Ulcerative colitis (UC) is a refractory chronic inflammatory disease involving the colon and rectum, falling under the category of inflammatory bowel disease (IBD). The accumulation of reactive oxygen species (ROS) in local tissues has been identified as a crucial contributor to the escalation of inflammatory responses. Therefore, eliminating ROS in the inflamed colon is a promising approach to treating UC. Nanomaterials with intrinsic enzyme-like activities (nanozymes) have shown significant therapeutic potential in UC. In this study, we found that platinum nanoparticles (Pt NPs) exhibited remarkable superoxide dismutase (SOD) and catalase (CAT) cascade catalytic activities, as well as effective hydroxyl radical (•OH) scavenging ability. The in vitro experiments showed that Pt NPs could eliminate excessive ROS to protect cells against oxidative stress. In the colitis model, oral administration of Pt NPs (loaded in chitosan/alginate hydrogel) could significantly alleviate UC, including reducing the colon length, the damaged epithelium, and the infiltration of inflammatory cells. Without appreciable systemic toxicity, Pt NPs represent a novel therapeutic approach to UC and are expected to achieve long-term inflammatory remission.

Traditional iron supplements for iron deficiency anemia (IDA) have several limitations, including suboptimal absorption, gastrointestinal discomfort, and concerns regarding long-term safety. In this study, we synthesized monodisperse 6-line ferrihydrite as an innovative iron supplement, featuring a structure analogous to the natural “iron core” present in ferritin. Notably, 6-line ferrihydrite (6-Fh) was internalized by Caco-2 cells via a process independent of divalent metal transporter 1 (DMT1). Additionally, its stability as nanoparticles within the gastrointestinal tract prevents the irritation typically associated with metal ions, thereby significantly enhancing iron utilization efficiency. Consequently, compared to FeSO₄ (a traditional oral iron supplement), 6-Fh effectively stabilized cellular free iron with low ROS toxicity and high biosafety, thereby effectively maintaining intestinal barrier integrity and avoiding liver injury. Furthermore, it restored intestinal dysbiosis caused by IDA and increased the proportion of beneficial bacterial strains, which was superior to FeSO₄. Characterized by low toxicity, efficient cellular absorption, intestinal stability, and superior iron supplementation efficacy compared with conventional iron supplements, 6-Fh demonstrates compelling therapeutic advantages and holds great promise for medical applications.

Ulcerative colitis (UC) is a common type of inflammatory bowel disease, where the vicious cycle of inflammation and oxidative stress poses a major challenge in its treatment, and existing therapies have limitations. Berberine (BBR) and curcumin (CUR) have the potential for synergistic treatment of UC, but this potential has not been verified in UC. Additionally, both BBR and CUR suffer from poor water solubility and low bioavailability. This study aims to construct prebiotic microcapsules (BBR/CUR@MC) for the co-delivery of BBR and CUR and explore their therapeutic mechanism in UC. Network pharmacology was used to predict the targets and pathways of BBR and CUR in UC. BBR/CUR@MC was prepared using microfluidic electrospray technology, and its colon targeting and biocompatibility were evaluated through in vivo experiments. In a Dextran sulfate sodium (DSS)-induced UC mouse model, the therapeutic effect was assessed using multiple indicators, and the mechanism of action was explored by transcriptome analysis. Network pharmacology showed that BBR and CUR can exert therapeutic effects on UC through synergistic regulation of TNF and AGE-RAGE signaling pathways. The successfully constructed BBR/CUR@MC had good colon targeting and biocompatibility. In the mouse colitis model, oral administration of BBR/CUR@MC inhibited ADAM17 in the TNF signaling pathway and MAPK11/13, COL4A1, and COL1A1 in the AGE-RAGE signaling pathway, thereby downregulating pro-inflammatory cytokines such as TNF-α and IL-1α, upregulating IL-10, scavenging ROS, significantly alleviating colonic inflammation and repairing the intestinal barrier in mice, with a therapeutic effect superior to that of single-drug microcapsules and 5-ASA. BBR/CUR@MC can exert synergistic anti-inflammatory and antioxidant effects in UC treatment by regulating TNF and AGE-RAGE signaling pathways, providing a new multi-mechanism therapeutic strategy for UC.

