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Abstract Chronic type 2 diabetes mellitus (T2DM) and its associated diseases are major concern among human population and also responsible for significant mortality rate. Hence, the present study aims to evaluate and correlate the invertase inhibition, antioxidant activity and control against DFU causing bacterial pathogens by Pandanus odoratissimus flowers. Two dimensional preparative thin layer chromatography (2D PTLC) was adopted to purify the phenolic acid component and LC-MS2 was done to predict the phenolic acid structures. Standard spectrophotometry methods were adopted to investigate the in vitro invertase inhibitory and antioxidant (CUPRAC and ABTS) activities. Agar well diffusion and broth dilution assays were used to record the antibacterial property against DFU causing pathogens isolated from clinical samples. Statistical analyses were used to validate the experiments. A new and novel diferuloyl glycerate related phenolic acid (m/z 442) purified from PTLC eluate has recorded satisfactory cupric ion reducing power (ED50= 441.4±2.5 µg), moderate ABTS radical scavenging activity (IC50= 450.3±10 µg; 32.5±1.5%), and a near moderate, in vitro, invertase mixed type inhibition (24.5±4.5%; Ki: 400 µg). Similarly, bacterial growth inhibitory kinetics has showed a significant inhibition against E. coli and S. aureus.

Alarmins are classified by their release from damaged or ruptured cells. Many alarmins have been found to increase vascular tone and oppose endothelium-dependent dilatation (EDD). Interleukin (IL)-33 plays a prominent role in lung injury and can be released during vascular injury and in chronic studies found to be cardioprotective. Our recent work has implicated IL-33 in acute vascular dysfunction following inhalation of engineered nanomaterials (ENM). However, the mechanisms linking IL-33 to vascular tone have not been interrogated. We therefore aimed to determine whether IL-33 directly influenced microvascular tone and endothelial function. Isolated feed arteries and in vivo arterioles from male and female Sprague-Dawley rats were used to determine direct vascular actions of IL-33. Mesenteric feed arteries and arterioles demonstrated reduced intraluminal diameters when treated with increasing concentrations of recombinant IL-33. IL-33 activated extracellular signal regulated kinase (ERK)1/2 of rat aortic smooth muscle cells but not phosphorylation of myosin light chain kinase. This suggested IL-33 may sensitize arterioles to Ca 2+ -mediated responses. Indeed, IL-33 augmented the myogenic- and phenylephrine-induced vasoconstriction. Additionally, incubation of arterioles with 1 ng IL-33 attenuated ACh-mediated EDD. Mechanistically, in human aortic endothelial cells, we demonstrate that IL-33-mediated ERK1/2 activation leads to inhibitory phosphorylation of serine 602 on endothelial nitric oxide synthase. Finally, we demonstrate that IL-33-ERK1/2 contributes to vascular tone following two known inducers of IL-33; ENM inhalation and the rupture endothelial cells. The present study provides novel evidence that IL-33 increases vascular tone via canonical ERK1/2 activation in microvascular smooth muscle and endothelium. Altogether, it is suggested IL-33 plays a critical role in microvascular homeostasis following barrier cell injury. KEY POINTS: Interleukin (IL)-33 causes a concentration-dependent reduction in feed artery diameter. IL-33 acts on vascular smooth muscle cells to augment Ca 2+ -mediated processes. IL-33 causes inhibitory phosphorylation of endothelial nitric oxide synthase and opposes endothelium-dependent dilatation. Engineered nanomaterial-induced lung injury and endothelial cell rupture in part act through IL-33 to mediate increased vascular tone., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Hexavalent chromium (Cr (VI)) contamination poses a significant threat to environmental and human health due to its ability to induce oxidative stress. Conventional strategies to counter Cr (VI)-induced oxidative stress, like antioxidants and chelating agents, face efficacy limitations and adverse effects. The present study is intended to counteract the limitations of conventional strategies by introducing a trypsin inhibitor isolated from Dioscorea bulbifera L. tubers, known as DbGTi protein, against Cr (VI)-induced developmental toxicity and oxidative stress. Through a comprehensive array of biochemical assays, behavioural tests, and gene expression analyses, this study interprets the underlying mechanisms of the DbGTi protein. Results demonstrated that the DbGTi protein effectively restored antioxidant defense systems, including superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione S-transferase (GST), and glutathione peroxidase (GTPx), thereby mitigating cellular damage, reducing cell death, and enhancing neuro-biomarkers. qRT-PCR analysis of mRNA expression profiling revealed the upregulation of genes associated with antioxidant defense (sod, cat, gpx) and defense pathway (nrf2, hmox-1a), further highlighting the protective effects of DbGTi protein against Cr (VI)-induced oxidative stress., Competing Interests: Declaration of competing interest There is no evidence that the authors have conflicting financial or social relationships, which may appear to bias the discoveries of this study. The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glioblastoma (GBM) is the most aggressive primary brain malignancy in adults, with high recurrence rates and resistance to standard therapies. This study explores mitochondrial transplantation as a novel method to enhance the radiobiological effect (RBE) of ionizing radiation (IR) by increasing mitochondrial density in GBM cells, potentially boosting reactive oxygen species (ROS) production and promoting radiation-induced cell death. Using cell-penetrating peptides (CPPs), mitochondria were transplanted into GBM cell lines U3020 and U3035. Transplanted mitochondria were successfully incorporated into recipient cells, increasing mitochondrial density significantly. Mitochondrial chimeric cells demonstrated enhanced ROS generation post-irradiation, as evidenced by increased electron paramagnetic resonance (EPR) signal intensity and fluorescent ROS assays. The transplanted mitochondria retained functionality and viability for up to 14 days, with mitochondrial DNA (mtDNA) sequencing confirming high transfection and retention rates. Notably, mitochondrial transplantation was feasible in radiation-resistant GBM cells, suggesting potential clinical applicability. These findings support mitochondrial transplantation as a promising strategy to overcome therapeutic resistance in GBM by amplifying ROS-mediated cytotoxicity, warranting further investigation into its efficacy and mechanisms in vivo .

The ability of air pollution to induce acute exacerbation of asthma is well documented. However, the ability of ozone (O 3 ), the most reactive gaseous component of air pollution, to function as a modulator during sensitization is not well established. C57BL/6 J male mice were intranasally sensitized to house dust mite (HDM) (40 μg/kg) for 3 weeks on alternate days in parallel with once-a-week O 3 exposure (1 ppm). Mice were euthanized 24 h following the last HDM challenge. Lung lavage, histology, lung function (both forced oscillation and forced expiration-based), immune cell profiling, inflammation (pulmonary and systemic), and immunoglobulin production were assessed. Compared to HDM alone, HDM + O 3 leads to a significant increase in peribronchial inflammation (p < 0.01), perivascular inflammation (p < 0.001) and methacholine-provoked large airway hyperreactivity (p < 0.05). Serum total IgG and IgE and HDM-specific IgG1 were 3-5 times greater in HDM + O 3 co-exposure compared to PBS and O 3 -exposed groups. An increase in activated/mature lung total and monocyte-derived dendritic cells (p < 0.05) as well as T-activated, and T memory lymphocyte subset numbers (p < 0.05) were noted in the HDM + O 3 group compared to HDM alone group. Concurrent O 3 inhalation and HDM sensitization also caused significantly greater (p < 0.05) lung tissue interleukin-17 pathway gene expression and mediator levels in the serum. Redox imbalance was manifested by impaired lung antioxidant defense and increased oxidants. O 3 inhalation during allergic sensitization coalesces in generating a significantly worse T H 17 asthmatic phenotype., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)