Production Of Nitrogen Species Research Articles

Application of ionic wind in sampling of bioaerosols: collection efficiency, ROS/RNS production, and viability assessment

Studies of bioaerosol particles in airborne particulate matter have revealed their omnipresence. Therefore, spot-on sampling and identification are pivotal for assessing exposure risks. Corona discharge-based sampling has been utilized for the bioaerosol sampling. However, one of the issues regarding corona discharge-based samplers is the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which can alter the viability of bioaerosols and damage nucleic acids. Herein, the use of ionic wind as a possible alternative to reduce ROS/RNS damage to microorganisms was studied. An aerosol-to-hydrosol (ATH) ionic wind (IW) sampler was developed and compared with an ATH electrostatic precipitation (ESP) sampler having the exact physical dimensions in terms of collection efficiency, ROS/RNS production, ozone generation, viability of collected biological particles, and damage to the nucleic acids of the particles. Overall, the ESP sampler showed a higher collection efficiency and less damage to the reproducibility of the sampled bioaerosols than the IW sampler. However, polymerase chain reaction analysis of the sampled bioaerosol nucleic acids showed similar results for both devices. The IW sampler has the potential for both bioaerosol sampling and deactivation, as well as for scenarios requiring neutralized sampled particles or particle deposition on any nonmetallic surface.

Abstract C019: IL27R signaling regulates neutrophils maturation, activation and function in colorectal cancer-liver metastases

Abstract Colorectal cancer (CRC) is the third most common cancer and fourth cause of cancer death worldwide. The liver is the most common organ for CRC metastasis, which is a major cause of death for CRC patients. Therefore, a better understanding of mechanisms facilitating CRC liver metastasis is in urgent need. IL27 is a member of IL6/IL12 cytokines superfamily which have a critical role in tumor microenvironment to affect tumorigenesis and metastasis. IL27 is secreted by activated macrophages and dendritic cells, and IL27R is expressed in various immune cells, mediating IL27-dependent pro-inflammatory or anti-inflammatory immune responses. However, the role of myeloid IL27 signaling in CRC-liver metastasis remains unclear. To study the role of IL27R signaling in myeloid cells, we generated Il27ra fl/fl mice and crossed them with LysM cre deleter to obtain LysM cre+ Il27ra f/f mice. Using MC-38 CRC cells portal vein injection model, we found that myeloid IL27Ra deletion leads to increased CRC-liver metastasis accompanied by increase in neutrophils, particularly Ly6G+Cxcr2-CD101- immature neutrophils, in circulation as well as tumors in LysM cre+ Il27ra f/f mice. Single-cell sequencing of tumor-infiltrating immune cells revealed that lack of IL27Ra in myeloid cells promoted neutrophil recruitment and degranulation as well as reactive oxygen species (ROS) and reactive nitrogen species (RNS) production but inhibited neutrophil maturation and production of pro-inflammatory chemokines and cytokines such as CXCL10, CSF1 and TNF. Furthermore, IL27Ra deficient neutrophils displayed heightened inflammatory response when stimulated with LPS in vitro. Collectively, our work reveals novel role of myeloid IL27Ra signaling that inhibits metastatic liver colonization by promoting neutrophil maturation, restricting neutrophil infiltration and degranulation. Citation Format: Jiani Zhu, Zhengzheng Shi, Ekaterina Koltsova. IL27R signaling regulates neutrophils maturation, activation and function in colorectal cancer-liver metastases [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C019.

Endothelial Dysfunction with Aging: Does Sex Matter?

Oxidative stress and inflammation accompany endothelial dysfunction that results from the excessive or uncontrolled production of reactive oxygen and nitrogen species (RONS) in older adults. This study was designed to assess the usefulness of serum oxi-inflammatory component combinations in vascular disease prediction and prevention with regard to sex. Women (n = 145) and men (n = 50) aged 72.2 ± 7.8 years participated in this project. The females demonstrated the elevated production of hydrogen peroxide (H2O2) and nitric oxide (NO) responsible for intravascular low-density lipoprotein oxidation. NO generation was enhanced in the women, but its bioavailability was reduced, which was expressed by a high 3-nitrotyrosine (3-NitroT) concentration. The relation of NO/3-NitroT (rs = 0.811, p < 0.001) in the women and NO/3-NitroT (rs = -0.611, p < 0.001) in the men showed that sex determines endothelial dysfunction. RONS generation in the women simultaneously promoted endothelial regeneration, as demonstrated by a ~1.5-fold increase in circulating progenitor cells. Inflammation-specific variables, such as the neutrophil-to-lymphocyte ratio, the systemic immune inflammation index, and the neutrophil-to-high-density lipoprotein (HDL) ratio, were reduced in the women and showed their diagnostic utility for clinical prognosis in vascular dysfunction, especially the C-reactive-protein-to-HDL ratio (AUC = 0.980, specificity 94.7%, sensitivity 93.3%, OR = 252, 95% CI 65-967, p < 0.001). This study is the first to have revealed sex-specific changes in the oxi-inflammatory response, which can generate the risk of cardiovascular events at an older age.

