Generation Of Nitrogen Species Research Articles

Melatonin/Sericin Wound Healing Patches: Implications for Melanoma Therapy.

Melatonin and sericin exhibit antioxidant properties and may be useful in topical wound healing patches by maintaining redox balance, cell integrity, and regulating the inflammatory response. In human skin, melatonin suppresses damage caused by ultraviolet radiation (UVR) which involves numerous mechanisms associated with reactive oxygen species/reactive nitrogen species (ROS/RNS) generation and enhancing apoptosis. Sericin is a protein mainly composed of glycine, serine, aspartic acid, and threonine amino acids removed from the silkworm cocoon (particularly Bombyx mori and other species). It is of interest because of its biodegradability, anti-oxidative, and anti-bacterial properties. Sericin inhibits tyrosinase activity and promotes cell proliferation that can be supportive and useful in melanoma treatment. In recent years, wound healing patches containing sericin and melatonin individually have attracted significant attention by the scientific community. In this review, we summarize the state of innovation of such patches during 2021-2023. To date, melatonin/sericin-polymer patches for application in post-operational wound healing treatment has been only sparingly investigated and it is an imperative to consider these materials as a promising approach targeting for skin tissue engineering or regenerative dermatology.

Imaging Findings and Toxicological Mechanisms of Nervous System Injury Caused by Diquat.

Diquat (DQ) is a nonselective bipyridine herbicide with a structure resembling paraquat (PQ). In recent years, the utilization of DQ as a substitute for PQ has grown, leading to an increase in DQ poisoning cases. While the toxicity mechanism of DQ remains unclear, it is primarily attributed to the intracellular generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) through the process of reduction oxidation. This results in oxidative stress, leading to a cascade of clinical symptoms. Notably, recent reports on DQ poisoning have highlighted a concerning trend: an upsurge in cases involving neurological damage caused by DQ poisoning. These patients often present with severe illness and a high mortality rate, with no effective treatment available thus far. Imaging findings from these cases have shown that neurological damage tends to concentrate on the brainstem. However, the specific mechanisms behind this poisoning remain unclear, and no specific antidote exists. This review summarizes the research progress on DQ poisoning and explores potential mechanisms. By shedding light on the nerve damage associated with DQ poisoning, we hope to raise awareness, propose new avenues for investigating the mechanisms of DQ poisoning, and lay the groundwork for the development of treatment strategies for DQ poisoning. Trial registration number: 2024PS174K.

An "All-In-One" Immunomodulator-Engineered Clinical Translatable Immunotherapy of Advanced Hepatocellular Carcinoma.

Clinical treatment of advanced hepatocellular carcinoma (HCC) remains a significant challenge. Utilizing1-bromoacetyl-3,3-dinitroazetidine (RRx-001) to downregulate the expression of innate immune checkpoint molecule, cluster of differentiation 47 (CD47), provides a powerful means for treating advanced HCC containing abundant immunosuppressive macrophages. Herein engineering of a previously optimized Doxorubicin (DOX)-delivery nanoplatform based on sodium alginate is reported to further co-deliver RRx-001 (biotinylated aldehyde alginate-doxorubicin micelle prodrug nanoplatform, BEA-D@R) for efficient immunotherapy of advanced HCC. Thisgroundbreaking technique reveals the "all-in-one" immunotherapeutic functionalities of RRx-001. Besides the previously demonstrated functions of downregulating CD47 expression and increasing reactive nitrogen species (RNS) generation, another key function of RRx-001 for downregulating the expression of the adaptive immune checkpoint molecule programmed cell death 1 ligand 1 (PDL1) is first uncovered here. Combined with the reactive oxygen species (ROS) generation and an upregulated "eat me" signal level of DOX, BEA-D@R collectively increases RNS generation, enhances T-cell infiltration, and maximizes macrophage phagocytosis, leading to an average of 40% tumor elimination in a mice model bearing an initial tumor volume of ≈300 mm3 that mimics advanced HCC. Overall, the "all-in-one" immunotherapeutic functionalities of a clinical translatable nanoplatform are uncovered for enhanced immunotherapy of advanced HCC.

