RNS2 is required for the biogenesis of a wounding responsive 16 nts tsRNA in Arabidopsis thaliana.

tRNA-derived small RNAs (tsRNAs), a new category of regulatory small non-coding RNA existing in almost all branches of life, have recently attracted broad attention. Increasing evidence has shown that tsRNAs are not random degradation debris of tRNAs, but products cleaved by specific endoribonucleases, with versatile functions in response to various developmental and environmental cues. However, it is still unclear about the diversity, biogenesis and function of tsRNAs in plants. In this study, we comprehensively profiled 10-60 nts small RNAs in Arabidopsis thaliana leaf with or without wounding stress and identified four 16 nts tiny tRFs (tRNA-derived fragments) sharply increased after wounding, namely tRF5'Ala. Notably, genetic, biochemical and bioinformatic data indicated that RNS2, a member of class II RNase T2 enzymes, was the main endoribonuclease responsible for the biogenesis of tRF5'Ala. Moreover, tRF5'Ala was highly abundant and conserved in Arabidopsis and rice pollen. However, tRF5'Ala did not associate with AGO 1 in vivo or display any inhibitory effect on the translation of a luciferase mRNA in vitro. Altogether, our study highlights the discovery of a novel class of tiny tsRNAs drastically increased under wounding stress as well as their generation by RNS2, which provides a new insight into tsRNAs research in plants.

Circadian changes in aperiodic activity are correlated with seizure reduction in patients with mesial temporal lobe epilepsy treated with responsive neurostimulation.

OBJECTIVES: Responsive neurostimulation (RNS) is an established therapy for drug-resistant epilepsy that delivers direct electrical brain stimulation in response to detected epileptiform activity. However, despite an overall reduction in seizure frequency, clinical outcomes are variable, and few patients become seizure-free. The aim of this retrospective study was to evaluate aperiodic electrophysiological activity, associated with excitation/inhibition balance, as a novel electrographic biomarker of seizure reduction to aid early prognostication of the clinical response to RNS. METHODS: We identified patients with intractable mesial temporal lobe epilepsy who were implanted with the RNS System between 2015 and 2021 at the University of Utah. We parameterized the neural power spectra from intracranial RNS System recordings during the first 3 months following implantation into aperiodic and periodic components. We then correlated circadian changes in aperiodic and periodic parameters of baseline neural recordings with seizure reduction at the most recent follow-up. RESULTS: Seizure reduction was correlated significantly with a patient's average change in the day/night aperiodic exponent (r = .50, p = .016, n = 23 patients) and oscillatory alpha power (r = .45, p = .042, n = 23 patients) across patients for baseline neural recordings. The aperiodic exponent reached its maximum during nighttime hours (12 a.m. to 6 a.m.) for most responders (i.e., patients with at least a 50% reduction in seizures). SIGNIFICANCE: These findings suggest that circadian modulation of baseline broadband activity is a biomarker of response to RNS early during therapy. This marker has the potential to identify patients who are likely to respond to mesial temporal RNS. Furthermore, we propose that less day/night modulation of the aperiodic exponent may be related to dysfunction in excitation/inhibition balance and its interconnected role in epilepsy, sleep, and memory.

Centromedian region thalamic responsive neurostimulation mitigates idiopathic generalized and multifocal epilepsy with focal to bilateral tonic-clonic seizures.

