Oxide Production Research Articles

Nanometabolomics Elucidated Biological Prospective of Mo4/3B2-x Nanosheets: Toward Metabolic Reprogramming of Amino Acid Metabolism.

Mo4/3B2-x nanosheets are newly developed, and 2D transition metal borides (MBene) were reported in 2021, but there is no report on their further applications and modification; hence, this article sheds light on the significance of potential biological prospects for future biomedical applications. Therefore, elucidation of the biocompatibility, biotoxicology, and bioactivity of Mo4/3B2-x nanosheets has been an urgent need to be fulfilled. Nanometabolomics (also referred as nanomaterials-based metabolomics) was first proposed and utilized in our previous work, which specialized in interpreting nanomaterials-induced metabolic reprogramming through aqueous metabolomics and lipidomics approach. Hence, nanometabolomics could be considered as a novel concept combining nanoscience and metabolomics to provide bioinformation on nanomaterials' biomedical applications. In this work, the safe range of concentration (<50 mg/L) with good biosafety toward human umbilical vein endothelial cells (HUVECs) was discovered. The low concentration (5 mg/L) and high concentration (50 mg/L) of Mo4/3B2-x nanosheets were utilized for the in vitro Mo4/3B2-x-cell interaction. Nanometabolomics has elucidated the biological prospective of Mo4/3B2-x nanosheets via monitoring its biocompatibility and metabolic shift of HUVECs. The results revealed that 50 mg/L Mo4/3B2-x nanosheets could lead to a stronger alteration of amino acid metabolism with disturbance of the corresponding amino acid-related pathways (including amino acid metabolism, amino acid degradation, fatty acid biosynthesis, and lipid biosynthesis and metabolism). These interesting results were closely involved with the oxidative stress and production of excess ROS. This work could be regarded as a pathbreaking study on Mo4/3B2-x nanosheets at a biological level, which also designates their further biochemical, medical, and industrial application and development based on nanometabolomics bioinformation.

In-situ impedance spectroscopy on copper oxide scales under potential controlled oxidation at high temperatures

In recent years, copper oxide (Cu2O) has gained significant attention for its multifaceted role as a catalyst, photocatalyst and semiconductor. Possessing a p-type conductivity and a bandgap of 2.17 eV, Cu2O emerges as an ideal candidate for applications such as water splitting and photovoltaic cells. However, to utilize its full potential, an in-depth understanding of the electrical properties of Cu2O in terms of defect density and defect mobility is required. This knowledge forms the basis for the targeted production of oxides with precisely tuned electrical properties.Extensive research on thermal oxidation under varied conditions has been performed to clarify the mechanisms governing oxide formation and growth. However, the in-situ investigation of the electrical properties of the oxide layers during their formation process is challenging.This work introduces a new method for the controlled oxidation of copper, while concurrently offering an in-depth investigation of the electrical properties of these nanometer-thick oxide layers. The implemented arrangement of potentiostat and frequency response analyzer enables their artifact-free combination. Performing HT-CV measurements in a solid electrolyte cell-setup allows to control the (potential-dependent) oxygen pressure at the copper surface. Using HT-CV, the current represents the kinetics of the redox reactions and the electric charge corresponds to the amount of substance converted. In-situ electrochemical impedance data are used to determine the electrical properties of the controlled grown layers. As a result, the defect density is obtained as a function of the oxygen partial pressure.

Chemical constituents from a marine medicinal brown alga-derived Xylaria acuta SC1019.