Experimental and theoretical study on reactive oxygen and nitrogen species generation in plasma bubbles with ammonia solution

AbstractLow‐temperature plasma‐assisted nitrogen fixation is a promising method for organic‐polluted soil/water remediation, that improves N‐fertilizer performance and mitigates ammonia emission. Our study explores a novel approach: plasma bubbles‐assisted ammonia treatment, and investigates the role played by various reactive substances in the oxidation of ammonia. The specific reaction pathways and the contribution of OH radicals in the ammonia oxidation process in O2 plasma treatment are determined. Air emerges as the optimal feed gas owing to a positive feedback loop in the reaction between NO2− and H2O2. Air plasma treatment enriches N in the ammonia solution and minimizes ammonia loss during treatment. This study offers new insights into an advanced plasma‐assisted ammonia treatment method.

Bacterial Decontamination of Water-Containing Objects Using Piezoelectric Direct Discharge Plasma and Plasma Jet.

Cold atmospheric plasma has become a widespread tool in bacterial decontamination, harnessing reactive oxygen and nitrogen species to neutralize bacteria on surfaces and in the air. This technology is often employed in healthcare, food processing, water treatment, etc. One of the most energy-efficient and universal methods for creating cold atmospheric plasma is the initiation of a piezoelectric direct discharge. The article presents a study of the bactericidal effect of piezoelectric direct discharge plasma generated using the multifunctional source "CAPKO". This device allows for the modification of the method of plasma generation "on the fly" by replacing a unit (cap) on the working device. The results of the generation of reactive oxygen and nitrogen species in a buffer solution in the modes of direct discharge in air and a plasma jet with an argon flow are presented. The bactericidal effect of these types of plasma against the bacteria E. coli BL21 (DE3) was studied. The issues of scaling the treatment technique are considered.

Oxidative versus Reductive Stress in Breast Cancer Development and Cellular Mechanism of Alleviation: A Current Perspective with Anti-breast Cancer Drug Resistance.

Redox homeostasis is essential for keeping our bodies healthy, but it also helps breast cancer cells grow, stay alive, and resist treatment. Changes in the redox balance and problems with redox signaling can make breast cancer cells grow and spread and make them resistant to chemotherapy and radiation therapy. Reactive oxygen species/reactive nitrogen species (ROS/RNS) generation and the oxidant defense system are out of equilibrium, which causes oxidative stress. Many studies have shown that oxidative stress can affect the start and spread of cancer by interfering with redox (reduction-oxidation) signaling and damaging molecules. The oxidation of invariant cysteine residues in FNIP1 is reversed by reductive stress, which is brought on by protracted antioxidant signaling or mitochondrial inactivity. This permits CUL2FEM1B to recognize its intended target. After the proteasome breaks down FNIP1, mitochondrial function is restored to keep redox balance and cell integrity. Reductive stress is caused by unchecked amplification of antioxidant signaling, and changes in metabolic pathways are a big part of breast tumors' growth. Also, redox reactions make pathways like PI3K, PKC, and protein kinases of the MAPK cascade work better. Kinases and phosphatases control the phosphorylation status of transcription factors like APE1/Ref-1, HIF-1, AP-1, Nrf2, NF-B, p53, FOXO, STAT, and -catenin. Also, how well anti-breast cancer drugs, especially those that cause cytotoxicity by making ROS, treat patients depends on how well the elements that support a cell's redox environment work together. Even though chemotherapy aims to kill cancer cells, which it does by making ROS, this can lead to drug resistance in the long run. The development of novel therapeutic approaches for treating breast cancer will be facilitated by a better understanding of the reductive stress and metabolic pathways in tumor microenvironments.

Pomalidomide Improves Motor Behavioral Deficits and Protects Cerebral Cortex and Striatum Against Neurodegeneration Through a Reduction of Oxidative/Nitrosative Damages and Neuroinflammation After Traumatic Brain Injury.

