Oxide Production Research Articles

The Role of Glutamine Synthetase on the Sensitivity to Radiotherapy of Hepatocellular Carcinoma.

The objective of this study was to investigate the relationship between radiotherapy sensitivity, glutamine synthetase (GS), and oxidative stress (OS) in human hepatocellular carcinoma (HCC) cells. HCC cells were X-ray irradiated, and the effect of glutamine synthetase inhibition on the proliferative capacity of HCC cells was examined using the CCK-8 colony formation assay. Real-time quantitative PCR assays were used to detect the effect of L-methionine sulfoximine (MSO) on cellular glutamine synthetase expression levels and the efficiency of glutamine synthetase knockdown in HepG2 cells. Glutamine synthetase activity assay kit was used to detect the viability of glutamine synthetase in cells and tissues. Oxidative stress production was assayed using an oxidative stress assay kit. Subcutaneous xenografts were used to detect the effects of L-methionine sulfoximine and radiation on tumor growth invivo. The results showed that the apparent cell proliferation capacity of HCC cells after glutamine synthetase inhibition was significantly reduced after radiotherapy, which was closely related to the increased production of oxidative stress after radiotherapy. Furthermore, the results of animal experiments also showed that the combination of L-methionine sulfoximine and radiation induced a stronger tumor suppressive effect and that L-methionine sulfoximine could act as a radiosensitizer after radiotherapy.

Critical review on the derivative of graphene with binary metal oxide-based nanocomposites for high-performance supercapacitor electrodes

Abstract Supercapacitors, owing to their high power density and rapid charge–discharge capabilities, have gained significant attention as energy storage devices in various applications. In the context of electrochemical supercapacitors, this article provides a comprehensive review of the production and electrochemical performance of binary metal oxide (BMO) and reduced graphene oxide (rGO) composite materials. The synthesis processes and synergistic benefits of BMO–rGO composites, with an emphasis on how they perform better than separate parts in terms of specific capacitance and cycle stability, are discussed. The potential of BMO–rGO composites as high-performance electrode materials for supercapacitors is highlighted in this research. In the context of electrochemical supercapacitors, this work provides a comprehensive review of the production and electrochemical performance of binary transition metal oxide (TMO) and rGO composite materials. Composite materials with enhanced electrochemical characteristics that are appropriate for supercapacitor applications are the primary novelty, which is the synergistic combination of rGO with a variety of TMOs. Compared to individual TMOs or other carbonaceous materials, these composites demonstrate enhanced specific capacitance, energy density, power density, cyclic stability, and rate capability. The synthesis processes and synergistic benefits of BMO–rGO composites are discussed, with an emphasis on their superior performance in specific capacitance and cycle stability compared to individual components. This research highlights the potential of BMO–rGO composites as high-performance electrode materials for supercapacitors, showcasing their enhanced specific capacitance, improved charge storage capacity, increased power density, excellent cycling stability, and overall durability even after numerous charge–discharge cycles.

Processes and microorganisms driving nitrous oxide production in the Benguela Upwelling System

AbstractUpwelling systems and their associated oxygen deficient zones (ODZs) are hotspots of nitrous oxide (N2O) production in the ocean. The Benguela Upwelling System (BUS) is a highly productive region and an important, yet variable source of N2O to the atmosphere. This study examined underlying processes and microbial key players governing N2O production in the BUS during the austral winter. 15N‐tracer incubation experiments were conducted to track N2O production from NH4+ oxidation and denitrification. N2O production and consumption mechanisms over a longer temporal scale were determined through natural‐abundance isotope analyses. Metagenomics and 16S rRNA gene amplicon sequencing were used to identify potential key prokaryotes driving N2O production. Our results showed that, compared with permanent ODZs, the BUS is characterized by a higher oxidative and a lower reductive N2O production, both of which exhibit substantial spatial variability. N2O production peaked in low‐oxygen (O2) waters, with nearly equal contributions of oxidative and reductive processes, suggesting their co‐occurrence across an O2 concentration range broader than previously thought. However, the observed N2O isotope signatures implied a legacy of recent and extensive N2O reduction to N2. Metagenomic and 16S rRNA gene data identified denitrifiers belonging to Thioglobaceae and the archaeal ammonia‐oxidizers Nitrosopumilaceae among the potential key drivers of N2O production. Our study provides a comprehensive picture of N2O production in the BUS, revealing significant variability in the N‐cycling regime and underlying N2O production mechanisms, and demonstrating the value of combining direct rate measurements with more integrative approaches, such as molecular omics and natural‐abundance stable isotope tracers.

