Nitric Oxide Release Research Articles

Experimental and ReaxFF MD study on the release characteristics of gaseous nitrogen during pressurized bituminous coal gasification

Coal gasification is the leading technology of clean coal technology such as Integrated Gasification Combined Cycle (IGCC). The release pattern of gaseous nitrogen during coal gasification is crucial for clean coal technology. This paper investigated the gaseous nitrogen emission characteristics of pressurized gasification through experiments and molecular dynamics studies. The experimental results show that the elevated temperatures promoted the release of NO and accelerated the conversion of nitrogen-containing precursors (HCN, NH3). However, high pressure weakened the effect of temperature and resulted in the decreased emissions of HCN, NH3, and NO. Because high pressure facilitated the conversion of fuel nitrogen to nitrogen. The emissions of HCN and NH3 decreased as the CO2 blending ratio increased, while NO emissions increased. The observed difference was primarily attributed to the amounts of free radicals and was also related to gas-phase reactions involving H2O and CO2. Furthermore, as the primary nitrogen-containing structure in bituminous coal, the pyrrole was used in Reactive force field molecular dynamics (ReaxFF MD) to study the release of gas-phase nitrogen during gasification process. The simulation results show that both temperature and pressure promote the migration of pyrrole nitrogen and also provided the main nitrogen migration paths during gasification which can be used to (indirectly) confirm the experimental analysis. The O2/N2/CO2 gasification system supplied additional O and OH radicals to enhance NO emissions, while H2O directly participated in reaction paths such as CN, NCO → NHi or provided H radicals to increase NH3 emissions.

IFNγ insufficiency during mouse intra-vaginal Chlamydia trachomatis infection exacerbates alternative activation in macrophages with compromised CD40 functions

Chlamydia trachomatis (C.tr), an obligate intracellular pathogen, causes asymptomatic genital infections in women and is a leading cause of preventable blindness. We have developed in vivo mouse models of acute and chronic C. trachomatis genital infection to explore the significance of macrophage-directed response in mediating immune activation/suppression. Our findings reveal that during chronic and repeated C. trachomatis infections, Th1 response is abated while Treg response is enhanced. Additionally, an increase in exhaustion (PD1, CTLA4) and anergic (Klrg3, Tim3) T cell markers is observed during chronic infection. We have also observed that M2 macrophages with low CD40 expression promote Th2 and Treg differentiation leading to sustained C. trachomatis genital infection. Macrophages infected with C. trachomatis or treated with supernatant of infected epithelial cells drive them to an M2 phenotype. C. trachomatis infection prevents the increase in CD40 expression as observed in western blots and flow cytometric analysis. Insufficient IFNγ, as observed during chronic infection, leads to incomplete clearance of bacteria and poor immune activation. C. trachomatis decapacitates IFNγ responsiveness in macrophages via hampering IFNγRI and IFNγRII expression which can be correlated with poor expression of MHC-II, CD40, iNOS and NO release even following IFNγ supplementation. M2 macrophages during C. trachomatis infection express low CD40 rendering immunosuppressive, Th2 and Treg differentiation which could not be reverted even by IFNγ supplementation. The alternative macrophages also harbour high bacterial load and are poor responders to IFNγ, thus promoting immunosuppression. In summary, C. trachomatis modulates the innate immune cells, attenuating the anti-chlamydial functions of T cells in a manner that involves decreased CD40 expression on macrophages.

Vibroacoustic therapy to treat pain in the temporomandibular joint

Pain in the temporomandibular joint (TMJ) affects about 4.8 % of the United States population. Pain is the most common symptom of TMJ and the chief reason patients seek care. Conventional treatments range from non-invasive therapies including physical therapy, dental guards and occlusal splints to interventions such as corticosteroid injections and surgery. At present, the most common challenge to healthcare providers in patients presenting with TMJ is the reduction of pain. Vibroacoustic therapy (VAT) is noninvasive and safe as a potential treatment for TMJ pain. VAT involves low-frequency vibrations from 30 to 120 + Hertz. Biological mechanisms to explain a beneficial effect include enhanced blood circulation, decreased swelling, and promotion of muscle relaxation. VAT also appears to have beneficial effects on skin and bone conduction as well as stimulates relaxation responses and the release of nitric oxide. Clinical studies of VAT to reduce TMJ pain are promising but limited in design and sample sizes. The most reliable design strategy to detect the most plausible small to moderate benefit of VAT on TMJ pain is a randomized trial. This trial should be of sufficient size, dose, and duration. If VAT has a favorable benefit-to-risk ratio, then it would represent a safe, noninvasive, feasible and cost-effective means to treat TMJ.