INFLUENCE OF SODIUM GLUTAMATE ON REACTIVE OXYGEN AND NITROGEN SPECIES PRODUCTION IN KIDNEY TISSUES OF RATS UNDER ACUTE DESYNCHRONIZATION AND LIPOPOLYSACCHARIDE-INDUCED SYSTEMIC INFLAMMATORY RESPONSE

The study investigated the effect of sodium glutamate on the production of reactive oxygen and nitrogen species (ROS/RNS) in kidney tissues of rats under conditions of acute desynchronization (AD) and lipopolysaccharide (LPS)-induced systemic inflammatory response (SIR) and, thus, contributed to a deeper understanding of the mechanisms involved in the development of renal dysfunction under these conditions. The experiment was conducted on 21 male Wistar rats (210-230 g), randomly divided into three groups: intact animals, a group exposed to AD modeling under LPS-induced systemic inflammatory response (Group II), and a group (Group 3) exposed to AD modeling under LPS-induced systemic inflammatory response, who received sodium glutamate in a dose of 20 mg/kg. The administration of sodium glutamate significantly increased the generation rate of the superoxide anion radical by 13.8% through microsomal monooxygenases, by 8.7% through the mitochondrial respiratory chain, and by 7.7% through leukocyte NADPH oxidase compared to Group 2. However, sodium glutamate did not affect the total NO synthase activity or the activity of its constitutive and inducible isozymes in the kidney homogenate compared to Group 2. The uncoupling index of constitutive NO synthases in kidney tissues also remained unchanged under the administration of sodium glutamate, but the peroxynitrites were 20.5% higher, and S-nitrosothiols were 11.6% higher, than in group 2. The findings indicate that sodium glutamate significantly increases oxidative-nitrosative stress in rat kidney tissues under AD and LPS-induced SIR, resulting in excessive ROS/RNS formation.

Essentials and Pertinence of Cold Plasma in Essential Oils, Metal–Organic Frameworks and Agriculture

ABSTRACTCold atmospheric pressure plasma (CAPP) comprises an ensemble of ionized gas, neutral particles, and/or reactive species. Electricity is frequently used to produce CAPP via a variety of techniques, including plasma jets, corona discharges, dielectric barrier discharges, and glow discharges. The type and flow rates of the carrier gas(es), temperature, pressure, and vacuum can all be altered to control the desired properties of the CAPP. Since a few decades ago, CAPP has become a widely used technology with applications in every walk of life. The plasma activated liquid mediums like water, ethanol, and methanol have been merged as novel sterilizers. With recent advancements in material science, particularly work on metal–organic frameworks (MOFs), essential oils, and agricultural technologies, CAPP has become a vital component of these advancements. Likewise, CAPP has been found as a green and benign technology to induce early seed germination and plant development. This review covers the critical components of CAPP, the production of reactive oxygen and nitrogen species, and mechanisms by which CAPP‐based technologies are applied to agricultural products, MOFs, and essential oils.

A host-directed adjuvant resuscitates and sensitizes intracellular bacterial persisters to antibiotics.

