Zhilong Xiu

Chronic diabetic wounds are difficult to treat due to persistent hyperglycemia, oxidative stress, and bacterial infections. Antibiotic therapy is prone to drug resistance, and likewise, photothermal therapy suffers from the risk of thermal injury to surrounding healthy tissues. This study developed a polyacrylic acid (PAA)-based eutectogel (EG) loaded with baicalein (BAI) and MXene nanosheets (BAI–MXene/PAA EG), which integrates multiple functions including anti-inflammatory, antioxidant, antimicrobial and pro-angiogenic properties. MXene generated a low-temperature photothermal effect at ca. 45 °C under near-infrared (NIR) irradiation. The incorporation of baicalein further improved the antibacterial and anti-inflammatory properties of the eutectogel with desired biosafety and biocompatibility. BAI–MXene/PAA EG exhibited excellent antibacterial performance against multidrug-resistant (MDR) E. coli and MDR S. aureus, with bacterial survival rates as low as 0.03% and 0.22%, respectively. In addition, BAI–MXene/PAA EG promoted the proliferation of HUVECs and HaCaT cells and effectively scavenged intracellular ROS. In vivo studies confirmed that BAI–MXene/PAA EG promoted cell proliferation and induced angiogenesis. By combining nanomaterials with active components from traditional Chinese medicine, this research provides new insights into the future development of wound dressings and holds great potential in the clinical treatment of diabetic infected wounds.

Corticosterone (CORT) is a glucocorticoid hormone whose prolonged elevation during stress can generate excessive reactive oxygen species (ROS), leading to hippocampal neuron dysfunction. Puerarin, a natural isoflavone extracted from Pueraria lobata, has known antioxidant and neuroprotective properties. However, its effects on CORT-induced neurotoxicity have not been well characterized. In this study, we investigated the effects of puerarin on CORT-induced damage in primary mouse hippocampal neurons. We found that CORT (100-800 μM) dose-dependently reduced neuronal viability, whereas cultured astrocytes remained viable except at the highest concentration (800 μM), indicating a relative resistance of astrocytes to CORT. CORT treatment also significantly impaired neurite outgrowth, increased lactate dehydrogenase (LDH) release, elevated intracellular ROS levels, and decreased antioxidant enzyme activities in neurons. Importantly, pretreatment with puerarin markedly ameliorated these CORT-induced effects: puerarin preserved neurite length, suppressed LDH leakage and ROS accumulation, and restored activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). These results demonstrate that puerarin can attenuate CORT-induced hippocampal neuron dysfunction in vitro. Our findings suggest that puerarin has potential therapeutic value for oxidative stress-related neural impairment in stress-related disorders.

Natural products have made significant contributions to human therapeutics. However, approximately 90% of these compounds face severe limitations in clinical application due to challenges such as poor water solubility, low bioavailability and instability. Although combining natural products with synthetic drugs has demonstrated synergistic advantages in treating various diseases, their therapeutic potential for diabetic wound healing remains largely unexplored. A key obstacle lies in the significant differences in solubility between these two drugs, which severely hinders the development of combination formulations. This study developed a dual-drug-loaded gel system (Bai-Met/DES-Gel) based on a deep eutectic solvent (DES) and carbomer 940. The solubility of baicalein was enhanced to 26.72 mg ml ⁻¹ , enabling its stable co-dissolution with the synthetic metformin. The drug delivery system exhibited sustained-release properties, good biocompatibility, significant antibacterial activity against E. coli and S. aureus , and excellent DPPH radical scavenging capacity. In the diabetic rat wound model, Bai-Met/DES-Gel effectively accelerated wound healing by inhibiting inflammatory responses, promoting granulation tissue formation, facilitating collagen alignment, stimulating angiogenesis, and enhancing cell proliferation. This study advanced the potential application of DES on co-delivery of natural and synthetic drugs, while providing a novel solution for the treatment of diabetic wounds.

Background: 1,3-Propanediol (PDO) is a high value-added product with significant potential for application and development in various industries including textiles, cosmetics, food, and chemicals. Microbial fermentation for 1,3-PDO production has advantage over chemical synthesis in response to environmental and energy challenges. In view of the complexity and benefits of biometabolic synthesis, there is a necessity to enhance the yield of 1,3-PDO to glycerol by means of co-substrates, whilst concomitantly reducing the cost of production. Results: In this study, the efficiency and cost-effectiveness of 1,3-PDO synthesis by Clostridium butyricum DL07 were improved through elucidating the regulatory mechanism of glucose-glycerol cometabolism and optimizing the ratio of co-substrates. Among the screened co-substrates, glucose emerged as the optimal choice for enhancing the yield and concentration of 1,3-PDO synthesized from glycerol. If the molar ratio of glucose to glycerol was 0.51 mol/mol, the 1,3-PDO yield reached 0.90 mol/mol in the co-substrate fermentation. Real-time quantitative PCR revealed that the dha operon expression was affected by glucose on inhibition of GDH ( dhaD ) and phasically upregulation of PDOR activity ( dhaT ). Stoichiometric analysis combined with further optimization of the different feeding strategies increased the 1,3-PDO yield to the highest level of fed-batch fermentation (0.86 mol/mol) reported to date for natural strains. The material cost analysis demonstrated that the co-substrate strategy reduced raw material cost by 13–20%. Conclusions: This study presents an investigation into the synthesis of 1,3-PDO through cometabolism in C. butyricum DL07. The research elucidates the synergistic impact of co-substrate ratios and temporal regulation on the synthesis of 1,3-PDO. Moreover, it offers a theoretical basis and a practical approach for achieving cost-effective and efficient industrial production.

