Adipose tissue plays a crucial role in regulating critical biological processes. Dysfunctional adipose tissue observed in obesity fosters a tumor-promoting microenvironment through the release of pro-inflammatory factors and metabolic alterations. These changes enhance the proliferation and migration of tumor cells, as well as their resistance to therapies. This study aims to characterize the interaction model between hypertrophic adipocytes and colon tumor cells. A secondary goal is to evaluate their resistance to antineoplastic drugs such as irinotecan and 5-fluorouracil.

A co-culture model was established between HCT-116 colon tumor cells and mature and hypertrophic adipocytes derived from SGBS preadipocytes. Migration and lipid metabolism were assessed via a Western blot analysis of key proteins, including fibronectin, CPT1, FABP4, pAKT, mTOR, and PPARγ. Reactive oxygen species (ROS) levels were measured, and the mitochondrial metabolic activity in tumor cells was evaluated using a Seahorse analyzer. Additionally, drug resistance was analyzed using cell viability assays and IC50 determination, including the effect of conditioned media (CM) from hypertrophic adipocytes. The impact of CM on the tumor cell cycle was measured with flow cytometry.

The HCT-116 cells co-cultured with hypertrophic adipocytes exhibited morphological and metabolic changes, including spheroid formation and the overexpression of CPT1, pAKT, and mTOR, suggesting increased reliance on fatty acids as an energy source. Tumor cells exposed to CM showed reduced oxidative phosphorylation, consistent with metabolic reprogramming, along with significantly elevated ROS levels. CM exposure also significantly increased resistance to irinotecan and 5-fluorouracil, reflected by higher IC50 values. Furthermore, the CM-treated cells showed a significant arrest in the G0/G1 phase of the cell cycle, potentially linked to the activation of survival pathways. Furthermore, in silico docking was also developed, aiming to identify inhibitors of key metabolic and survival pathways, paving the way for novel therapeutic strategies targeting the adipose–tumor axis in obesity-related cancers.

The study of the gut microbiota's impact on brain functions has revealed a significant correlation, with the dysregulation of the gut–brain axis being linked to neurological disorders. The gut microbiota and brain communicate via four main routes, with the vagus nerve being the most crucial mode connecting the GI tract to the brain stem. Recent studies reveal that enteric pathogens and probiotics can influence host behaviors like anxiety, feeding, and depression by altering GABA, oxytocin, and BDNF signaling in the brain. Certain gut bacteria metabolites are linked to an increase in reactive oxygen species levels, a significant risk factor for neurodegeneration. Gut bacteria metabolites not only contribute to the development of life-threatening brain disorders but also play a crucial role in their prevention. Recent studies highlight two crucial connections between the gut microbiota and the brain: "gut microbiota–oxidative stress–neurodegeneration" and "gut microbiota–antioxidant–neuroprotection." This review provides a comprehensive overview of studies examining gut microbiota-mediated oxidative stress in neurodegeneration and the microbiota's role in neuroprotection. Traumatic Brain Injury (TBI), a prevalent injury with an annual incidence of around 1.4 million in the US, is a major cause of death and disability worldwide. TBI disabilities involve primary brain damage, secondary cellular and molecular damage, and metabolic anomalies, leading to temporary or lifelong cognitive impairments. TBI, a heterogeneous pathobiological condition, presents with multiorgan damage and lacks therapies due to its heterogeneous nature, necessitating the consideration of novel therapeutic regimens. Gut eubiotic therapeutics have gained significant attention due to their ability to restore the bifacial relationship between gut dysbiosis and type 2 diabetes. The detection of gut microbiota modulation could serve as a diagnostic tool for identifying TBI severity, thereby enabling the development of targeted therapeutic approaches.