TGG1 and TGG2 mutations impair allyl isothiocyanate-mediated stomatal closure in Arabidopsis thaliana.

Myrosinase, referred to as thioglucoside glucohydrolase (TGG), plays a crucial role in plant physiology through catalyzing the hydrolysis of glucosinolates into bioactive isothiocyanates. In Arabidopsis thaliana, the myrosinases TGG1 and TGG2 are essential for abscisic acid- and methyl jasmonate-induced stomata closure. Allyl isothiocyanate (AITC), one of myrosinase products, triggers stomatal closure in A. thaliana. We investigated stomatal responses to AITC to clarify the role of TGG1 and TGG2 in Arabidopsis guard-cell signaling. Allyl isothiocyanate at 50μM and 100μM induced stomatal closure in the tgg1 and tgg2 single mutants but not in the tgg1 tgg2 double mutant. Furthermore, AITC at 50μM induced the production of reactive oxygen species and nitric oxide, cytosolic alkalization, and oscillations in cytosolic free calcium concentration in guard cells of both wild-type and mutant plants. These findings suggest that TGG1 and TGG2 are involved in AITC signaling pathway through interaction with signal component(s) downstream of these signaling events, which is not accompanied by hydrolysis of glucosinolates because of the difference in subcellular localization between enzymes (myrosinases) and substrates (glucosinolates).

Effect of different moisture content on nitrous oxide production in aggregated soil of Shintoku, Japan

Agricultural soils are the major source of the potent greenhouse gas and ozone-depleting substance, N2O. An incubation study was carried out using the volcanic ash fine textured soil of Shintoku. Soil samples used in this study were taken from managed grassland at Shintoku Experimental Livestock Farm of Hokkaido University in Southern Hokkaido, Japan (N43º05′, E142º51′). Soil aggregates were air-dried, and sieved with 4.5 mm and 2 mm and adjusted the soil moisture of 60% and 80% of field water capacity (FWC). Just after the moistening, the aggregates were incubated for 9 days under a temperature of 20°C. Just after starting the incubation, the flush of N2O production was observed. Similar flushes of carbon dioxide (CO2) and nitric oxide (NO) productions were also observed. All of the gas productions were higher in larger aggregates with 80% of field water capacity. The concentrations of Water Extractable Organic Carbon (WEOC), NH4+-N, pH and total N were significantly different before and after incubation. Shintoku soil showed a significant correlation between before and after incubation for all soil chemical properties except pH. Especially WEOC and NH4+-N changed immediately after the addition of water and this situation continued during the incubation. Larger aggregates showed higher amounts of NH4+-N and NO3-–N and were responsible for higher N2O production compared to smaller aggregates. In Shintoku the results of N2O-N/NO-N ratio in both moisture contents indicated nitrification as a main process of N2O production. It is very well known that N2O is produced more from the denitrification process than nitrification. Poor aeration and less diffusion of NO3-N and WEOC from the aerobic area to the anaerobic area reduce N2O production in the denitrification process of fine textured Shintoku soil. Int. J. Agril. Res. Innov. Tech. 14(2): 99-110, December 2024

Isobavachin attenuates FcεRI-mediated inflammatory allergic responses by regulating SHP-1-dependent Fyn/Lyn/Syk/Lck signaling

