Skin disorders associated with inflammation and oxidative stress remain challenging to treat, highlighting the need for safe and effective topical therapies. This study investigated the association of aqueous extract of Mitracarpus frigidus aerial parts (MFAq) and hydroalcoholic extract of Lantana camara leaves (LCHA) incorporated into chitosan-based films for potential dermatological applications. Different extract ratios were initially evaluated for phytochemical composition, cytotoxicity, antioxidant, and anti-inflammatory activities. The 1:1 MFAq:LCHA association was selected based on its balanced phytochemical profile, low cytotoxicity, and significant biological activity, with eleven major compounds identified by UFLC-QTOF-MS. This association reduced nitric oxide production by 88.83% and lipid droplet accumulation by 59.48%, while showing pronounced antioxidant activity. Chitosan films containing 0.5%, 1.0%, and 2.5% (w/w) of the selected association were homogeneous, thermally stable, and exhibited suitable mechanical and physicochemical properties for topical application. The films maintained high cell viability and demonstrated significant antioxidant, anti-inflammatory, and wound-healing activities, including reductions in nitric oxide (up to 59.58%), reactive oxygen species, and pro-inflammatory cytokines (up to 40.57% and 62.27% for IL-6 and IL-12), as well as enhanced fibroblast migration. Overall, these findings indicate that MFAq:LCHA-loaded chitosan films represent a promising biodegradable and multifunctional platform for the treatment of skin disorders associated with inflammation and oxidative stress. Further in vivo studies are warranted to confirm their therapeutic efficacy and safety.

Gas plasma exposure and plasma-activated water (PAW) containing long-lived reactive oxygen species (H2O2) and nitrogen species (NO2 ‒, NO3 ‒) generated by a multielectrode cylindrical dielectric barrier discharge plasma effectively inactivated oral bacteria Streptococcus mutans, opportunistic pathogen Staphylococcus aureus, and foodborne or intestinal Escherichia coli strains, which were used as comparator organisms. Gas plasma exposure to the water alters the water pH, H2O2, and NOx (Combined NO2 ‒ & NO3 ‒) concentrations. Gas Plasma (NOx and O3) achieved a 4-6 log reduction of bacteria within 16 min, while PAW induced a 5-6 log reduction within 3 days and reduced biofilm formation by 50 ± 0.21% ~ 40 ± 8.65%. These results show that bacteria, surface morphology, live/dead and RONS imaging, and flow cytometry consistently demonstrate that biocompatible plasma treatment significantly controls oral pathogens. Plasma gas and both distilled and tap-water PAW effectively inhibited S. mutans, with higher selectivity than that of other bacteria. This study highlights the potential of PAW as a novel, biocompatible strategy to mitigate the virulence of oral bacteria.

Nowadays, an increasing number of emerging therapeutic modalities are flourishing due to the high recurrence and intractability of cancer. Among them, NO gas therapy (NO GT) relies on NO donors that release NO radicals upon external or internal stimulation. Photodynamic therapy (PDT) is realized by the specific photosensitizers and light source. However, the clinical translation of NO is limited by its gaseous nature and the need for precise control over dosage and spatiotemporal distribution. Meanwhile, the efficacy of PDT is often compromised by tumor hypoxia. Consequently, the synergistic integration of PDT and NO GT has emerged as a cutting-edge paradigm in cancer treatment. Among the various NO donors, 4-nitro-3-trifuoromethylaniline (NTA) and its derivatives, as a prominent class of NO photodonors, have garnered sustained attention, which displayed various advantages such as high and controllable NO release ability and outstanding structural modification. In this review, we highlight the design of such bimodal therapeutic systems based on two methods of the combination of NTA and photosensitizers, namely, nanoassembly and molecular hybridization. By elucidating the design principles and synergistic antitumor effects of these two strategies, we summarize future development directions and remaining bottlenecks to provide rational guidelines for subsequent molecular design and biomedical research.

Mineralocorticoid receptor (MR) overactivation and high salt intake drive vascular dysfunction, characterized by endothelial impairment and stiffening. While the novel non-steroidal MR antagonist (MRA), finerenone improves cardiovascular outcomes in patients with heart failure, its specific effects on vascular sodium accumulation remain unknown. We investigated the effects of finerenone on vascular function, remodeling, and aortic sodium content. Uninephrectomized (UNx) Sprague Dawley rats were subjected to chronic aldosterone infusion (0.75 μg/h) and salt-loading (1% NaCl in drinking water) for 4 weeks, with concurrent oral administration of finerenone (10 mg/kg). Finerenone intervention improved survival and significantly decreased systolic blood pressure. Vascular function analyses revealed that both endothelium-dependent and -independent relaxation were impaired in the model group; however, finerenone significantly preserved these functions. Importantly, sodium content in the aortic tissues as well as plasma was markedly elevated in aldosterone/salt-loaded UNx rats but was significantly reduced by finerenone, concurrent with the downregulation of the MR target gene serum glucocorticoid-regulated kinase 1 (Sgk1). In addition, finerenone attenuated vascular fibrosis and hypertrophy, and restored the aortic nitric oxide level. Altogether, these findings suggest that finerenone ameliorates vascular dysfunction by targeting MR/Sgk1-mediated vascular sodium accumulation and maladaptive remodeling, in concert with systemic blood pressure reduction.