Ligand environment and light: two triggers for controlling cytotoxicity of ruthenium nitrosyl complexes

Photoinduced nitric oxide (NO) release for complexes [RuNO(L)2(NO2)2OH], where L = methyl isonicotinate (1), ethyl isonicotinate (2), methyl nicotinate (3) and ethyl nicotinate (4) was studied in DMSO, MeCN and water solutions (PBS, CTAB) using spectroscopic methods (UV‐vis, IR, EPR) and spectrometric techniques (ESI‐МS). Additionally, we present methodological evidence for improving the calculation of the quantum yield (QY) of NO release through the utilization of a combined IR‐UV‐vis‐spectroscopy flow‐through setup. According to DFT calculations, the production of nitric oxide occurs through the photoinduced cleavage of the Ru‐NO bond, triggered by irradiation at 445 or 532 nm. This cleavage is a consequence of charge transfer from the orbitals of the Ru‐OH group and the equatorial ligands (HOMO, HOMO‐1) to the Ru‐NO antibonding orbital (LUMO). The cytotoxicity and photoinduced cytotoxicity of the investigated compounds were assessed against the breast adenocarcinoma cell line MCF‐7. Moreover, the investigation of the lipophilic properties of compounds 1‐4 unveiled a significant influence of their lipophilicity on cytotoxic behavior, allowing for the modification of cytotoxicity through changes in the ligand L or by light irradiation.

Achieving Biomedically Desirable Nitric Oxide Release from Glucose Monitor Surfaces Via a Cu-Based Catalyst Coating.

We report the design of a blood-contacting glucose monitor with a nitric oxide (NO)-releasing metal-organic framework (MOF) embedded within the outer polymer layer of a glucose sensor to promote the release of NO from endogenous NO donors. The sensors were tested by using amperometry across a range of glucose concentrations to assess whether the presence of either the MOF or NO decreased the performance of the glucose monitor. Even though signal response was diminished, the sensors maintained a good regression fit (R2 = 0.9944) and a similar dynamic range and reproducibility in the presence of S-nitrosoglutathione.

NIR-Triggered Multifunctional NO Nanoplatform for Conquering Thermal Resistance in Biofilms.

Photothermal treatment (PTT) has emerged as a promising avenue for biofilm elimination, yet its potential drawbacks, such as local hyperpyrexia and bacterial heat resistance, have posed challenges. To address these concerns, an innovative nanoplatform (Au@mSiO2 -arg/ICG) is devised that integrates phototherapeutic and gas therapeutic functionalities. This multifaceted nanoplatform is composed of mesoporous silica-coated Au nanorods (Au@mSiO2 ), supplemented with l-arginine (l-arg) and indocyanine green (ICG), and is engineered for mild temperature PTT aimed at biofilm eradication. Au@mSiO2 -arg/ICG nanoparticles (NPs) show excellent antibacterial effects through the generation of nitric oxide (NO) gas, heat, and reactive oxygen species (ROS) under 808nm light irradiation. The ROS generated by ICG initiates a cascade reaction with l-arg, ultimately yielding NO gas molecules. This localized release of NO not only effectively curbs the expression of heat shock proteins 70 mitigating bacterial thermoresistance, but also reduces extracellular polymeric substance allowing better penetration of the therapeutic agents. Furthermore, this nanoplatform achieves an outstanding biofilm elimination rate of over 99% in an abscess model under 808nm light irradiation (0.8 W·cm-2 ), thereby establishing its potential as a dependable strategy for NO-enhanced mild PTT and antibacterial photodynamic therapy (aPDT) in clinical settings.