Isobavachin, isolated from Psoralea corylifolia L. exhibits therapeutic potential for osteoporosis or skin disease. Here, we evaluated the pharmacological effects of isobavachin on IgE-dependent inflammatory allergic reactions, as well as the underlying mechanisms, in bone marrow-derived mast cells and a mouse model of passive cutaneous anaphylaxis (PCA). Isobavachin reduced IgE/Ag-stimulated degranulation, eicosanoid (leukotriene C4 and prostaglandin D2) generation, and release of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin (IL)-6). Mechanistic studies revealed that isobavachin suppressed activation of Fyn, Lyn, spleen tyrosine kinase (Syk), and lymphocyte-specific-protein-kinase (Lck), receptor-proximal tyrosine kinases that initiate and play a central role in FcɛRI-mediated mast cell activation, as well as their common downstream signaling molecules including linker for activation of T cells, phospholipase Cγ1, AKT, mitogen-activated protein kinases (MAPKs), and intracellular Ca2+. Additionally, isobavachin increased phosphorylation of Src homology region 2 domain-containing phosphatase-1 (SHP-1), thereby strengthening its interaction with Syk and Lck as well as Fyn and Lyn, resulting in de-phosphorylation of these proximal tyrosine kinases. Genetic knockdown of SHP-1 reversed the inhibitory effects of isobavachin on mast cell activation, as well as the related signaling pathways, indicating that the inhibitory effects of isobavachin are mediated by negative regulation of SHP-1-dependent Fyn, Lyn, Syk and Lck. The anti-inflammatory properties of isobavachin were also examined in macrophages. Isobavachin suppressed production of lipopolysaccharide-stimulated production of pro-inflammatory cytokines and nitric oxide. Furthermore, oral administration of isobavachin attenuated mast cell-mediated PCA reactions in mice. These results suggest that isobavachin is a potential treatment for mast cell-mediated allergic inflammatory diseases.

Scalable and cost-effective ultra-dispersible graphene oxide blended ultrafiltration mixed matrix membrane: Assessment of mechanical, water flux, and anti-biofouling properties

Graphene oxide-modified pressure-driven membranes are attractive due to their enhanced water flux and mechanical properties. However, the large-scale use of membranes such as ultra-filtration (UF) is hindered due to the challenges in bulk production of graphene oxide at an affordable cost. The present work reports the application of ultra-dispersible graphene oxide (UDGO) synthesized through a single-step scalable approach in fabricating UF membranes. Compared to Hummers' graphene oxide, the UDGO is highly dispersed in solvents and is 8-10 times more cost-effective. Various microscopic and macroscopic studies were performed to study the physicochemical properties of UDGO and UDGO-modified UF membranes. The influence of UDGO content on the membrane efficiency and anti-fouling potential was elucidated. The UDGO-modified UF membranes showed ~18% enhancement in flux and ~64% increment in protein rejection compared to pristine membranes. The modified membranes also showed a ~20% greater flux recovery ratio and ~60% lesser bovine serum albumin adsorption, indicating a better level of anti-fouling potential. The higher biofilm inhibition potential of UDGO with an increase in dead biomass makes it a potential candidate for developing anti-biofouling membranes with enhanced water flux.

Structure Modulation and Self-Lubricating Properties of Porous TiN–MoS2 Composite Coating Under Humidity–Fluctuating Conditions

To improve the friction performance and service life of protective coatings in humidity-fluctuating environments, porous hard titanium nitride (TiN)–molybdenum disulfide (MoS2) composite coatings were prepared by using direct current magnetron sputtering (DCMS) with the mode of oblique angle deposition (OAD) and chemical vapor deposition (CVD) technologies. The structure and chemical component were characterized by field emission scanning electron microscopy (FESEM), energy dispersive spectrometer (EDS), grazing incidence X-ray diffraction (GIXRD), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. The tribological properties of these TiN–MoS2 composite coatings were investigated. The results indicate that the porous TiN–MoS2 composite coating exhibited outstanding friction performance and long service life under humidity-fluctuating environments. At the initial 20% relative humidity (RH) stage, the MoS2 on the porous TiN–MoS2 composite coating surface worked as an effective lubricant; thus, the coating demonstrated excellent lubrication performance, and the friction coefficient (COF) was about 0.05. As the humidity was alternated to 70% RH, the lubrication effect diminished due to the production of molybdenum oxide (MoO3), and the COF was about 0.2, which was attributed to the degradation of MoS2 on the wear track and the release of fresh MoS2 from the porous TiN matrix. After the environmental conditions shifted from 70% to 20% RH, the MoO3 was removed, and the lubrication effect was restored. In summary, TiN–MoS2 porous composite coating offers a promising approach for lubrication in humidity-fluctuating environments.