OBJECTIVE: Although >30% of epilepsy patients have drug-resistant epilepsy (DRE), typically those with generalized or multifocal disease have not traditionally been considered surgical candidates. Responsive neurostimulation (RNS) of the centromedian (CM) region of the thalamus now appears to be a promising therapeutic option for this patient population. We present outcomes following CM RNS for 13 patients with idiopathic generalized epilepsy (IGE) and eight with multifocal onsets that rapidly generalize to bilateral tonic-clonic (focal to bilateral tonic-clonic [FBTC]) seizures. METHODS: A retrospective review of all patients undergoing bilateral CM RNS by the senior author through July 2022 were reviewed. Electrodes were localized and volumes of tissue activation were modeled in Lead-DBS. Changes in patient seizure frequency were extracted from electronic medical records. RESULTS: Twenty-one patients with DRE underwent bilateral CM RNS implantation. For 17 patients with at least 1 year of postimplantation follow-up, average seizure reduction from preoperative baseline was 82.6% (SD = 19.0%, median = 91.7%), with 18% of patients Engel class 1, 29% Engel class 2, 53% Engel class 3, and 0% Engel class 4. There was a trend for average seizure reduction to be greater for patients with nonlesional FBTC seizures than for other patients. For patients achieving at least Engel class 3 outcome, median time to worthwhile seizure reduction was 203.5 days (interquartile range = 110.5-343.75 days). Patients with IGE with myoclonic seizures had a significantly shorter time to worthwhile seizure reduction than other patients. The surgical targeting strategy evolved after the first four subjects to achieve greater anatomic accuracy. SIGNIFICANCE: Patients with both primary and rapidly generalized epilepsy who underwent CM RNS experienced substantial seizure relief. Subsets of these patient populations may particularly benefit from CM RNS. The refinement of lead targeting, tuning of RNS system parameters, and patient selection are ongoing areas of investigation.

Low-temperature plasma jet suppresses bacterial colonisation and affects wound healing through reactive species.

An argon-based low-temperature plasma jet (LTPJ) was used to treat chronically infected wounds in Staphylococcus aureus-laden mice. Based on physicochemical property analysis and in vitro antibacterial experiments, the effects of plasma parameters on the reactive nitrogen and oxygen species (RNOS) content and antibacterial capacity were determined, and the optimal treatment parameters were determined to be 4 standard litre per minute and 35 W. Additionally, the plasma-treated activation solution had a bactericidal effect. Although RNOS are related to the antimicrobial effect of plasma, excess RNOS may be detrimental to wound remodelling. In vivo studies demonstrated that medium-dose LTPJ promoted MMP-9 expression and inhibited bacterial growth during the early stages of healing. Moreover, LTPJ increased collagen deposition, reduced inflammation, and restored blood vessel density and TGF-ß levels to normal in the later stages of wound healing. Therefore, when treating chronically infected wounds with LTPJ, selecting the medium dose of plasma is more advantageous for wound recovery. Overall, our study demonstrated that low-temperature plasma jets may be a potential tool for the treatment of chronically infected wounds.

Melatonin as a key regulator in seed germination under abiotic stress.

Seed germination (SG) is the first stage in a plant's life and has an immense importance in sustaining crop production. Abiotic stresses reduce SG by increasing the deterioration of seed quality, and reducing germination potential, and seed vigor. Thus, to achieve a sustainable level of crop yield, it is important to improve SG under abiotic stress conditions. Melatonin (MEL) is an important biomolecule that interplays in developmental processes and regulates many adaptive responses in plants, especially under abiotic stresses. Thus, this review specifically summarizes and discusses the mechanistic basis of MEL-mediated SG under abiotic stresses. MEL regulates SG by regulating some stress-specific responses and some common responses. For instance, MEL induced stress specific responses include the regulation of ionic homeostasis, and hydrolysis of storage proteins under salinity stress, regulation of C-repeat binding factors signaling under cold stress, starch metabolism under high temperature and heavy metal stress, and activation of aquaporins and accumulation of osmolytes under drought stress. On other hand, MEL mediated regulation of gibberellins biosynthesis and abscisic acid catabolism, redox homeostasis, and Ca2+ signaling are amongst the common responses. Nonetheless factors such as endogenous MEL contents, plant species, and growth conditions also influence above-mentioned responses. In conclusion, MEL regulates SG under abiotic stress conditions by interacting with different physiological mechanisms.

Dynamic interplay of reactive oxygen and nitrogen species (ROS and RNS) in plant resilience: unveiling the signaling pathways and metabolic responses to biotic and abiotic stresses.