There are two major problems in the field of antimicrobial chemotherapy-antibiotic resistance and antibiotic tolerance. In the case of antibiotic tolerance, antibiotics fail to kill the bacteria as their phenotypic state affords them protection from the bactericidal activity of the antibiotic. Antibiotic tolerance can affect an entire bacterial population, or a subset of cells known as persister cells. Interaction with the host induces the formation of persister cells in numerous pathogens, with reactive oxygen and nitrogen species production being heavily implicated in the collapse of bacterial energy levels and entrance into an antibiotic tolerant state. Here, we developed a high-throughput screen to identify energy modulators for intracellular Staphylococcus aureus . The identified compound, KL1 , increases intracellular bacterial energy and sensitizes the persister population to antibiotics, without causing cytotoxicity or bacterial outgrowth. We demonstrate that KL1 exhibits adjuvant activity in a murine model of S. aureus bacteremia and intracellular infection of Salmonella Typhimurium . Transcriptomic analysis and further studies on its mechanism of action reveal that KL1 modulates host immune response genes and suppresses the production of reactive species in host macrophages, alleviating one of the major stressors that induce antibiotic tolerance. Our findings highlight the potential to target intracellular persister cells by stimulating their metabolism and encourage larger efforts to address antibiotic tolerance at the host-pathogen interface, particularly within the intracellular milieu.

Antioxidants as adjuvant in cancer therapy: A systematic review

While cancer therapies can effectively remove malignant cells from the body, their efficacy is mostly limited to a number of harmful side effects. Antioxidant treatment is therefore frequently necessary to lessen these negative effects by lowering reactive species levels and minimizing chronic oxidative damage. Antioxidants have a crucial role in inhibiting the production of reactive nitrogen and oxygen species as well as their activities. Reviewing the role of antioxidants in the development or prevention of cancer was the goal of this study. It is thought that antioxidants can both prevent and treat different kinds of cancer. As of right now, cancer prevention and treatment have primarily involved consuming natural antioxidant substances. These are unquestionably cell-type- and Reactive Oxygen Species (ROS)-specific, as evidenced by alterations in gene expression, cellular activities, and mechanisms of cell death. By decreasing hydrogen donors or quenching singlet oxygen and postponing oxidative reactions in cancer cells that are actively developing, natural antioxidants eliminate an overabundance of free radical intermediates. The primary topics covered in this study are antioxidant categorization, metabolic regulation, and antioxidant involvement in cancer treatment.

Comparative cellular toxicity between silver and poly (lactic-co-glycolic acid) nanoparticles

Nanoparticles composed of poly (lactic‑co‑glycolic acid) (PLGANPs) and silver (AgNPs) are relevant in the context of their interactions with biological systems. This study aims to evaluate the potential in vitro cytotoxic effects of both PLGANPs and AgNPs on a human colorectal adenocarcinoma cell line (Caco‑2). The impact of nanoparticles on cellular toxicity, morphology, microvilli density and viscoelasticity were assessed. After 48 hours incubation with PLGANPs, cells exhibited a modest proliferation compared to the control (6 to14%), low reactive nitrogen species (RNS) production (2 μM) and higher microvilli densities. In contrast, AgNPs displayed significant toxicity (LC50 = 3.76 μg/mL) and elevated RNS production.

Human microglia polarization following infection with the Lyme disease spirochete.

Infection with Borrelia burgdorferi can spread and cause central nervous system involvement, known as neuroborreliosis. Microglia phagocytose bacteria, mediate inflammation, and elicit an immune response toward the spirochete. Like other tissue macrophages, microglia can polarize into two different modulatory phenotypes, M1 and M2. We explored human microglial polarization changes upon infection with B. burgdorferi. HMC3 human microglia cell line was infected with B. burgdorferi for 24 h. Expression of polarization markers was evaluated via flow cytometry at 4 and 24 h. Secreted immunological mediators were evaluated using a multiplex ELISA system at 4, 18, and 24 h. An early decrease followed by a later increase in expression of M1 polarization marker iNOS was observed at 4 h, and 24 h, respectively. A decrease in M2 marker CX3CR1 occurred at 24 h. There were no changes in expression of M1 markers CD14, or in M2 markers CD163 and CD206. Multiplex ELISA evidenced an increase in secretion of activation markers MIP-1α, MIP- 1β, IP-10, chemotactic factor MCP-1, M1 polarization cytokine IL-8, and VEGF, at 4, 18, and 24 h. A decrease of iNOS at 4 h of infection suggests a diminished production of reactive nitrogen species that are a critical component of innate defense against infection. Increased iNOS and simultaneously decreased expression of CX3CR1 at 24 h, may suggest initiation of neuroprotective regulation of microglia recruitment to neuroinflammation. The dynamics of major inflammatory cytokines appear to be important in the microglial response to B. burgdorferi and should be further studied as these could become therapeutic targets in neuroborreliosis.

