Oxygen Species Research Articles

Sperm DNA fragmentation (SDF) was most effectively improved by a sperm separation device compared to different gradient and swimup methods

SDF is correlated with poor embryo development, implantation, and ongoing pregnancy rates. Reducing DNA fragmentation index (DFI) in the sample used for insemination may improve IVF outcomes. Prospective study to compare different sperm preparation techniques on the same semen sample to determine which methods most effectively improves DFI and other sperm health biomarkers, oxidative stress adducts (OSA) and high DNA stainability (HDS) index. Thirty samples from semen analysis patients were obtained. Samples sent to ReproSource (Woburn, MA) were blinded by freezing the samples in vials labeled with a random number. An aliquot of 0.3 mL of neat semen was frozen and the remainder of the semen allocated between 5 preparation methods (1-5). A sterile syringe was used to load 0.8 mL of raw semen in ZyMōt Sperm Separation Device (1,DxNow) then layered with G-IVF+ and incubated for 30 minutes. At the end of incubation, 0.3 mL of sperm was removed from the out port and frozen. Approximately 0.8 mL of semen was layered over the Isolate gradient (2,Irvine) and SpermGrad gradient (3,Vitrolife) per package insert and centrifuged for 15 minutes. The samples were reconstituted with GIVF+ and an aliquot of each was frozen. The pellet was re-formed and the tube incubated at an angle to obtain the swim-up (SU) Isolate + SU (4) and Spermgrad + SU (5), for each gradient. After one hour, an aliquot from the top of the top of the tube was frozen. Each blinded sample, 6 per semen sample, was analyzed using the Sperm DNA Fragmentation Assay (acridine orange/flow cytometry SDFA™) and the OSA™ test which directly measures sperm damage from oxidative stress by quantifying the presence of “adducts,” molecules in semen covalently modified by free radicals/reactive oxygen species. Statistical analysis was performed in JMP (SAS 2017). The mean age of men in the study was 37±8.3 years. Neat sperm concentrations ranged from 7 to 104 million/mL with 23.3% oligospermic. The motility of the samples ranged from 15 to 80% motility with an average of 52.2±16.9%. DFI, OSA, and HDS were compared between preparation methods on the same ejaculate using Wilcoxon Rank Sums between each pair with P<0.05 considered significant (See table).Tabled 1Prep Method 1Prep Method 2DFI p-valueOSA p-valueHDS p-valueNeatIsolate0.00520.00020.0011NeatIsolate + SU0.00230.0002<0.0001NeatSpermGrad0.0740.05740.2837NeatSpermGrad + SU0.01840.00240.0002NeatDxNow<0.0001<0.0001<0.0001IsolateIsolate + SU0.67890.83600.0389IsolateSpermGrad0.37500.06560.0326IsolateSpermGrad + SU0.65200.73940.1808IsolateDxNow<0.00010.0657<0.0001SpermGradSpermGrad + SU0.44640.31830.0044SpermGradIsolate + SU0.17610.06560.0005SpermGradDxNow<0.00010.0004<0.0001DxNowIsolate + SU<0.00010.0224<0.0001DxNowSpermGrad + SU<0.00010.0428<0.0001SpermGrad + SUIsolate + SU0.47790.97640.0044DFI, OSA, and HDS were compared between preparation methods on the same ejaculate using Wilcoxon Rank Sums between each preparation method. Open table in a new tab DFI, OSA, and HDS were compared between preparation methods on the same ejaculate using Wilcoxon Rank Sums between each preparation method. Sperm preparation methods have changed very little even with the rapid advances in the IVF laboratory. The sperm separation device is a novel method that effectively reduced DFI (p<0.0001) compared to two different gradients (2,3) and gradients followed by swim-up (4,5). The device also has eliminated centrifugation, a step known to increase oxidative stress. The device reduced OSA levels, a measurement of oxidative stress, and HDS, which is a measurement of immature cells and high histone retention. These are both indicators of sperm health and function. Overall, the quality of the sperm obtained post-processing was improved by the use of the separation device, which may increase the chance of a healthy sperm being used for fertilization.