KEY MESSAGE: Plants respond to environmental challenges by producing reactive species such as ROS and RNS, which play critical roles in signaling pathways that lead to adaptation and survival strategies. Understanding these pathways, as well as their detection methods and effects on plant development and metabolism, provides insight into increasing crop tolerance to combined stresses. Plants encounter various environmental stresses (abiotic and biotic) that affect plant growth and development. Plants sense biotic and abiotic stresses by producing different molecules, including reactive species, that act as signaling molecules and stimulate secondary messengers and subsequent gene transcription. Reactive oxygen and nitrogen species (ROS and RNS) are produced in both physiological and pathological conditions in the plasma membranes, chloroplasts, mitochondria, and endoplasmic reticulum. Various techniques, including spectroscopy, chromatography, and fluorescence methods, are used to detect highly reactive, short-half-life ROS and RNS either directly or indirectly. In this review, we highlight the roles of ROS and RNS in seed germination, root development, senescence, mineral nutrition, and post-harvest control. In addition, we provide information on the specialized metabolism involved in plant growth and development. Secondary metabolites, including alkaloids, flavonoids, and terpenoids, are produced in low concentrations in plants for signaling and metabolism. Strategies for improving crop performance under combined drought and pathogen stress conditions are discussed in this review.

Sodium nitroprusside modulates oxidative and nitrosative processes in Lycopersicum esculentum L. under drought stress.

KEY MESSAGE: Sodium nitroprusside mediates drought stress responses in tomatoes by modulating nitrosative and oxidative pathways, highlighting the interplay between nitric oxide, hydrogen sulfide, and antioxidant systems for enhanced drought tolerance. While nitric oxide (NO), a signalling molecule, enhances plant tolerance to abiotic stresses, its precise contribution to improving tomato tolerance to drought stress (DS) through modulating oxide-nitrosative processes is not yet fully understood. We aimed to examine the interaction of NO and nitrosative signaling, revealing how sodium nitroprusside (SNP) could mitigate the effects of DS on tomatoes. DS-seedlings endured 12% polyethylene glycol (PEG) in a 10% nutrient solution (NS) for 2 days, then transitioned to half-strength NS for 10 days alongside control plants. DS reduced total plant dry weight, chlorophyll a and b, Fv/Fm, leaf water potential (ΨI), and relative water content, but improved hydrogen peroxide (H2O2), proline, and NO content. The SNP reduced the DS-induced H2O2 generation by reducing thiol (-SH) and the carbonyl (-CO) groups. SNP increased not only NO but also the activity of L-cysteine desulfhydrase (L-DES), leading to the generation of H2S. Decreases in S-nitrosoglutathione reductase (GSNOR) and NADPH oxidase (NOX) suggest a potential regulatory mechanism in which S-nitrosylation [formation of S-nitrosothiol (SNO)] may influence protein function and signaling pathways during DS. Moreover, SNP improved ascorbate (AsA) and glutathione (GSH) and reduced oxidized glutathione (GSSG) levels in tomato plants under drought. Furthermore, the interaction of NO and H2S, mediated by L-DES activity, may serve as a vital cross-talk mechanism impacting plant responses to DS. Understanding these signaling interactions is crucial for developing innovative drought-tolerance strategies in crops.

The progression of inorganic nanoparticles and natural products for inflammatory bowel disease.

There is a growing body of evidence indicating a close association between inflammatory bowel disease (IBD) and disrupted intestinal homeostasis. Excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with an increase in M1 proinflammatory macrophage infiltration during the activation of intestinal inflammation, plays a pivotal role in disrupting intestinal homeostasis in IBD. The overabundance of ROS/RNS can cause intestinal tissue damage and the disruption of crucial gut proteins, which ultimately compromises the integrity of the intestinal barrier. The proliferation of M1 macrophages contributes to an exaggerated immune response, further compromising the intestinal immune barrier. Currently, intestinal nanomaterials have gained widespread attention in the context of IBD due to their notable characteristics, including the ability to specifically target regions of interest, clear excess ROS/RNS, and mimic biological enzymes. In this review, we initially elucidated the gut microenvironment in IBD. Subsequently, we delineate therapeutic strategies involving two distinct types of nanomedicine, namely inorganic nanoparticles and natural product nanomaterials. Finally, we present a comprehensive overview of the promising prospects associated with the application of nanomedicine in future clinical settings for the treatment of IBD (graphic abstract). Different classes of nanomedicine are used to treat IBD. This review primarily elucidates the current etiology of inflammatory bowel disease and explores two prominent nanomaterial-based therapeutic approaches. First, it aims to eliminate excessive reactive oxygen species and reactive nitrogen species. Second, they focus on modulating the polarization of inflammatory macrophages and reducing the proportion of pro-inflammatory macrophages. Additionally, this article delves into the treatment of inflammatory bowel disease using inorganic metal nanomaterials and natural product nanomaterials.