Colorectal cancer is one of the most prevalent malignancies and the second leading cause of cancer-related deaths worldwide. Conventional treatments such as chemotherapy and radiotherapy are often associated with severe side effects and limited effectiveness. On the other hand, curcumin, a polyphenol derived from Curcuma longa, has demonstrated anti-inflammatory and anticancer properties. However, the effects of curcumin on colorectal cancer remain unknown. A systematic review of recent scientific literature was conducted following PRISMA guidelines to evaluate the benefits of a curcumin-enriched diet for adults with colorectal cancer. Articles published between 2018 and 2024 were retrieved from PubMed, SciELO, Google Scholar, and Scopus. A total of 129 articles were identified during the initial search process. In the first screening phase, 19 duplicate articles were removed. Subsequently, in the second screening phase, an evaluation of titles and abstracts excluded an additional 95 articles. Ultimately, 15 original articles met the inclusion criteria and were used for the final analysis. Studies meeting inclusion criteria focused on curcumin, adults, and colorectal cancer outcomes. Data on survival rates, quality of life, tumor reduction, and inflammatory markers were extracted and analyzed. Administration of curcumin was associated with improved survival rates, enhanced quality of life, tumor reduction, and anti-inflammatory effects. Its mechanisms of action include inhibiting cellular proliferation, inducing apoptosis, and reducing oxidative stress. However, limited bioavailability and potential side effects, including gastrointestinal discomfort, were noted. A curcumin-enriched diet may serve as an effective adjunct therapy for colorectal cancer patients. Future research should focus on optimizing curcumin formulations to address bioavailability and long-term safety concerns.

The bioavailability of natural antioxidants remains a critical challenge in the development of effective nutraceuticals. Instability during digestion and limited intestinal absorption often compromise the efficacy of these compounds when administered orally. Encapsulation technologies offer a promising approach to improve the stability and absorption of natural compounds, particularly those derived from agri-food by-products, contributing to their valorisation.

The aim of this work is to obtain encapsulated olive leaf extract formulations and to evaluate the available fraction and intestinal permeability of these formulations. An in vitro gastrointestinal digestion test was carried out according to the harmonised INFOGEST protocol, in which the fluids and enzymatic processes of the oral, gastric and intestinal phases are successively simulated. This was followed by an intestinal permeability test using the Caco-2 cell monolayer model. For this, samples of fully digested formulations were placed in the donor chamber, and samples were collected from the acceptor chamber at different time points. Transport across the membrane in both directions from the apical or basolateral domain of the epithelium was also studied. The major component of the extract in all samples was quantified by high-performance liquid chromatography coupled to mass spectrometry.

Apparent permeability coefficients were calculated in the apical–basolateral direction and vice versa, allowing for the calculation of the efflux ratio and for the assessment of the type of transport and the permeation rate. Three of the four encapsulated formulations showed moderate permeability values, together with the non-encapsulated extract. Formulation B showed significant differences; however, formulation C decreased the efflux rate, which, together with a higher available fraction, improved the permeation rate. This evaluation provides information on the usefulness of encapsulation in enhancing the absorption of bioactive compounds, useful for the development of more effective nutraceutical products.

Chitosan, a biopolymer derived from chitin, has garnered significant interest in the cosmetic industry due to its biocompatibility, biodegradability, and photoprotective properties. These features make it a key ingredient for developing innovative products that not only enhance cosmetic functionality but also address the growing demand for sustainability by reducing our reliance on fossil-based resources. In this context, the present study investigates the use of chitosan in the encapsulation of antioxidants through microspheres designed to optimize the stability, bioactivity, and efficacy of antioxidant compounds against oxidative stress.

Microspheres were synthesized using advanced techniques such as spray drying, ensuring high reproducibility and adherence to sustainability standards. The microspheres were characterized through spectroscopy and thermal and chemical stability assays, confirming their capacity to protect the encapsulated active compounds. Subsequently, the microspheres were incorporated into cosmetic formulations containing at least 95% natural ingredients, aligning with current ecological cosmetic regulations. In vitro assays on human keratinocyte and fibroblast models were performed to evaluate the safety, stability, and antioxidant efficacy of these formulations.

The characterization of chitosan was optimized to evaluate its physicochemical properties, such as molecular weight, degree of deacetylation, and density, which are critical for its encapsulation efficiency and functionality in cosmetic formulations. After this, the results indicated that certain chitosan-based microspheres functioned as effective physical filters in keratinocytes, providing relevant photoprotective properties. In fibroblasts, the microspheres demonstrated an ability to mitigate UVA-induced cellular damage and reduce the generation of reactive oxygen species (ROS), a key marker of oxidative stress. These findings highlight the potential of chitosan not only as an encapsulating material but also as a multifunctional ingredient in advanced cosmetic formulations. Its ability to combine sustainability with innovation positions it as a promising solution for a constantly evolving cosmetic sector, addressing consumer demands and environmental regulations.