Neuronal damage resulting from traumatic brain injury (TBI) causes disruption of neuronal projections and neurotransmission that contribute to behavioral deficits. Cellular generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is an early event following TBI. ROS often damage DNA, lipids, proteins, and carbohydrates while RNS attack proteins. The products of lipid peroxidation 4-hydroxynonenal (4-HNE) and protein nitration 3-nitrotyrosine (3-NT) are often used as indicators of oxidative and nitrosative damages, respectively. Increasing evidence has shown that striatum is vulnerable to damage from TBI with a disturbed dopamine neurotransmission. TBI results in neurodegeneration, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy in the striatum and contribute to motor or behavioral deficits. Pomalidomide (Pom) is a Food and Drug Administration (FDA)-approved immunomodulatory drug clinically used in treating multiple myeloma. We previously showed that Pom reduces neuroinflammation and neuronal death induced by TBI in rat cerebral cortex. Here, we further compared the effects of Pom in cortex and striatum focusing on neurodegeneration, oxidative and nitrosative damages, as well as neuroinflammation following TBI. Sprague-Dawley rats subjected to a controlled cortical impact were used as the animal model of TBI. Systemic administration of Pom (0.5 mg/kg, intravenous [i.v.]) at 5 h post-injury alleviated motor behavioral deficits, contusion volume at 24 h after TBI. Pom alleviated TBI-induced neurodegeneration stained by Fluoro-Jade C in both cortex and striatum. Notably, Pom treatment reduces oxidative and nitrosative damages in cortex and striatum and is more efficacious in striatum (93% reduction in 4-HNE-positive and 84% reduction in 3-NT-positive neurons) than in cerebral cortex (42% reduction in 4-HNE-positive and 55% reduction in 3-NT-positive neurons). In addition, Pom attenuated microgliosis, astrogliosis, and elevations of proinflammatory cytokines in cortical and striatal tissue. We conclude that Pom may contribute to improved motor behavioral outcomes after TBI through targeting oxidative/nitrosative damages and neuroinflammation.

Amphiphilic Janus nanoparticles for nitric oxide synergistic photodynamic eradication of MRSA biofilms.

Biofilms pose significant threats to public health by causing persistent clinical infections. The development of innovative antibacterial approaches for eliminating biofilms is an urgent necessity. In this study, we developed amphiphilic Janus nanoparticles (JNPs), loaded with hydrophobic chlorin e6 (Ce6) and hydrophilic S-nitrosoglutathione (GSNO), denoted as Ce6-PDA/CaP-GSNO, with the aim to effectively eradicate biofilms and combat methicillin-resistant Staphylococcus aureus (MRSA) infections through nitric oxide (NO) synergistic photodynamic therapy (PDT). Ce6-PDA/CaP-GSNO demonstrated remarkable biofilm penetration ability, efficiently reaching the acidic inner layers, which triggered the rapid release of GSNO, resulting in the generation of an abundant supply of NO. NO not only exhibited potent bactericidal activity but also effectively lowered the GSH level of the biofilm, leading to enhanced efficacy of Ce6. Additionally, the interaction between NO and reactive oxygen species (ROS) resulted in the generation of reactive nitrogen species (RNS), further enhancing PDT efficacy both in vitro and in vivo. In summary, Ce6-PDA/CaP-GSNO demonstrated remarkable biofilm penetration capacity and effective reduction of the GSH level in the biofilms, leading to enhanced PDT efficacy at low photosensitizer doses and laser intensities, thereby minimizing adverse effects on normal tissues. These findings highlight the promising potential of our approach for combating biofilm-related infections.