Widely Targeted Metabolomic Analysis Reveals the Improvement in Panax notoginseng Triterpenoids Triggered by Arbuscular Mycorrhizal Fungi via UPLC-ESI-MS/MS.

Panax notoginseng is a highly valued perennial medicinal herb in China and is widely used in clinical treatments. The main purpose of this study was to elucidate the changes in the composition of P. notoginseng saponins (PNSs), which are the main bioactive substances, triggered by arbuscular mycorrhizal fungi (AMF) via ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). A total of 202 putative terpenoid metabolites were detected, of which 150 triterpene glycosides were identified, accounting for 74.26% of the total. Correlation analysis, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) of the metabolites revealed that the samples treated with AMF (group Ce) could be clearly separated from the CK samples. In total, 49 differential terpene metabolites were identified between the Ce and CK groups, of which 38 and 11 metabolites were upregulated and downregulated, respectively, and most of the upregulated differentially abundant metabolites were mainly triterpene glycosides. The relative abundances of the two major notoginsenosides (MNs), ginsenosides Rd and Re, and 13 rare notoginsenosides (RNs), significantly increased. The differential saponins, especially RNs, were more easily clustered into one branch and had a high positive correlation. It could be concluded that the biosynthesis and accumulation of some RNs share the same pathways as those triggered by AMF. This study provides a new way to obtain more notoginsenoside resources, particularly RNs, and sheds new light on the scientization and rationalization of the use of AMF agents in the ecological planting of medicinal plants.

Functions of Melatonin during Postharvest of Horticultural Crops.

Melatonin, a tryptophan-derived molecule, is endogenously generated in animal, plant, fungal and prokaryotic cells. Given its antioxidant properties, it is involved in a myriad of signaling functions associated with various aspects of plant growth and development. In higher plants, melatonin (Mel) interacts with plant regulators such as phytohormones, as well as reactive oxygen and nitrogen species including hydrogen peroxide (H2O2), nitric oxide (NO) and hydrogen sulfide (H2S). It shows great potential as a biotechnological tool to alleviate biotic and abiotic stress, to delay senescence and to conserve the sensory and nutritional quality of postharvest horticultural products which are of considerable economic importance worldwide. This review provides a comprehensive overview of the biochemistry of Mel, whose endogenous induction and exogenous application can play an important biotechnological role in enhancing the marketability and hence earnings from postharvest horticultural crops.

Aurozyme: A Revolutionary Nanozyme in Colitis, Switching Peroxidase-Like to Catalase-Like Activity.

A therapeutic strategy that could address colitis of multiple etiologies while restoring the dysbiosis of gut microbiota is attractive. Here, Aurozyme, a novel nanomedicine comprised of gold nanoparticles (AuNPs) and glycyrrhizin (GL) with a glycol chitosan coating layer, as a promising approach for colitis, is demonstrated. The unique feature of Aurozyme is the conversion of harmful peroxidase-like activity of AuNPs to beneficial catalase-like activity due to the amine-rich environment provided by the glycol chitosan. This conversion process enables Aurozyme to oxidize the hydroxyl radicals derived from AuNP, producing water and oxygen molecules. In fact, Aurozyme effectively scavenges reactive oxygen/reactive nitrogen species (ROS/RNS) and damage-associated molecular patterns (DAMPs), which can attenuate the M1 polarization of macrophage. It exhibits prolonged adhesion to the lesion site, promoting sustained anti-inflammatory effects and restoring intestinal function in colitis-challenged mice. Additionally, it increases the abundance and diversity of beneficial probiotics, which are essential for maintaining microbial homeostasis in the gut. The work highlights the transformative potential of nanozymes for the comprehensive treatment of inflammatory disease and represents an innovative switching technology of enzyme-like activity by Aurozyme.