Introduction: Plant extracts contain a wide variety of phytochemicals that provide valuable biological activities, notably antioxidant properties. Enhancing antioxidant capacity offers significant advantages for applications in healthcare, food, and cosmetics. The pursuit of process optimization has evolved with the advent of artificial intelligence (AI), offering unprecedented opportunities to obtain highly antioxidant extracts. In this study, AI-driven methodologies were applied to optimize antioxidant extraction from Cistus salviifolius while promoting more sustainable processes.

Methods: Optimization of aqueous C. salviifolius extracts was achieved using AIReviewer, a validated free AI-based tool for scientific literature analysis (https://doi.org/10.3390/antibiotics12020327), and a Python-coded Jupyter Notebook for data analysis and response surface methodology optimization via a Box—Behnken design. Antioxidant capacity was measured using TEAC and FRAP assays and total phenolic content by he Folin—Ciocalteu method. This optimization method is also compatible with the results of any antioxidant capacity quantification method including ORAC or DPPH, among others.

Results: AIReviewer literature analysis helped us to identify key extraction variables and their suitable ranges: time (0–240 min), temperature (25–50 °C), and ultrasonic energy (50–150 J/mL). Then, fifteen extractions were performed combining different variables using a Box—Behnken design. The optimal conditions (240 min, 25 °C, and 89.65 J/mL) predicted the maximum antioxidant capacity, yielding experimental results of 510.21 ± 24.69 mmol Trolox equivalents/100 g extract (TEAC) and 804.46 ± 22.11 mmol FeSO₄ equivalents/100 g extract (FRAP). The total phenolic content was 31.42 ± 1.45%, with a 30.11 ± 1.25% yield. These values surpass those reported in the literature, even for extracts obtained with non-aqueous solvents like ethanol.

Conclusion: AI-based optimization techniques effectively enhanced the antioxidant properties of C. salviifolius extracts, producing a phenolic-rich extract with superior antioxidant capacity. These methods also offer a more sustainable approach to extraction by significantly reducing the number of empirical trials needed to determine optimal conditions. The results demonstrate the value of AI in optimizing extraction processes, improving both the quality and sustainability of bioactive product development.

The spice Allium ampeloprasum, commonly known as “sibujing,” is a key ingredient in the "palapa" condiment, popular in Maranao dishes, and is traditionally used by the Maranao people in the Lanao regions of Mindanao, Philippines, to treat inflammatory diseases, fever, and cough. This study investigates the total phenolic content (TPC), total flavonoid content (TFC), and the antioxidant and anti-inflammatory activities of the crude ethanolic extract of A. ampeloprasum and its solvent fractions. TPC was determined using the Folin–Ciocalteu method, while TFC was assessed using the aluminum chloride colorimetric method. Anti-inflammatory activity and antioxidant activity were measured using the egg albumin denaturation assay and the DPPH radical scavenging assay, respectively. The results showed that the ethyl acetate fraction had the highest TPC (68.54 ± 1.44 mg GAE/g) and a moderately strong antioxidant capacity (EC₅₀ = 221.40 ± 2.97 μg/mL). On the other hand, the hexane fraction had the highest TFC (169.88 ± 0.64 mg QE/g) and showed promising anti-inflammatory activity (IC₅₀ = 205.83 ± 6.73 μg/mL). Interestingly, a very strong inverse correlation was observed between TPC and antioxidant EC₅₀, while a moderate inverse correlation was noted between the TFC and anti-inflammatory IC₅₀ of the plant’s extract and fractions. These correlations suggest that the phenolic and flavonoid compounds in the plant’s extract and fractions may significantly contribute to A. ampeloprasum’s antioxidant and anti-inflammatory effects. These findings support the traditional medicinal use of A. ampeloprasum for treating inflammatory diseases, highlight its natural antioxidant properties, and underscore its potential as a valuable source of bioactive compounds. This study recommends further research to identify the specific active compounds responsible for the observed biological activities.

