scholarly journals Light-triggered nitric oxide delivery to malignant sites and infection

2013 ◽  
Vol 371 (1995) ◽  
pp. 20120368 ◽  
Author(s):  
Brandon Heilman ◽  
Pradip K. Mascharak
Keyword(s):  
Nitric Oxide ◽  
Site Specific ◽  
No Donors ◽  
On Demand ◽  
The Past ◽  
Signalling Molecule ◽  
Recent Developments ◽  
Nitric Oxide Delivery ◽  
Metal Nitrosyls

The discovery of nitric oxide (NO) as a signalling molecule in various physiological and pathological pathways has spurred research in the design of exogenous NO donors as drugs. In recent years, metal nitrosyls (NO complexes of metals) have been investigated as NO-donating agents. Results from our laboratory during the past few years have demonstrated that metal nitrosyls derived from designed ligands can deliver NO under the total control of light of various frequencies. Careful incorporation of these photoactive nitrosyls into polymer matrices has afforded a set of nitrosyl–polymer composites that can be used to make such NO delivery site-specific. The composite materials have shown excellent antineoplastic and antimicrobial actions in several in vitro experiments. This review highlights our key results in the context of recent developments in this area of NO donors that deliver NO on demand.

scholarly journals Nanomaterial Nitric Oxide Delivery in Traumatic Orthopedic Regenerative Medicine

2021 ◽  
Vol 8 ◽  
Author(s):  
Albert Thomas Anastasio ◽  
Ariana Paniagua ◽  
Carrie Diamond ◽  
Harrison R. Ferlauto ◽  
Joseph S. Fernandez-Moure
Keyword(s):  
Nitric Oxide ◽  
Bone Fractures ◽  
Sol Gel ◽  
Vascular Wall ◽  
Patient Specific ◽  
Organic Nitrates ◽  
Valuable Insight ◽  
No Donors ◽  
Recent Developments ◽  
Nitric Oxide Delivery

Achieving bone fracture union after trauma represents a major challenge for the orthopedic surgeon. Fracture non-healing has a multifactorial etiology and there are many risk factors for non-fusion. Environmental factors such as wound contamination, infection, and open fractures can contribute to non-healing, as can patient specific factors such as poor vascular status and improper immunologic response to fracture. Nitric oxide (NO) is a small, neutral, hydrophobic, highly reactive free radical that can diffuse across local cell membranes and exert paracrine functions in the vascular wall. This molecule plays a role in many biologic pathways, and participates in wound healing through decontamination, mediating inflammation, angiogenesis, and tissue remodeling. Additionally, NO is thought to play a role in fighting wound infection by mitigating growth of both Gram negative and Gram positive pathogens. Herein, we discuss recent developments in NO delivery mechanisms and potential implications for patients with bone fractures. NO donors are functional groups that store and release NO, independent of the enzymatic actions of NOS. Donor molecules include organic nitrates/nitrites, metal-NO complexes, and low molecular weight NO donors such as NONOates. Numerous advancements have also been made in developing mechanisms for localized nanomaterial delivery of nitric oxide to bone. NO-releasing aerogels, sol- gel derived nanomaterials, dendrimers, NO-releasing micelles, and core cross linked star (CCS) polymers are all discussed as potential avenues of NO delivery to bone. As a further target for improved fracture healing, 3d bone scaffolds have been developed to include potential for nanoparticulated NO release. These advancements are discussed in detail, and their potential therapeutic advantages are explored. This review aims to provide valuable insight for translational researchers who wish to improve the armamentarium of the feature trauma surgeon through use of NO mediated augmentation of bone healing.

scholarly journals In vitro anticancer activity of hydrogen sulfide and nitric oxide alongside nickel nanoparticle and novel mutations in their genes in CRC patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zjwan Housein ◽  
Tayeb Sabir Kareem ◽  
Abbas Salihi
Keyword(s):  
Nitric Oxide ◽  
Cell Proliferation ◽  
Hydrogen Sulfide ◽  
Direct Sequencing ◽  
Scorpion Venom ◽  
Enos Gene ◽  
Cytotoxic Activities ◽  
No Donors ◽  
The Impact

