RBio (South Korea)

Acute kidney injury (AKI) remains a major clinical challenge resulting from the intertwined processes of oxidative stress and macrophage-driven inflammation, both converging on mitochondrial dysfunction. We developed a glucosylated albumin nanoplatform (Glc6-AD11-Alb) designed to exploit glucose transporter 1-mediated uptake in inflammatory M1 macrophages while preserving the intrinsic antioxidant properties of albumin. Physicochemical characterization confirmed reproducible synthesis with defined degrees of functionalization and stable physicochemical properties. In vitro, Glc6-AD11-Alb demonstrated selective uptake in M1 macrophages and significantly reduced intracellular reactive oxygen species, validating its dual role in immune modulation and redox regulation. Positron emission tomography imaging with Cu-64 radiolabeling revealed preferential renal accumulation in ischemia-reperfusion injury (IRI) models, supporting macrophage-targeted delivery. In vivo, administration of Glc6-AD11-Alb attenuated renal dysfunction, suppressed pro-inflammatory and oxidative markers, and promoted tubular regeneration in pre- and post-treatment settings. Importantly, Glc6-AD11-Alb directly protected renal tubular epithelial cells by restoring mitochondrial membrane potential under oxidative and hypoxic stress. Seahorse metabolic flux analysis further confirmed enhanced oxidative phosphorylation, reduced glycolytic dependency, and improved coupling efficiency, indicating recovery of mitochondrial bioenergetics. Transmission electron microscopy demonstrated preservation of mitochondrial ultrastructure, including intact cristae and elongated morphology, consistent with improved ATP synthesis capacity. Glc6-AD11-Alb acts through complementary mechanisms of macrophage-targeted immune modulation and mitochondrial protection, thereby disrupting the vicious cycle of inflammation and oxidative stress in AKI. This nanoplatform represents a clinically translatable therapeutic strategy with potential to improve outcomes in patients with ischemic kidney injury.

BackgroundAllergic asthma involves chronic inflammation, airway remodeling, and hyperresponsiveness. Inhaled corticosteroids combined with long-acting β2 agonists are effective; however, some patients experience side effects, highlighting the need for safer natural alternatives suitable for long-term use. Chinese quince (Q) and Saururus chinensis (SC) are used to treat various diseases, including asthma and inflammation. Q and SC extracts contain bioactive compounds that help modulate airway inflammation. Therefore, combining the two may enhance their immunomodulatory effects. However, the effects of a Q/SC mixture on allergic asthma remain unclear. The aim of this study is to assess the therapeutic effectiveness of a Q/SC mixture in treating asthma.MethodsThe therapeutic efficacy of the Q/SC extract was evaluated in an ovalbumin (OVA)-induced allergic airway inflammation model. After euthanasia, we assessed cell counts, cytokine expression in the bronchoalveolar lavage fluid (BALF), blood immunoglobulin (Ig) E levels, inflammatory cell infiltration, mucus production in the lung tissue, and the expression of protein and cytokine.ResultsA high-concentration Q/SC extract significantly reduced total cell and eosinophil counts, cytokine expression in BALF, and serum IgE levels. Furthermore, it reduced the expression of type 2 cytokines (IL-4, IL-5, IL-13) and inducible nitric oxide synthase in lung tissue. The extract also attenuated inflammatory cell infiltration and mucus production while inhibiting the STAT6 signaling pathway.ConclusionA high concentration of Q/SC extract effectively alleviates allergic airway inflammation by reducing eosinophilic inflammation, type 2 cytokine secretion, and mucus hyperproduction. This suggests that it could be a potential remedy for managing allergic airway inflammation.

The prevalence of lipid metabolism disorders, including obesity, increases with age in cats and humans. Obesity is a condition characterized by systemic low-grade inflammation and oxidative stress caused by excessive visceral fat accumulation. Resveratrol (RSV), a natural plant polyphenol, modulates the expression of anti-inflammatory factors. This study aimed to investigate the effects of resveratrol supplementation on lipid metabolism in both healthy and obese cats and assess its potential as a dietary supplement for improving lipid metabolism disorders in this population. Plasma metabolite and hormone concentrations, and enzyme activities were measured in healthy, obese, and overweight cats supplemented with RSV for 4 weeks. RVS was supplemented at 1 mg/kg body weight/day (low dose) and 5 mg/kg/day (high dose) in capsules for 4 weeks. Body weight, body condition score, BUN, and insulin concentrations did not change in obese or overweight cats with RSV supplementation for 4 weeks. Plasma triglyceride, free fatty acids, and serum amyloid A (SAA) concentrations and lactate dehydrogenase (LDH) activities decreased, and adiponectin concentrations increased markedly in obese and overweight cats after RSV supplementation. Decreased plasma SAA concentrations and LDH activities and increased plasma adiponectin concentrations in obese and overweight cats seem to be induced by the improvement in liver function and the anti-inflammatory effect of RSV. Moreover, RSV supplementation may be useful in treating lipid metabolism disorders, including obesity, in cats.