Neurostimulation in generalized epilepsy: A systematic review and meta-analysis.

OBJECTIVE: There are three neurostimulation devices available to treat generalized epilepsy: vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). However, the choice between them is unclear due to lack of head-to-head comparisons. A systematic comparison of neurostimulation outcomes in generalized epilepsy has not been performed previously. The goal of this meta-analysis was to determine whether one of these devices is better than the others to treat generalized epilepsy. METHODS: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review of PubMed, Embase, and Web of Science was performed for studies reporting seizure outcomes following VNS, RNS, and DBS implantation in generalized drug-resistant epilepsy between the first pivotal trial study for each modality through August 2022. Specific search criteria were used for VNS ("vagus", "vagal", or "VNS" in the title and "epilepsy" or "seizure"), DBS ("deep brain stimulation", "DBS", "anterior thalamic nucleus", "centromedian nucleus", or "thalamic stimulation" in the title and "epilepsy" or "seizure"), and RNS ("responsive neurostimulation" or "RNS" in the title and "epilepsy" or "seizure"). From 4409 articles identified, 319 underwent full-text reviews, and 20 studies were included. Data were pooled using a random-effects model using the meta package in R. RESULTS: Sufficient data for meta-analysis were available from seven studies for VNS (n = 510) and nine studies for DBS (n = 87). Data from RNS (five studies, n = 18) were insufficient for meta-analysis. The mean (SD) follow-up durations were as follows: VNS, 39.1 (23.4) months; DBS, 23.1 (19.6) months; and RNS, 22.3 (10.6) months. Meta-analysis showed seizure reductions of 48.3% (95% confidence interval [CI] = 38.7%-57.9%) for VNS and 64.8% (95% CI = 54.4%-75.2%) for DBS (p = .02). SIGNIFICANCE: Our meta-analysis indicates that the use of DBS may lead to greater seizure reduction than VNS in generalized epilepsy. Results from RNS use are promising, but further research is required.

Recent advances in cold atmospheric plasma (CAP) for breast cancer therapy.

The serious problems of conventional breast cancer therapy strategies such as drug resistance, severe side effects, and lack of selectivity prompted the development of various cold atmospheric plasma (CAP) devices. Due to its advanced technology, CAP can produce a unique environment rich in reactive oxygen and nitrogen species (RONS), photons, charged ions, and an electric field, making it a promising revolutionary platform for cancer therapy. Despite substantial technological successes, CAP-based therapeutic systems are encounter with distinct limitations, including low control of the generated RONS, poor knowledge about its anticancer mechanisms, and challenges concerning designing, manufacturing, clinical translation, and commercialization, which must be resolved. The latest developments in CAP-based therapeutic systems for breast cancer treatment are discussed in this review. More significantly, the integration of CAP-based medicine approaches with other breast cancer therapies, including chemo- and nanotherapy is thoroughly addressed.

Neuro-stimulation in focal epilepsy: A systematic review and meta-analysis.

OBJECTIVES: Different neurostimulation modalities are available to treat drug-resistant focal epilepsy when surgery is not an option including vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS). Head-to-head comparisons of efficacy do not exist between them nor are likely to be available in the future. We performed a meta-analysis on VNS, RNS, and DBS outcomes to compare seizure reduction efficacy for focal epilepsy. METHODS: We systematically reviewed the literature for reported seizure outcomes following implantation with VNS, RNS, and DBS in focal-onset seizures and performed a meta-analysis. Prospective or retrospective clinical studies were included. RESULTS: Sufficient data were available at years one (n = 642, two (n = 480), and three (n = 385) for comparing the three modalities with each other. Seizure reduction for the devices at years one, two, and three respectively were: RNS: 66.3%, 56.0%, 68.4%; DBS- 58.4%, 57.5%, 63.8%; VNS 32.9%, 44.4%, 53.5%. Seizure reduction at year one was greater for RNS (p < 0.01) and DBS (p < 0.01) compared to VNS. CONCLUSIONS: Our findings indicate the seizure reduction efficacy of RNS is similar to DBS, and both had greater seizure reductions compared to VNS in the first-year post-implantation, with the differences diminishing with longer-term follow-up. SIGNIFICANCE: The results help guide neuromodulation treatment in eligible patients with drug-resistant focal epilepsy.