Nitric oxide-dependent regulation of sweet pepper fruit ripening.

Ripening is a complex physiological process that involves changes in reactive nitrogen and oxygen species that govern the shelf-life and quality of fruits. Nitric oxide (NO)-dependent changes in the sweet pepper fruit transcriptome were determined by treating fruits at the initial breaking point stage with NO gas. Fruits were also harvested at the immature (green) and ripe (red) stages. Fruit ripening in the absence of NO resulted in changes in the abundance of 8805 transcripts whose function could be identified. Among these, functional clusters associated with reactive oxygen/nitrogen species and lipid metabolism were significantly modified. NO treatment resulted in the differential expression of 498 genes framed within these functional categories. Biochemical analysis revealed that NO treatment resulted in changes in fatty acid profiling, glutathione and proline contents, and the extent of lipid peroxidation, as well as increases in the activity of ascorbate peroxidase and lipoxygenase. These data provide supporting evidence for the crucial role of NO in the ripening of pepper fruit.

Effects of MnO2 of different structures on activation of peroxymonosulfate for bisphenol A degradation under acidic conditions

MnO2 with various structures, including three tunnel structures (α-, β-, γ-MnO2) and a layered structure (δ-MnO2), were synthesized and investigated for peroxymonosulfate (PMS) activation. The effects of different structured MnO2 on PMS activation in contaminant degradation, as quantified by the pseudo-first order rate constants of bisphenol A (BPA) oxidation, followed the order: α-MnO2 > γ-MnO2 > β-MnO2 > δ-MnO2. Results showed that under acidic conditions, BPA was degraded by both catalytic oxidation by PMS-MnO2 and direct oxidation by MnO2, and the relative importance of the two mechanisms differed for different MnO2. The direct oxidation accounted for 25.2, 7.4, 34.1, and 94.5% of the total reactivity of α-, β-, γ-, and δ-MnO2, respectively. Physicochemical properties of MnO2 including crystal structure, morphology, surface Mn oxidation states, surface area, oxygen species and conductivity were characterized and correlated with the catalytic reactivity. The results demonstrated that the crystallinity of MnO2 was the dominant factor in the catalytic reactivity, resulting in the lowest reactivity for the least crystalline δ-MnO2. For the crystalline MnO2, the catalytic reactivity linearly correlated with Mn average oxidation state, Mn(III) content, and conductivity. Electron spin resonance (ESR) and quenching experiments with ethanol and tert-butanol suggested that sulfate radicals (SO4−) were the dominant radicals in the systems, while hydroxyl radicals (OH) played a minor role. In addition, nonradical mechanisms such as singlet oxygen (1O2) also contributed to the BPA degradation, especially when δ-MnO2 was the catalyst. These findings offered new insights into the contaminant degradation mechanisms in PMS-MnO2 and provided guidance to develop cost-effective catalysts for water/wastewater treatment.

Induction of apoptosis by piperine in human cervical adenocarcinoma via ROS mediated mitochondrial pathway and caspase-3 activation.

Piperine (1-piperoylpeperdine), a nitrogenous pungent substance, is present in the fruits of black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.). It possesses several pharmacological properties and has been extensively explored for its anti-cancerous activities. The mechanism underlying its anti-cancer potential in human cervical adenocarcinoma (HeLa) cells is not well interpreted. The anti-proliferative effect and the mode of action of piperine were investigated through some potent markers of apoptosis viz.reactive oxygen species (ROS) generation, cellular apoptosis and loss of mitochondrial membrane potential (MMP). DNA fragmentation, cell cycle kinetics, caspase-3 activity and cell migration assays were also conducted to observe the efficacy of piperine against HeLa cells. The results showed that piperine exposure induces apoptosis significantly in a dose-dependent manner and inhibits the growth of HeLa cells with an increase in ROS generation, nuclear condensation and delayed wound healing. In addition, piperine also encourages cell death by the loss of MMP, DNA fragmentation and the activation of caspase-3. Growth inhibition of HeLa cells was found to be associated with G2/M phase arrest and sub-G1 accumulation. The present study provides useful insight into the apoptotic potential of piperine and further in vivo and clinical studies will be needed for its validation and in the finding of more effective and least toxic regimens against cervical cancer.