Applications of L-Arginine in Pregnancy and Beyond: An Emerging Pharmacogenomic Approach.

L-arginine is a semi-essential amino acid that plays a critical role in various physiological processes, such as protein synthesis, wound healing, immune function, and cardiovascular regulation. The use of L-arginine in pregnancy has been an emerging topic in the field of pharmacogenomics. L-arginine, an amino acid, plays a crucial role in the production of nitric oxide, which is necessary for proper placental development and fetal growth. Studies have shown that L-arginine supplementation during pregnancy can have positive effects on fetal growth, maternal blood pressure, and the prevention of preeclampsia. This emerging pharmacogenomic approach involves using genetic information to personalize L-arginine dosages for pregnant women based on their specific genetic makeup. By doing so, it may be possible to optimize the benefits of L-arginine supplementation during pregnancy and improve pregnancy outcomes. This paper emphasizes the potential applications of L-arginine in pregnancy and the use of pharmacogenomic approaches to enhance its effectiveness. Nonetheless, the emerging pharmacogenomic approach to the application of L-arginine offers exciting prospects for the development of novel therapies for a wide range of diseases.

Repeated social defeat in male mice induced unique RNA profiles in projection neurons from the amygdala to the hippocampus

Chronic stress increases the incidence of psychiatric disorders including anxiety, depression, and posttraumatic stress disorder. Repeated Social Defeat (RSD) in mice recapitulates several key physiological, immune, and behavioral changes evident after chronic stress in humans. For instance, neurons in the prefrontal cortex, amygdala, and hippocampus are involved in the interpretation of and response to fear and threatful stimuli after RSD. Therefore, the purpose of this study was to determine how stress influenced the RNA profile of hippocampal neurons and neurons that project into the hippocampus from threat appraisal centers. Here, RSD increased anxiety-like behavior in the elevated plus maze and reduced hippocampal-dependent novel object location memory in male mice. Next, pan-neuronal (Baf53b-Cre) RiboTag mice were generated to capture ribosomal bound mRNA (i.e., active translation) activated by RSD in the hippocampus. RNAseq revealed that there were 1,694 differentially expressed genes (DEGs) in hippocampal neurons after RSD. These DEGs were associated with an increase in oxidative stress, synaptic long-term potentiation, and neuroinflammatory signaling. To further examine region-specific neural circuitry associated with fear and anxiety, a retrograde-adeno-associated-virus (AAV2rg) expressing Cre-recombinase was injected into the hippocampus of male RiboTag mice. This induced expression of a hemagglutinin epitope in neurons that project into the hippocampus. These AAV2rg-RiboTag mice were subjected to RSD and ribosomal-bound mRNA was collected from the amygdala for RNA-sequencing. RSD induced 677 DEGs from amygdala projections. Amygdala neurons that project into the hippocampus had RNA profiles associated with increased synaptogenesis, interleukin-1 signaling, nitric oxide, and reactive oxygen species production. Using a similar approach, there were 1,132 DEGs in neurons that project from the prefrontal cortex. These prefrontal cortex neurons had RNA profiles associated with increased synaptogenesis, integrin signaling, and dopamine feedback signaling after RSD. Collectively, there were unique RNA profiles of stress-influenced projection neurons and these profiles were associated with hippocampal-dependent behavioral and cognitive deficits.