Abstract Acute liver failure (ALF) is a critical inflammatory condition characterized by rapid hepatocyte death, impaired liver regeneration due to the delayed removal of necroptotic cells, and high mortality rates. This study introduces a novel dual-mode action therapeutic approach using extracellular vesicles expressing Signal Regulatory Protein Alpha (SIRP-EVs) derived from genetically engineered mesenchymal stem cells (MSCs). These SIRP-EVs are designed to concurrently resolve necroptosis and promote liver regeneration. Our studies identified CD47 and SIRPα as promising therapeutic targets for ALF. We developed a scalable 3D bioreactor-based process that produces high-purity SIRP-EVs, which preserve MSC properties and achieve significant production levels. SIRP-EVs target both macrophages and necroptotic hepatocytes in ALF models, enhancing macrophage phagocytic activity against necroptotic cells via CD47 blockade and promoting liver regeneration by reprogramming macrophages with MSC-derived cargo. Comprehensivein vitroandin vivostudies demonstrate that SIRP-EVs decrease CD47+necroptotic cells and promote liver regeneration in ALF models, leading to reduced liver damage markers and enhanced survival rates. These findings highlight the potential of SIRP-EVs as a dual-mode action therapeutic for ALF, offering promising prospects for their application in other inflammatory diseases. Moreover, these results pave the way for advancing engineered EV-based therapies toward clinical implementation.

In this study, extracellular vesicles (EVs) are reimagined as more than just a cellular waste disposal system and are repurposed for cancer immunotherapy. Potent oncolytic EVs (bRSVF-EVs) loaded with misfolded proteins (MPs) are engineered, which are typically considered cellular debris. By impairing lysosomal function using bafilomycin A1 and expressing the respiratory syncytial virus F protein, a viral fusogen, MPs are successfully loaded into the EVs expressing RSVF. bRSVF-EVs preferentially transplant a xenogeneic antigen onto cancer cell membranes in a nucleolin-dependent manner, triggering an innate immune response. Furthermore, bRSVF-EV-mediated direct delivery of MPs into the cancer cell cytoplasm initiates endoplasmic reticulum stress and immunogenic cell death (ICD). This mechanism of action leads to substantial antitumor immune responses in murine tumor models. Importantly, when combined with PD-1 blockade, bRSVF-EV treatment elicits robust antitumor immunity, resulting in prolonged survival and complete remission in some cases. Overall, the findings demonstrate that utilizing tumor-targeting oncolytic EVs for direct cytoplasmic delivery of MPs to induce ICD in cancer cells represents a promising approach for enhancing durable antitumor immunity.

Abstract Two experiments were conducted to investigate effects of dietary flavor as a feed additive on growth performance of weaned pigs. The flavor used in experiments was a commercial product (Luctarom®, Lucta Guangzhou, China) containing milky cream flavor. In Exp. 1, 72 weaned pigs (initial BW = 6.51 ± 0.21 kg) were randomly assigned to 2 dietary treatments (4 pigs/pen; 9 replicates/treatment): an experimental diet based on corn and soybean meal (CON1) and CON1 supplemented with 0.05% flavor (FLA). In Exp. 2, 72 weaned pigs (initial BW = 6.66 ± 0.32 kg) were randomly assigned to 2 dietary treatments (4 pigs/pen; 9 replicates/treatment): a commercial diet based on corn and soybean meal with spray dried plasma, fish meal, and zinc oxide (CON2) and CON2 supplemented with FLA. Pigs were fed respective dietary treatment for 6 weeks. Growth performance was measured on day 1, 7, 14, 21, and 42 after weaning. Data were analyzed using the PROC GLM procedure of SAS. The statistical model for every measurement included dietary effect and BW as a covariate in a randomized complete block design (block = BW). In Exp. 1, pigs fed FLA tended to increase ADG (0.493 vs. 0.451 kg/d; P < 0.10) during the experimental period compared with those fed CON1. However, there were no differences in ADFI and G:F between CON1 and FLA. In Exp. 2, pigs fed FLA had greater ADG (0.548 vs. 0.463 kg/d; P < 0.05) and tended to increase ADFI (0.870 vs. 0.753 kg/d; P < 0.10) during the experimental period than those fed CON2. However, there was no difference in G:F between CON2 and FLA. In conclusion, the addition of dietary flavor in experimental and commercial nursery diets improved growth performance of weaned pigs.

A study was conducted to determine the efficacy of β-mannanase supplementation to a diet based on corn and soya bean meal (SBM) on growth performance, nutrient digestibility, blood urea nitrogen (BUN), faecal coliforms and lactic acid bacteria, and noxious gas emission in growing pigs. A total of 140 pigs [(Landrace × Yorkshire) × Duroc; average body weight 25 ± 3 kg] were randomly allotted to a 2 × 2 factorial arrangement with dietary treatments consisting of hulled or dehulled SBM without or with supplementation of 400 U β-mannanase/kg. During the 6 weeks of experimental feeding, β-mannanase supplementation had no effect on body weight gain, feed intake and gain:feed (G:F) ratio. Compared with dehulled SBM, feeding hulled SBM caused an increased feed intake of pigs in the entire trial (p = 0.05). The G:F ratio was improved in pigs receiving dehulled SBM (p < 0.05). Dietary treatments did not influence the total tract digestibility of dry matter, nitrogen and gross energy. Enzyme supplementation reduced (p < 0.05) the population of faecal coliforms and tended to reduce the NH3 concentration after 24 h of fermentation in a closed box containing faecal slurry. Feeding hulled SBM tended to reduce NH3 emission on days 3 and 5 of fermentation. In conclusion, mannanase supplementation had no influence on growth performance and nutrient digestibility but showed a positive effect on reducing coliform population and tended to reduce NH3 emission. Dehulled SBM increased G:F ratio and hulled SBM tended to reduce NH3 emission.