Boosting the Performance of on-Chip Vertically-Aligned Carbon Nanotube Supercapacitors Via Solvent-Free Radiofrequency Nitrogen Plasma Treatment

Supercapacitors are essential components for energy storage devices in many fields, including renewable energy systems, electric vehicles, and portable electronics [1]. Carbon nanotube arrays have shown great promise for use in supercapacitors due to their high surface area and excellent electrical conductivity. However, the specific capacitance of these arrays needs to be increased to improve the overall energy storage capacitance of the supercapacitor.This study presents an innovative approach to enhance the specific capacitance of on-chip vertically-aligned carbon nanotube (VACNT) structures for the development of high-performance supercapacitors. The proposed technique involves employing a solvent-free radiofrequency (RF) nitrogen plasma treatment to dope nitrogen onto VACNT surfaces. The plasma doping process utilizes reactive ion etching-induced coupled plasma (RIE-ICP) to optimize the parameters for nitrogen incorporation [2]. The nitrogen plasma treatment introduces nitrogen-containing functional groups, thereby improving their specific capacitance. The dry process is compatible with semiconductor fabrication and can be integrated into existing manufacturing techniques [1]. This study provides a promising avenue for tailoring the nitrogen doping process to achieve desired performance enhancements for on-chip VACNT supercapacitors.The plasma doping process involves the generation of reactive nitrogen species in the plasma, which subsequently interact with the VACNT surfaces. Under the influence of the RF electric field, nitrogen gas molecules are ionized and can react with the carbon atoms of the VACNTs, resulting in the formation of nitrogen-containing functional groups and the substitution of carbon atoms with nitrogen atoms within the carbon lattice [3].The improved capacitance can be attributed to the incorporation of nitrogen functional groups and to the modification of the electronic properties of the carbon nanotubes, including additional charge carriers, leading to an increase in electrical conductivity [4] and introduction of the pseudocapacitance effect [5]. There are various types of nitrogen species in the carbon lattice, such as pyridinic, pyrrolic, and graphitic nitrogen. Among these, pyridinic and pyrrolic nitrogen are known to be more electrochemically active [5], contributing to the enhanced specific capacitance. The increased electrical conductivity stems from the introduction of nitrogen dopants, which alter the electronic structure of the VACNTs, creating localized states near the Fermi level and thus facilitating charge transport [4].The level of nitrogen doping depends on several process factors, including the plasma power, gas pressure, and treatment duration. Higher plasma power generates a larger number of reactive nitrogen, while lower gas pressure results in a higher ionization efficiency. Furthermore, a longer treatment duration increases the chance of nitrogen incorporation into the VACNT structures [3]. By carefully controlling these parameters during the nitrogen plasma treatment, it is possible to tailor the nitrogen doping process to achieve the desired performance enhancement for on-chip VACNT supercapacitors.The treatment is performed in a chamber with a pressure of 10 Pa, a nitrogen gas flow rate of 10 sccm, an ICP power of 200W, and a bias voltage of -120 V. We report a specific capacitance of modified VACNTs of 18 mF/cm2(Figure 1), nearly twice that of pristine samples (Figure1(B)), for dense arrays of 1012 CNTs/ cm2. XPS result confirms 11.76% nitrogen content and 13% oxygen content in treated samples (N-VACNTs), aligning with previous studies on wet process nitrogen-doped carbon nanotubes [5]. Oxygen content also plays a crucial role in VACNT-based supercapacitor performance, improving surface wettability which will reduce the resistance between electrode and electrolyte [6, 7]. However, excessive oxygen content can negatively affect VACNT supercapacitor lifetime. By finding the trade-off between nitrogen and oxygen content, we optimized the doping process, enhancing specific capacitance, stability (Figure 2), and lifetime for on-chip VACNT structures.In conclusion, our study demonstrates that the solvent-free RF nitrogen plasma treatment can effectively enhance the specific capacitance of on-chip VACNT structures by up to 100%, making them suitable for integration into high-performance on-chip supercapacitor.