Coupling of mitochondrial state with active zone plasticity in early brain aging

Neurodegenerative diseases typically emerge after an extended prodromal period, underscoring the critical importance of initiating interventions during the early stages of brain aging to enhance later resilience. Changes in presynaptic active zone proteins ("PreScale") are considered a dynamic, resilience-enhancing form of plasticity in the process of early, still reversible aging of the Drosophila brain. Aging, however, triggers significant changes not only of synapses but also mitochondria. While the two organelles are spaced in close proximity, likely reflecting a direct functional coupling in regard to ATP and Ca2+ homeostasis, the exact modes of coupling in the aging process remain to understood.We here show that genetic manipulations of mitochondrial functional status, which alters brain oxidative phosphorylation, ATP levels, or the production of reactive oxygen species (ROS), can bidirectionally regulate PreScale during early Drosophila brain aging. Conversely, genetic mimicry of PreScale resulted in decreased oxidative phosphorylation and ATP production, potentially due to reduced mitochondrial calcium (Ca2+) import.Our findings indicate the existence of a positive feedback loop where mitochondrial functional state and PreScale are reciprocally coupled to optimize protection during the early stages of brain aging.

Co-occurrence of cadmium and ciprofloxacin in environmental media decreases ciprofloxacin degradation by biogenic manganese oxides.

The coexistence of antibiotics with heavy metals is detrimental to humans and the environment. In urban water environments, Cadmium (Cd) and ciprofloxacin (CIP) frequently co-occur. Biogenic manganese oxides (BMOs) are a promising environmental bioremediation material due to their remarkable adsorption and oxidation properties. However, BMOs' removal mechanism in an environment where Cd and CIP co-occur is not yet unknown. We identified a manganese (Mn)-oxidising bacterium, Bacillus sp. XM02, with a strong ability for Mn (II) oxidation (85.23%) and BMOs production, and investigated its competitive removal mechanism in an environment with Cd and CIP co-occurrence. The BMOs exhibited a glorious CIP degradation ability and led to a marked decrease in the toxicity of CIP following oxidative degradation in Escherichia coli experiments. In contrast, in the co-existence of Cd and CIP, Cd hindered CIP removal by BMOs, but CIP did not affect Cd removal. Kinetic experiments combined with XPS characterisation revealed that the k value of Cd (297.39 h-1) was much higher than that of CIP (5.53 h-1), demonstrating that Cd was immediately adsorbed onto the surface of BMOs through a Cd-O bond. The surface potentials of BMOs carrying Cd alone and both Cd and CIP on the surface were similar, revealing that the electronegativity of Cd-carrying BMOs was greatly weakened (from -34.8mV to -21 mV/-23 mV), which further reduced the BMOs' electrostatic interaction with CIP. Moreover, the concentration of dissolved Mn (III) in the co-existence group was lower than that in the CIP alone, indicating that the presence of Cd reduced the transformation of Mn (IV) to Mn (III) by BMOs. Consequently, Cd attenuated the effect of active Mn (IV) sites of BMOs on CIP's piperazine ring oxidative degradation. These results offer a theoretical direction for the use of BMOs to reduce the risk posed by antibiotics and heavy metals pollution in co-occurrence environments.

Essential role of sulfide oxidation in brain health and neurological disorders.

