Search Results (7,520)

The lower airways are a dynamic environment where physical, microbial, and molecular factors intersect to regulate respiratory health and disease. The muco-microbiotic (MuMi) layer, composed of mucus, resident microbes, and extracellular vesicles (EVs), is not just a passive barrier but also an active site for host–microbe communication. This layer integrates epithelial cell biology, microbial activity, and immune responses within the bronchial environment. New transcriptomic and metatranscriptomic technologies show that it is not only which microbes are present but also their gene activity that closely links to airway inflammation and disease. EV-associated RNAs from both host and microbial cells act as key messengers, influencing epithelial responses, immune activity, mucus properties, and microbial behaviour. This review highlights evidence that positions the MuMi layer as central to understanding lower airway disease, particularly asthma and chronic obstructive pulmonary disease (COPD). Distinct gene expression programs and biomarker profiles, such as exhaled nitric oxide, may reflect different disease mechanisms even in cases with similar clinical features, such as eosinophilia. Multi-omic approaches focused on the MuMi layer enable better disease classification, biomarker discovery, and therapy selection. By putting the MuMi interface at the core of precision pulmonology, we provide a framework for advancing personalised care in chronic respiratory diseases. Full article

Background/Objectives: Propolis is well recognized for its antioxidant, anti-inflammatory, and wound-healing properties, supporting its cutaneous application in phytopharmaceuticals for the management of ultraviolet B (UVB)-induced skin damage. However, the application of propolis is limited by its intense coloration, stickiness, and poor user convenience. In situ film-forming systems (FFS) represent a novel dosage form designed to overcome these challenges, although efficacy data for using FFS remains limited. Consequently, this study aimed to develop a propolis-based FFS and evaluate its efficacy in mitigating UVB-irradiated HaCaT keratinocytes. Methods: Apis mellifera propolis was macerated and analyzed for total phenolic content (TPC) and total flavonoid content (TFC), radical scavenging activity (DPPH assay), and nitric oxide scavenging capability. Bioactive compounds were identified using high-performance liquid chromatography analysis (HPLC). The propolis extract was formulated into FFS and investigated on UVB-damaged HaCaT keratinocytes. An MTT viability assay, propidium iodide flow cytometry for cell cycle analysis, and a scratch wound healing assay were used to evaluate the therapeutic effects of the FFS. Results: The 72 h macerated propolis extract contained high levels of TPC, TFC, and targeted phytochemicals. The propolis extract exhibited free radical scavenging and nitric oxide inhibitory activities. Seven formulations exhibited suitable performance, with formulation F7 (FFS-F7) demonstrating superior drying time and dose-dependent free radical scavenging. Notably, FFS-F7 (≥12.5 µg/mL) significantly enhanced HaCaT proliferation, mitigated UVB-induced cell cycle arrest, reduced cellular damage, and accelerated wound closure. Conclusions: This study successfully developed an FFS that not only overcomes these physical drawbacks but also preserves the biological activity of the extract. The significant protective and restorative effects against UVB-induced HaCaT damage demonstrate the therapeutic potential of Thai Apis mellifera propolis and establish the FFS as a versatile base with the potential for delivering other bioactive compounds. Full article

Chronic kidney disease (CKD) is a progressive disorder characterized by declining renal function and increased cardiovascular risk. Experimental models are essential for investigating these mechanisms, and the 5/6 nephrectomy (5/6 Nx) model is widely used to reproduce cardiorenal alterations observed in CKD. This review aims to critically evaluate how effectively the 5/6 Nx model reproduces vasoactive and redox mechanisms relevant for pharmacological testing. A narrative synthesis of experimental studies using the 5/6 Nx model in rodents was performed, focusing on vascular, inflammatory, and oxidative pathways. The 5/6 Nx model reproduces major CKD features, including hypertension, proteinuria, glomerulosclerosis, and cardiovascular remodeling. Early activation of the renin–angiotensin–aldosterone system, endothelin signaling, and sympathetic pathways contributes to vascular dysfunction. Sustained oxidative stress reduces nitric oxide bioavailability and promotes endothelial dysfunction. Dysregulation of natriuretic peptides and increased 20-HETE signaling further contribute to vascular imbalance and remodeling. These alterations occur in a well-defined temporal progression, supporting the use of this model for mechanistic and pharmacological studies. The 5/6 Nx model remains a robust and translationally informative platform for investigating CKD progression, provided that pathway-specific reproducibility and experimental variables are carefully considered. Full article

