Jingjie Zhang

Background: Chronic low-grade inflammation underlies numerous chronic diseases, yet the molecular targets of dietary bioactive compounds remain largely unknown. Methods: We developed a deep learning model integrating heterogeneous network propagation, stacked denoising autoencoders, and a CNN classifier to predict inflammation-related targets of food-derived compounds. The model was validated by cross-validation and on eight compounds from distinct structural categories. Avn A, Avn B, and Avn C were then input into the model to predict their anti-inflammatory targets, followed by network analysis, docking, and cellular assays for validation. Results: The model achieved a mean AUC of 0.9587 and an AUPR of 0.9590, with validation on eight structurally diverse compounds confirming its generalizability. For Avn A, Avn B, and Avn C, 118 overlapping anti-inflammatory targets were predicted. Network analysis and KEGG pathway enrichment identified ERK1/2 as a key node within the MAPK and PI3K-AKT signaling pathways, while COX-2 was prioritized for further validation based on its high prediction score. Molecular docking revealed that Avns bound at the cyclooxygenase channel entrance of COX-2 with binding energies of −7.7 to −8.0 kcal/mol, and at the ATP-binding pockets of ERK1/2 with binding energies of −7.0 to −7.7 kcal/mol. In LPS-stimulated macrophages, Avns dose-dependently inhibited COX-2 enzymatic activity and PGE2 production, attenuated ERK1/2 and c-Fos phosphorylation, and suppressed IL-6 and IL-1β expression. Conclusions: Our deep learning model successfully identified COX-2 and ERK1/2 as key mediators of the anti-inflammatory effects of Avns, revealing a dual mechanism involving COX-2 inhibition and ERK/c-Fos pathway blockade. This study provides new evidence for the molecular targets of Avns and demonstrates the utility of deep learning-based approaches for target discovery of dietary bioactive compounds.

Medium-chain triglycerides (MCTs) are functional lipids with unique physicochemical properties and metabolic advantages. Recently, their regulatory roles in various chronic diseases have attracted considerable attention. This review systematically summarizes recent research progress and the proposed mechanisms of MCTs and their metabolites in metabolic diseases, neurological disorders, gut health, and muscle function. In the metabolic field, MCTs offer potential nutritional strategies for managing obesity, type 2 diabetes mellitus (T2DM), and various metabolic liver diseases. These effects are primarily mediated by improving insulin sensitivity, regulating lipid metabolism, and modulating energy expenditure. In neurological diseases, MCTs demonstrate potential for preventing and treating Alzheimer’s disease (AD), Parkinson’s disease (PD), and epilepsy through multiple pathways, including ketogenic energy supply, anti-inflammatory and antioxidant effects, and mitochondrial protection. Regarding gut health, MCTs and their derivatives may benefit digestive health by modulating gut microbiota and enhancing barrier function. For muscle health, MCTs help optimize energy metabolism and protein homeostasis, showing promise for countering sarcopenia and improving exercise performance. In conclusion, the prospects for MCTs are broad. Future research should focus on promoting their scientific application in precision nutrition and disease therapy, and more rigorous clinical trials are needed to confirm their efficacy and safety.

Exosomes, small molecules with phospholipid bilayer structures derived from cell membranes, usually contain many biomacromolecules, such as proteins, mRNAs, and miRNAs. Exosomes have been verified to be among the most important mediators of material and information exchange within or between individuals. In recent decades, exosomes have attracted increasing attention from researchers. In this review, the structure, methods of separation and identification, and cell origination of exosomes are described in detail. The potential applications of exosomes, such as anti-inflammatory and immunomodulatory effects, tissue damage repair and regeneration, antioxidant function, drug delivery, and cancer therapy, are summarized. Food-derived exosomes from animals, plants and microorganisms have become a research hotspot. Exosomes carrying biomacromolecules are important mediators of signal transduction and regulation between cells from the same individual and between individuals of the same or different species. It is widely considered a promising intermediate for food nutrition and chronic disease prevention.

Compound–target interaction (CTI) prediction plays a critical role in drug discovery and the functional study of food-derived bioactive compounds. However, traditional experimental methods for CTI identification are limited by high costs, long cycle times, and high false-positive rates, highlighting an urgent need for more efficient approaches. Machine learning (ML) has become a revolutionary tool to address these challenges. In this review, we focus on recent developments in ML-based CTI prediction. We first systematically outline the commonly used public databases and feature extraction methods for both compounds (molecular fingerprints) and proteins (sequence-derived features), followed by elaborating on four types of ML approaches, including classical supervised learning, matrix factorization, graph topology-based inference, and deep neural network frameworks. In particular, this review explores the emerging application of these computational approaches in identifying targets of food-derived bioactive compounds, underscoring its significant potential to advance functional food research. Moreover, we analyze key challenges, such as limited model interpretability, high data dependency, and insufficient multi-source information integration, and put forth future prospects to improve the prediction of food-derived CTIs, thereby facilitating their application in functional food research.