As organisms age, mitochondrial metabolic activity declines, and disrupted gene expression regulation mediated by histone acetylation induces the emergence of senescent physiological phenotypes in tissues. In this study, we found that periodic exposure to red light significantly increased histone H3 Lys9 acetylation (H3K9ac) levels in the tissues and organs of aged mice. Following red light exposure, silent information regulation factor 4 (SIRT4) protein levels in keratinocytes were notably reduced, whereas glycolysis, fatty acid metabolism, and the tricarboxylic acid (TCA) cycle were significantly activated in keratinocytes. The reduction in mitochondrial SIRT4 levels enhances the acetylation of mitochondrial metabolic proteins, particularly malonyl-CoA decarboxylase (MCD), a potent inhibitor of the key rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A) in fatty acid oxidation. This process promotes mitochondrial fatty acid oxidation and TCA cycle. Additionally, the decrease in SIRT4 activates SIRT1 through feedback mechanisms, thereby alleviating its inhibition on PPAR-α in senescent keratinocytes and comprehensively activating the expression of genes related to lipid metabolism. This lipid metabolism activation ultimately facilitates the accumulation of acetyl-CoA within keratinocytes, increases H3K9ac levels, and reshapes the expression patterns of senescence-related genes. Eventually, cellular aging is effectively mitigated by the synergistic regulation of metabolism, inflammation, and gene expression. Graphical Mechanism of anti-aging action of red light: Red light can reduce SIRT4 signalling in keratinocytes, thereby reactivating lipid metabolism and increasing levels of acetyl-CoA. This promotes histone acetylation, which in turn reverses the expression of age-related inflammatory factors and genes.

As organisms age, mitochondrial metabolic activity declines, and disrupted gene expression regulation mediated by histone acetylation induces the emergence of senescent physiological phenotypes in tissues. In this study, we found that periodic exposure to red light significantly increased histone H3 Lys9 acetylation (H3K9ac) levels in the tissues and organs of aged mice. Following red light exposure, silent information regulation factor 4 (SIRT4) protein levels in keratinocytes were notably reduced, whereas glycolysis, fatty acid metabolism, and the tricarboxylic acid (TCA) cycle were significantly activated in keratinocytes. The reduction in mitochondrial SIRT4 levels enhances the acetylation of mitochondrial metabolic proteins, particularly malonyl-CoA decarboxylase, a potent inhibitor of the key rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A) in fatty acid oxidation. This process promotes mitochondrial fatty acid oxidation and the TCA cycle. Additionally, the decrease in SIRT4 activates SIRT1 through feedback mechanisms, thereby alleviating its inhibition on PPAR-α in senescent keratinocytes and comprehensively activating the expression of genes related to lipid metabolism. This lipid metabolism activation ultimately facilitates the accumulation of acetyl-CoA within keratinocytes, increases H3K9ac levels, and reshapes the expression patterns of senescence-related genes. Eventually, cellular aging is effectively mitigated by the synergistic regulation of metabolism, inflammation, and gene expression.

As organisms age, mitochondrial metabolic activity declines, and disrupted gene expression regulation mediated by histone acetylation induces the emergence of senescent physiological phenotypes in tissues. In this study, we found that periodic exposure to red light significantly increased histone H3 Lys9 acetylation (H3K9ac) levels in the tissues and organs of aged mice. Following red light exposure, silent information regulation factor 4 (SIRT4) protein levels in keratinocytes were notably reduced, whereas glycolysis, fatty acid metabolism, and the tricarboxylic acid (TCA) cycle were significantly activated in keratinocytes. The reduction in mitochondrial SIRT4 levels enhances the acetylation of mitochondrial metabolic proteins, particularly malonyl-CoA decarboxylase (MCD), a potent inhibitor of the key rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A) in fatty acid oxidation. This process promotes mitochondrial fatty acid oxidation and TCA cycle. Additionally, the decrease in SIRT4 activates SIRT1 through feedback mechanisms, thereby alleviating its inhibition on PPAR-α in senescent keratinocytes and comprehensively activating the expression of genes related to lipid metabolism. This lipid metabolism activation ultimately facilitates the accumulation of acetyl-CoA within keratinocytes, increases H3K9ac levels, and reshapes the expression patterns of senescence-related genes. Eventually, cellular aging is effectively mitigated by the synergistic regulation of metabolism, inflammation, and gene expression.