Antioxidant and signaling functions of the plastoquinone pool in higher plants.

The review covers data representing the plastoquinone pool as the component integrated in plant antioxidant defense and plant signaling. The main goal of the review is to discuss the evidence describing the plastoquinone-involved biochemical reactions, which are incorporated in maintaining the sustainability of higher plants to stress conditions. In this context, the analysis of the reactions of various redox forms of plastoquinone with oxygen species is presented. The review describes how these reactions can constitute both the antioxidant and signaling functions of the pool. Special attention is paid to the reaction of superoxide anion radicals with plastohydroquinone molecules, producing hydrogen peroxide as signal molecules. Attention is also given to the processes affecting the redox state of the plastoquinone pool because the redox state of the pool is of special importance for antioxidant defense and signaling.

Nitroxyl (HNO) targets phospholamban cysteines 41 and 46 to enhance cardiac function.

Nitroxyl (HNO) positively modulates myocardial function by accelerating Ca2+ reuptake into the sarcoplasmic reticulum (SR). HNO-induced enhancement of myocardial Ca2+ cycling and function is due to the modification of cysteines in the transmembrane domain of phospholamban (PLN), which results in activation of SR Ca2+-ATPase (SERCA2a) by functionally uncoupling PLN from SERCA2a. However, which cysteines are modified by HNO, and whether HNO induces reversible disulfides or single cysteine sulfinamides (RS(O)NH2) that are less easily reversed by reductants, remain to be determined. Using an 15N-edited NMR method for sulfinamide detection, we first demonstrate that Cys46 and Cys41 are the main targets of HNO reactivity with PLN. Supporting this conclusion, mutation of PLN cysteines 46 and 41 to alanine reduces the HNO-induced enhancement of SERCA2a activity. Treatment of WT-PLN with HNO leads to sulfinamide formation when the HNO donor is in excess, whereas disulfide formation is expected to dominate when the HNO/thiol stoichiometry approaches a 1:1 ratio that is more similar to that anticipated in vivo under normal, physiological conditions. Thus, 15N-edited NMR spectroscopy detects redox changes on thiols that are unique to HNO, greatly advancing the ability to detect HNO footprints in biological systems, while further differentiating HNO-induced post-translational modifications from those imparted by other reactive nitrogen or oxygen species. The present study confirms the potential of HNO as a signaling molecule in the cardiovascular system.

Low pressure chemical vapor deposition synthesis of large area hetero-doped mono- and few- layer graphene with nitrogen and oxygen species

The doping graphene helps breaks its surface inertness providing it an intrinsic degree of catalytic activity. While single elemental doping of graphene (e.g. with N) enhances its catalytic potential, the current trend is to develop graphene doped with multiple elements. These heterodoped graphene species have improved electro-catalytic activities as compared to their corresponding single heteroatom doped counterparts because of strong charge redistribution and synergistic effects due to differences in the dopant electro-negativities. Hence, they are better suited for multiple catalytic reactions to better cope with reaction intermediates. Never-the-less, to date only a few examples exist. In this work we show it is possible to synthesize in a single CVD step, large area single- and few- layer graphene doped with oxygen and nitrogen species. Moreover, this is achieved using a solid precursor in a pure H2 environment with growth being achieved in under 5 min.

Fabrication and optical emission spectroscopy of enhanced corrosion-resistant CPEO films on Q235 low carbon steel

The oxide films on Q235 low carbon steel as a cathode were quickly prepared by cathodic plasma electrolytic oxidation (CPEO) in 80 vol% glycerol electrolyte within 9 min. The morphology, composition and microhardness of oxide films were analyzed. The corrosion behaviors of bare steel and CPEO films were evaluated by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). The optical emission spectroscopy (OES) was collected and the electron temperature in plasma discharge envelope was calculated. It was found that the CPEO oxide films contained FeO phase, Fe2O3 phase and some dispersed carbon particles. The plasma discharge envelope contained many active carbon, iron and oxygen species. The electron temperature in the plasma discharge region was over 5000 K and meanwhile the surface temperature of steel is over 1000 °C. The CPEO oxide film on Q235 steel grew linearly with 10.89 μm/min. The CPEO treated Q235 low carbon steel had a good corrosion resistance with lower corrosion current density and higher impedance.