As a chronic inflammatory and autoimmune disease, rheumatoid arthritis (RA) leads to joint dysfunction and deformities due to joint inflammation, bone erosion, and cartilage destruction, potentially resulting in permanent disability, which significantly reduces patients’ quality of life. Compared with refined grains, whole grains retain components such as the endosperm, germ, and bran, which are rich in higher levels of phytochemicals and nutrients. Recent studies suggest that the components in whole grains may play essential roles in the alleviation of RA. This review summarizes the potential effects of whole grain ingredients on alleviating RA via the inhibition of synovial fibroblast migration, cartilage degradation, and osteoclast activity and further elaborates their mechanisms that phytochemicals and nutrients in whole grains inhibit RA via anti-inflammatory, antioxidant, and immune system modulation pathways. We anticipate that nutritional interventions with whole grains may offer new avenues for the prevention and treatment of RA.

With increasing research, the nutritional value of oats is gaining recognition. Fermentation is an emerging biotransformation pattern that changes the nutritional structure of whole grains. Currently, research on whole-grain fermentation is relatively focused on phenolic compounds and their antioxidants, but less attention has been given to avenanthramides (Avns) and the glycemic index (GI) in fermented oats. In this study, oats were subjected to solid-state fermentation (SSF) by Monascus purpureus for 21 days, and samples were taken at different time points. Changes in the contents of nutrients, phytochemicals, and antinutritional factors were analyzed using one-way ANOVA. Additionally, a simulated in vitro digestion experiment was conducted to assess the estimated glycemic index (eGI) of SSF oats. The results revealed that the nutritional structure of oats was changed by SSF, and the Avns content significantly increased, with 3.2 times more Avns in SSF oats than in unfermented oats, including 3.05, 3.09, 3.09, and 3.7 times more Avn A, Avn B, Avn C, and Avn D, respectively, and the eGI was reduced from 40.22 to 39.97 with increasing fermentation time. In general, SSF with Monascus purpureus has improved nutritional value, significantly increased the content of active ingredients, and reduced the level of eGI and two antinutritional factors (phytate and oxalate), which provides an effective way to improve the nutritional and digestive characteristics of oats.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that commonly causes pain in joints and the progressive destruction of cartilage and bone, which significantly reduces the quality of life and increases the social burden. However, there is still no cure for RA, so it is highly important to explore additional adjuvant treatment methods. Studies have indicated that malnutrition, changes in intestinal microbiota, and changes in immune status caused by dietary imbalance are directly related to the onset of RA, indicating that dietary intervention may offer a simple, economical, and practical avenue to relieve RA. Therefore, in this review, we discuss the pathogenesis of RA and summarize the influence of different dietary patterns on RA. In particular, we pointed out that high-fat, high-sugar, and high-salt diets contribute to RA progression, whereas the Mediterranean diet (MD) is beneficial for preventing RA. Furthermore, the ingredients of food, such as dietary fiber, probiotics, and vitamins, help reduce the level of inflammation and relieve joint pain, which may play critical roles in the treatment of RA. Therefore, dietary intervention provides a potential effective approach for adjuvant therapy of RA.

Osteoporosis commonly occurs in the older people and severe patients, with the main reason of the imbalance of bone metabolism (the rate of bone resorption exceeding the rate of bone formation), resulting in a decrease in bone mineral density and destruction of bone microstructure and further leading to the increased risk of fragility fracture. Recent studies indicate that protein nutritional support is beneficial for attenuating osteoporosis and improving bone health. This review summarized the classical mechanisms of protein intervention for alleviating osteoporosis on both suppressing bone resorption and regulating bone formation related pathways (promoting osteoblasts generation and proliferation, enhancing calcium absorption, and increasing collagen and mineral deposition), as well as the potential novel mechanisms via activating autophagy of osteoblasts, altering bone related miRNA profiles, regulating muscle-bone axis, and modulating gut microbiota abundance. Protein nutritional intervention is expected to provide novel approaches for the prevention and adjuvant therapy of osteoporosis. GRAPHICAL ABTSRACT

Yu Y, et al. Nutr Res Pract. 2022 Oct;16(5):589-603. https://doi.org/10.4162/nrp.2022.16.5.589