Applications of nitric oxide-releasing nanomaterials in dermatology: Skin infections and wound healing

Nitric oxide (NO) is produced in most cells in the skin and is an important regulator of essential cutaneous functions, including responses to UV irradiation, microbial defense, wound healing, melanogenesis and epidermal permeability barrier homeostasis. Harnessing the physiological activities of NO for therapeutic use is difficult because the molecule is highly reactive and unstable. A variety of exogenous NO delivery platforms have been developed and evaluated; however, they have limited clinical applications in dermatology due to instability and poor cutaneous penetration. NO-releasing nanomaterials overcome these limitations, providing targeted tissue delivery, and sustained and controlled NO release. This review provides a comprehensive and up-to-date evaluation of the use of NO-releasing nanomaterials in dermatology for the treatment of skin and soft tissue infections and wound healing.

DEFB114 protein enhances host resistance to fungal infection through the NOD1/2-ATG16L1-NF-κB signaling pathway

The overuse of antibiotics has led to the enhanced resistance of many pathogenic bacteria, posing a threat to human health. Therefore, there is a need to develop green and safe alternatives to antibiotics. Beta-defensins play a crucial role in host defense against pathogens and have multifunctional properties, exerting key roles in innate and adaptive immunity, as well as non-immune processes. In this study, a 210 bp long cDNA sequence of yak DEFB114 gene was amplified and successfully expressed in a prokaryotic system. The DEFB114 protein exhibited significant inhibitory effects on the growth of Aspergillus fumigatus in vitro. When co-cultured with yak macrophages, DEFB114 protein enhanced macrophage phagocytic activity and increased nucleic acid fluorescence intensity (P < 0.05). DEFB114 protein also enhanced the activity of yak macrophages stimulated by inactivated Aspergillus fumigatus spores, increased the release of nitric oxide (NO), and promoted the expression of genes such as γ-actin, Lgals, Man2b, and Capg (P < 0.05). In mice experiments, DEFB114 protein promoted resistance against Aspergillus fumigatus infection, by regulating the NOD1/2-ATG16L1-NF-κB pathway to modulate the host immune response and exert its anti-infective effects. In summary, the yak DEFB114 protein could inhibit the growth of Aspergillus fumigatus and enhance the animal's resistance to pathogenic microorganisms, thereby having significant implications in the treatment and prevention of fungal infections.

Potential Anti-Inflammatory Constituents from Aesculus wilsonii Seeds.

A chemical study of Aesculus wilsonii Rehd. (also called Suo Luo Zi) and the in vitro anti-inflammatory effects of the obtained compounds was conducted. Retrieving results through SciFinder showed that there were four unreported compounds, aeswilosides I-IV (1-4), along with fourteen known isolates (5-18). Their structures were elucidated by extensive spectroscopic methods such as UV, IR, NMR, [α]D, and MS spectra, as well as acid hydrolysis. Among the known ones, compounds 5, 6, 8-10, and 12-16 were obtained from the Aesculus genus for the first time; compounds 7, 11, 17, and 18 were first identified from this plant. The NMR data of 5 and 18 were reported first. The effects of 1-18 on the release of nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW264.7 cells were determined. The results showed that at concentrations of 10, 25, and 50 μM, the novel compounds, aeswilosides I (1) and IV (4), along with the known ones, 1-(2-methylbutyryl)phloroglucinyl-glucopyranoside (10) and pisuminic acid (15), displayed significant inhibitory effects on NO production in a concentration-dependent manner. It is worth mentioning that compound 10 showed the best NO inhibitory effect with a relative NO production of 88.1%, which was close to that of the positive drug dexamethasone. The Elisa experiment suggested that compounds 1, 4, 10, and 15 suppressed the release of TNF-α and IL-1β as well. In conclusion, this study enriches the spectra of compounds with potential anti-inflammatory effects in A. wilsonii and provides new references for the discovery of anti-inflammatory lead compounds, but further mechanistic research is still needed.