Hydrogen sulfide (H2S) is an environmental hazard well known for its neurotoxicity. In mammalian cells, H2S is predominantly generated by transsulfuration pathway enzymes. In addition, H2S produced by gut microbiome significantly contributes to the total sulfide burden in the body. Although low levels of H2S is believed to exert various physiological functions such as neurotransmission and vasomotor control, elevated levels of H2S inhibit the activity of cytochrome c oxidase (i.e., mitochondrial complex IV), thereby impairing oxidative phosphorylation. To protect the electron transport chain from respiratory poisoning by H2S, the compound is actively oxidized to form persulfides and polysulfides by a mitochondrial resident sulfide oxidation pathway. The reaction, catalyzed by sulfide:quinone oxidoreductase (SQOR), is the initial and critical step in sulfide oxidation. The persulfide species are subsequently oxidized to sulfite, thiosulfate, and sulfate by persulfide dioxygenase (ETHE1 or SDO), thiosulfate sulfurtransferase (TST), and sulfite oxidase (SUOX). While SQOR is abundantly expressed in the colon, liver, lung, and skeletal muscle, its expression is notably low in the brains of most mammals. Consequently, the brain's limited capacity to oxidize H2S renders it particularly sensitive to the deleterious effects of H2S accumulation. Impaired sulfide oxidation can lead to fatal encephalopathy, and the overproduction of H2S has been implicated in the developmental delays observed in Down syndrome. Our recent findings indicate that the brain's limited capacity to oxidize sulfide exacerbates its sensitivity to oxygen deprivation. The beneficial effects of sulfide oxidation are likely to be mediated not only by the detoxification of H2S but also by the formation of persulfide, which exerts cytoprotective effects through multiple mechanisms. Therefore, pharmacological agents designed to scavenge H2S and/or enhance persulfide levels may offer therapeutic potential against neurological disorders characterized by impaired or insufficient sulfide oxidation or excessive H2S production.

Comparing sewage sludge vs. digested sludge for starting-up thermophilic two-stage anaerobic digesters: Operational and economic insights.

Despite advances in anaerobic digestion (AD), full-scale implementation faces significant challenges, particularly during the start-up phase, where inoculum selection is crucial. This study examines the impact of inoculum choice on the operational and economic performance of thermophilic digesters during the start-up phase. Methanogenic reactors R3 and R4 were inoculated with digested sludge (DiS) and diluted sewage sludge (DSS), respectively, and fed with hydrolyzed source-sorted organic fraction of municipal solid waste (SS-OFMSW) and thickened sewage sludge, which were processed in R1 and R2, serving as acidogenic reactors. A two-stage AD configuration was employed to mitigate inhibitory effects associated with the undigested inoculum (DSS). This approach enabled the establishment of methanogenic activity in R4 when the AD system is initiated with DSS. However, R3 outperformed R4, achieving 49 % of the feedstock's theoretical methane potential compared to 15 % in R4. Methane production and volatile solids (VS) processing costs in R4 were 18 and 3 times higher than in R3, respectively. R3's superior performance was attributed to DiS's diverse bacterial community, with over 66 % of genera involved in hydrolysis, volatile fatty acid production, and syntrophic methane production. In contrast, DSS was dominated by Trichococcus and Lactococcus (75.4 %), primarily involved in butyrate oxidation and lactate production. This study provides valuable insights into effective inoculum selection for the start-up of full-scale digesters.

In vitro and in vivo anti-inflammatory and antinociceptive activities of a synthetic hydrangenol derivative: 5-hydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one.

In the present study, we developed and synthesized novel hydrangenol derivatives and featured their anti-inflammatory activities. Especially, a synthetic derivative 11 (compound 11), which possesses the 4H-1-benzopyran-4-one moiety, 5-hydroxyl group in A-ring, and 4'-hydroxyl group in B-ring, most dominantly downregulated nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. In addition, compound 11 suppressed the inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) expression by inhibiting nuclear factor kappa-B (NF-κB), activator protein 1 (AP-1), and signal transducer and activator of transcription protein (STAT) pathways in LPS-provoked RAW264.7 macrophages. Additionally, we confirmed that compound 11 had better plasma stability than hydrangenol with a plasma-labile δ-valerolactone moiety. In carrageenan-induced rats, compound 11 potently reduced paw inflammation (as measured by paw volume, width, and thickness) by inhibiting the iNOS and COX-2 expression in paw tissue, thereby reducing inflammatory pain. All things considered, as compound 11 shows anti-inflammatory and antinociceptive properties, converting metabolically unstable hydrangenol into a stable compound 11 could be a promising strategy for developing new drugs.

Biosafety and Efficacy Studies of Colchicine-Encapsulated Liposomes for Ocular Inflammatory Diseases.