Nitric oxide (NO) and nitroxyl (HNO) are closely related reactive nitrogen species with distinct biological functions, yet differentiating their chemistry remains challenging because of their high reactivity and overlapping reaction pathways. Developing simple protein-based platforms to study their reactivity is therefore of considerable interest. Rubredoxins are small, stable iron-thiolate proteins widely used as model systems for investigating metal-thiolate coordination and electron transfer. Here, we investigated the reactivity of native iron-rubredoxin (Fe-Rd) and its nickel-substituted analog (Ni-Rd) toward NO and HNO to determine whether cysteine ligand modification could disrupt metal-thiolate coordination and induce demetallation. Electronic absorption and fluorescence spectroscopy showed that Fe-Rd is highly resistant to both species, whereas Ni-Rd exhibited pronounced spectral changes consistent with metal release, including loss of the Ni─S ligand-to-metal charge-transfer band and increased intrinsic fluorescence. Inductively coupled plasma atomic emission spectroscopy confirmed partial nickel release following treatment with both NO and HNO donors. Despite demetallation, circular dichroism, thermal denaturation, and size-exclusion chromatography demonstrated that Ni-Rd largely retains its secondary structure, thermal stability, and monomeric state. These findings establish Ni-Rd as a robust minimal metalloprotein platform for probing reactive nitrogen species-induced thiolate chemistry.

This study evaluated the in vivo effects of hirudotherapy (medicinal leech therapy) on microcirculation and inflammation following global ischemia‑induced cerebral ischemia/reperfusion (I/R) in rats. Rats were divided into three groups of eight (control, I/R, and hirudotherapy) for this study. Global ischemia was created in the I/R and treatment groups by occluding both common carotid arteries. According to the I/R procedure, two Hirudo verbana leeches were applied bilaterally to the mastoid regions. Serum and tissue samples were analyzed for biochemical parameters including superoxide dismutase (SOD), interleukin 6 (IL‑6), nitric oxide (NO), calcitonin gene‑related peptide (CGRP), glutathione peroxidase (GPx), catalase (CAT), endothelin‑1, tumor necrosis factor alpha (TNF‑α), ischemia modified albumin (IMA), and hypoxia‑inducible factor‑1 alpha (HIF‑1α). Histopathological methods were used to examine edema, degeneration, necrosis, and hemorrhagic changes in brain tissue samples. The I/R group showed significantly increased tissue TNF‑α levels compared to controls. Tissue IMA and HIF‑1α levels were significantly higher in the treatment group. Treatment significantly reduced degeneration, necrosis, edema, and hemorrhage in brain tissues, as shown by histopathology. Histopathological analysis shows significantly less tissue damage in the hirudotherapy group compared to the I/R group, suggesting that hirudotherapy reduces brain damage after cerebral ischemia and reperfusion.

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with rising global prevalence and no effective pharmacological treatments. Early-life stress, such as maternal separation (MS), is a known risk factor that can lead to neuroinflammation and oxidative stress, contributing to autistic-like behaviors. This study addresses the knowledge gap by exploring the potential of Morus nigra L. (black mulberry) extract, known for its anti-inflammatory and antioxidant properties, in mitigating these behaviors in a mouse model of MS. In this study, 40 male NMRI mice were used. Hydroalcoholic extract of M. nigra was isolated by maceration method; then, it was administered to MS-exposed mice (20, 40, or 60 mg/kg), and its effects on social interaction, memory, aggression, and spatial learning were assessed by using behavioral tests, including a three-chamber test, resident-intruder test, shuttle box test, and Morris water maze test. Oxidative stress markers in the serum and hippocampus as well as gene expression of inflammatory mediators in the hippocampus were assessed. Behavioral tests revealed significant improvements in social preference and passive avoidance memory and reduced aggressive behaviors. The Morris Water Maze test indicated enhanced spatial learning and memory. Biochemically, M. nigra extract reduced malondialdehyde levels and nitrite levels and increased total antioxidant capacity in the hippocampus. Gene expression analysis showed decreased levels of pro-inflammatory cytokines, including Tnf-α, Il-1β, and Tlr4. These findings suggest that M. nigra extract mitigates autistic-like behaviors in MS mice by possibly attenuating neuroinflammation and oxidative stress, highlighting its potential for further investigation in ASD-related behavioral phenotypes. Further research is warranted to elucidate the precise mechanisms and optimize dosing strategies.

Acute respiratory distress syndrome (ARDS) arises from a heterogenous set of inciting injuries and produces its classic sequelae of hypoxia and lung damage through multiple pathways. Over decades, therapeutic efforts have focused on targeting the inflammatory response and providing excellent supportive care. Volatile anesthetics have been proposed as agents that could achieve both of these aims by protecting against inflammatory lung injury, allowing effective sedation, and through respiratory effects including bronchodilation and maintenance of respiratory drive. Promising preliminary data demonstrated reductions in inflammatory mediators and improvements in oxygenation with volatile anesthetics for patients with ARDS. However, a recent multicenter randomized controlled trial found that sevoflurane sedation for patients with moderate-to-severe ARDS reduced ventilator free days at day 28 and increased mortality compared to propofol sedation. Ongoing and recently completed clinical trials may provide additional context for patients with respiratory failure including ARDS, although none are being conducted solely in ARDS patients. Priorities for future trials of volatile anesthetic sedation in ARDS include reconsideration of the dose, agent selection, and duration of volatile sedation, and potential heterogeneity of treatment effect across ARDS sub-phenotypes. Pending further high-quality data suggesting benefit, routine clinical use of volatile ICU sedation in ARDS is currently not recommended outside of clinical trials.