In this study, a marine medicinal brown alga Sargassum cristaefolium-derived fungal strain Xylaria acuta SC1019 was isolated and identified. Column chromatography of the extracts from liquid- and solid-fermented products of the fungal strain was carried out, and led to the isolation of twenty-one compounds. Their structures were characterized by spectroscopic analysis, and the absolute configurations were further established by single X-ray diffraction analysis or modified Mosher's method as nine previously undescribed compounds, namely xylarilactones A-C (1-3), ent-gedebic acid 8-O-α-D-glucopyranoside (4), 5R-hydroxylmethylmellein 11-O-α-D-glucopyranoside (5), ent-hymatoxin E 16-O-α-D-mannopyranoside (6), 19,20-epoxycytochalasin S (7), 19,20-epoxycytochalasin T (8), and (2R)-butylitaconic acid (9), along with twelve known compounds 10-21. All the isolates were subjected to anti-inflammatory and anti-angiogenic assays. Compounds 1, 5, 7, 10, and 17 showed moderate nitric oxide production inhibitory activities in lipopolysaccharide-activated BV-2 microglial cells with IC50 values of 19.55 ± 0.35, 16.10 ± 0.57, 15.20 ± 0.87, 11.76 ± 0.49, and 11.30 ± 0.32 μM, respectively, as compared to curcumin (IC50 = 2.69 ± 0.34 μM) without any significant cytotoxicity. Compounds 7, 8, and 21 displayed potent anti-angiogenic activities by suppressing the growth of human endothelial progenitor cells with IC50 values of 0.44 ± 0.01, 0.47 ± 0.03, and 0.53 ± 0.01 μM, respectively, as compared to sorafenib (IC50 = 5.50 ± 1.50 μM).

Mitochondrial injury induced by triclopyr in the rat liver

The herbicide triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) is already considered an environmental problem due to damage caused by incorrect disposal, leaching, and aerial dispersion, which may pose risks to the environment and human health. Studies have evaluated metabolism, absorption, excretion, and active transport but there is no clear information about its mode of action (MoA) and its cytotoxic action potential remains unknown. In this context, mitochondria have been used to assess the toxicity of xenobiotics, for this reason, to identify the toxic mechanism of triclopyr, hepatic mitochondria from Wistar rats were exposed in vitro to different concentrations of triclopyr (0.5–500 µM). There was neither formation/accumulation of reactive oxygen and nitrogen species, nor lipid peroxidation or changes in the mitochondrial antioxidant system, in addition to proper functioning of oxidative phosphorylation and ATP production. Changes were found in NAD(P)H oxidation, membrane potential dissipation and mitochondrial calcium gradient. These results demonstrate that mitochondria suffer damage related to their bioenergetics and redox status but not to their structure when exposed to concentrations of triclopyr considered higher than those described as found in the environment so far. Highlights Triclopyr has a low mitochondrial uncoupling potential. The damage caused to the bioenergetics and redox state of the mitochondria is related to concentrations considered higher than those found in the environment. Even at high concentrations, triclopyr was not able to change the structure of the organelle after exposure. Oxidative phosphorylation and ATP production were not impaired after exposure. NAD(P)H oxidation resulted in potential membrane dissipation and mitochondrial calcium gradient dissipation. Triclopyr does not have RONS-forming properties, as well as it does not peroxide membrane lipids, it preserves membrane sulfhydryl groups and maintains the normality of the GSH/GSSG ratio.

Innovative torque-based control strategy for hydrogen internal combustion engine

Over the past years, several efforts have been made to reduce greenhouse gas emissions coming from the transport sector. Due to the highly efficient CO2-free combustion and low manufacturing costs, Hydrogen Internal Combustion engines (H2ICEs) are considered one of the most promising solutions for the future of medium and heavy duty vehicles. However, the combustion of an air-hydrogen mixture presents challenges related to the production of nitrogen oxides (NOx) and high knock tendency, mainly due to the chemical characteristics of the fuel. Although these problems can be mitigated by the use of a lean mixture, which is also useful to increase the combustion efficiency, the presence of excess air reduces exhaust temperatures and, consequently, the enthalpy content in the exhaust would be limited, leading to a reduced boosting capability. Therefore, a proper control of mixture preparation and combustion phasing is mandatory to limit NOx emissions, avoid abnormal combustions, and maximize efficiency without performance limitations.This paper focuses on the design of a dedicated control strategy for H2ICEs. Starting from a previously validated 1-D engine model operated with hydrogen, a 0-D Artificial Neural Network (ANN) - based engine model has been designed and calibrated. By using the obtained fast running ANN-based model, an innovative torque-based engine controller has been developed and both engine and controller models have been tested covering different torque profiles. The results show good accuracy within a range of ±5% on producing the requested torque by controlling the centre of combustion.

