.

Ultrasound-assisted extraction (UAE) is an efficient and sustainable method for extracting bioactive compounds from agro-industrial by-products. Moreover, it has been reported that ultraviolet A (UVA) radiation can induce the biosynthesis and accumulation of bioactive phenolic compounds. This study optimized the efficiency of ultrasound-assisted extraction (UAE) for recovering ultraviolet A (UVA)-induced phenolic compounds in strawberry by-products (RF-N). The impact of three factors (solid-liquid ratio, ethanol concentration, and ultrasound power) on total phenolic compound (TPC) kinetics using Peleg’s model was investigated. The developed model showed a suitable fit for both RF-N and strawberry by-products treated with UVA (RF-E). The optimal UAE conditions obtained were of a 1:30 ratio, 46% ethanol, and 100% ultrasound power, resulting in an average yield of 13 g total phenolics kg−1. The bioaccessibility of phenolic compounds during in-vitro digestion was 36.5%, with agrimoniin being the predominant compound. UAE combined with UVA treatment increased the bioactivity of RF extracts, displaying significant anti-proliferative effects on HT29 and Caco-2 cancer cell lines, as well as anti-inflammatory potential and cellular antioxidant activity. The ultrasound proved to be a sustainable and effective technique for extracting phenolic compounds from RF, contributing to the valorization of strawberry agro-industrial by-products, and maximizing their nutraceutical potential.

The SARS-CoV-2 virus was first identified at the end of December 2019, causing the disease known as COVID-19, which, due to the high degree of contagion, was declared a global pandemic as of 2020. The end of the isolation was in 2022, thanks to the global multidisciplinary work of the massive vaccination campaigns. Even with the current knowledge about this virus and the COVID-19 disease, there are many questions and challenges regarding diagnosis and therapy in the fight against this virus. One of the big problems is the so-called "long COVID", prolonged symptomatology characterized as a multiorgan disorder manifested as brain fog, fatigue, and shortness of breath, which persist chronically after the disease resolution. Therefore, this review proposes using extracellular vesicles (EVs) as a therapeutic or diagnostic option to confront the sequelae of the disease at the central nervous system level. Development: the review of updated knowledge about SARS-CoV-2 and COVID-19 is generally addressed as well as the current classification of extracellular vesicles and their proposed use in therapy and diagnosis. Through an analysis of examples, extracellular vesicles are highlighted to learn what happens in the central nervous system during and after COVID-19 and as a therapeutic option. Conclusions: even though there are limitations in the knowledge of the neurological manifestations of COVID-19, it is possible to observe the potential use of extracellular vesicles in therapy or as a diagnostic method and even the importance of their study for the knowledge of the pathophysiology of the disease

Alzheimer’s disease (AD) is the most common type of dementia affecting regions of the central nervous system that exhibit synaptic plasticity and are involved in higher brain functions such as learning and memory. AD is characterized by progressive cognitive dysfunction, memory loss and behavioral disturbances of synaptic plasticity and energy metabolism. Cell therapy has emerged as an alternative treatment of AD. The use of adult stem cells, such as neural stem cells and Mesenchymal Stem Cells (MSCs) from bone marrow and adipose tissue, have the potential to decrease cognitive deficits, possibly by reducing neuronal loss through blocking apoptosis, increasing neurogenesis, synaptogenesis and angiogenesis. These processes are mediated primarily by the secretion of many growth factors, anti-inflammatory proteins, membrane receptors, microRNAs (miRNA) and exosomes. Exosomes encapsulate and transfer several functional molecules like proteins, lipids and regulatory RNA which can modify cell metabolism. In the proteomic characterization of the content of MSC-derived exosomes, more than 730 proteins have been identified, some of which are specific cell type markers and others are involved in the regulation of binding and fusion of exosomes with adjacent cells. Furthermore, some factors were found that promote the recruitment, proliferation and differentiation of other cells like neural stem cells. Moreover, within exosomal cargo, a wide range of miRNAs were found, which can control functions related to neural remodeling as well as angiogenic and neurogenic processes. Taking this into consideration, the use of exosomes could be part of a strategy to promote neuroplasticity, improve cognitive impairment and neural replacement in AD. In this review, we describe how exosomes are involved in AD pathology and discuss the therapeutic potential of MSC-derived exosomes mediated by miRNA and protein cargo.

The presenilin genes (PSEN1 and PSEN2) are mainly responsible for causing early-onset familial Alzheimer’s disease, harboring ~300 causative mutations, and representing ~90% of all mutations associated with a very aggressive disease form. Presenilin 1 is the catalytic core of the γ-secretase complex that conducts the intramembranous proteolytic excision of multiple transmembrane proteins like the amyloid precursor protein, Notch-1, N- and E-cadherin, LRP, Syndecan, Delta, Jagged, CD44, ErbB4, and Nectin1a. Presenilin 1 plays an essential role in neural progenitor maintenance, neurogenesis, neurite outgrowth, synaptic function, neuronal function, myelination, and plasticity. Therefore, an imbalance caused by mutations in presenilin 1/γ-secretase might cause aberrant signaling, synaptic dysfunction, memory impairment, and increased Aβ42/Aβ40 ratio, contributing to neurodegeneration during the initial stages of Alzheimer’s disease pathogenesis. This review focuses on the neuronal differentiation dysregulation mediated by PSEN1 mutations in Alzheimer’s disease. Furthermore, we emphasize the importance of Alzheimer’s disease-induced pluripotent stem cells models in analyzing PSEN1 mutations implication over the early stages of the Alzheimer’s disease pathogenesis throughout neuronal differentiation impairment.