Background: Shikonins are natural naphthoquinones that exhibit a range of biological activities. They are typically extracted using nonpolar solvents; however, green extraction approaches remain underexplored. Methods: Phytochemical profiling of E. vulgare root extracts was performed using HPLC-ESI-QTOF-MS/MS and quantitative analysis using HPLC-PDA. Shikonin extraction was performed using VNADESs based on thymol, camphor, menthol and benzyl alcohol. The feasibility of removing the VNADES from the extracts via freeze-drying was assessed. The cytotoxic, antioxidant, anti-inflammatory and antimicrobial activities of the hexane extract and the selected VNADES-based extract (TBa 2:8) were compared. Results: Eight shikonin derivatives were identified in the extracts. VNADES extracts contained comparable amounts of shikonin to hexane extracts; however, freeze-drying resulted in significant shikonin content loss. TBa 2:8 extract exhibited noticeably lower cytotoxicity than the hexane extract while its antioxidant potential depended on the assay applied. In contrast to the hexane extract, TBa 2:8 demonstrated the ability to reduce intracellular ROS and NO levels. However, the hexane extract exhibited stronger antimicrobial activity. Conclusions: VNADES systems enable efficient extraction of shikonin derivatives with performance comparable to hexane. Although the resulting extracts exhibit multidirectional biological activity, it remains challenging to remove the VNADESs effectively without losing the shikonins. Full article

Heart inflammation and oxidative stress are pivotal pathological drivers in the pathophysiology of various cardiovascular diseases. The present study aims to investigate the beneficial effects induced by extracts derived from edible plants, such as Olea europaea, and sugar cane on heart health. In particular, we investigated the effects of a novel combination constituting Olea europaea, Scutellaria baicalensis, and policosanol extracts on heart, in in vitro and ex vivo models. Olea europaea, S. baicalensis, policosanol extracts and their combination prevented H₂O₂-induced reduction in H9c2 cell (immortalized myoblasts, isolated from rat heart tissue) viability. Moreover, pre-incubation with the combination significantly reduced H₂O₂-induced ROS levels in the same cells. Our present findings also showed that Olea europaea, S. baicalensis and policosanol extracts, as well as their combination, increased lipopolysaccharide (LPS)-induced catalase gene expression at all concentrations tested, in mouse heart specimens. In addition, we also observed that Olea europaea, S. baicalensis and policosanol extracts, as well as their combination, significantly inhibited LPS-induced inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-kB, and tumor necrosis factor-α gene expression, in the same experimental model. Interestingly, the combination was more effective at decreasing the mRNA levels of all pro-inflammatory markers investigated. Finally, the combination was also able to suppress LPS-induced B-type natriuretic peptide and cardiac troponin I gene expression ex vivo. In conclusion, these findings suggest that this plant-based combination could offer potential benefits for cardiovascular health and support overall heart function in humans. Full article

Background/Objectives: Neuroinflammation is characterized by the sustained activation of neuroglial cells, resulting in the production of cytokines and chemokines. It is associated with neurodegenerative processes. This study aims to assess the potential mitigating effect of a novel coumarin–quinoline hybrid by evaluating oxidative stress, apoptosis, and pyroptosis in an experimentally induced model of neuroinflammation. Methods: The study was conducted on 60 mice, allocated into six groups of ten: Group I served as the control; Group II received the new coumarin–quinoline hybrid; Group III received lipopolysaccharide (LPS); Group IV received LPS followed by the coumarin–quinoline hybrid; Group V received LPS followed by dexamethasone (DEX); and Group VI received LPS followed by the coumarin–quinoline hybrid and DEX. The model was validated by behavioral assessments, while oxidative stress was quantified via nitric oxide (NO), malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, apoptosis by caspase-3, and pyroptosis by NLRP3. Results: An anti-inflammatory effect of a new coumarin–quinoline hybrid, evidenced by decreased NLRP3 and NF-κB expression, reduced NO and MDA production, elevated SOD activity, and brought about suppression of caspase-3. Additionally, the newly formulated coumarin–quinoline hybrid demonstrated favorable ADMET characteristics, with in silico molecular studies indicating a stable energetic profile and dynamic equilibrium. Conclusions: Findings suggest that the new coumarin–quinoline hybrid holds significant potential as an adjuvant therapeutic option for neuroinflammation. Full article