AbstractThis study was carried out to assess the impact of nickel nanoparticles (NiNPs) as well as scorpion venom on colorectal cancer (CRC) cells in the presence and/or absence of 5-fluorouracil (5-FU), hydrogen sulfide (H2S), and nitric oxide (NO) donors and to determine alterations in endothelial NO synthase (eNOS) and cystathionine γ-lyase (CSE) enzyme-producing genes in CRC patients. The IC50 of both H2S and NO donors, along with NiNPs, were determined. The CRC cells were treated for 24hrs, and the cytotoxic activities were assessed using the MTT test. Moreover, the apoptosis was determined after 24hrs and 48hrs using TUNEL assay. Furthermore, the mutations in the eNOS gene (intron 4, -786T>C and 894 G>T) and CSE gene (1364GT) were determined using direct sequencing. The IC50 values for sodium disulfide (Na2S) and sodium nitroprusside (SNP) at 24hrs treatment were found to be 5 mM and 10−6 M, respectively, while the IC50 value for 5-FU was reached after 5-days of treatment in CRC cell line. Both black and yellow scorpion venoms showed no inhibition of cell proliferation after 24hrs treatment. Furthermore, Na2S showed a significant decrease in cell proliferation and an increase in apoptosis. Moreover, a co-treatment of SNP and 5-FU resulted in inhibition of the cytotoxic effect of 5-FU, while a combination treatment of NiNPs with Na2S, SNP, and 5-FU caused highly significant cytotoxicity. Direct sequencing reveals new mutations, mainly intronic variation in eNOS gene that has not previously been described in the database. These findings indicate that H2S promotes the anticancer efficiency of 5-FU in the presence of NiNPs while NO has antiapoptotic activity in CRC cell lines.

scholarly journals Cell-Free Synthetic Biology Platform for Engineering Synthetic Biological Circuits and Systems

2019 ◽  
Vol 2 (2) ◽  
pp. 39 ◽  
Author(s):  
Dohyun Jeong ◽  
Melissa Klocke ◽  
Siddharth Agarwal ◽  
Jeongwon Kim ◽  
Seungdo Choi ◽  
...  
Keyword(s):  
Synthetic Biology ◽  
Free Expression ◽  
Dna Nanostructures ◽  
Expression Systems ◽  
Natural Systems ◽  
The Past ◽  
Current Cell ◽  
Recent Developments ◽  
Biological Circuits

Synthetic biology integrates diverse engineering disciplines to create novel biological systems for biomedical and technological applications. The substantial growth of the synthetic biology field in the past decade is poised to transform biotechnology and medicine. To streamline design processes and facilitate debugging of complex synthetic circuits, cell-free synthetic biology approaches has reached broad research communities both in academia and industry. By recapitulating gene expression systems in vitro, cell-free expression systems offer flexibility to explore beyond the confines of living cells and allow networking of synthetic and natural systems. Here, we review the capabilities of the current cell-free platforms, focusing on nucleic acid-based molecular programs and circuit construction. We survey the recent developments including cell-free transcription–translation platforms, DNA nanostructures and circuits, and novel classes of riboregulators. The links to mathematical models and the prospects of cell-free synthetic biology platforms will also be discussed.

scholarly journals SPINK3 modulates mouse sperm physiology through the reduction of nitric oxide level independently of its trypsin inhibitory activity

Reproduction ◽  
2012 ◽  
Vol 143 (3) ◽  
pp. 281-295 ◽  
Author(s):  
L Zalazar ◽  
T E Saez Lancellotti ◽  
M Clementi ◽  
C Lombardo ◽  
L Lamattina ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Activity ◽  
Secretory Protein ◽  
No Donors ◽  
Mouse Sperm ◽  
Tyrosine Residues ◽  
Nitric Oxide Level ◽  
Exogenous Addition ◽  
Trypsin Inhibitory Activity

Serine protease inhibitor Kazal-type (SPINK3)/P12/PSTI-II is a small secretory protein from mouse seminal vesicle which contains a KAZAL domain and shows calcium (Ca2+)-transport inhibitory (caltrin) activity. This molecule was obtained as a recombinant protein and its effect on capacitated sperm cells was examined. SPINK3 inhibited trypsin activityin vitrowhile the fusion protein GST-SPINK3 had no effect on this enzyme activity. The inactive GST-SPINK3 significantly reduced the percentage of spermatozoa positively stained for nitric oxide (NO) with the specific probe DAF-FM DA and NO concentration measured by Griess method in capacitated mouse sperm; the same effect was observed when sperm were capacitated under low Ca2+concentration, using either intracellular (BAPTA-AM) or extracellular Ca2+(EDTA) chelators. The percentage of sperm showing spontaneous and progesterone-induced acrosomal reaction was significantly lower in the presence of GST-SPINK3 compared to untreated capacitated spermatozoa. Interestingly, this decrease was overcome by the exogenous addition of the NO donors, sodium nitroprusside (SNP), andS-nitrosoglutathione (GSNO). Phosphorylation of sperm proteins in tyrosine residues was partially affected by GST-SPINK3, however, only GSNO was able to reverse this effect. Sperm progressive motility was not significantly diminished by GST-SPINK3 or BAPTA-AM but enhanced by the addition of SNP. This is the first report that demonstrates that SPINK3 modulates sperm physiology through a downstream reduction of endogenous NO concentration and independently of SPINK3 trypsin inhibitory activity.