Inflammation is a critical component in the progression of various ocular diseases, such as age-related macular degeneration, diabetic retinopathy, and uveitis, leading to significant vision loss. Colchicine has been used for treating gout with its anti-inflammatory effect. However, free colchicine demonstrated cytotoxicity to ocular cells and cannot directly be used for eye disease. Thus, this study introduces, for the first time, the development and use of colchicine-encapsulated liposomes as a novel therapeutic approach for managing inflammation-driven ocular conditions. The encapsulation of colchicine within liposomes represents a significant innovation, aimed at enhancing biocompatibility and therapeutic efficacy while minimizing cytotoxic effects associated with free colchicine. Our research synthesized colchicine-loaded liposomes and assessed their therapeutic impact on human monocytes, macrophages, and retinal pigment epithelium (RPE) cells in an inflammatory environment. The findings reveal a groundbreaking improvement in treatment strategies, with a substantial reduction in TNF-alpha-induced reactive oxygen species (ROS) and nitric oxide (NO) production in RPE cells. Moreover, the colchicine-loaded liposomes significantly inhibited the proliferation and ROS production in activated monocytes and macrophages and effectively decreased interleukin (IL)-1β and IL-6 secretion, highlighting their strong anti-inflammatory properties and showed slightly better suppression of these two cytokines than dexamethasone-liposomes.

Connexin 43 Affects Pulmonary Artery Reactivity via Changes in Nitric Oxide Production and Influences Proliferative and Migratory Responses in Mouse Pulmonary Artery Fibroblasts

Pulmonary hypertension (PH) is a complex condition characterized by pulmonary artery constriction and vascular remodeling. Connexin 43 (Cx43), involved in cellular communication, may play a role in PH development. Cx43 heterozygous (Cx43+/−) mice show partial protection against hypoxia-induced pulmonary remodeling, with prior research highlighting its role in rat pulmonary artery fibroblast (PAF) proliferation and migration. However, inhibiting Cx43 may compromise nitric oxide (NO)-mediated vascular relaxation. This study evaluated the effects of Cx43 on mouse PAF (MPAF) proliferation, migration, NO-dependent and independent pulmonary vascular relaxation, and NO synthesis. Proliferation and migration were assessed in Cx43+/− MPAFs under normoxic and hypoxic conditions. Vascular responses were analyzed in intra-lobar pulmonary artery rings with acetylcholine (ACh), SNAP, and U46619, while NO production was measured in lung tissue. Both genetic knockdown and pharmacological inhibition of Cx43 significantly reduced serum-induced proliferation but not migration under normoxia, while 37,43Gap27 inhibited hypoxia-induced proliferation and migration. The effects of genetic knockdown and pharmacological inhibition of Cx43 on vascular reactivity were also investigated. NO-dependent and independent relaxations and NO production were reduced in Cx43+/− mice by 37,43Gap27. In conclusion, while Cx43 inhibition may protect against PAF proliferation and migration, it could also impair pulmonary vascular relaxation, at least in part through a reduction in NO signaling. Further studies are needed to fully understand the mechanisms by which Cx43 influences NO signaling.

Alkaloids from Dendrobium nobile and their anti-inflammatory activities

To identify anti-inflammatory alkaloids, we investigated the aerial parts of cultivated Dendrobium nobile Lindl. Thirteen alkaloids, including a new one, were isolated from the chloroform extract, and their structures were determined using spectroscopic methods. Bioassays assessed the anti-inflammatory activities of these isolates. Compounds 1 and 9 demonstrated inhibition of nitric oxide production in LPS-activated RAW264.7 macrophages, with IC50 values of 16.7μM and 24.4μM, respectively.

