Nonalcoholic fatty liver disease is the most common liver disease worldwide. Hepatic steatosis and oxidative stress are the main characteristics of NAFLD (nonalcoholic fatty liver disease), which also affect its prognosis. Bixin acts as novel Nrf2 (NF‐E2 p45‐related factor 2) activator with the cytoprotection against oxidative stress and inflammation; this study mainly focused on the mechanism of Nrf2 activation by bixin and explored its potential feasibilities in long‐term high‐fat diet‐ (HFD‐) caused hepatic steatosis and inflammatory response in vitro and in vivo. Bixin was found to activate Nrf2 signals by the modification of critical Keap1 (Kelch‐like ECH‐associated protein 1) cystine and competitive interaction with Keap1 with upregulating P62 mRNA and protein expression. In human liver cells exposed to FFA (free fatty acid), bixin displayed a pronounced cytoprotective activity with upregulation of Nrf2‐mediated gene expression, such as PPARα and its targets related with fatty acid oxidation. In HFD‐fed mice, systemic administration of bixin attenuated lipid accumulation, decreased oxidant inflammatory damage in the liver, and reduced circulating lipid levels through Nrf2. Different from most of other established inducers, bixin activated Nrf2 signals through two different mechanisms with safe administration for protection of oxidant inflammatory damage and attenuation of lipid accumulation in the in vivo long‐term HFD‐fed mice. Bixin represents a prototype Nrf2 activator that displays cytoprotective activity upon system administration targeting hepatic steatosis and oxidant inflammation originating from long‐term HFD‐fed mice. And bixin‐based Nrf2‐directed systemic intervention may also provide therapeutic benefit in protecting other organs in the process of metabolic syndrome.

Background: Diabetic foot ulcer (DFU) is a common and debilitating complication of diabetes, often leading to delayed wound healing. The peroxisome proliferator-activated receptors (PPARs) play a crucial role in regulating cellular metabolism and promoting angiogenesis. This study aims to elucidate the mechanisms through which the activation of PPARs enhances wound healing, particularly under diabetic conditions, as these mechanisms remain inadequately understood. Methods: Differentially expressed genes in DFU wounds and normal skin tissues were identified using the GEO database. PPAR expression in DFU neovascularization was validated by quantitative reverse transcription polymerase chain reaction, immunofluorescence, and western blotting. In vivo, diabetic mice treated with PPAR agonists (chiglitazar) underwent wound healing assessment, including collagen deposition and angiogenesis. In vitro, advanced glycation end-products (AGEs)—induced endothelial cell models were used to evaluate PPAR activation effects on cell migration, tube formation, and mitochondrial function. Whole transcriptome sequencing and mitochondrial analysis were performed to explore the underlying mechanisms, particularly the sonic hedgehog (SHH)–mitochondrial axis. Results: PPAR expression was significantly downregulated in DFU tissues (p < 0.05), and PPAR activation in diabetic mice enhanced wound healing, collagen deposition, granulation tissue proliferation, and angiogenesis (p < 0.05). In vitro, PPAR activation protected endothelial cells, promoting vascular endothelial growth factor-A (VEGF-A) and CD31 expression, reducing apoptosis, and enhancing cell migration and tube formation (p < 0.05). Mechanistically, PPARs activated mitochondrial oxidative phosphorylation and membrane function through the SHH signaling pathway. SHH gene silencing reversed the effects of PPAR activation on mitochondrial function and angiogenesis. Conclusions: PPAR signaling plays a critical role in DFU healing, with its inhibition linked to vascular dysfunction. Activation of the PPARs/SHH–mitochondrial axis significantly enhances endothelial cell metabolism and angiogenesis. This study provides insights into the molecular mechanisms of diabetic wound healing and supports the clinical potential of PPAR agonists for DFU treatment.

Introduction: Gout is a chronic disease characterized by deposition of monosodium urate crystals. Tophi develop in some individuals with untreated or uncontrolled gout, which leads to ulcerations, cosmetic problems, mechanical obstruction of joint movement, joint damage and musculoskeletal disability. Currently, the treatment of gouty tophi is controversial and challenging. Both surgical and internal medical treatments have limitations and require further exploration in clinical practice. Patient concerns: In Case 1, we treated a patient with severe infection of diabetic foot ulcers with concomitant multiple gouty tophi in the same limb. A systematic management strategy was formulated to close the wound and save the limb. The ulcers healed successfully after half a year. In Case 2, a giant gouty tophi located in the first metatarsophalangeal joint of the left foot was removed by surgical treatment and vancomycin-loaded bone cement implantation. In Case 3, we present a case of gouty tophi that was resolved by standardized systemic medical management. Diagnosis: Three patients were all diagnosed with gout accompanied by gouty deposition, although there were other different comorbidities. Interventions: In case 1, we used debridement to gradually remove gouty tophi. In case 2, the giant gouty tophi was removed by surgical operation. In case 3, the gouty tophi disappeared after standardized treatment with medicine, diet and lifestyle management. Outcomes: Three patients underwent different treatment therapies to remove gouty tophi based on their specific conditions. Lessons: We explored effective interventions for tophi in gout by surgical or other interventions in combination with pharmacotherapy.

Peripheral artery disease (PAD) is rapidly emerging as a global health priority, with projections indicating a dramatic rise in prevalence, mortality, and disability by 2050. Recent forecasts project an approximately 220% increase in PAD prevalence, with more than 360 million individuals affected globally by mid-century, largely driven by metabolic diseases—particularly diabetes and obesity. A recent population-based study forecasting the global burden of PAD provides compelling evidence that metabolic disease is the dominant driver of this alarming trend. This commentary highlights the critical interplay between metabolic risk factors and PAD progression, underscores the disproportionate burden expected in low- and middle-income countries, and calls for urgent, integrated strategies targeting metabolic health. Without decisive action to reduce diabetes, obesity, and related metabolic disorders, the looming global PAD crisis will further strain healthcare systems and deepen health inequities worldwide.