Characterization of an exopolysaccharide synthesized by Lacticaseibacillus rhamnosus B6 and its immunomodulatory activity in vitro

An exopolysaccharide, designated F1, was purified from the fermented milk by Lacticaseibacillus rhamnosus strain B6 (CGMCC No. 13310). F1, with the weight average molecular weight of 1.577 × 106 Da, is consisted of rhamnose, glucose and galactose in a molar ratio of 3.7:1.5: 1. The backbone included 1,3-linked Rha, 1,2,3-linked Rha, 1,2-linked Glc and 1,3-linked Glc residues, with the branching point located at O2 position of 1,2,3-linked Rha residue, and the branch chain composed of terminal linked galactose residue with a pyruvate substituent. F1 could significantly stimulate the phagocytic activity and TNF-α expression in RAW 264.7 macrophages in a dose-dependent manner, and the release of NO at 200 μg/mL as well. F1 at 200 μg/mL could stimulate the expression of the pro-inflammatory cytokine encoding genes including TNF-α and iNOS, but with a negligible upregulating effect on the mRNA expression of IL-10. F1 could up-regulate the expression of NF-κBp65 and skew macrophage polarization towards M1 phenotype. These results suggest F1 elicit an immunomodulatory effect through the NF-κB signaling pathway.

Ultrasound triggered local sequential reactive oxygen species and nitric oxide release for enhanced cerasomal drug delivery

Liposomal drug delivery for tumor therapy was still suffered from low stability, limited delivering efficiency and poor tumor penetration, greatly compromising the therapeutic efficacy. Herein, a stable and ultrasound triggered cerasomal drug delivery system was developed by loading doxorubicin (DOX) into stable liposomal cerasome, which was self-assembled from cerasome-forming lipid (CFL), sonosensitizer of porphyrin lipid (PL), nitric oxide (NO) donor of DSPE-PEG2000-SNO and unsaturated phospholipids DOPC, resulting in DOX@PC-SNO with stable siloxane network and S-nitrosothiol on surface, sonosensitizer in lipid bilayer and DOX in the core. DOX@PC-SNO can prevent drug leakage during blood circulation and efficiently accumulate at the tumor site at 24 h post-injection, while controllably generate reactive oxygen species (ROS) upon local ultrasound irradiation on tumor, which can not only use for SDT, but also operate as a switch for on-demand controlled release of internal DOX and external NO, resulting in specific delivery and high penetration of chemotherapeutic drug into the deep tumor, thus greatly improved antitumor efficacy without observed side effects.

Construction of poly (ionic liquid)-derived gold/silver alloy@nitrogen-doped carbon shell and its application for ratiometric electrochemical detection of nitric oxide

A nitrogen-doped carbon shell loaded with a gold and silver alloy (Au/Ag@NCS) was constructed for highly sensitive electrochemical detection of NO. The Au/Ag@NCS material was prepared by use of SiO2 particles as a template to polymerize imidazolium-based ionic liquids loaded with gold and silver salts, and subsequent carbonization treatment and template removal. The hollow structure of the carbon material acted as a carrier for electrochemical sensing, offering high specific surface area, large pore capacity, robust electron conductivity, and excellent mechanical stability. The inclusion of gold in the composite enhanced its catalytic and sensing capabilities, while silver oxidation was employed as a reference signal for accurate detection. By utilization of the Au/Ag@NCS-modified electrode, a wide detection range from 0.5 nM to 1.05 μM with a low detection limit of 0.32 nM was achieved for NO detection. The electrochemical sensor also exhibited high selectivity and excellent stability. The fabricated sensor was further utilized to explore the release of NO from breast cancer cells, revealing that the electrochemical platform could be regarded as an important method to study the daily tests of NO in clinical application.

Hyperchloremia and Hypernatremia Decreased Microglial and Neuronal Survival during Oxygen-Glucose Deprivation/Reperfusion.