Study and scaling-up of multi-tip pulsed-corona air discharges for degradation of paracetamol

Abstract This study investigates the paracetamol removal efficiency by multi-tip pulsed corona discharges, highlighting the conditions avoiding mutual effects between two consecutive streamer branching discharges generated by each tip. The results show that the production of reactive oxygen and nitrogen species (RONS) in the liquid phase and the efficiency of paracetamol removal are influenced by the distance between two contiguous tips due to the mutual effects for small inter-tip distances between 4 mm and 8 mm in the case of a fixed inter-electrode distance of 5 mm (i.e. distance between the tip summit and the water surface). Beyond an inter-tip distance of 12 mm (over twice the gap distance), the mutual effects of branching discharges were no longer observed since the field lines did not overlap, making the production and absorption of liquid-phase species more efficient. Furthermore, RONS production was almost linear when moving from one to four tip electrodes: [H2O2]1tip: 0.52 mg l–1 versus [H2O2]4tips: 1.99 mg l–1, a ratio of 3.82. Optimum values were reached for an inter-tip distance of 16 mm. In this case, the enhancement factor in this reactor configuration is the surface integration between the plasma and the liquid surface to be treated. Furthermore, the results show a quasi-exponential increase in the percentage of paracetamol degradation as a function of the number of electrodes, from 4% with a mono-tip configuration to over 78% for a treatment with a four tip one.

Multifunctional MnGA Nanozymes for the Treatment of Ulcerative Colitis by Reducing Intestinal Inflammation and Regulating the Intestinal Flora.

In ulcerative colitis (UC), the formation of an inflammatory environment is due to the combined effects of excess production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), overproduction of proinflammatory cytokines, and disruption of immune system function. There are many kinds of traditional drugs for the clinical treatment of UC, but long-term drug use can cause toxic side effects and drug resistance and can also reduce patient compliance and other drawbacks. Hence, in light of the clinical challenges associated with UC, including the limitations of existing treatments, intense adverse reactions and the development of resistance to medications, no novel therapeutic agents that offer effective relief and maintain a high level of biosafety are urgently needed. Although many anti-inflammatory nanomedicines have been developed by researchers, the development of efficient and nontoxic nanomedicines is still a major challenge in clinical medicine. Using the natural product gallic acid and the metal compound manganese chloride, a highly effective and nontoxic multifunctional nanoenzyme was developed for the treatment of UC. Nanozymes can effectively eliminate ROS and RNS to reduce the inflammation of intestinal epithelial cells caused by oxidation, facilitate the restoration of the intestinal epithelial barrier through the upregulation of tight junction protein expression, and balance the intestinal microbiota to maintain the stability of the intestinal environment. Using a rodent model designed to mimic UC, we monitored body weight, colon length, the spleen index, and the degree of tissue damage and demonstrated that manganese gallate (MnGA) nanoparticles can reduce intestinal inflammation by clearing ROS and active nitrogen. Intestinal flora sequencing revealed that MnGA nanoparticles could regulate the intestinal flora, promote the growth of beneficial bacteria and decrease the levels of detrimental bacteria within the intestinal tract in a mouse model of UC. Thus, MnGA nanoparticles can maintain the balance of the intestinal flora. This study demonstrated that MnGA nanoparticles are excellent antioxidant and effective anti-inflammatory agents, have good biosafety, and can effectively treat UC.

Serotonin Availability Shapes the Effects of Phenelzine on Inflammatory Response and Gene Expression in Macrophages.