One Pot Synthesis of FeCo/N‐Doped 3D Porous Carbon Nanosheets as Bifunctional Electrocatalyst for the Oxygen Reduction and Evolution Reactions

AbstractIn this work, FeCo/N‐doped porous carbon nanosheets (FeCo/NPC) were in‐situ synthesised as bifunctional oxygen catalyst following a sodium chloride (NaCl) template‐assisted strategy. The results show that this strategy assists in generating a 3D interconnected carbon nanosheets network with hierarchical pores and a larger specific surface area through a stencil effect. X‐ray photoelectron spectroscopy (XPS) results show that the Fe 2p3/2 and Co 2p3/2 core‐level binding energy (BE) of the FeCo/NPC catalyst exhibits a positive shift compared to monometallic catalysts, which is associated with downshifts of the d‐band position of the metal by alloying and weakening of the interaction between oxygenic species and metal surfaces, thereby improving the catalytic activity. The FeCo/NPC catalyst shows excellent electrocatalytic activity for bothoxygen reduction reaction (ORR) and oxygen evolution reaction (OER) in alkaline solution: a high onset potential of 0.92 V (vs. RHE), only 10 mV difference of half‐wave potential comparable with commercial Pt/C (20 wt%), a high current retention of 95.7 % after stability test of 20000 s for ORR and a potential of 1.68 V (vs. RHE) for OER at 10 mA ⋅ cm−2. The high catalytic performance of the FeCo/NPC catalyst and the simplicity of the synthesis method provide a possibility for its practical application in metal‐air batteries.

S-Nitrosoglutathione Reductase-The Master Regulator of Protein S-Nitrosation in Plant NO Signaling.

S-nitrosation has been recognized as an important mechanism of protein posttranslational regulations, based on the attachment of a nitroso group to cysteine thiols. Reversible S-nitrosation, similarly to other redox-base modifications of protein thiols, has a profound effect on protein structure and activity and is considered as a convergence of signaling pathways of reactive nitrogen and oxygen species. In plant, S-nitrosation is involved in a wide array of cellular processes during normal development and stress responses. This review summarizes current knowledge on S-nitrosoglutathione reductase (GSNOR), a key enzyme which regulates intracellular levels of S-nitrosoglutathione (GSNO) and indirectly also of protein S-nitrosothiols. GSNOR functions are mediated by its enzymatic activity, which catalyzes irreversible GSNO conversion to oxidized glutathione within the cellular catabolism of nitric oxide. GSNOR is involved in the maintenance of balanced levels of reactive nitrogen species and in the control of cellular redox state. Multiple functions of GSNOR in plant development via NO-dependent and -independent signaling mechanisms and in plant defense responses to abiotic and biotic stress conditions have been uncovered. Extensive studies of plants with down- and upregulated GSNOR, together with application of transcriptomics and proteomics approaches, seem promising for new insights into plant S-nitrosothiol metabolism and its regulation.

Removal of gaseous Hg0 using novel seaweed biomass-based activated carbon

Compared to land, the ocean is much richer in biomass resources. As an attempt to actively explore the utilization of these vast marine biomass resources, in this study, novel activated carbons were prepared from two representative seaweed species (sargassum and enteromorpha), and their efficiencies and mechanisms for Hg0 removal were evaluated in a fixed bed reactor. The effects of modification methods, modification temperatures and reaction temperatures on Hg0 removal were also studied. The experimental data were also tested with different adsorption kinetic models for the best fits, and standard thermodynamic parameters evaluated in order to elucidate Hg0 adsorption mechanisms. The results appear to reveal that the performances of seaweed biomass-based activated carbons (denoted SAC and EAC, respectively) for Hg0 removal, are by far more superior to those of seaweed biomass-based the same pyrolysis chars. The best activation temperature for both samples was found to be 800 °C (and hence denoted SAC-800 and EAC-800); and the Hg0 removal efficiency of both samples also increased with increasing reaction temperature. The kinetic results show that the Hg0 removal is controlled by the external mass transfer at 80 °C and controlled by the chemisorption at 120 °C and 160 °C. It was determined that the Hg0 process was a combination of physisorption and chemisorption; with the excellent physical properties (specific surface area and pore structure), and the surface active sites (C-Cl groups and oxygen species) responsible for the physisorption and chemisorption, respectively.