Hyperchloremia and hypernatremia are associated with higher mortality in ischemic stroke, but it remains unclear whether their influence directly contributes to ischemic injury. We investigated the impact of 0.9% sodium chloride (154 mM NaCl), 0.9% sodium acetate (167 mM CH3COONa), and their different combinations (3:1, 2:1, and 1:1) on microglial (HMC-3) and neuronal (differentiated SH-SY5Y) survival during oxygen-glucose deprivation/reperfusion (OGD/R). Further, we assessed the effect of hyperchloremia and hypernatremia-treated and OGD/R-induced HMC-3-conditioned media on differentiated SH-SY5Y cells under OGD/R conditions. We performed cell viability, cell toxicity, and nitric oxide (NO) release assays and studied the alteration in expression of caspase-1 and caspase-3 in different cell lines when exposed to hyperchloremia and hypernatremia. Cell survival was decreased in 0.9% NaCl, 0.9% CH3COONa, combinations of HMC-3 and differentiated SH-SY5Y, and differentiated SH-SY5Y cells challenged with HMC-3-conditioned media under normal and OGD/R conditions. Under OGD/R conditions, differentiated SH-SY5Y cells were less likely to survive exposure to 0.9% NaCl. Expression of caspase-1 and caspase-3 in HMC-3 and differentiated SH-SY5Y cells was altered when exposed to 0.9% NaCl, 0.9% CH3COONa, and their combinations. A total of 0.9% NaCl and 0.9% CH3COONa and their combinations decreased the NO production in HMC-3 cells under normal and OGD/R conditions. Both hypernatremia and hyperchloremia reduced the survival of HMC-3 and differentiated SH-SY5Y cells under OGD/R conditions. Based on the OGD/R in vitro model that mimics human ischemic stroke conditions, it possibly provides a link for the increased death associated with hyperchloremia or hypernatremia in stroke patients.

Berberine attenuates inflammation and oxidative stress and modulates lymphocyte E-NTPDase in acute hyperlipidemia.

Hyperlipidemia is a common clinically encountered health condition worldwide that promotes the development and progression of cardiovascular diseases, including atherosclerosis. Berberine (BBR) is a natural product with acknowledged anti-inflammatory, antioxidant, and metabolic effects. This study evaluated the effect of BBR on lipid alterations, oxidative stress, and inflammatory response in rats with acute hyperlipidemia induced by poloxamer-407 (P-407). Rats were pretreated with BBR (25 and 50 mg/kg) for 14 days and acute hyperlipidemia was induced by a single dose of P-407 (500 mg/kg). BBR ameliorated hypercholesterolemia, hypertriglyceridemia, and plasma lipoproteins in P-407-adminsitered rats. Plasma lipoprotein lipase (LPL) activity was decreased, and hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity was enhanced in hyperlipidemic rats. The expression of low-density lipoprotein receptor (LDL-R) and ATP-binding cassette transporter 1 (ABCA1) was downregulated in hyperlipidemic rats. BBR enhanced LPL activity, upregulated LDL-R, and ABCA1, and suppressed HMG-CoA reductasein P-407-administered rats. Pretreatment with BBR ameliorated lipid peroxidation, nitric oxide (NO), pro-inflammatory mediators (interleukin [IL]-6,IL-1β, tumor necrosis factor [TNF]-α, interferon-γ, IL-4 and IL-18) and enhanced antioxidants. In addition, BBR suppressed lymphocyte ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase (E-ADA) as well as NO and TNF-α release by macrophages isolated from normal and hyperlipidemic rats. In silico investigations revealed the binding affinity of BBR towardLPL, HMG-CoA reductase, LDL-R, PSK9, ABCA1, and E-NTPDase. In conclusion, BBR effectively prevented acute hyperlipidemia and its associated inflammatory responses by modulating LPL, cholesterolgenesis, cytokine release, and lymphocyte E-NTPDase and E-ADA. Therefore, BBR is an effective and safe natural compound that might be employed as an adjuvant against hyperlipidemia and its associated inflammation.

Hematohidrosis in Pediatric Practice – a Case Report and Review of the Literature

Hematohidrosis (bloody sweat) is a symptom of trophic damage to the vascular wall, in which sweat mixes with blood and seeps onto undamaged areas of the skin in the form of red or pink liquid (depending on the ratio of sweat to blood). In our study we have analyzed 25 case reports of hematohidrosis in children, reported throughout the world using PubMed, ResearchGate with detailed description and opened access. We took into consideration: age of the patient, sex, location of bloody excretion, cause or trigger, treatment and its effectiveness.Our clinical case present a 9-year-old girl complained of a periodic bleeding from the intact skin of the face, neck, thighs (without visible damage to the skin) manifested by red or pink liquid, nosebleeds, and bloody discharge from the mucous membrane of the eyes. The secretions were of varying intensity and lasted up to several hours. Most of all episodes are associated with a strong emotional exertion. One of the theories of hematohidrosis pathogenesis is evident vasoconstriction of the blood vessels surrounding the sweat glands, provoked by hyperactivation of the sympathetic nervous system, which is followed by their excessive vasodilation up to rupture and blood entering the sweat gland ducts. Capillary endothelial cells are known to contain β2-adrenoceptors, which, through the modulation of nitric oxide release, cause endothelium-dependent vasodilation. Blocking β-adrenoceptors (for example, propranolol) prevents excessive vasodilation of blood vessels and, accordingly, their rupture and blood flow to the sweat gland.We managed to find out that the patient’s bloody sweat was a manifestation of a separate pathological phenomenon, and not one of the symptoms of another disease. A properly formed treatment complex and the great trust of the parents enabled to stabilize the child’s condition, and later to cure her. Currently, hematohidrosis is recognized as an independent disease that requires in-depth study of the triggering mechanisms of development, pathogenetic and clinical features.