Trypanosoma cruzi infection modulates secreted phospholipase A2 expression in the salivary glands of Rhodnius prolixus

Phospholipases A2 (PLA2) comprise a superfamily of enzymes that specifically catalyze hydrolysis of the ester bond at the sn-2 position of glycerophospholipids, generating lysophospholipids and fatty acids. In Rhodnius prolixus, one of the main vectors of the Chagas's disease etiologic agent Trypanosoma cruzi, it was previously shown that lysophosphatidylcholine, a bioactive lipid, found in the insect's saliva, contributes to the inhibition of platelet aggregation, and increases the production of nitric oxide, an important vasodilator. Due to its role in potentially generating LPC, here we studied the PLA2 present in the salivary glands of R. prolixus. PLA2 activity is approximately 100 times greater in the epithelium than in the contents of salivary glands. Our study reveals the role of the RpPLA2XIIA gene in the insect feeding performance and in the fatty acids composition of phospholipids extracted from the salivary glands. Knockdown of RpPLA2XIIA significantly altered the relative amounts of palmitic, palmitoleic, oleic and linoleic acids. A short-term decrease in the expression of RpPLA2III and RpPLA2XIIA in the salivary glands of R. prolixus was evident on the third day after infection by T. cruzi. Taken together, our results contribute to the understanding of the role of PLA2 in the salivary glands of hematophagous insects and show that the parasite is capable of modulating even tissues that are not colonized by it.

Bioactives of the essential oil from the leaves of Eugenia pyriformis Cambess (Myrtaceae) on the effects of tobacco.

Lung cancer is the most commonly diagnosed and the main cause of cancer death, usually related to cigarette smoking. Furthermore, the microbiota of people exposed to cigarette smoke can be modified, making it difficult to eliminate opportunistic microorganisms. The leaves of Eugenia pyriformis are a by-product of fruit production and, to date, there have been no studies addressing the antiproliferative, anti-inflammatory, and antimicrobial activities. Investigate the antimicrobial, Nitric Oxide (NO)-production inhibition, and antiproliferative activities of the essential oil from E. pyriformis leaves and its possible effect on the treatment and prevention of damage caused by tobacco. The essential oil (EO) was obtained by hydrodistillation (3h). Its chemical composition was investigated by GC-MS. It was proposed to investigate antiproliferative activity against human tumor cell lines, namely, breast adenocarcinoma (MCF-7), lung (NCI-H460), cervical (HeLa), and hepatocellular (HepG2) carcinomas. A non-tumor primary culture from pig liver (PLP2) was also tested. The EO capacity to inhibit nitric oxide (NO) production was evaluated by a lipopolysaccharide stimulated murine macrophage cell line. Antibacterial and antifungal activities against opportunistic pathogens were investigated against seven strains of bacteria and eight fungi. The results indicated the presence of 23 compounds in the essential oil, the majority were spathulenol (45.63%) and β-caryophyllene oxide (12.72%). Leaf EO provided 50% inhibition of nitric oxide production at a concentration of 92.04µgmL-1. The EO also demonstrated antiproliferative activity against all human tumor cell lines studied, with GI50 values comprised between 270.86 and 337.25µgmL-1. The essential oil showed antimicrobial potential against the bacteria Listeria monocytogenes (Murray et al.) Pirie (NCTC 7973) and Salmonella Typhimurium ATCC 13311 (MIC 1870µgmL-1) and fungi Aspergillus versicolor ATCC 11730, Aspergillus ochraceus ATCC 12066, Penicillium ochrochloron ATCC 90288, Penicillium verrucosum var. cyclopium (Westling) Samson, Stolk & Hadlok (food isolate) (MIC 1870µgmL-1) and Trichoderma viride Pers. IAM 5061 (1,400µg mL-1). The demonstrated anti-inflammatory, antiproliferative, and antimicrobial activities in the leaves of E. pyriformis can add value to the production chain of this plant, being a possible option for preventing and combating cancer, including lung cancer.

Abietane Diterpenes from Medusantha martiusii and Their Anti-Neuroinflammatory Activity.