The redox mechanisms of RAW 264.7 macrophages exposed to 2.45 GHz RF-EMF at subthermal specific absorption rates and to lipopolysaccharide (LPS) and/or the SARS-CoV-2 spike protein (CSP) were investigated. To this end, cellular responses (lysosomal and mitochondrial activity, nitric oxide (NO) production, and cell survival/death) were measured after 6, 24, and 48 h. Selective loss of viability in cells exposed to RF and LPS was observed at 6 h, consistent with early defects in membrane permeability. Lysosomal activity was significantly enhanced in cells treated with RF + LPS. Mitochondrial activity decreased in cells exposed to RF + LPS at 6 h and increased in cells treated with RF + CPS/LPS. Cell viability decreased greatly in cells treated with LPS and CSP + LPS after 24, particularly after 48 h. Nitrite levels peaked in non-irradiated cells treated with RF + LPS and in CSP + LPS at 24 h and decreased in irradiated cells after 48 h. Irradiation affected selection of the death mode: apoptosis decreased or remained unchanged in cells subjected to any of the treatments, while necrosis increased in cells treated with CPS, LPS, or both for 48 h. The combination of RF-EMF and infectious agents reprogrammed the interaction between mitochondria/lysosomes/nitric oxide (NO)/cell death in macrophages in a time- and stimulus-dependent manner. Full article

Delayed cerebral ischemia (DCI) is a major complication of aneurysmal subarachnoid hemorrhage (aSAH), strongly associated with neurological deterioration and poor outcomes. Its pathophysiology remains incompletely understood and involves multiple interacting processes. Increasing evidence highlights the role of redox imbalance triggered by hemoglobin breakdown and the subsequent generation of reactive species, leading to vascular dysfunction, impaired nitric oxide signaling, and inflammatory activation This review aims to summarize current knowledge on redox-related mechanisms involved in DCI and to explore the potential role of the peroxiredoxin (PRDX) family in this setting. A narrative review of experimental and preclinical studies was performed, focusing on molecular pathways associated with vascular regulation, cellular injury, and antioxidant defense. Particular attention was given to the distribution and biological functions of PRDX isoforms within the central nervous system. This work addresses a topic not previously systematically discussed, the potential involvement of PRDX proteins in aSAH-related complications. By integrating available data, it provides a conceptual framework linking PRDX to mechanisms relevant for DCI. The manuscript serves as a starting point for future research, particularly translational and clinical studies in humans, which are necessary to verify the relevance of these findings and to better understand their potential clinical implications. Full article

Background: Intracerebral hemorrhage (ICH) is a devastating subtype of stroke, in which neuroinflammation and blood–brain barrier (BBB) disruption are secondary pathophysiological events that drive progressive brain injury. Histone lysine demethylase JMJD3 (Jumonji C domain-containing protein 3) is a master epigenetic switch governing inflammatory signaling; however, its participation in ICH-induced vascular disruption and its possible mechanism remain elusive. Objective: To examine the expression patterns of JMJD3 in the context of ICH and to evaluate the therapeutic potential of its specific inhibitor, GSK-J4, in attenuating neuroinflammation and BBB disruption in a murine ICH model. Methods: Hemin treatment of a mouse C8-D1A astrocytic cell line was used to develop an in vitro ICH model. The transcript level of the Jmjd3 gene and its correlation with pro-inflammatory signaling were analyzed with or without GSK-J4 pretreatment. ICH in vivo was created experimentally in adult male C57BL/6 mice through stereotactic striatal injection of collagenase IV, and the mice were randomly assigned to sham, ICH + vehicle, and ICH + GSK-J4 (30 mg/kg intraperitoneally (i.p.), every other day starting three days before ICH) groups. At three days post-ICH, ipsilateral brain tissues were collected to detect JMJD3 cellular localization, pro-inflammatory mediator levels, tight junction protein expression, BBB ultrastructure, and hematoma volume. White matter integrity and neuronal recovery were assessed on day 7, and sensorimotor function was assessed longitudinally on days 1, 3, 5, 7, and 14. Results: Jmjd3 gene transcription was upregulated in hemin-treated astrocytes and correlated positively with IL-6 pro-inflammatory signaling activation. In vivo, the co-localization of JMJD3 with the astrocytic identifier glial fibrillary acidic protein (GFAP) was markedly increased in the area adjacent to the hematoma at three days post-ICH. GSK-J4 administration significantly suppressed the pro-inflammatory signaling cascade by decreasing the levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-9 (MMP-9), enhanced brain vascular structural and functional integrity by upregulating tight junction proteins zonula occludens protein-1 (ZO-1) and claudin-5, improved BBB ultrastructural integrity, and decreased hematoma volume at three days post-ICH. Furthermore, GSK-J4 administration promoted white matter integrity (increased myelin basic protein [MBP] expression) and neuronal recovery (increased neuron-specific nuclear protein [NeuN] expression) at seven days post-ICH and significantly improved the performance of ICH mice in sensorimotor behavioral tests. Conclusions: Astrocytic JMJD3 is upregulated following ICH and promotes neuroinflammation, which in turn mediates BBB disruption. Pharmacological inhibition of JMJD3 by GSK-J4 attenuates neuroinflammation and subsequent BBB damage, accelerates hematoma resolution, and promotes histological and functional recovery after ICH, likely by downregulating MMP-9 expression. These findings identify astrocytic JMJD3 as a novel epigenetic therapeutic target for acute ICH. Full article