Background Serotonin (5-HT) is a neurotransmitter with extensive physiological influence in the central nervous system (CNS) and various behavioral and biological functions, including immune regulation through 5-HT receptors (5-HTRs) expressed by immune cells. A variety of serotonin-modulating drugs have been developed to treat neurological disorders. Phenelzine, a drug indicated for the management of treatment-resistant depression, is a potent, non-selectiveinhibitor of monoamine oxidase (MAO), the enzyme that metabolizes serotonin to 5-hydroxyindole acetic acid (5-HIAA). Given the emerging evidence of a bidirectional link between depression and inflammation, as well as the potential therapeutic applications of serotonin-modulating drugs in autoimmune diseases and cancer, our study investigated the pro-inflammatory and anti-inflammatory factors influenced by serotonin and phenelzine. Methodology We conducted experiments on RAW264.7 macrophages, exposing them to various combinations and concentrations of serotonin, 5-HIAA, and phenelzine. We assessed the relative gene expression of monoamine oxidase-A (MAO-A), CYP1B1, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) using real-time PCR and measured the production of IL-6, TNF-α, and IL-10 cytokines using enzyme-linked immunosorbent assays (ELISA). Results Our findings revealed that phenelzine can downregulate genes associated with the production of reactive oxygen and nitrogen species, reduce aryl hydrocarbon receptor (AHR)-related gene expression induced by serotonin, and enhance the production of inflammatory cytokines. These effects were significantly influenced by the concentration of available serotonin. Conclusions Our study demonstrates that various mechanisms, including AHR activation, modulation of reactive oxygen and nitrogen speciesproduction, and others, in addition to the increased availability of serotonin due to phenelzine treatment, can significantly influence the inflammatory state.

Inhibition of phototrophic iron oxidation by nitric oxide in ferruginous environments

Anoxygenic phototrophic Fe(II) oxidizers (photoferrotrophs) are thought to have thrived in Earth’s ancient ferruginous oceans and played a primary role in the precipitation of Archaean and Palaeoproterozoic (3.8–1.85-billion-year-old) banded iron formations (BIFs). The end of BIF deposition by photoferrotrophs has been interpreted as the result of a deepening of water-column oxygenation below the photic zone, concomitant with the proliferation of cyanobacteria. However, photoferrotrophs may have experienced competition from other anaerobic Fe(II)-oxidizing microorganisms, altering the formation mechanism of BIFs. Here we utilize microbial incubations to show that nitrate-reducing Fe(II) oxidizers metabolically outcompete photoferrotrophs for dissolved Fe(II). Moreover, both experiments and numerical modelling show that the nitrate-reducing Fe(II) oxidizers inhibit photoferrotrophy via the production of toxic intermediates. Four different photoferrotrophs, representing both green sulfur and purple non-sulfur bacteria, are susceptible to this toxic effect despite having genomic capabilities for nitric oxide detoxification. Indeed, despite nitric oxide detoxification mechanisms being ubiquitous in some groups of phototrophs at the genomic level (for example, Chlorobi and Cyanobacteria) it is likely that they would still be affected. We suggest that the production of reactive nitrogen species during nitrate-reducing Fe(II) oxidation in ferruginous environments may have inhibited the activity of photoferrotrophs in the ancient oceans and thus impeded their role in the precipitation of BIFs.

Cytotoxicity induced by three commercial neonicotinoid insecticide formulations in differentiated human neuroblastoma SH-SY5Y cells.

Neonicotinoid insecticides are used worldwide for crop protection. They act as agonists at postsynaptic nicotinic acetylcholine receptors (nAChRs), disrupting normal neurotransmission in target insects. Human exposure is high due to the widespread use of neonicotinoids and their residues in food. This study aimed to evaluate the in vitro neurotoxicity of three neonicotinoid commercial formulations Much 600 FS® (imidacloprid 600gL-1), Evidence 700 WG® (imidacloprid 700gkg-1), and Actara 250 WG® (thiamethoxam 250gkg-1) in differentiated human neuroblastoma SH-SY5Y cell line. Cells were incubated with the pesticides for 96h, and the cytotoxicity was evaluated through the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium·bromide (MTT) reduction and neutral red (NR) uptake assays. Toxicological pathways such as reactive oxygen (ROS) and nitrogen species (RNS) production, mitochondrial membrane potential, cell death mode, and the expression of the pro-apoptotic protein Bax were also evaluated. EC50 values of 266.4, 4,175, and 653.2mgL-1 were found for Much®, Evidence® and Actara®, respectively. Significant increases in ROS and RNS generation were observed for all pesticides, while mitochondrial membrane potential and Bax protein expression showed no significant changes. Analysis of cell death mode revealed an increase in early apoptotic cells. Therefore, neonicotinoid insecticides are potentially neurotoxic, reinforcing concerns about human exposure to these commercial formulations.

The multifaceted role of mitochondria in autism spectrum disorder.