Antioxidant and Anti-inflammatory Capacity of Ferulic Acid Released from Wheat Bran by Solid-state Fermentation of Aspergillus niger

ObjectiveA strain of Aspergillus niger (A. niger), capable of releasing bound phenolic acids from wheat bran, was isolated. This strain was identified by gene sequence identification. The antioxidant and anti-inflammatory capacity of ferulic acid released from wheat bran by this A. niger strain (FA-WB) were evaluated. MethodsMolecular identification techniques based on PCR analysis of specific genomic sequences were conducted; antioxidant ability was examined using oxygen radical absorbance capacity (ORAC), cellular antioxidant activity (CAA) assays, and erythrocyte hemolysis assays. RAW264.7 cells were used as a model to detect anti-inflammatory activity. ResultsThe filamentous fungal isolate was identified to be A. niger. ORAC and CAA assay showed that FA-WB had better antioxidant activity than that of the ferulic acid standard. The erythrocyte hemolysis assay results suggested that FA-WB could attenuate AAPH-induced oxidative stress through inhibition of reactive oxy gen species (ROS) generation. FA-WB could significantly restore the AAPH-induced increase in intracellular antioxidant enzyme activities to normal levels as well as inhibit the intracellular malondialdehyde formation. TNF-α, IL-6, and NO levels indicated that FA-WB can inhibit the inflammation induced by lipopolysaccharide (LPS). ConclusionFerulic acid released from wheat bran by a new strain of A. niger had good anti-inflammatory activity and better antioxidant ability than standard ferulic acid.

One Simple Strategy towards Nitrogen and Oxygen Codoped Carbon Nanotube for Efficient Electrocatalytic Oxygen Reduction and Evolution

The development of advanced electrocatalysts for oxygen reduction and evolution is of paramount significance to fuel cells, water splitting, and metal-air batteries. Heteroatom-doped carbon materials have exhibited great promise because of their excellent electrical conductivity, abundance, and superior durability. Rationally optimizing active sites of doped carbons can remarkably enhance their electrocatalytic performance. In this study, nitrogen and oxygen codoped carbon nanotubes were readily synthesized from the pyrolysis of polydopamine-carbon nanotube hybrids. Different electron microscopes, Raman spectra and X-ray photoelectron spectroscopy (XPS) were employed to survey the morphological and componential properties. The newly-obtained catalyst features high-quality nitrogen and oxygen species, favourable porous structures and excellent electric conductivity, and thus exhibits remarkably bifunctional oxygen electrode activity. This research further helps to advance the knowledge of polydopamine and its potential applications as efficient electrocatalysts to replace noble metals.

Preparation of Ce⁻Mn Composite Oxides with Enhanced Catalytic Activity for Removal of Benzene through Oxalate Method.

The catalytic activities of CeO2-MnOx composite oxides synthesized through oxalate method were researched. The results exhibited that the catalytic properties of CeO2-MnOx composite oxides were higher than pure CeO2 or MnOx. When the Ceat/Mnat ratio was 3:7, the catalytic activity reached the best. In addition, the activities of CeO2-MnOx synthesized through different routes over benzene oxidation were also comparative researched. The result indicated that the catalytic property of sample prepared by oxalate method was better than others, which maybe closely related with their meso-structures. Meanwhile, the effects of synergistic interaction and oxygen species in the samples on the catalytic ability can’t be ignored.