Asthma is a heterogeneous inflammatory airway disease with variable clinical phenotypes. Dysregulation of the arginine–nitric oxide (NO) pathway contributes to airway hyperresponsiveness and endothelial dysfunction, but its role across stages of pediatric asthma remains unclear. In order to replicate real-world clinical heterogeneity, this investigation assessed serum levels of L-arginine, symmetric dimethylarginine (SDMA), asymmetric dimethylarginine (ADMA), L-citrulline, and the SDMA/ADMA ratio in children with managed asthma, asthma exacerbation, upper respiratory tract infections (URTIs), pneumonia, COVID-19, and healthy controls. Discovering stage-specific arginine pathway changes and evaluating their ability to distinguish asthma and asthma exacerbations from other clinically similar respiratory disorders was the primary aim of our research study. Receiver operating characteristic (ROC) analysis demonstrated that the SDMA/ADMA ratio achieved the strongest individual discriminative performance for distinguishing asthma exacerbation from controlled asthma (AUC: 0.917), while the combined multimarker model incorporating all four metabolites yielded an AUC of 0.983 with a sensitivity of 87.5% and specificity of 95.5%. These results indicate that arginine pathway metabolites, especially the SDMA/ADMA ratio, may merit additional research as possible markers of acute disease activity in asthma, even though they are exploratory and need external confirmation. Full article

The immune system plays a pivotal role in the maintenance of homeostasis and protection from pathogens. With increasing public interest in immune health, functional foods and herbal formulations are gaining attention as potential immunomodulators. Therefore, we aimed to investigate the combined immune-enhancing effects of HemoHIM (HIM) and Hwaljingigo (HGG) through combination treatment based on the recommended daily intake in RAW 264.7 macrophages. Cell viability, nitric oxide (NO) production, and cytokine (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) expression levels were assessed using the XTT, Griess, and enzyme-linked immunosorbent assay (ELISA), respectively. Immunoblotting was conducted to confirm changes in protein expression. Neither HIM nor HGG was cytotoxic at any of the tested concentrations. Both the single and combination treatments increased NO production and cytokine expression in a concentration-dependent manner. Furthermore, the combination of HIM (one sachet) and HGG (three sachets) resulted in the highest levels of NO and cytokine production. Bliss Independence analysis revealed synergistic interactions for IL-1β and IL-6, while NO and TNF-α showed additive effects. These findings suggest that the combination of HIM and HGG enhances immune responses by stimulating macrophage activity, thereby supporting the potential application of multi-herbal formulations as functional immunomodulatory agents. Full article