Characterization of tripartite motif containing 59 (TRIM59) in Epinephelus akaara: Insights into its immune involvement and functional properties in viral pathogenesis, macrophage polarization, and apoptosis regulation

The tripartite motif-containing (TRIM) superfamily is the largest family of RING-type E3 ubiquitin ligases that is conserved across the metazoan kingdom. Previous studies in mammals have demonstrated that TRIM59 possesses ubiquitin-protein ligase activity and acts as a negative regulator of NF-κB signaling. However, TRIM59 has rarely been characterized in fish. This study aimed to characterize TRIM59 from Epinephelus akaara (Eatrim59) and elucidate its structural features, expression patterns, and functional properties in innate immune responses and in the regulation of apoptosis. Eatrim59 is composed of 406 amino acids with a molecular weight of 45.84 kDa and a theoretical isoelectric point of 5.25. It comprises a conserved RING domain, a B-box motif, and a coiled-coil region. Subcellular localization analysis revealed that Eatrim59 was localized in the endoplasmic reticulum. Eatrim59 was ubiquitously expressed in all tissues examined, with the highest relative expression detected in the blood, followed by the brain and spleen. Temporal expression of Eatrim59 was dynamically regulated in response to in vivo immune stimulation by Toll-like receptor ligands and nervous necrosis virus infection. In FHM cells overexpressing Eatrim59, an increase in viral replication was observed upon infection with the Viral hemorrhagic septicemia virus. This phenomenon is attributed to Eatrim59-mediated downregulation of interferon, pro-inflammatory cytokines, and other antiviral pathways. Moreover, macrophages stably overexpressing Eatrim59 exhibited a decrease in nitric oxide production and the formation of a filamentous actin structure upon lipopolysaccharide stimulation, indicating dampened M1 polarization. Furthermore, a decrease in apoptosis was observed in Eatrim59-overexpressing FHM cells under oxidative stress induced by H2O2. In conclusion, these findings demonstrate the multifaceted role of Eatrim59 as a regulator of innate immune response and apoptosis in E. akaara.

Spiroplasma endosymbiont reduction of host lipid synthesis and Stomoxyn-like peptide contribute to trypanosome resistance in the tsetse fly Glossina fuscipes.

Tsetse flies (Glossina spp.) vector African trypanosomes that cause devastating diseases in humans and domestic animals. Within the Glossina genus, species in the Palpalis subgroup exhibit greater resistance to trypanosome infections compared to those in the Morsitans subgroup. Varying microbiota composition and species-specific genetic traits can significantly influence the efficiency of parasite transmission. Notably, infections with the endosymbiotic bacterium Spiroplasma have been documented in several Palpalis subgroup species, including Glossina fuscipes fuscipes (Gff). While Spiroplasma infections in Gff are known to hinder trypanosome transmission, the underlying mechanisms remain unknown. To investigate Spiroplasma-mediated factors affecting Gff vector competence, we conducted high-throughput RNA sequencing of the gut tissue along with functional assays. Our findings reveal elevated oxidative stress in the gut environment in the presence of Spiroplasma, evidenced by increased expression of nitric oxide synthase, which catalyzes the production of trypanocidal nitric oxide. Additionally, we observed impaired lipid biosynthesis leading to a reduction of this important class of nutrients essential for parasite and host physiologies. In contrast, trypanosome infections in Gff's midgut significantly upregulated various immunity-related genes, including a small peptide, Stomoxyn-like, homologous to Stomoxyn first discovered in the stable fly, Stomoxys calcitrans. We observed that the Stomoxyn-like locus is exclusive to the genomes of Palpalis subgroup tsetse species. GffStomoxyn is constitutively expressed in the cardia (proventriculus) and synthetic GffStomoxyn exhibits potent activity against Escherichia coli and bloodstream form of Trypanosoma brucei parasites, while showing no effect against insect stage procyclic forms or tsetse's commensal endosymbiont Sodalis in vitro. Reducing GffStomoxyn levels significantly increased trypanosome infection prevalence, indicating its potential trypanocidal role in vivo. Collectively, our results suggest that the enhanced resistance to trypanosomes observed in Spiroplasma-infected Gff may be due to the reduced lipid availability necessary for parasite metabolic maintenance. Furthermore, GffStomoxyn could play a crucial role in the initial immune response(s) against mammalian parasites early in the infection process in the gut and prevent gut colonization. We discuss the molecular characteristics of GffStomoxyn, its spatial and temporal expression regulation and its microbicidal activity against Trypanosome parasites. Our findings reinforce the nutritional influences of microbiota on host physiology and host-pathogen dynamics.