Seven new abietane diterpenoids, comprising medusanthol A-G (1-3, 5, 7-9) and two previously identified analogs (4 and 6), were isolated from the hexane extract of the aerial parts of Medusantha martiusii. The structures of the compounds were elucidated by HRESIMS, 1D/2D NMR spectroscopic data, IR spectroscopy, NMR calculations with DP4+ probability analysis, and ECD calculations. The anti-neuroinflammatory potential of compounds 1-7 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and the proinflammatory cytokine TNF-α in BV2 microglia stimulated with LPS and IFN-γ. Compounds 1-4 and 7 exhibited decreased NO levels at a concentration of 12.5 µM. Compound 1 demonstrated strong activity with an IC50 of 3.12 µM, and compound 2 had an IC50 of 15.53 µM; both compounds effectively reduced NO levels compared to the positive control quercetin (IC50 11.8 µM). Additionally, both compounds significantly decreased TNF-α levels, indicating their potential as promising anti-neuroinflammatory agents.

Cardiohemodynamic responses and heart rate variability following an active orthostatic test among male residents of the North with different NOS3 (rs2070744) genotypes

AIM: This study explored associations between the -786TC (rs2070744) genetic polymorphism of the NOS3 gene and the main indices of systemic hemodynamics and heart rate variability following an active orthostatic test in men living in the North. MATERIAL AND METHODS: Eighty-three healthy men aged 33.5±1.5 yеаrs on average, who were permanent residents of the Magadan Region, comprised the sample. The participants underwent both resting and active orthostatic testing modes. Cardiovascular system variables were recorded using an automatic tonometer. Hemodynamic indices were then calculated. Short-term heart rate variability in frequency and spectral areas was simultaneously measured using the Varikard hardsoft complex unit. Genotyping was conducted using polymerase chain reaction. The sample was then divided into two groups: Group 1 consisted of homozygotes with the TT genotype (n=34), while Group 2 comprised carriers of the NOS3*C allele variant (genotypes TC+CC) associated with reduced nitric oxide production (n=49). RESULTS: By examining the complex vasomotor, chrono- and inotropic reactions of hemodynamic and heart rate variables during the active orthostatic test, we were able to discern unique patterns in the response of the two groups under study. Men in Group 1 demonstrated an elevated cardiac output response during orthostatic changes, while maintaining consistent vascular resistance values. This was accompanied by a shift towards sympathetic autonomic activity and an increase in the very low-frequency component of heart rate variability. In Group 2, individuals with sympathetic insufficiency and increased vascular resistance during the orthostatic test showed a 35% increase in the low-frequency component of the cardiac rhythm reflecting the importance of this indicator as a stimulator of blood pressure rhythm fluctuations mediated by baroreflex mechanisms. CONCLUSION: Our findings suggest that men lacking the NOS3*С allele variant in their genotype demonstrate more favorable responses to the active orthostatic test. This may reflect higher level of cardiovascular functional reserves. The 786TC (rs2070744) polymorphism of the NOS3 gene can be considered as a marker of cardiohemodynamic status and autonomic regulations during functional exercise, such as an active orthostatic test.

Pro-angiogenic Terbium Hydroxide Nanorods Improve Critical Limb Ischemia in Part by Amelioration of Ischemia-Induced Endothelial Injury.

Critical limb ischemia (CLI) refers to a severe condition resulting from gradual obstruction in the supply of blood, oxygen, and nutrients to the limbs. The most promising clinical solution to CLI is therapeutic angiogenesis. This study explored the potency of pro-angiogenic terbium hydroxide nanorods (THNR) for treatment of CLI, with a major focus on their impact on ischemia-induced maladaptive alterations in endothelial cells as well as on vascularization in ischemic limbs. This study demonstrated that, in hypoxia-exposed endothelial cells, THNR improve survival and promote proliferation, migration, restoration of nitric oxide production, and regulation of vascular permeability. Based on molecular studies, these attributes of THNR can be traced to the stimulation of PI3K/AKT/eNOS signaling pathways. Besides, Wnt/GSK-3β/β-catenin signaling pathways may also play a role in the therapeutic actions of THNR. Furthermore, in the murine model of CLI, THNR administration can integrally re-establish blood perfusion with concomitant reduction of muscle damage and inflammation. Additionally, improvement of locomotor activities and motor coordination in ischemic limbs in THNR treated mice is also evident. Overall, the study demonstrates that THNR have the potential to be developed as an efficacious and cost-effective alternative clinical therapy for CLI, using a nanomedicine approach.