Effect of preparation method of pyrolysis liquid mixed with coal on its ignition and combustion characteristics

Relevance. The need to develop technological solutions to increase the competitiveness of pyrolysis processing of various wastes. Combustion of pyrolysis liquid in a mixture with coal is one of these solutions, which makes it possible to stabilize the properties of the obtained fuel and use in standard energy equipment. Aim. To determine the influence of the method of preparing a mixture of pyrolysis liquid and low-grade coal on its ignition and combustion characteristics, as well as on composition of the released gas-phase products, depending on the temperature of heating medium and concentration of the additive. Methods. Pyrolysis and oxidation characteristics were studied using thermogravimetric analysis, and formal kinetic constants were calculated using the Coates–Radfern method. Samples of mixed fuels were prepared by the methods of homogeneous mixing and surface wetting of pyrolysis liquid of rubber processing and low-grade coal. Ignition and combustion characteristics were determined using an experimental stand, and composition of gas-phase combustion products was determined using once-through gas analyzer. Results. The authors have determined the features of pyrolysis and oxidation of the pyrolysis liquid as well as the values of formal kinetics constants, indicating the physical nature of the factors that defining the rate of these processes. It was found that at 600 °C the ignition of the studied mixtures weakly depended on concentration of the additive, while at 700 and 800 °C the dependence was linear, and the differences between the samples prepared using different methods were insignificant. For samples obtained by the method of surface wetting, combustion of the additive occurred in the gas phase near the surface of the sample. For the samples obtained by the method of uniform mixing, it occurred predominantly in the bulk of the backfill. This led to more intense and complete coal combustion in these compositions due to more uniform releasing of heat and initiation of coal particles. The concentration curves of the NO, CO and CO2 release demonstrated, that behavior of the fuel mixture components was additive in terms of released gas-phase combustion products, as well as the absence of significant nonlinear effects over the entire studied range of temperatures and additive concentrations.

Chickpea Sprouts as a Potential Dietary Support in Different Prostate Disorders-A Preliminary In Vitro Study.

Prostate cancer (PC) and benign prostatic hyperplasia (BPH) are common health problems in the aging male population. Due to the unexplored and unconfirmed impact of food containing isoflavones, like sprouts, on the development of the management of BPH and prostate cancer, we decided to extend the knowledge in this area. We have demonstrated for the first time that chickpea sprouts may play an important role in the chemoprevention of prostate disorders. However, attention should be paid to the isoflavone content in the sprouts, as in our study, chickpea sprouts with a moderate concentration of the compounds, harvested in natural light conditions (CA10L) and blue LED light (CA7B), showed the best scores in terms of their potential towards prostate disorders. Chickpea seeds were grown in LED chambers. The methanol extracts from sprouts were quantitatively defined using the HPLC system. Experiments such as the determination of PSA, 5-α-reductase, and dihydrotestosterone were performed on PNT2 and LNCaP cells. For anti-inflammatory assays (determination of NO, IL-6, and TNF-alpha release), murine RAW264.7 macrophages were used. The role of legume products as a diet element should be deeply evaluated for the development of future dietary recommendations for prostate cancer and BPH prevention.

Accurate Spatio-Temporal Delivery of Nitric Oxide Facilitates the Programmable Repair of Avascular Dense Connective Tissues Injury.