S-glutathionylation and S-nitrosylation as modulators of redox-dependent processes in cancer cell

The development of oxidative/nitrosative stress associated with the activation of oncogenic pathways is a consequence of an increase in the level of generation of reactive oxygen and nitrogen species (ROS/RNS) in tumor cells. The action of ROS/RNS is dual: high levels cause cell death and limit tumor growth at certain phases of malignant neoplasm development, while low concentrations allow oxidative/nitrosative modifications of key redox-dependent residues in regulatory proteins. The reversibility of such modifications as S-glutathionylation/S-nitrosylation, which occur through the electrophilic attack of ROS/RNS on the nucleophilic residues of Cys, provides redox switching in the activity of signaling proteins and the ability to control the processes of proliferation and programmed death. The level of S-glutathionylated and S-nitrosylated proteins is controlled by the balance between S-glutathionylation/deglutathionylation and S-nitrosylation/denitrosylation, the ratio of which depends on the cellular redox status. The degree of S-glutathionylation and S-nitrosylation of protein targets and their ratio largely determines the state and directions of signaling pathways in cancer cells. The review discusses the features of S-glutathionylation and S-nitrosylation reactions in cancer cells, the balance of systems that control their activity and their relationship with redox-dependent processes and tumor growth.

Bioavailable Phenolic Compounds from Olive Pomace Present Anti-Neuroinflammatory Potential on Microglia Cells.

The neuroinflammatory process is considered one of the main characteristics of central nervous system diseases, where a pro-inflammatory response results in oxidative stress through the generation of reactive oxygen and nitrogen species (ROS and RNS). Olive (Olea europaea L.) pomace is a by-product of olive oil production that is rich in phenolic compounds (PCs), known for their antioxidant and anti-inflammatory properties. This work looked at the antioxidant and anti-neuroinflammatory effects of the bioavailable PC from olive pomace in cell-free models and microglia cells. The bioavailable PC of olive pomace was obtained through the process of in vitro gastrointestinal digestion of fractionated olive pomace (OPF, particles size < 2 mm) and micronized olive pomace (OPM, particles size < 20 µm). The profile of the PC that is present in the bioavailable fraction as well as its in vitro antioxidant capacity were determined. The anti-neuroinflammatory capacity of the bioavailable PC from olive pomace (0.03-3 mg L-1) was evaluated in BV-2 cells activated by lipopolysaccharide (LPS) for 24 h. The total bioavailable PC concentration and antioxidant activity against peroxyl radical were higher in the OPM than those observed in the OPF sample. The activation of BV-2 cells by LPS resulted in increased levels of ROS and nitric oxide (NO). The bioavailable PCs from both OPF and OPM, at their lowest concentrations, were able to reduce the ROS generation in activated BV-2 cells. In contrast, the highest PC concentration of OPF and OPM was able to reduce the NO levels in activated microglial cells. Our results demonstrate that bioavailable PCs from olive pomace can act as anti-neuroinflammatory agents in vitro, independent of particle size. Moreover, studies approaching ways to increase the bioavailability of PCs from olive pomace, as well as any possible toxic effects, are needed before a final statement on its nutritional use is made.

Amplification of oxidative damage using near-infrared II-mediated photothermal/thermocatalytic effects for periodontitis treatment.

Periodontitis is a biofilm-related disease characterized by damage to the periodontal tissue and the development of systemic diseases. However, treatment of periodontitis remains unsatisfactory, especially with deep-tissue infections. This study describes rationally designed multifunctional photothermocatalytic agents for near-infrared-II light-mediated synergistic antibiofilm treatment, through modification of Lu-Bi2Te3 with Fe3O4 and poly(ethylene glycol)-b-poly(l-arginine) (PEG-b-PArg). Notably, 1064-nm laser irradiation led to photothermal/thermocatalytic effects, resulting in the synergistic generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and consequent damage to the biofilm. This treatment was based on the thermoelectric and photothermal conversion properties of Lu-Bi2Te3, the peroxidase-like catalytic capacity of Fe3O4, and the guanidinium polymer, PEG-b-PArg. Oxidative damage to biofilm was further enhanced by H2O2, resulting in the effective elimination of biofilm both in vitro and in vivo. These findings suggest that this synergistic therapeutic strategy is effective for the clinical treatment of periodontitis. STATEMENT OF SIGNIFICANCE: The current treatment for periodontitis involves time-consuming and labor-intensive clinical scaling of the teeth. The present study is the first to assess the efficacy of a photothermal catalyst for periodontitis treatment. This used near-infrared-II light at 1064 nm to induce oxidative damage in the biofilm, resulting in its degradation. The synergistic photothermal/thermoelectric effect produced deep tissue penetration and was well tolerated, and can kill the biofilm formed by periodontitis pathogens up to 5 orders of magnitude, effectively treating the biofilm-induced periodontitis.