Impact of p-cresol on hydrogen sulfide and ammonia treatment by biotrickling filter and the production of nitrous oxide

Biotrickling filter (BTF) is often used for purification of waste gas from swine houses, with vital information still needed regarding interaction effects among multiple gas pollutants removal and also the formation of byproducts especially nitrous oxide (N2O, a strong greenhouse gas) due to the relative high NH3 concentration level compared to other gases. In this study, gas removal and N2O production were compared between two BTFs, where the inlet gas of BTF-1 contained NH3 and H2S while p-cresol was additionally supplied to BTF-2. At inlet load (IL) between 3.67 and 18.91 g m−3 h−1, removal efficiencies of NH3 exceeded 95% for both BTFs. As alternative strategy, adding thiosulfate improved H2S removal. Interestingly, presence of p-cresol to some extent promoted H2S removal at IL of 0.56 g m−3 h−1possibly due to effect on pH value of circulating solution. Similar to NH3, removal efficiencies of p-cresol were higher than 95% at an average IL of 2.98 g m−3 h−1. Gas residence time, pH of circulating solution and inlet loading were identified as key factors affecting BTF performance, but the response of individual gas compound to these factors was not consistent. Overall, p-cresol enhanced N2O generation although the effects were not always significant. High-throughput sequencing results showed that Proteobacteria accounted for the largest proportion of relative abundance and BTF-2 had much richer microbial diversity compared to BTF-1. Thermomonas, Comamonas, Rhodanobacter and other bacterial genus capable of denitrification were detected in both BTFs, and their corresponding abundances in BTF-2 (10.9%, 8.7% and 5.2%) were all greater than those in BTF-1 (0.4%, 0.3% and 2.0%), indicating that more denitrification may occur within BTF-2 and higher N2O could have been generated. This study provided evidence that organic gas components, served as carbon source, may increase the N2O production from BTF when treating waste gases containing NH3.

Combined therapeutic strategy based on blocking the deleterious effects of AGEs for accelerating diabetic wound healing

Abstract Diabetic foot ulcer is a serious complication of diabetes. Excessive accumulation of advanced glycation end products (AGEs) is one of the critical pathogenic factors in postponing diabetic wound healing. The main pathogenic mechanisms of AGEs include inducing cellular dysfunction, prolonging inflammatory response, increasing oxidative stress, and reducing endogenous nitric oxide (NO) production. Combination therapy of blocking the deleterious effects of AGEs and supplementing exogenous NO is hypothesized to promote diabetic wound healing. Here, we presented nanoparticles/hydrogel composite dressings to co-delivery rosiglitazone and S-nitroso glutathione into the wound bed. The designed co-delivery system augmented the survival of fibroblasts, reduced oxidative stress levels, reversed the change of mitochondrial membrane potential, and decreased the proinflammatory cytokine expression. Local sustained release of therapeutic agents significantly improved the wound healing of diabetic rats including increasing the wound closure rate, alleviating inflammation, promoting collagen fiber production and angiogenesis. Our finding indicated this local deliver strategy aimed at inhibiting the toxic effects of AGEs has great clinical potential for diabetic wound treatment.

The Factors Affecting the Stability of IOP Homeostasis.

Shear-induced nitric oxide (NO) production by Schlemm's canal (SC) endothelial cells provides a fast, IOP-sensitive feedback signal that normally contributes to IOP homeostasis. Our goal was to analyze the response of this homeostatic system under constant flow perfusion (as occurs in vivo) vs. constant pressure perfusion (as typical for laboratory perfusions). A mathematical model of aqueous humor dynamics, including shear-mediated NO signaling, was formulated and analyzed for stability. The model includes Goldmann's equation, accounting for proximal and distal outflow resistance, and describes how elevated IOP causes narrowing of SC lumen that increases the shear stress on SC cells. Elevated shear stress stimulates NO production, which acts to reduce outflow resistance and relax trabecular meshwork cells to decrease trabecular meshwork stiffness, affecting the SC luminal caliber. During constant flow perfusion, the outflow system is typically stable, returning to baseline IOP after a perturbation. In contrast, during constant pressure perfusion, the outflow system can become unstable and exhibit a time-dependent change in outflow resistance that diverges from baseline. The stability of shear mediated IOP homeostasis is predicted to differ critically between constant flow vs. constant pressure perfusion. Because outflow facility is typically measured at a constant pressure in the laboratory, this instability may contribute to the characteristic time-dependent increase in outflow facility, known as washout, observed in many nonhuman species. Studies of IOP homeostasis should consider how the outflow system may respond differently under constant pressure vs. constant flow perfusion.