Normal brain functioning relies on high aerobic energy production provided by mitochondria. Failure to supply a sufficient amount of energy, seen in different brain disorders, including autism spectrum disorder (ASD), may have a significant negative impact on brain development and support of different brain functions. Mitochondrial dysfunction, manifested in the abnormal activities of the electron transport chain and impaired energy metabolism, greatly contributes to ASD. The aberrant functioning of this organelle is of such high importance that ASD has been proposed as a mitochondrial disease. It should be noted that aerobic energy production is not the only function of the mitochondria. In particular, these organelles are involved in the regulation of Ca2+ homeostasis, different mechanisms of programmed cell death, autophagy, and reactive oxygen and nitrogen species (ROS and RNS) production. Several syndromes originated from mitochondria-related mutations display ASD phenotype. Abnormalities in Ca2+ handling and ATP production in the brain mitochondria affect synaptic transmission, plasticity, and synaptic development, contributing to ASD. ROS and Ca2+ regulate the activity of the mitochondrial permeability transition pore (mPTP). The prolonged opening of this pore affects the redox state of the mitochondria, impairs oxidative phosphorylation, and activates apoptosis, ultimately leading to cell death. A dysregulation between the enhanced mitochondria-related processes of apoptosis and the inhibited autophagy leads to the accumulation of toxic products in the brains of individuals with ASD. Although many mitochondria-related mechanisms still have to be investigated, and whether they are the cause or consequence of this disorder is still unknown, the accumulating data show that the breakdown of any of the mitochondrial functions may contribute to abnormal brain development leading to ASD. In this review, we discuss the multifaceted role of mitochondria in ASD from the various aspects of neuroscience.

Taxifolin-iron nanozymes with excellent RONS scavenging ability for alleviating ethanol-induced gastric ulcer

Gastric ulcer, a chronic disease of the digestive system, presents a high incidence rate and poses significant health risks. It is closely associated with the excessive production of reactive nitrogen and oxygen species (RONS), inflammation and cell apoptosis. In this study, taxifolin (Tax)-iron nanozymes (Fe-Tax) was developed by conjugating Tax with iron ions (Fe3+), which exhibited the activities of catalase and superoxide dismutase in the gastrointestinal environment. Our results revealed that Fe-Tax nanozymes effectively scavenge RONS, mitigate oxidative damage, inflammation and cell apoptosis in vitro. Additionally, Fe-Tax could alleviate tissue inflammation and gastric mucosal damage by regulating NRF2, NF-κB, Bax/Bcl-2, and VEGF signal pathways in gastric ulcer ethanol-induced. Crucially, the Fe-Tax has been shown to have excellent biocompatibility in vitro and in vivo. Overall, this study developed Fe-Tax nanozymes with enzyme cascade reactions and provided a highly efficient strategy to prevent and alleviate gastric ulcers.

Linking GERD and the Peptide Bombesin: A New Therapeutic Strategy to Modulate Inflammatory, Oxidative Stress and Clinical Biochemistry Parameters.

Gastroesophageal reflux disease (GERD) represents one of the most prevalent foregut illnesses, affecting a large portion of individuals worldwide. Recent research has shown that inflammatory mediators such as cytokines, chemokines, and enzymes are crucial for causing esophageal mucosa alterations in GERD patients. It seems likely that the expression of various cytokines in the esophageal mucosa also induces oxidative stress by increasing the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). As humoral agents and peptidergic neurotransmitters that may support the enterogastric axis, bombesin and its related bombesin-like peptide, GRP (gastrin releasing peptide), have not been fully investigated. Therefore, considering all these assumptions, this study aimed to evaluate the influence of bombesin in reestablishing biochemical markers linked with inflammation and oxidative/nitrosative stress in GERD pathological settings. C57BL/6 mice were alternatively overfed and fasted for 56 days to induce GERD and then treated with bombesin (0.1, 0.5, and 1 mg/kg intraperitoneally) once daily for 7 days, and omeprazole was used as the positive control. After 7 days of treatment, gastric pain and inflammatory markers were evaluated. Abdominal pain was significantly reduced following bombesin administration, which was also successful in diminishing inflammatory and oxidative/nitrosative stress markers in a manner overlapping with omeprazole. Moreover, bombesin was also able to appreciably modulate gastric pH as a result of the restoration of gastric homeostasis. Overall, these observations indicated that the upregulation of bombesin and interconnected peptides is a promising alternative approach to treat GERD patients.

Multiple RONS-Loaded Plasma-Activated Ice Microneedle Patches for Transdermal Treatment of Psoriasis.