A review on plasma-activated water and its application in the meat industry.

Meat is a nutritious food with a short shelf life, making it challenging to ensure safety, quality, and nutritional value. Foodborne pathogens and oxidation are the main concerns that lead to health risks and economic losses. Conventional approaches like hot water, steam pasteurization, and chemical washes for meat decontamination improve safety but cause nutritional and quality issues. Plasma-activated water (PAW) is a potential alternative to thermal treatment that can reduce oxidation and microbial growth, an essential factor in ensuring safety, quality, and nutritional value. This review explores the different types of PAW and their physiochemical properties. It also outlines the reaction pathways involved in the generation of short-lived and long-lived reactive nitrogen and oxygen species (RONS) in PAW, which contribute to its antimicrobial abilities. The review also highlights current studies on PAW inactivation against various planktonic bacteria, as well as critical processing parameters that can improve PAW inactivation efficacy. Promising applications of PAW for meat curing, thawing, and decontamination are discussed, with emphasis on the need to understand how RONS in PAW affect meat quality. Recent reports on combining PAW with ultrasound, mild heating, and non-thermal plasma to improve inactivation efficacy are also presented. Finally, the need to develop energy-efficient systems for the production and scalability of PAW is discussed for its use as a potential meat disinfectant without compromising meat quality.

Effects of Nitro-Oxidative Stress on Biomolecules: Part 1-Non-Reactive Molecular Dynamics Simulations.

Plasma medicine, or the biomedical application of cold atmospheric plasma (CAP), is an expanding field within plasma research. CAP has demonstrated remarkable versatility in diverse biological applications, including cancer treatment, wound healing, microorganism inactivation, and skin disease therapy. However, the precise mechanisms underlying the effects of CAP remain incompletely understood. The therapeutic effects of CAP are largely attributed to the generation of reactive oxygen and nitrogen species (RONS), which play a crucial role in the biological responses induced by CAP. Specifically, RONS produced during CAP treatment have the ability to chemically modify cell membranes and membrane proteins, causing nitro-oxidative stress, thereby leading to changes in membrane permeability and disruption of cellular processes. To gain atomic-level insights into these interactions, non-reactive molecular dynamics (MD) simulations have emerged as a valuable tool. These simulations facilitate the examination of larger-scale system dynamics, including protein-protein and protein-membrane interactions. In this comprehensive review, we focus on the applications of non-reactive MD simulations in studying the effects of CAP on cellular components and interactions at the atomic level, providing a detailed overview of the potential of CAP in medicine. We also review the results of other MD studies that are not related to plasma medicine but explore the effects of nitro-oxidative stress on cellular components and are therefore important for a broader understanding of the underlying processes.