Sarcanoids A and B, two new lindenane-type sesquiterpenoid dimers from the aerial parts of Sarcandra glabra

Sarcanoids A and B (1 and 2), two new lindenane-type sesquiterpenoid dimers with a γ-hydroxysenecioate moiety at C-15′, were isolated from the ethyl acetate extract of Sarcandra glabra. The structures were elucidated by extensive analysis of spectroscopic data, and their absolute configurations were determined by single-crystal X-ray crystallography. Compounds 1 and 2 showed moderate inhibitory activities on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages.

Citronellal improves endothelial dysfunction by affecting the stability of the GCH1 protein.

Endothelial dysfunction (ED) serves as the pathological basis for various cardiovascular diseases. Guanosine triphosphate cyclopyrrolone 1 (GCH1) emerges as a pivotal protein in sustaining nitric oxide (NO) production within endothelial cells, yet it undergoes degradation under oxidative stress, contributing to endothelial cell dysfunction. Citronellal (CT), a monoterpenoid, has been shown to ameliorate endothelial dysfunction induced by in atherosclerosis rats. However, whether CT can inhibit the degradation of GCH1 protein is not clear. It has been reported that ubiquitination may play a crucial role in regulating GCH1 protein levels and activities. However, the specific E3 ligase for GCH1 and the molecular mechanism of GCH1 ubiquitination remain unclear. Using data-base exploration analysis, we find that the levels of the E3 ligase Smad-ubiquitination regulatory factor 2 (Smurf2) negatively correlate with those of GCH1 in vascular tissues and HUVECs. We observe that Smurf2 interacts with GCH1 and promotes its degradation via the proteasome pathway. Interestingly, ectopic Smurf2 expression not only decreases GCH1 levels but also reduces cell proliferation and reactive oxygen species (ROS) levels, mostly because of increased GCH1 accumulation. Furthermore, we identify BH 4/eNOS as downstream of GCH1. Taken together, our results indicate that CT can obviously improve vascular endothelial injury in Type 1 diabetes mellitus (T1DM) rats and reverse the expressions of GCH1 and Smurf2 proteins in aorta of T1DM rats. Smurf2 promotes ubiquitination and degradation of GCH1 through proteasome pathway in HUVECs. We conclude that the Smurf2-GCH1 interaction might represent a potential target for improving endothelial injury.

Naturally occurring benzophenones and xanthones from Garcinia smeathmannii (Planch. & Triana) Oliv. displayed anti-inflammatory effects by modulating the activities of inflammatory mediators in LPS-stimulated RAW 264.7 macrophages.

Introduction: There is a growing interest in studying natural products for the identification of novel lead compounds for drug development for treating inflammatory diseases. Although some studies have focused anti-inflammatory activity of benzophenones and xanthones, exploring additional targets such as enzymes and cytokines, involved in their inflammatory response could provide more comprehensive understanding of the compounds' anti-inflammatory effects. In this study, four xanthones ananixanthone (1), smeathxanthone A (2), smeathxanthone B (3), and 1,3,5,8-tetrahydroxy-2-(3-methybut-2-enyl)-4-(3,7-dimethyloct-2,6-dienyl) xanthone (4); and three benzophenones guttiferone O (5), guttiferone M (6), and aristophenone A (7) from Garcinia smeathmannii (Planch. & Triana) Oliv. were investigated for their effect on nitric oxide production, cyclooxygenase, lipoxygenase inhibition, and Th1/Th2 cytokines production in activated RAW 264.7 macrophages. Methods: The Griess reagent method and the ferrous oxidation-xylenol orange assay were used to evaluate the inhibition of NO production and the 15-lipoxygenase activity respectively. Cyclooxygenase activity was assessed using the fluorometric COX activity assay kit and measurement of Th1/Th2 cytokines was performed using a flow cytometer. Results: All the tested compounds exhibited a dose-dependent inhibition of NO production with varying degrees of inhibitory effects on 15-LOX activity. Compound (6), displays the best inhibitory effect on COX-1/COX-2 activity. A general trend of the tested compounds on cytokines profiles revealed that compound (5) showed a pronounced enhancement of anti-inflammatory cytokines (IL-4 and IL-10). Conclusion: This observation supports future exploration of ananixanthone (1), guttiferone O (5), and guttiferone (6) as potential candidates for the development of anti-inflammatory drugs.