Adsorption of Organic Constituents from Reverse Osmosis Concentrate in Coal Chemical Industry by Coking Coal

To solve the unwieldy problem of coal chemical wastewater reverse osmosis concentrate (ROC), a novel treatment method in which coking coal was used to adsorb the organic from ROC and the adsorption mechanism involved was investigated. The results showed that the organic components in the ROC of coal chemical industry can be effectively absorbed by the coking coal and the total organic carbon, UV254 and chromaticity of treated ROC reduced by 70.18%, 70.15% and 59.55%, respectively, at the coking coal dosage of 80 g/L. The isothermal adsorption data were fitted to the Langmuir model well. The kinetics were expressed well by the quasi-second-order kinetic model. The intragranular diffusion model and the BET (Acronym for three scientists: Brunauer–Emmett–Teller) test showed that the adsorption occurred mainly on the surface of the coking coal and its macropores and mesopores. When the pollutants further diffused to the mesopores and micropores, the adsorption rate decreased. The result of X-ray photoelectron spectroscopy and fourier transform infrared spectroscopy spectra showed that the coking coal mainly adsorbed the nitrogen and oxygen species and the halogenated hydrocarbon organic compounds in the ROC. The chlorinated hydrocarbons and heterocyclic organics in ROC are adsorbed on the surface of coking coal.

Cause of wear-resistance enhancement of a polyurethane film composite by plasma-functionalized carbon nanotubes

Our previous investigation demonstrated that the wear-resistance of polyurethane (PU) film was enhanced by making the film composite utilize carbon nanotubes (CNTs). The use of plasma-treated CNTs further provides enhancement; this led to the hypothesis that the improvement could be more effective by applying isocyanate groups modified on CNTs treated with plasma. This was determined as the plasma contained nitrogen and oxygen species and because a material with isocyanate groups can function as a hardener of polyurethane. This article documents findings ensuant to our previous publication. Here, we present our investigation of the microscopic morphology of the PU film (physical aspect) and identified the chemical bonds (chemical aspect) in order to present the theorem of the enhancement. Observation of the morphology showed no specialty on the PU films with plasma-treated CNTs. On the other hand, an observation with an organic fluorescence, acridine yellow, showed evidence of the chemical aspect used to enhance the film composite with CNTs. Therefore, we concluded that the most effective method was to use isocyanate groups attached through plasma treatment, in order to improve PU wear-resistance.

The miR-183/96/182 Cluster Regulates Macrophage Functions in Response to Pseudomonas aeruginosa

Macrophages (Mϕ) are an important component of the innate immune system; they play critical roles in the first line of defense to pathogen invasion and modulate adaptive immunity. MicroRNAs (miRNAs) are a newly recognized, important level of gene expression regulation. However, their roles in the regulation of Mϕ and the immune system are still not fully understood. In this report, we provide evidence that the conserved miR-183/96/182 cluster (miR-183/96/182) modulates Mϕ function in their production of reactive nitrogen (RNS) and oxygen species (ROS) and their inflammatory response to Pseudomonas aeruginosa (PA) infection and/or lipopolysaccharide (LPS) treatment. We show that knockdown of miR-183/96/182 results in decreased production of multiple proinflammatory cytokines in response to PA or LPS treatment in Mϕ-like Raw264.7 cells. Consistently, peritoneal Mϕ from miR-183/96/182-knockout versus wild-type mice are less responsive to PA or LPS, although their basal levels of proinflammatory cytokines are increased. In addition, overexpression of miR-183/96/182 results in decreased production of nitrite and ROS in Raw264.7 cells. We also provide evidence that DAP12 and Nox2 are downstream target genes of miR-183/96/182. These data suggest that miR-183/96/182 imposes global regulation on various aspects of Mϕ function through different downstream target genes.

