Polymicrobial wound infections are a major cause of infectious disease-related morbidity and mortality worldwide. In this study, we prepared a nitric oxide (NO)-releasing oxidized bacterial cellulose/chitosan (BC_TO/CHI) crosslinked hydrogel to effectively treat polymicrobial wound infections. Linear polyethyleneimine diazeniumdiolate (PEI/NO) was used as the NO donor. The aldehyde group of BC_TO and the amine of CHI were used as crosslinked hydrogel-based materials; their high NO loading capacity and antibacterial activity on the treatment of polymicrobial-infected wounds were investigated. The blank and NO-loaded crosslinked hydrogels, namely BC_TO-CHI and BC_TO-CHI-PEI/NO, were characterized according to their morphologies, chemical properties, and drug loading. BC_TO-CHI-PEI/NO exhibited sustained drug release over four days. The high NO loading of BC_TO-CHI-PEI/NO enhanced the bactericidal efficacy against multiple bacteria compared with BC_TO-CHI. Furthermore, compared with blank hydrogels, BC_TO-CHI-PEI/NO has a favorable rheological property due to the addition of a polymer-based NO donor. Moreover, BC_TO-CHI-PEI/NO significantly accelerated wound healing and re-epithelialization in a mouse model of polymicrobial-infected wounds. We also found that both crosslinked hydrogels were nontoxic to healthy mammalian fibroblast cells. Therefore, our data suggest that the BC_TO-CHI-PEI/NO developed in this study improves the efficacy of NO in the treatment of polymicrobial wound infections.

The olive tree (Olea europaea) and olive oil hold significant cultural and historical importance in Europe. The health benefits associated with olive oil consumption have been well documented. This paper explores the mechanisms of the anti-cancer effects of olive oil and olive leaf, focusing on their key bioactive compounds, namely oleocanthal, oleacein, and oleuropein. The chemopreventive potential of oleocanthal, oleacein, and oleuropein is comprehensively examined through this systematic review. We conducted a systematic literature search to identify eligible articles from Scopus, PubMed, and Web of Science databases published up to 10 October 2023. Among 4037 identified articles, there were 88 eligible articles describing mechanisms of chemopreventive effects of oleocanthal, oleacein, and oleuropein. These compounds have the ability to inhibit cell proliferation, induce cell death (apoptosis, autophagy, and necrosis), inhibit angiogenesis, suppress tumor metastasis, and modulate cancer-associated signalling pathways. Additionally, oleocanthal and oleuropein were also reported to disrupt redox hemostasis. This review provides insights into the chemopreventive mechanisms of O. europaea-derived secoiridoids, shedding light on their role in chemoprevention. The bioactivities summarized in the paper support the epidemiological evidence demonstrating a negative correlation between olive oil consumption and cancer risk. Furthermore, the mapped and summarized secondary signalling pathways may provide information to elucidate new synergies with other chemopreventive agents to complement chemotherapies and develop novel nutrition-based anti-cancer approaches.

The escalating prevalence of diabetes represents a critical challenge to global health and quality of life. Indonesia, particularly the Sulawesi region, is home to a diverse array of endemic plants with potential as sources of novel antidiabetic compounds. However, traditional preclinical models for evaluating these candidates are limited by high costs and lengthy timelines. The aim of this study was to explore the antidiabetic potential of Cordia myxa and Syzygium malaccense extracts using Drosophila melanogaster as a novel, cost-effective and efficient in vivo model. Hyperglycemia was induced in D. melanogaster larvae through a high-sugar diet, and the plant extracts were incorporated into the larval diets at concentrations ranging from 0.3125% to 2.5%. Phenotypic parameters, including body size, body weight, crawling activity, and hemolymph glucose levels, were evaluated, and the expression of metabolism-related genes (dilp2, dilp5, and srl) was analyzed using RT-qPCR. This study found that C. myxa and S. malaccense extracts improved crawling activity and body size in hyperglycemic larvae. Notably, C. myxa extract significantly reduced hemolymph glucose levels (p<0.01), increased body weight (p<0.01), and upregulated the expression of metabolic genes such as dilp2 (p<0.001), dilp5 (p<0.001), and srl (p<0.0001). In contrast, S. malaccense extract showed less pronounced effects, highlighting the efficacy of C. myxa extract in alleviating hyperglycemia and restoring metabolic homeostasis. The study highlights that C. myxa extract demonstrated promising antidiabetic properties in the Drosophila model, underscoring the utility of this model for early-stage antidiabetic drug screening and supporting further preclinical investigation into the therapeutic potential of C. myxa for managing hyperglycemia.

Laportea decumana (Roxb.) Wedd. is known for its analgesic, antioxidant, anti‐inflammatory, and antibacterial properties. This study aimed to evaluate the wound‐healing effects of LDE incorporated into a biocellulose dressing for the treatment of polymicrobial‐infected wounds. The metabolite profile of LDE was characterized using UPLC‐Q‐TOF/MS. Biocellulose dressings were prepared with and without 4% LDE for the in vivo study. Fifteen male rats were each subjected to three biopsy punch wounds, which were infected with a polymicrobial mix of Staphylococcus aureus , Staphylococcus epidermidis , and Pseudomonas aeruginosa . The wounds were treated with either blank or 4% LDE‐fortified biocellulose dressing, or left untreated for 14 days. Wound diameters were measured daily, and histological analyses were conducted on Days 3, 7, and 11 to evaluate the inflammatory, proliferative, and maturation phases of wound healing. In vivo experiments showed that wounds treated with 4% LDE‐fortified biocellulose had significantly smaller diameters from Day 11 onward compared to untreated wounds or blank control. While all wounds exhibited edema and leukocyte infiltration during the inflammatory phase, treatment with 4% LDE significantly enhanced granulation tissue formation, fibroblast activity, and collagen deposition in the proliferative phase. During maturation, LDE‐fortified dressings accelerated re‐epithelialization. In conclusion, the 4% LDE‐fortified biocellulose dressing exhibited wound‐healing effects in a rat model of infected wounds by promoting cell proliferation and accelerating the maturation phase of wound repair. Further studies are needed to clarify the underlying antimicrobial and inflammatory mechanisms.

Catch-up growth following early life undernutrition is a major risk factor for metabolic dysfunction, including insulin resistance and type 2 diabetes mellitus. Here, we developed a Drosophila melanogaster model of catch-up-growth-associated metabolic dysregulation and used clomiphene citrate (CC) as a pharmacological probe to explore conserved metabolic regulatory pathways. Larvae were maintained on a low-calorie diet until the early third instar and subsequently returned to a standard diet to induce compensatory growth. Metabolic phenotyping included glucose levels, reactive oxygen species (ROS), triglycerides, locomotor performance, and transcriptional analysis of insulin- and hormone-related regulators (dilp2, dInR, dPHM, and dHNF4). Catch-up growth flies exhibited sustained hyperglycemia, elevated ROS, and increased triglyceride levels, indicating dysregulated glucose and lipid homeostasis, while locomotor function remained relatively preserved at the early adult stages. CC supplementation was associated with attenuation of hyperglycemia and oxidative stress, together with modulation of insulin- and hormone-related transcriptional markers. Molecular docking and molecular dynamics simulations provided hypothesis-generating structural insights into potential interactions of CC with metabolic regulators. Collectively, these findings establish Drosophila as a tractable model for investigating early-stage metabolic consequences of catch-up growth and support the use of CC as a tool compound for mechanistic exploration, while highlighting the need for further validation in mammalian systems.

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