Metabolites of Culinary-medicinal Mushroom Hericium erinaceus Showed Anti-neuroinflammatory Activity in BV2 Cells and Anti-H2O2-induced Oxidative Stress Activity in SH-SY5Y Cells

Background: Hericium erinaceus is a versatile mushroom with potential therapeutic benefits. A variety of bioactive compounds have been found in this mushroom that have anti-ulcer, antiinflammatory, immunomodulatory, and blood sugar and lipid regulating effects. Objectives: The aim is to isolate and characterize compounds from the rice medium of H. erinaceus and evaluate their potential therapeutic effects on oxidative stress-associated diseases. Methods: Fifteen compounds were isolated and characterized using NMR spectra and ESI-MS. The effects of compounds 3 and 7 on LPS-induced nitric oxide (NO) generation in BV2 cells and H2O2- induced cytotoxicity in SH-SY5Y cells were investigated. The regulation of nitric oxide production and apoptosis-associated proteins Bcl-2 and Bax were also examined. Results: Compounds 3 and 7 exhibited potent inhibitory effects on LPS-induced NO generation in microglial cells and significant resistance to H2O2-induced cytotoxicity in neuronal cells. Molecular docking simulations demonstrated the interaction of compounds 3 and 7 with iNOS and Bax, respectively. Western blot analysis revealed that 7 inhibited NO production and regulated the expression of Bax and Bcl-2, suggesting a protective effect against H2O2-induced apoptosis. Conclusion: Compounds 3 and 7 isolated from H. erinaceus are potential therapeutic candidates for oxidative stress-associated diseases, possibly through their regulation of nitric oxide production and apoptosis-related proteins. Further investigations are warranted to elucidate their mechanisms of action and therapeutic potential.

Anti-Inflammatory Effects of Paraprobiotic Lactiplantibacillus plantarum KU15122 in LPS-Induced RAW 264.7 Cells.

Inflammation is a biodefense mechanism that provides protection against painful conditions such as inflammatory bowel disease, other gastrointestinal problems, and irritable bowel syndrome. Paraprobiotics have probiotic characteristics of intestinal modulation along with merits of safety and stability. In this study, heat-killed Lactiplantibacillus plantarum KU15122 (KU15122) was investigated for its anti-inflammatory properties. KU15122 was subjected to heat-killed treatment for enhancement of its safety, and its concentration was set at 8 log CFU/mL for conducting different experiments. Nitric oxide production was most remarkably reduced in the KU15122 group, whereas it was increased in the LPS-treated group. In RAW 264.7 cells, KU15122 inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. ELISA revealed that among the tested strains, KU15122 exhibited the most significant reduction in PGE2, IL-1β, and IL-6. Moreover, KU15122 inhibited various factors involved in the nuclear factor-kappa B, activator protein-1, and mitogen-activated protein kinase pathways. In addition, KU15122 reduced the generation of reactive oxygen species. The anti-inflammatory effect of KU15122 was likely attributable to the bacterial exopolysaccharides. Conclusively, KU15122 exhibits anti-inflammatory potential against inflammatory diseases.

Connecting GSK-3β Inhibitory Activity with IKK-β or ROCK-1 Inhibition to Target Tau Aggregation and Neuroinflammation in Alzheimer's Disease-Discovery, In Vitro and In Cellulo Activity of Thiazole-Based Inhibitors.