In this study, hydrolysis tests were conducted on casein at different incubation times to assess the antioxidant activity of hydrolysates produced by Bromelia serra leaf extracts (BLEs). The hydrolysis reaction was carried out at 90, 120, and 240 minutes (treatments) at 55°C in an incubator with constant agitation at 300 rpm. The reaction was stopped by thermal shock (boiling above 100°C) for 15 minutes. The degree of hydrolysis (%DH) was determined using the Adler-Nissen TNBS method. The antioxidant capacity of a sample was measured based on its ability to neutralize the ABTS cation radical. The progression of the percentage of %DH over digestion time showed no significant differences between 90 and 180 minutes, with 5.68% and 6.91% DH, respectively. At 240 minutes of incubation, the highest DH value was obtained, at 12%. The antioxidant activity of the hydrolysates obtained from each treatment was measured. Dilutions of the hydrolysates from each treatment were also prepared to determine the percentage of inhibition as a function of protein concentration and to calculate the IC50 values. Antioxidant activity, expressed as TEAC (Trolox Equivalent Antioxidant Capacity), showed that casein exhibits antioxidant activity even without hydrolysis. Additionally, it was observed that the antioxidant activity of casein significantly decreased when exposed to hydrolysis at 55°C for 90 and 180 minutes with BLE. After 240 minutes of hydrolysis with BLE, its antioxidant activity significantly increased by approximately 18%. Regarding IC50, a similar trend was observed. The lowest IC50 value was obtained for the 240-minute hydrolysate, followed by unhydrolyzed casein. This indicates that 1.68 mg/mL of hydrolyzed casein (55°C for 240 minutes) is required to achieve 50% inhibition of the ABTS cation radical, compared to 1.98 mg/mL for unhydrolyzed casein.

This study explores the optimization and scale-up of polyphenol extraction from rice straw (Oryza sativa), a lignocellulosic by-product with significant environmental impact. Annually, up to 790 million tons of rice straw are generated worldwide, much of which is improperly disposed of, often through open burning. On the one hand, this practice releases harmful gases, detrimentally affecting environmental quality and human health. On the other hand, the high antioxidant and antimicrobial value of rice straw-derived polyphenols presents a promising solution for repurposing this waste, aligning with circular economy principles.

To maximize the recovery of these bioactive compounds, artificial intelligence was utilized to optimize critical extraction parameters, including temperature, ultrasound energy (J/mL), enzyme quantities and straw-to-water ratios. Laboratory-scale optimization identified conditions yielding high polyphenolic content and antioxidant capacity.

Progressing to a semi-industrial scale, advanced technologies such as steam explosion and affinity resin purification were employed. Equipment such as semi-industrial reactors, plate filters, rotary evaporators and vacuum dryers were integrated to refine and scale the process.

Following the optimization of the scaling-up process, different assays were conducted to determine the polyphenolic content, antioxidant capacity and cosmetic potential of the obtained extracts. The results of these tests confirmed the scalability and industrial feasibility of the aqueous extraction method. The residues and by-products of this process have been also valorized for alternative industrial and value-added applications, adhering to the principles of circular economy and sustainable development.

In this sense, the obtained polyphenol-rich extract demonstrated potential for incorporation into anti-aging cosmetic formulations and as additives in footwear components. Additionally, residual by-products from the process were successfully repurposed into biomaterials for construction applications, further enhancing the sustainability of the system.

The agri-food industry is responsible for generating high volumes of byproducts, representing a largely available and low-cost source of value-added compounds, including, notably, polyphenolic compounds. Among these, lignin has gained increasing attention as a functional additive in a variety of sectors due to its remarkable antioxidant properties. Despite the promising potential of this complex and heterogeneous polyphenol polymer, its exploitation has remained underexplored, mostly due to difficulties related to its recovery from natural sources, primarily woody materials. Recently, common lignin extraction methods, relying on the use of conventional solvents, have been replaced by efficient, sustainable, and cost-effective deep eutectic solvents (DESs). These solvents are easily prepared by mixing a hydrogen bond acceptor and a hydrogen bond donor to form a new solvent with a melting point lower than those of the individual components. The ability to form hydrogen bonds or to donate/accept protons confers DESs good dissolution properties toward phenolic compounds. In this context, we report herein the application of DESs for the efficient extraction of lignin from natural sources, very rich in this polyphenol polymer. For instance, a combination of ball milling and DES-based treatment proved an effective strategy for lignin recovery from edible nut shells. Following ball milling treatment, shells were treated with 1:2 mol/mol chlorine chloride/lactic acid (ChCl/LA2) as DESs at 120 °C for 24 h, yielding lignin at 19- 27% w/w. The extracted lignin exhibited antioxidant properties, particularly in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay (EC₅₀ values ranging from 0.03 to 0.19 mg/mL). In addition, a full valorization of spent coffee grounds and tomato seeds as source of antioxidant compounds was implemented by developing a DES-based (ChCl/LA2) extraction protocol, allowing for the sequential recovery of low-molecular-weight phenols and lignin. The examples that will be presented showcase the potential of lignin as natural antioxidant compound for different applications.