Recasting as a booster of Ag-Pd alloy cytotoxicity: Induction of cell senescence prior to mass cell death

The biological quality and chemical composition of alloys used in dental practice change during heat treatment. Often the residues of the previous cast are not disposed of but are reused and recycled until consumed. Thus, manufactured dental restorations have modified biological quality and chemical composition, and compromised biocompatibility. The aim of this study was to investigate the influence of repeated casting on the cytotoxicity of the silver-palladium (Ag-Pd) alloy. Our results showed that repeated casting of the Ag-Pd dental alloy affected its biocompatibility by promoting toxicity against transformed fibroblasts in a contact-independent manner. A strong decrease in cell proliferation, induction of senescence and massive cell death were observed in cultures exposed only to a medium previously incubated with dental alloy samples. The obtained data indicated that toxicity mediated by the accumulation of the Ag, Pd, Cu and Zn cations released from the Ag-Pd material was enhanced by recasting. The induction of cell senescence and subsequent apoptotic and necrotic death were accompanied by amplified intracellular production of reactive oxygen and nitrogen species, suggesting their involvement in the cell destruction process. Therefore, compromised biocompatibility after recasting with the Ag-Pd alloy can be the cause of serious local cell destruction, as observed in clinical practice.

GSH-sensitive Pt(IV) prodrug-loaded phase-transitional nanoparticles with a hybrid lipid-polymer shell for precise theranostics against ovarian cancer.

Background: Platinum (II) (Pt(II))-based anticancer drugs dominate the chemotherapy field of ovarian cancer. However, the patient's quality of life has severely limited owing to dose-limiting toxicities and the advanced disease at the time of diagnosis. Multifunctional tumor-targeted nanosized ultrasound contrast agents (glutathione (GSH)-sensitive platinum (IV) (Pt(IV)) prodrug-loaded phase-transitional nanoparticles, Pt(IV) NP-cRGD) were developed for precise theranostics against ovarian cancer.Methods: Pt(IV) NP-cRGD were composed of a perfluorohexane (PFH) liquid core, a hybrid lipid-polymer shell with PLGA12k-PEG2k and DSPE-PEG1k-Pt(IV), and an active targeting ligand, the cRGD peptide (PLGA: poly(lactic-co-glycolic acid), PEG: polyethylene glycol, DSPE: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, cRGD: cyclic Arg-Gly-Asp). Pt(IV), a popular alternative to Pt(II), was covalently attached to DSPE-PEG1k to form the prodrug, which fine-tuned lipophilicity and improved cellular uptake. The potential of Pt(IV) NP-cRGD as contrast agents for ultrasound (US) imaging was assessed in vitro and in vivo. Moreover, studies on the antitumor efficiency and antitumor mechanism of Pt(IV) NP-cRGD assisted by US were carried out.Results: Pt(IV) NP-cRGD exhibited strong echogenic signals and excellent echo persistence under an US field. In addition, the GSH-sensitive and US-triggered drug delivery system maximized the therapeutic effect while reducing the toxicity of chemotherapy. The mechanistic studies confirmed that Pt(IV) NP-cRGD with US consumed GSH and enhanced reactive oxy gen species (ROS) levels, which further causes mitochondria-mediated apoptosis.Conclusion: A multifunctional nanoplatform based on phase-transitional Pt(IV) NP-cRGD with US exhibited excellent echogenic signals, brilliant therapeutic efficacy and limited side effect, suggesting precise theranostics against ovarian cancer.

Role of Melatonin Supplementation on Inflammatory and Oxidative Stress Markers in Critically Ill Patients

Critically ill patients are diagnosed with signs such as oxidative stress, mitochondrial function impairment, dysfunction of the immune system, and acute inflammation. Inflammation and oxidative stress play a major role in the pathogenicity of most diseases in patients, especially those in intensive care units. Because of the side effects of chemical anti-inflammatory drugs, which include large intestinal ulcers, bleeding, and perforation, it seems that the use of natural anti-inflammatory compounds like melatonin could be very helpful. Melatonin productively interacts with different receptive nitrogen and oxygen species (receptor autonomous activities), up-regulates antioxidant chemicals, and down-regulates pro-oxidant chemicals (receptor-dependent activities). Melatonin attenuates molecular and cellular damage resulting from inflammation and oxidative stress. Previous studies have shown that melatonin reduces inflammation and oxidative stress levels. Thus, the use of safe doses of melatonin can reduce inflammation and oxidative stress. However, further studies are needed to verify these results.