GSK-3β, IKK-β, and ROCK-1 kinases are implicated in the pathomechanism of Alzheimer's disease due to their involvement in the misfolding and accumulation of amyloid β (Aβ) and tau proteins, as well as inflammatory processes. Among these kinases, GSK-3β plays the most crucial role. In this study, we present compound 62, a novel, remarkably potent, competitive GSK-3β inhibitor (IC50 = 8 nM, Ki = 2 nM) that also exhibits additional ROCK-1 inhibitory activity (IC50 = 2.3 µM) and demonstrates anti-inflammatory and neuroprotective properties. Compound 62 effectively suppresses the production of nitric oxide (NO) and pro-inflammatory cytokines in the lipopolysaccharide-induced model of inflammation in the microglial BV-2 cell line. Furthermore, it shows neuroprotective effects in an okadaic-acid-induced tau hyperphosphorylation cell model of neurodegeneration. The compound also demonstrates the potential for further development, characterized by its chemical and metabolic stability in mouse microsomes and fair solubility.

Does water transparency control the banding in shallow water iron formations?

Abstract Iron formations (IFs) are marine chemical sediments that are conined to the Precambrian rock record and provide unique insights into the co-evolution of the atmosphere-hydrosphere and biosphere through almost three billion years of Earth’s history. IFs commonly appear throughout the Archaean until the Palaeoproterozoic ca. 1.8 billion years ago and re-appear during the “Snowball Earth” epoch in the Neoproterozoic. The formation and deposition mechanism(s) of IFs are, however, still incompletely understood, hindering unique interpretations of palaeoenvironments. Many IFs are banded iron formations (BIFs) with layer thickness of alternating Fe- and Si-rich layers ranging over several orders of magnitude from the nanometre to the metre scale. A second textural type, so called granular iron formations (GIFs) that form above storm wave base become widespread in the Palaeoproterozoic. Understanding the fundamental mechanisms that are responsible for the textural types and the periodicity of banding in BIFs is crucial to link these features to the environmental and geochemical evolution of the Earth. We here provide a conceptual model that highlights the role of changing light conditions and water transparency for Iron Formation (IF) precipitation. We show that the model is particularly feasible for IFs deposited in shallow waters but may also be applicable for some IFs deposited in deeper water settings. The model builds on other primary Banded Iron Formation (BIF) precipitation models postulating that Fe(III)-(oxyhydr)oxide production can be dominated by anoxygenic photoautotrophic Fe2+-oxidising bacteria. These so called photoferrotrophs are adapted to very low light levels corresponding to about 1% of the light level required by oxygen-producing phototrophs allowing them to thrive deep down in the water column. The depth of Fe(III)-(oxyhydr)oxide production is mainly controlled by water turbidity which controls how deep photosynthetically available radiation (PAR) penetrates the water column. Eutrophic conditions result in relatively shallow Fe(III)-(oxyhydr)oxide production depth due to turbidity either induced by the biomass itself and/or by particles that are actively or passively produced by microorganisms (e.g., Fe(III) and Mn(IV)-(oxyhydr)oxides, sulphides), triggering the formation of Fe-rich bands. During oligotrophic stages, Fe(III)-(oxyhydr)oxides are only produced relatively deep down in the water column, so that only silica-rich bands form in the Fe(III)-(oxyhydr)oxide free upper water column. Reactive transport modelling adopted from Ozaki et al., (2019) shows that besides upwelling and nutrient supply, alternating Fe(III) production depth is mainly associated with changing light conditions as a result of water transparency. Periodicities reflected by alternating Fe- and Si-rich bands in IFs in our model can thus be associated with: (1) nutrient supply patterns; (2) additional sources of turbidity in the water column such as Fe(III) and Mn(IV) oxide particles, sulphides, and wind-blown silicate particles; or (3) formation and clearing of organic haze in the atmosphere. One or all of these reasons for low light conditions seem to become more important in the Palaeoproterozoic (&amp;lt;2.4 Ga) and could be partly responsible for the more widespread occurrences of shallow marine granular IFs relative to former epochs, which is often assigned to the gradual oxidation of the ocean. Our model shows that variable water transparency should be considered as additional factor for IF deposition especially for shallow marine settings. This model also reasonably explains the prominent layering in BIFs as syn-depositional feature.