A highly sensitive and specific luminescent MOF determines nitric oxide production and quantifies hydrogen sulfide-mediated inhibition of nitric oxide in living cells.

The synthesis of a novel carboxylate-type organic linker-based luminescent MOF (Zn(H2L) (L1)) (named PUC2) (H2L = 2-aminoterephtalic acid, L1 = 1-(3-aminopropyl) imidazole) is reported by the solvothermal method and comprehensively characterized using single-crystal XRD, PXRD, FTIR, TGA, XPS, FESEM, HRTEM, and BET. PUC2 selectively reacts with nitric oxide (▪NO) with a detection limit of 0.08 µM, and a quenching constant (0.5 × 104 M-1) indicating a strong interaction with ▪NO. PUC2 sensitivity remains unaffected by cellular proteins or biologically relevant metals (Cu2+/ Fe3+/Mg2+/ Na+/K+/Zn2+), RNS/ROS, or H2S to score ▪NO in living cells. Lastly, we used PUC2 to demonstrate that H2S inhibition increases ▪NO production by ~ 14-30% in various living cells while exogenous H2S suppresses ▪NO production, indicating that the modulation of cellular ▪NO production by H2S is rather generic and not restricted to a particular cell type. In conclusion, PUC2 can successfully detect ▪NO production in living cells and environmental samples with considerable potential for its application in improving the understanding of the role of ▪NO in biological samples and study the inter-relationship between ▪NO and H2S.

Activation of NLRP3 Inflammasome in Liver of Long Evans Lactating Rats and Its Perinatal Effects in the Offspring after Bisphenol F Exposure.

The liver is the organ responsible for the metabolism and detoxification of BPF, the BPA analogue that is replacing it in plastic-based products. It is not known whether BPF can trigger inflammatory responses via the NLRP3 inflammasome, which plays a major role in the development of liver disease. The aim of this study was to evaluate nitrosative stress species (RNS) and NLRP3 inflammasome activation in the liver of lactating dams after BPF exposure. Moreover, it was studied whether this effect could also be observed in the liver of female and male offspring at postnatal day 6 (PND6). 36 Long Evans rats were randomly distributed according to oral treatment into three groups: Control, BPF-low dose (LBPF; 0.0365 mg/kg b.w./day) group and BPF-high dose (HBPF; 3.65 mg/kg b.w./day) group. The levels of nitrosative stress-inducing proteins (eNOS, iNOS, HO-1d), NLRP3 inflammasome components (NLRP3, PyCARD, CASP1) and proinflammatory cytokines (IL-1ß, IL-18, IFN-γ and TNF-α) were measured by gene and protein expression in the liver of lactating dams and in female and male PND6 offspring. Lactating dams treated with LBPF showed a significant increase in iNOS and HO-1d, activation of NLRP3 components (NLRP3, PyCARD, CASP1) and promoted the release of proinflammatory cytokines such as IL-1ß, IL-18, IFN-γ and TNF-α. Similar effects were found in female and male PND6 offspring after perinatal exposure. LBPF oral administration and perinatal exposure caused an increase of nitrosative stress markers and proinflammatory cytokines. Also, NLRP3 inflammasome activation was significantly increased in in the liver of lactating dams and PND6 offspring.

COVID-19 Complications: Oxidative Stress, Inflammation, and Mitochondrial and Endothelial Dysfunction.