scholarly journals 1705 Nitric Oxide Delivery with a Novel Ventilator Circuit Connector - An In Vitro Study under Neonatal Ventilatory Conditions

2012 ◽  
Vol 97 (Suppl 2) ◽  
pp. A482-A482
Author(s):  
J. Mazela ◽  
K. Chmura ◽  
C. Henderson ◽  
T. Gregory ◽  
M. Keszler ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
In Vitro Study ◽  
Vitro Study ◽  
Ventilator Circuit ◽  
Nitric Oxide Delivery

scholarly journals Transition-Metal Nitrosyls for Photocontrolled Nitric Oxide Delivery

2017 ◽  
Vol 2017 (12) ◽  
pp. 1586-1595 ◽  
Author(s):  
Hui-Jing Xiang ◽  
Min Guo ◽  
Jin-Gang Liu
Keyword(s):  
Nitric Oxide ◽  
Transition Metal ◽  
Nitric Oxide Delivery ◽  
Metal Nitrosyls

Restoring Oxygen Carrying Capacity of Sickle Erythrocytes with Nitric Oxide Donors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3785-3785
Author(s):  
Borys Hrinczenko
Keyword(s):  
Nitric Oxide ◽  
Oxygen Affinity ◽  
Red Cell ◽  
No Donors ◽  
Sickle Erythrocytes ◽  
Low Levels ◽  
Pre Treatment ◽  
Normal Controls

Abstract Sickle cell anemia (SCA) is an inherited blood disorder of hemoglobin function. A genetic mutation results in the substitution of a valine for glutamic acid residue at position 6 of the beta-globin chain yielding the mutant hemoglobin S (HbS). HbS polymerizes within erythrocytes during deoxygenation resulting in altered affinity of oxygen binding. The slightly different P50 (PO2 at which Hb is half-saturated with oxygen) values of sickle erythrocytes obtained during either oxygenation or deoxygenation (hysteresis) demonstrate HbS polymerization induced inhibition of oxygen affinity. Nitric oxide (NO) has been found to be an important signaling molecule in the circulatory system. NO derivatives of Hb provide insights into the physiological role of Hb. NO can bind to Hb at either the heme moiety forming nitrosylhemoglobin (HbNO) or to the conserved beta-93 cysteine yielding S-nitrosohemoglobin (SNO-Hb). In deoxygenated venous blood NO preferentially binds to the hemes of Hb forming HbNO while in oxygenated arterial blood NO binds to the beta-93 cysteine residues forming SNO-Hb. Increased oxygen affinity is seen in both SNO-Hb (Bonaventura C, et al, 1999) and also with HbNO. Decreasing the HbS P50 inhibits intra-erythrocyte HbS polymerization that may be an effective strategy to treat SCA. Clinical trials of NO breathing effects on oxygen affinity are conflicting. One study found an increased oxygen affinity of blood from SCA patients breathing 80 ppm NO with no effect seen in normal controls (Head A, et al, 1997). Another study found that levels of NO bound to Hb are too low to affect overall oxygen affinity (Gladwin M, et al, 1999). The purpose of this in vitro study was to determine the oxygen affinity of deoxygenated sickle erythrocytes pre-treated with exogenous NO donors. Blood from SCA (HbSS) and normal controls (HbAA) were collected and suspended in PBS buffer and deoxygenated with argon gas. The Hb concentration of each sample was calculated and then was either left untreated (control) or treated with varying concentrations of NO donors. The NO donors included: 2-(N, N-diethylamino)-diazenolate-2-oxide (DEANO), S-nitroso-N-acetylpenicillamine (SNAP), sodium nitroprusside (SNP), an aqueous solution of NO, and sodium trioxodinitrate (Angeli’s salt, AS). Methemoglobin and protein degradation were negligible. Samples were then transferred via airtight syringes into a stirred and temperature controlled (37°C) chamber of PBS solution at ambient oxygen pressure fitted with a very sensitive oxygen electrode. Oxygen levels were measured in real time. The amount of oxygen extracted from the PBS medium followed first order kinetics. Studies with HbSS red cell suspensions showed that the largest increment in oxygen extraction from the medium was obtained with DEANO pre-treatment. Calculations indicated that low levels of NO treatment, at approximately a 1:1000 ratio of [NO]/[heme], yielded the largest oxygen consumption. The effects of pre-treatment with the other NO donors on sickle erythrocytes (HbSS) were not as pronounced. DEANO is an NO donor yielding a “pure” NO radical as opposed to other redox forms. Similar studies with HbAA and HbSC did not show increases in oxygen extraction. Taken together the data suggest that low levels of NO perturb the quaternary structure of intraerythrocyte HbS polymer allowing depolymerization and increased oxygen affinity. The hope is that these in vitro studies will better characterize the role of NO in its interactions with Hb and the red cell and to use this knowledge for potential therapies in diseases such as SCA.

