Diabetes mellitus is a metabolic disorder with persistent hyperglycemia caused by a variety of underlying factors. Chronic hyperglycemia can lead to diverse serious consequences and diversified complications, which pose a serious threat to patients. Among the major complications are cardiovascular disease, kidney disease, diabetic foot ulcers, diabetic retinopathy, and neurological disorders. Heme oxygenase 1 (HO-1) is a protective enzyme with antioxidant, anti-inflammatory and anti-apoptotic effects, which has been intensively studied and plays an important role in diabetic complications. By inducing the expression and activity of HO-1, it can enhance the antioxidant, anti-inflammatory, and anti-apoptotic capacity of tissues, and thus reduce the degree of damage in diabetic complications. The present study aims to review the relationship between HO-1 and the pathogenesis of diabetes and its complications. HO-1 is involved in the regulation of macrophage polarization and promotes the M1 state (pro-inflammatory) towards to the M2 state (anti-inflammatory). Induction of HO-1 expression in dendritic cells inhibits them maturation and secretion of pro-inflammatory cytokines and promotes regulatory T cell (T_reg cell) responses. The induction of HO-1 can reduce the production of reactive oxygen species, thereby reducing oxidative stress and inflammation. Besides, HO-1 also has an important effect in novel programmed cell death such as pyroptosis and ferroptosis, thereby playing a protective role against diabetes. In conclusion, HO-1 plays a significant role in the occurrence and development of diabetic complications and is closely associated with a variety of complications. HO-1 is anticipated to serve as a novel target for addressing diabetic complications, and it holds promise as a potential therapeutic agent for diabetes and its associated complications. We hope to provide inspiration and ideas for future studies in the mechanism and targets of HO-1 through this review.

Diabetic nephropathy is one of the most significant complications of diabetes, resulting in increased patient mortality. Dapagliflozin is an inhibitor of sodium‑glucose cotransporter 2 that has an important protective effect on the kidney. Recent studies showed that pyroptosis is involved in the advancement of diabetic nephropathy (DN). However, the potential molecular mechanisms underlying the association between pyroptosis and renal podocyte injury in DN remain unclear. Thus, the present study investigated the anti‑pyroptotic function of dapagliflozin in podocytes and further clarified the potential mechanisms. In this study, a model of lipid metabolism disturbance was established through palmitic acid (PA) induction in a mouse podocyte clone 5 (MPC5) cell line. MPC5 PA‑induced pyroptosis was measured by ELISA, western blotting, quantitative PCR and Hoechst 33342/propidium iodide double‑fluorescence staining. The protective role of HO‑1 was measured using knockdown and overexpression experiments. It was found that dapagliflozin attenuated the expression of pyroptosis‑related proteins, including nucleotide oligomerization domain‑like receptor thermal protein domain associated protein 3, apoptosis‑associated speck‑like protein containing a caspase activation and recruitment domain, caspase‑1, IL‑18 and IL‑1β in the PA group. Meanwhile, the heme oxygenase 1 (HO‑1) expression level decreased within PA, an effect that was reversed by dapagliflozin. Furthermore, the expression of pyroptosis‑related proteins and inflammatory cytokines was reduced following HO‑1 overexpression. Therefore, these results suggested that dapagliflozin ameliorates MPC5 pyroptosis by mediating HO‑1, which has a protective effect on diabetic nephropathy.

Schisandrin A (SchA), a bioactive lignan that was isolated from the dried fruit of Schisandra chinensis, has attracted much attention because of its diverse spectrum of pharmacological effects. The aim of this study is to clarify the function of SchA in diabetes-related fear memory impairment and its molecular causes. Four rat groups are chosen at random: the control group (Con group), the DM group, the DM + SchA group, and the Con + SchA group. These findings demonstrate that SchA treatment improves insulin sensitivity, reduced blood glucose, and significantly reduced memory impairment. SchA treatment also prevents histological damage, enhances synaptic protein production, and significantly decreases Aβ₄₂ formation in the diabetic prefrontal cortex. Further research reveals that SchA therapy decreases microglial activation and the expression levels of variables linked to inflammation while increasing the phosphorylation of proteins implicated in the insulin resistance signaling pathway. Furthermore, in the prefrontal cortex of diabetic patients, SchA decreases ferroptosis by increasing the protein expression of GPX4, SLC7A11, Nrf2, HO-1, and SIRT1. Overall, our findings suggest that SchA may lessen diabetes-associated fear memory impairment symptoms by, most likely, lowering ferroptosis and inflammatory responses in the prefrontal brain of diabetic patients. SchA may prove to be a useful therapy for diabetes, including for memory impairment.

The design of novel aggregation-induced emission (AIE)-active molecules represents a cutting-edge strategy for integrated phototheranostics in the second near-infrared (NIR-II) window. This review systematically outlines rational molecular engineering approaches based on D-A, D-A-D, and A-D-A systems to achieve red-shifted NIR-II absorption/emission, enhanced AIE characteristics, and balanced radiative and non-radiative decay pathways. These AIEgens enable high-contrast NIR-II fluorescence imaging (FLI) and photoacoustic imaging (PAI) for precise tumor localization, while concurrently facilitating efficient photothermal therapy (PTT) and robust photodynamic therapy (PDT) through both type-I and type-II mechanisms. Nanoformulations of these molecules exhibit excellent stability, biocompatibility, and passive targeting via the enhanced permeability and retention (EPR) effect. We further highlight representative “all-in-one” AIE platforms that demonstrate synergistic PTT/PDT under multimodal imaging guidance, offering a promising paradigm for precision cancer theranostics. Challenges and future directions in clinical translation and combination therapy are also discussed.