Impact of weak radiofrequency and static magnetic fields on key signaling molecules, intracellular pH, membrane potential, and cell growth in HT-1080 fibrosarcoma cells

There are substantial concerns that extended exposures to weak radiofrequency (RF) fields can lead to adverse health effects. In this study, HT-1080 fibrosarcoma cells were simultaneously exposed to a static magnetic flux density between 10 mathrm{mu T} and 300 mathrm{mu T} and RF magnetic fields with amplitudes ranging from 1 nT to 1.5 μT in the frequency range from 1.8 to 7.2 MHz for four days. Cell growth rates, intracellular pH, hydrogen peroxide, peroxynitrite, membrane potential and mitochondrial calcium were measured. Results were dependent on carrier frequency and the magnitude of the RF magnetic field, modulation frequencies and the background static magnetic field (SMF). Iron sulphur (Fe-S) clusters are essential for the generation of reactive oxygen species and reactive nitrogen species (ROS and RNS). We believe the observed changes are associated with hyperfine couplings between the chemically active electrons and nuclear spins. Controlling external magnetic fields may have important clinical implications on aging, cancer, arthritis, and Alzheimer’s.

The pentose phosphate pathway in health and disease.

The pentose phosphate pathway (PPP) is a glucose-oxidizing pathway that runs in parallel to upper glycolysis to produce ribose 5-phosphate and nicotinamide adenine dinucleotide phosphate (NADPH). Ribose 5-phosphate is used for nucleotide synthesis, while NADPH is involved in redox homoeostasis as well as in promoting biosynthetic processes, such as the synthesis of tetrahydrofolate, deoxyribonucleotides, proline, fatty acids and cholesterol. Through NADPH, the PPP plays a critical role in suppressing oxidative stress, including in certain cancers, in which PPP inhibition may be therapeutically useful. Conversely, PPP-derived NADPH also supports purposeful cellular generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) for signalling and pathogen killing. Genetic deficiencies in the PPP occur relatively commonly in the committed pathway enzyme glucose-6-phosphate dehydrogenase (G6PD). G6PD deficiency typically manifests as haemolytic anaemia due to red cell oxidative damage but, in severe cases, also results in infections due to lack of leucocyte oxidative burst, highlighting the dual redox roles of the pathway in free radical production and detoxification. This Review discusses the PPP in mammals, covering its roles in biochemistry, physiology and disease.

Analysis of In Vitro Leukocyte Responses to Biomaterials in the Presence of Antimicrobial Porcine Neutrophil Extract (AMPNE).

Implant insertion can evoke excessive inflammation which disrupts the healing process and potentially leads to complications such as implant rejection. Neutrophils and macrophages play a vital role in the early inflammatory phase of tissue repair, necessitating the study of cellular responses in host-implant interactions. In order to deepen the knowledge about these interactions, the response of neutrophils and macrophages to contact with selected biomaterials was examined in vitro on the basis of secretory response as well as reactive oxygen species/reactive nitrogen species (ROS/RNS) generation. Porcine neutrophils exposed to hydroxyapatite (HA) released more enzymes and generated higher levels of ROS/RNS compared to the control group. The addition of AMPNE diminished these responses. Although the results from porcine cells can provide valuable preliminary data, further validation using human cells or clinical studies would be necessary to fully extrapolate the findings to human medicine. Our study revealed that human neutrophils after contact of with HA increased the production of nitric oxide (NO) (10.00 ± 0.08 vs. control group 3.0 ± 0.11 µM, p < 0.05), while HAP or FAP did not elicit a significant response. Human macrophages cultured with HA produced more superoxide and NO, while HAP or FAP had a minimal effect, and curdlan reduced ROS/RNS generation. The addition of AMPNE to cultures with all biomaterials, except curdlan, reduced neutrophil activity, regardless of the peptides' origin. These results highlight the potential of antimicrobial peptides in modulating excessive biomaterial/host cell reactions involving neutrophils and macrophages, enhancing our understanding of immune reactions, and suggesting that AMPNE could regulate leukocyte response during implantation.

BTK inhibition potentiates anti-PD-L1 treatment in murine melanoma: potential role for MDSC modulation in immunotherapy.