scholarly journals An argument for broad use of high efficacy treatments in early multiple sclerosis

2019 ◽  
Vol 7 (1) ◽  
pp. e636 ◽  
Author(s):  
James M. Stankiewicz ◽  
Howard L. Weiner
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Approach ◽  
Disease Course ◽  
Long Term Outcomes ◽  
The Past ◽  
Recent Developments ◽  
The Brain

Two different treatment paradigms are most often used in multiple sclerosis (MS). An escalation or induction approach is considered when treating a patient early in the disease course. An escalator prioritizes safety, whereas an inducer would favor efficacy. Our understanding of MS pathophysiology has evolved with novel in vivo and in vitro observations. The treatment landscape has also shifted significantly with the approval of over 10 new medications over the past decade alone. Here, we re-examine the treatment approach in light of these recent developments. We believe that recent work suggests that early prediction of the disease course is fraught, the amount of damage to the brain that MS causes is underappreciated, and its impact on patient function oftentimes is underestimated. These concerns, coupled with the recent availability of agents that allow a better therapeutic effect without compromising safety, lead us to believe that initiating higher efficacy treatments early is the best way to achieve the best possible long-term outcomes for people with MS.

In Vitro Activation of Soluble Guanylyl Cyclase and Nitric Oxide Release:  A Comparison of NO Donors and NO Mimetics†

Biochemistry ◽  
2001 ◽  
Vol 40 (31) ◽  
pp. 9256-9264 ◽  
Author(s):  
Jennifer D. Artz ◽  
Violeta Toader ◽  
Sergei I. Zavorin ◽  
Brian M. Bennett ◽  
Gregory R. J. Thatcher
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
No Donors ◽  
Nitric Oxide Release ◽  
In Vitro Activation

scholarly journals Involvement of nitric oxide donor compounds in the bactericidal activity of human neutrophils in vitro

2003 ◽  
Vol 52 (4) ◽  
pp. 303-308 ◽  
Author(s):  
Magdalena Klink ◽  
Maciej Cedzyński ◽  
Anna St Świerzko ◽  
Henryk Tchórzewski ◽  
Zofia Sulowska
Keyword(s):  
Nitric Oxide ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Bactericidal Activity ◽  
Nitric Oxide Donor ◽  
Human Neutrophils ◽  
Bacterial Strains ◽  
No Donor ◽  
No Donors

The bactericidal activity of human neutrophils against extracellular and facultatively intracellular bacteria was studied in the presence of the nitric oxide (NO) donors sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), a molsidomine metabolite. SNP and molsidomine are drugs commonly used as nitrovasodilators in coronary heart disease. It is demonstrated here that the NO donor compounds themselves did not affect the viability and survival of the bacterial strains tested. Neither SNP nor SIN-1 had any effect on the process of bacteria ingestion. In contrast, NO donors enhanced the ability of neutrophils to kill Escherichia coli, Proteus vulgaris and Salmonella Anatum. However, strains differed in their susceptibility to SNP- and SIN-1-mediated killing by neutrophils. Removal of the superoxide anion reduced the bactericidal activity of SNP- and SIN-1-treated neutrophils against E. coli and S. Anatum. This suggests that the NO derivatives formed in the reaction of NO generated from donors with the reactive oxygen species released by phagocytosed neutrophils potentiate the bactericidal activity of human neutrophils in vitro. The above original observation discussed here suggests clinical significance for the treatment of patients with nitrovasodilators in the course of coronary heart disease therapy.

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