Type 2 diabetes mellitus (T2DM), one of the most rapidly growing metabolic disorders globally, poses a substantial public health burden. In this study, a novel edible eutectogel was innovatively developed for the co‐delivery of natural active ingredients, baicalein (Bai), and 1‐deoxynojirimycin (DNJ). Utilizing a deep eutectic solvent (DES) system, the hydrophobic Bai and hydrophilic DNJ were co‐dissolved and encapsulated within the eutectogel (Bai‐DNJ/EG), enabling gastric protection and targeted intestinal release. Animal experimental demonstrated that the Bai‐DNJ/EG significantly ameliorated multiple pathological features, including blood glucose reduction, improved insulin sensitivity, attenuated systemic inflammation, decreased fat accumulation, and mitigated organ damage. Compared with Bai/EG and DNJ/EG, Bai‐DNJ/EG exhibited superior therapeutic efficacy across all parameters, indicating a synergistic effect between the Bai and DNJ. The dose of Bai in Bai‐DNJ/EG was reduced by 50% relative to previous studies, and DNJ was 7.5 times less than that of clinical use in a Chinese herbal preparation for lowering blood glucose. In addition, comparison of lipid metabolism and inflammatory factors between Bai HG and Bai/EG groups indicated that DES enhanced the pharmacological activity of Bai by improving its solubility. Furthermore, 16S rRNA sequencing revealed that Bai‐DNJ/EG positively regulates gut microbiota homeostasis and repairs the intestinal barrier. Bai‐DNJ/EG inhibited deleterious bacteria including Methanobacteriaceae, Pseudomonadota , Campylobacterota , and Spirochaetota , while promoted the SCFA‐producing bacteria, for example, Muribaculaceae and Butyricicoccaceae. This study presents a groundbreaking strategy for the synergistic delivery of natural bioactives and establishes a new paradigm for modernized traditional natural medicine formulations.

Cardiovascular complications arising from vascular endothelial injury are the main cause of mortality in individuals with diabetes. Hesperetin, a typical flavanone derived from citrus fruits, has shown various biological activities beneficial to health, yet its effects on diabetes-induced vascular endothelial damage remain unexplored. In the present study, hesperetin intervention improved serum lipid metabolism, ameliorated aortic endothelial pathology, reduced aortic adhesion factor expression, and enhanced glucose tolerance with attenuated insulin resistance in type 2 diabetes mellitus rats. Mechanism studies revealed that intervention with hesperetin regulated the structure of gut microbiota, resulting in lower levels of trimethylamine oxide, the metabolite of gut microbiota, which in turn reduced its damage to the vascular endothelium. Simultaneously, hepatic cholesterol homeostasis regulation by hesperetin contributes to attenuated atherogenesis. Our study indicated that hesperetin, as a dietary supplement, exhibited potential for inhibiting the development diabetes-associated vascular endothelial damage.

This study aimed to develop an environmentally friendly and relatively efficient method for extracting natural antioxidants from avocado by-products while investigating the antioxidant mechanisms of their core bioactive components on multiple dimensions. In vitro antioxidant assays (ABTS, FRAP, SAFR, SFR, ORAC, DPPH) demonstrated that flavonoid procyanidin was the primary antioxidant component in avocado seeds, exhibiting the strongest activity (DPPH EC₅₀ = 3.6 µg/mL). The Hill model indicated a positive synergistic effect (n = 3.1). Chemical and molecular mechanism analyses revealed that avocado seeds exert antioxidant activity predominantly through hydrogen atom transfer (HAT) and electron transfer (ET) pathways. The model predictions suggested procyanidins may stably bind to protein targets in the Keap1-Nrf2 pathway and NOX2 via hydrogen bonding, hydrophobic interactions, and π-cation interactions. Furthermore, response surface methodology (RSM) was employed to optimize the extraction process of avocado seed antioxidants in an ethanol-water system. This study underscores the considerable health benefits and antioxidant capacity of avocado by-products, supporting their promising application in functional foods formulations.

Diabetes constitutes a risk factor for cognitive impairment, whereas insulin resistance serves as the shared pathogenesis underlying both diabetes and cognitive decline. The use of metformin for treating cognitive impairment remains controversial. The present study found that hesperetin, a flavanone derived from citrus peel, enhanced metformin’s efficacy in reducing blood sugar levels, improving insulin sensitivity, and ameliorating cognitive impairment in diabetic rats. Additionally, it reduced the required dosage of metformin to one-third of its conventional dose. Transcriptome analysis and 16S rRNA sequencing revealed that the activation of insulin and cyclic-adenosine monophosphate response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathways benefited from the regulation of gut microbiota and the promotion of short-chain fatty acid (SCFA) producers such as Romboutsia. Furthermore, this study demonstrated that hesperetin supplementation counteracted the upregulation of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), a pathological factor of Alzheimer’s disease (AD) that was induced by metformin. Our findings reveal that hesperetin can be used in supplementary treatment for cognitive impairment associated with diabetes.

SCIEPublish is an international open-access journal publishing service provider run by SCIE Publishing Limited, dedicated to supporting and inspiring scientists or institutions/societies who aspire to publish high-quality journals.