Cold atmospheric plasma (CAP) is a fledgling therapeutic technique for psoriasis treatment with noninvasiveness, but clinical adoption has been stifled by the insufficient production and delivery of plasma-generated reactive oxygen and nitrogen species (RONS). Herein, patches of air-discharge plasma-activated ice microneedles (PA-IMNs) loaded with multiple RONS are designed for local transdermal delivery to treat psoriasis as an alternative to direct CAP irradiation treatment. By mixing two RONS generated by the air-discharge plasma in the NOx mode and O3 mode, abundant high-valence RONS are produced and incorporated into PA-IMNs via complex gas-gas and gas-liquid reactions. The PA-IMNs abrogate keratinocyte overproliferation by inducing reactive oxygen species (ROS)-mediated loss of the mitochondrial membrane potential and apoptosis of keratinocytes. The in vivo transdermal treatment confirms that PA-IMNs produce significant anti-inflammatory and therapeutic actions for imiquimod (IMQ)-induced psoriasis-like dermatitis in mice by inhibiting the release of associated inflammatory factors while showing no evident systemic toxicity. Therefore, PA-IMNs have a large potential in transdermal delivery platforms as they overcome the limitations of using CAP directly in the clinical treatment of psoriasis.

Ivermectin-induced toxicity in HepG2 cells and the protective effect of tetrahydrocurcumin and vitamin C

Ivermectin (IVM) is a semi-synthetic antiparasitic derived from abamectin, one of the natural avermectins. The liver promotes metabolism and excretion of IVM, representing a risk of toxicity to this organ. The use of antioxidants to alleviate damage caused by chemicals has been increasingly studied. Thus, the aim of this study was to evaluate the effects of IVM on HepG2 cells to elucidate the mechanisms related to its toxicity and the possible protection provided by tetrahydrocurcumin (THC) and vitamin C. HepG2 cells were treated with IVM (1–25 μM) for 24 and 48 h. IVM was cytotoxic to HepG2 cells, denoted by a dose-dependent decrease in cell proliferation and metabolic activity. In addition, IVM induced damage to the cell membrane at all tested concentrations and for both incubation times. IVM significantly decreased the mitochondrial membrane potential from concentrations of 5 μM (24 h) and 1 μM (48 h). Additionally, IVM showed a time- and dose-dependent decrease in cellular adenosine triphosphate levels. The levels of reduced glutathione were decreased in a time- and dose-dependent manner, while IVM stimulated the production of reactive oxygen and nitrogen species (RONS) at all tested doses, reaching rates above 50% following treatment at 7.5 μM (24 h) or 5 μM (48 h). Treatment with THC (50 μM) and vitamin C (50 μM) protected against IVM-induced cytotoxicity and RONS production. These results suggest that oxidative damage is involved in IVM-induced toxicity in HepG2 cells, and that THC and vitamin C can mitigate the toxic effects caused by the compound.

Peptide hydrogel based electrochemical biosensor for simultaneous monitoring ofH2O2 and NO released from three-dimensional cultured breast cancer cells.

Anantifouling peptide hydrogel-based electrochemical biosensor was developedfor real-time monitoring of hydrogen peroxide (H2O2) and nitric oxide (NO) released by 3D cultured breast cancer cells upon drug stimulation. Platinum nanoparticles (Pt NPs) were electrodeposited on titanium mesh (Pt NPs/TM) to enhance sensitivity and shown topossess excellent electrocatalytic ability toward H2O2 and NO. The composite hydrogel formed by co-assembling of N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) and a fluorine methoxycarbonyl group-functionalized Lys-(Fmoc)-Asp was coated on Pt NPs/TM electrode surface to provide cellular scaffolding. Their favorable biocompatibility promoted cell adhesion and growth, while good hydrophilicity endowed the sensor with greatly enhanced antifouling capability in complex cell culture environments. The biosensor successfully determined H2O2 and NO secretion from both non-metastatic and metastatic breast cancer cells in real time. Our results demonstrated robust associations between reactive oxygen species (ROS) and reactive nitrogen species (RNS) production and cell malignancy, with the main difference in oxidative stress between the two subtypes of cells being NO release, particularly emphasizing RNS's critical leading in driving cancer metastasis and invasion progression. This sensor holds great potential for cell-release research under the in vivo-like microenvironment and could reveal RNS as an attractive therapeutic target for treating breast cancer.