Avascular dense connective tissues (e.g., the annulus fibrosus (AF) rupture, the meniscus tear, and tendons and ligaments injury) repair remains a challenge due to the "biological barrier" that hinders traditional drug permeation and limits self-healing of the injured tissue. Here, accurate delivery of nitric oxide (NO) to penetrate the "AF biological barrier" is achieved thereby enabling programmable AF repair. NO-loaded BioMOFs are synthesized and mixed in a modified polyvinyl alcohol and PCL-composited electrospun fiber membrane with excellent reactive oxygen species-responsive capability (LN@PM). The results show that LN@PM could respond to the high oxidative stress environment at the injured tissue and realize continuous and substantial NO release. Based on low molecular weight and lipophilicity, NO could penetrate through the "biological barrier" for accurate AF drug delivery. Moreover, the dynamic characteristics of the LN@PM reaction can be matched with the pathological microenvironment to initiate programmable tissue repair including sequential remodeling microenvironment, reprogramming the immune environment, and finally promoting tissue regeneration. This tailored programmable treatment strategy that matches the pathological repair process significantly repairs AF, ultimately alleviating intervertebral disc degeneration. This study highlights a promising approach for avascular dense connective tissue treatment through intelligent NO release, effectively overcoming "AF biological barriers" and programmable treatment.

Anti-inflammatory and anti-arthritic potential of Coagulansin-A: in vitro and in vivo studies.

The current work was designed to evaluate the anti-inflammatory and anti-arthritic potential of Coagulansin-A (Coag-A) using mouse macrophages and arthritic mice. In the LPS-induced RAW 264.7 cells, the effects of Coag-A on the release of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory cytokines were analyzed. In addition, the mediators involved in the nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways were evaluated by the RT-qPCR and western blotting. Coag-A did not show significant cytotoxicity in the RAW 264.7 cells in the tested concentration range (1-100 µM). Coag-A significantly inhibited the production of NO, ROS, and key pro-inflammatory cytokines. The anti-inflammatory effects of Coag-A might be through inhibiting the NF-κB pathway and activating the Nrf2 pathway. In the arthritic mouse models, behavioral studies and radiological and histological analyses were performed. We found that the i.p. injection of Coag-A dose-dependently (1-10 mg/kg) reduced the Carrageenan-induced acute inflammation in the mice. In Complete Freund's Reagent-induced arthritic mouse model, Coag-A (10 mg/kg) showed significant anti-inflammatory and anti-arthritic effects in terms of the arthritic index, hematological parameters, and synovium inflammation. After the Coag-A treatment, the bone and tissue damage was ameliorated significantly in the arthritic mice. Moreover, immunohistochemistry of mouse paw tissues revealed a significant reduction in the expression of pro-inflammatory cytokines in the NF-κB pathway, confirming Coag-A's therapeutic potential and mechanism.

Glu and GSH double-unlocked immunomodulatory tri-cascade nanoreactor for biofilm-infected diabetic wounds healing

The treatment of diabetic wounds remains a challenge due to the interaction between hyperglycemia, immune imbalance and bacterial infection. Herein, we developed a Glu and GSH double-unlocked immunomodulatory nanocascade reactor to accelerate diabetic wounds healing which dynamically manages the wound microenvironment by controlling blood glucose levels, restoring immune regulation and eliminating bacteria. On the one hand, ultra-small gold nanoparticles with GOx activity can catalyse glucose at the diabetic wound site, which can be further enhanced by photothermal effects, thus destroying bacterial biofilm structures, reversing wounds pH, and reducing bacterial reproduction. On the other hand, the sustained controlled release of NO at specific sites was achieved by depleting over-expressed GSH in the wounds to restore normal immune regulation, which not only promotes M2 macrophage polarisation and expressions of anti-inflammatory factors such as IL-10 and TGF-β1, but also produces VEGF and CD31 via the PI3K/AKT signalling pathway. Especially, the chemical resonance energy transfer (CRET) strategy was first applied to diabetic wounds treatment, achieving chemical photodynamic therapy (PDT) while reducing the secondary tissue damage caused by catalytically-generated H2O2. In summary, the nanocascade reactor provides a new reference for bacterialy-infected diabetic wounds treatment mode by reducing blood glucose and restoring immune regulation in parallel.