Myeloid-derived suppressor cells (MDSC) have been linked to loss of immune effector cell function through a variety of mechanisms such as the generation of reactive oxygen and nitrogen species and the production of inhibitory cytokines. Our group has shown that signaling through Bruton's tyrosine kinase (BTK) is important for MDSC function. Ibrutinib is an orally administered targeted agent that inhibits BTK activation and is currently used for the treatment of B cell malignancies. Using a syngeneic murine model of melanoma, the effect of BTK inhibition with ibrutinib on the therapeutic response to systemic PD-L1 blockade was studied. BTK was expressed by murine MDSC and their activation was inhibited by ibrutinib. Ibrutinib was not directly cytotoxic to cancer cells in vitro, but it inhibited BTK activation in MDSC and reduced expression of inducible nitric oxide synthase (NOS2) and production of nitric oxide. Ibrutinib treatments decreased the levels of circulating MDSC in vivo and increased the therapeutic efficacy of anti-PD-L1 antibody treatment. Gene expression profiling showed that ibrutinib decreased Cybb (NOX2) signaling, and increased IL-17 signaling (upregulating downstream targets Mmp9, Ptgs2, and S100a8). These results suggest that further exploration of MDSC inhibition could enhance the immunotherapy of advanced melanoma.PrécisInhibition of Bruton's tyrosine kinase, a key enzyme in myeloid cellular function, improves therapeutic response to an anti-PD-L1 antibody in an otherwise fairly resistant murine melanoma model.

An Approach to Treat Conundrum of Skin Cancer: Bioactive Loaded Niosomes

Background: Skin cancer is one of the most life-threatening and progressive diseases nowadays, majorly resulting from the cumulative effect of genetic and environmental exposure including UV rays and numerous pollutants. UV radiation stimulates the excessive generation of Reactive oxygen species (ROS) and Reactive nitrogen species (RNS), altering numerous signaling and inflammatory pathways and cumulatively causing alteration at numerous genetic and inflammatory levels. Numerous treatment strategies have been proposed for this purpose, and it has been found that antioxidants could play a crucial role in regulating inflammation at certain levels. Among numerous treatment strategies, natural flavonoid quercetin could play a vital role in protecting cells from oxidative stress as it is enriched with anticancer, antioxidant, and anti-inflammatory properties. The activities of quercetin could be further enhanced by administrating it through novel systems. Objective: Thus, the present article focuses on the delivery of natural flavonoid quercetin via novel carrier noisome to enhance targeting potency and safety efficacy. Method: Optimized quercetin-loaded niosomes were prepared by mechanical shaking method followed by solvent evaporation and altering the ratio of cholesterol and span 80. In vitro characterization was performed for morphology, zeta potential (ZP), entrapment efficiency and drug release. Result: The optimized niosome was reported to have a size range of 120 nm, entrapment efficiency (80%-85%) and followed zero order kinetics. Conclusion: Optimized quercetin-loaded niosomes were successfully formulated and characterized for controlled drug delivery.

PLASMA BIOMEDICINE: MODERN STATE-OF-ART AND PERSPECTIVES IN REGENERATIVE MEDICINE

Abstract The purpose of the review was a comprehensive analysis of the biological effects and applications of cold plasma. First of all, physical principles of cold atmospheric plasma, including generation of reactive oxygen and nitrogen species as intermediates, were discussed. The analysis of the specialized literature on plasma medicine as an innovative interdisciplinary direction allowed us to show the physical mechanisms of biological effects of cold plasma associated with the modulation of free radical processes in the biological objects. That is why correction of oxidative stress and other disorders of redox balance was determined as direct target of the effect of studied factor. Among the most significant aspects of the biological action of cold plasma, antibacterial and pro-regenerative activity, as well as modulation of apoptosis, should be cited. On this basis, the factor in question determines its application in oncology, surgery, dermatology and other fields of medicine. One of the most important effects of cold plasma was its antibacterial and antifungal activity, which in useful for wound healing, sterilization etc. Special attention was paid to possibilities of cold plasma therapy in combustiology. Molecular, tissue and systemic mechanisms of sanogenic effects of cold plasma was demonstrated and analyzed. Results of own studied in this field was observed. Further discovery of the biological effects of cold plasma can significantly expand the range of its medical applications.