As a key type of precursor material in the nuclear fuel cycle process, plutonium oxalate has long played a critical role in the purification and conversion of plutonium. Its crystallization behavior directly affects the subsequent production process and properties of plutonium oxide. This review systematically summarizes the research progress of plutonium oxalate crystals in thermodynamics, crystallization kinetics, and crystal morphology. It introduces the structural characteristics of plutonium oxalate crystals, their solubility in nitric acid-oxalic acid mixed systems, and the thermodynamic properties such as the redox stability of plutonium oxalate crystals of different valence states. It also summarizes the nucleation, growth, and coprecipitation kinetics of plutonium oxalate crystals. The diversity of plutonium oxalate crystal morphologies and their influence on subsequent thermal decomposition are discussed. Full article

Targeted delivery systems offer a promising approach for selectively modulating cellular processes; yet the intracellular consequences of targeted nutrient delivery to trophoblast cells remain poorly defined. Here, we investigated a previously validated placenta-targeting peptide conjugated to liposomes encapsulating stable isotope-labelled L-arginine and L-lysine to examine cellular uptake and downstream molecular responses in a trophoblast-like cell model. Peptide-dependent uptake of fluorescently labelled liposomes was confirmed in BeWo cells, demonstrating selective internalisation compared with non-targeted controls. Encapsulation of isotope-labelled amino acids enabled direct quantification of intracellular delivery and incorporation into the cellular proteome using stable isotope labelling by amino acids in cell culture (SILAC). Quantitative proteomic analysis revealed coordinated changes in proteins associated with translation, metabolism, and nitric oxide synthase regulation following targeted liposomal uptake. Notably, V-type proton ATPase subunit G1 (ATP6V1G1) and large neutral amino acid transporter small subunit 1 (SLC7A5) showed increased incorporation of labelled amino acids and were independently validated by Western blotting. Together, these findings establish a proof-of-concept platform for targeted intracellular amino acid delivery to trophoblast-like cells and define the resulting proteomic responses. This work provides mechanistic insight into intracellular amino acid utilisation and a framework for future studies in placental cell biology. Full article

The gut microbiota serves as a critical interface for host immunity, making it a promising target for probiotic intervention. In this study, we investigated the immunomodulatory potential of the strain Bifidobacterium breve (B. breve) MN15965 and the underlying role of gut bacterial communities in this process. We first assessed its in vitro immunomodulatory activity by measuring nitric oxide and cytokine secretion in THP-1 macrophages. Subsequently, an immunosuppressed mouse model was established by treating BALB/c mice with cyclophosphamide (CTX), a chemotherapeutic agent known to cause immune dysfunction and mucosal damage. In this model, we performed a series of analyses, including H&E staining, measurement of hematological parameters and serum cytokines/immunoglobulins, quantification of fecal short-chain fatty acids (SCFAs) by gas chromatography, and profiling of gut microbiota composition via 16S rRNA gene amplicon sequencing. The results showed that MN15965 supernatant enhanced TNF-α, IL-1β, and GM-CSF secretion in THP-1 cells, promoting M1 macrophage activation in vitro. In the in vivo model, MN15965 administration restored spleen and thymus tissue integrity and improved physiological indices, hematological parameters, and immunoglobulin levels. Furthermore, MN15965 increased fecal SCFAs, particularly butyric and valeric acid, increased gut bacterial diversity, and enriched potentially beneficial SCFA-producing taxa, including Lachnospiraceae and Eubacterium. These findings demonstrate that B. breve MN15965 alleviated CTX-induced immunosuppression by activating immune responses, regulating gut bacterial communities, and boosting SCFA production. Full article

Studies have shown that dietary fibers have many health benefits. Soluble dietary fibers (SDF) extracted from wheat, corn, rice, or several herbaceous plants have been shown to have either pro- or anti-inflammatory effects depending on the mode of preparation of the fibers, the fibers’ structures and the biological or cellular context. However, much less is known regarding the immunomodulatory properties of dry bean-derived SDF. The goal of this study was to fill this gap in knowledge. Using RAW 264.7 macrophages, we show that dry bean-derived SDF stimulated the production of nitric oxide (NO), tumor necrosis factor (TNF) α, interleukin (IL)-1β and IL-6. We show that these changes were partly dependent on toll-like receptor TLR-4 signaling. More importantly, we observed that the levels of NO, TNF-α, IL-1β and IL-6 were significantly lower when the SDF were extracted from heat-processed bean flour. Overall, our results demonstrate that dry bean-derived SDF-rich fractions modulate macrophage activation in vitro, promoting a pro-inflammatory response that is partially mediated by TLR-4 signaling. Full article