SARS-CoV-2 infection, discovered and isolated in Wuhan City, Hubei Province, China, causes acute atypical respiratory symptoms and has led to profound changes in our lives. COVID-19 is characterized by a wide range of complications, which include pulmonary embolism, thromboembolism and arterial clot formation, arrhythmias, cardiomyopathy, multiorgan failure, and more. The disease has caused a worldwide pandemic, and despite various measures such as social distancing, various preventive strategies, and therapeutic approaches, and the creation of vaccines, the novel coronavirus infection (COVID-19) still hides many mysteries for the scientific community. Oxidative stress has been suggested to play an essential role in the pathogenesis of COVID-19, and determining free radical levels in patients with coronavirus infection may provide an insight into disease severity. The generation of abnormal levels of oxidants under a COVID-19-induced cytokine storm causes the irreversible oxidation of a wide range of macromolecules and subsequent damage to cells, tissues, and organs. Clinical studies have shown that oxidative stress initiates endothelial damage, which increases the risk of complications in COVID-19 and post-COVID-19 or long-COVID-19 cases. This review describes the role of oxidative stress and free radicals in the mediation of COVID-19-induced mitochondrial and endothelial dysfunction.

Dental Pulp Inflammation Initiates the Occurrence of Mast Cells Expressing the α1 and ß1 Subunits of Soluble Guanylyl Cyclase.

The binding of nitric oxide (NO) to heme in the ß1 subunit of soluble guanylyl cyclase (sGC) activates both the heterodimeric α1ß1 and α2ß1 isoforms of the enzyme, leading to the increased production of cGMP from GTP. In cultured human mast cells, exogenous NO is able to inhibit mast cell degranulation via NO-cGMP signaling. However, under inflammatory oxidative or nitrosative stress, sGC becomes insensitive to NO. The occurrence of mast cells in healthy and inflamed human tissues and the in vivo expression of the α1 and ß1 subunits of sGC in human mast cells during inflammation remain largely unresolved and were investigated here. Using peroxidase and double immunohistochemical incubations, no mast cells were found in healthy dental pulp, whereas the inflammation of dental pulp initiated the occurrence of several mast cells expressing the α1 and ß1 subunits of sGC. Since inflammation-induced oxidative and nitrosative stress oxidizes Fe2+ to Fe3+ in the ß1 subunit of sGC, leading to the desensitization of sGC to NO, we hypothesize that the NO- and heme-independent pharmacological activation of sGC in mast cells may be considered as a regulatory strategy for mast cell functions in inflamed human dental pulp.

Effect of Plasma On-Time with a Fixed Duty Ratio on Reactive Species in Plasma-Treated Medium and Its Significance in Biological Applications.

Optimizing the therapeutic range of nonthermal atmospheric pressure plasma (NTAPP) for biomedical applications is an active research topic. For the first time, we examined the effect of plasma on-times in this study while keeping the duty ratio and treatment time fixed. We have evaluated the electrical, optical, and soft jet properties for two different duty ratios of 10% and 36%, using the plasma on-times of 25, 50, 75, and 100 ms. Furthermore, the influence of plasma on-time on reactive oxygen and nitrogen species (ROS/RNS) levels in plasma treated medium (PTM) was also investigated. Following treatment, the characteristics of (DMEM media) and PTM (pH, EC, and ORP) were also examined. While EC and ORP rose by raising plasma on-time, pH remained unchanged. Finally, the PTM was used to observe the cell viability and ATP levels in U87-MG brain cancer cells. We found it interesting that, by increasing the plasma on-time, the levels of ROS/RNS dramatically increased in PTM and significantly affected the viability and ATP levels of the U87-MG cell line. The results of this study provide a significant indication of advancement by introducing the optimization of plasma on-time to increase the efficacy of the soft plasma jet for biomedical applications.

Structural Features of Small Molecule Antioxidants and Strategic Modifications to Improve Potential Bioactivity.

This review surveys the major structural features in various groups of small molecules that are considered to be antioxidants, including natural and synthetic compounds alike. Recent advances in the strategic modification of known small molecule antioxidants are also described. The highlight is placed on changing major physicochemical parameters, including log p, bond dissociation energy, ionization potential, and others which result in improved antioxidant activity.