Understanding mechanisms of antioxidant action in health and disease.

The free radical nitric oxide (·NO) is a key mediator in different physiological processes such as vasodilation, neurotransmission, inflammation, and cellular immune responses, and thus preserving its bioavailability is essential. In several disease conditions, superoxide radical (O2·-) production increases and leads to the rapid "inactivation" of ·NO by a diffusion-controlled radical termination reaction that yields a potent and short-lived oxidant, peroxynitrite. This reaction not only limits ·NO bioavailability for physiological signal transduction but also can divert and switch the biochemistry of ·NO toward nitrooxidative processes. Indeed, since the early 1990s peroxynitrite (and its secondary derived species) has been linked to the establishment and progression of different acute and chronic human diseases and also to the normal aging process. Here, we revisit an earlier and classical review on the role of peroxynitrite in human physiology and pathology (Pacher P, Beckman J, Liaudet L. Physiol Rev 87: 315-424, 2007) and further integrate, update, and interpret the accumulated evidence over 30 years of research. Innovative tools and approaches for the detection, quantitation, and sub- or extracellular mapping of peroxynitrite and its secondary products (e.g., protein 3-nitrotyrosine) have allowed us to unambiguously connect the complex biochemistry of peroxynitrite with numerous biological outcomes at the physiological and pathological levels. Furthermore, our current knowledge of the ·NO/O2·- and peroxynitrite interplay at the cell, tissue, and organ levels is assisting in the discovery of therapeutic interventions for a variety of human diseases. 

The superoxide radical switch in the biology of nitric oxide and peroxynitrite.

With the significant increase of patients suffering from different types of cancer, it is evident that prompt measures in the development of novel and effective agents need to be taken. Pyrrole moiety has been found in various active compounds with anti-inflammatory, antiseptic, antibacterial, lipid-lowering and anticancer properties. Recent advances in the exploration of highly active and selective cytotoxic structures containing pyrrole motifs have shown promising data for future investigations. Accordingly, this review presents an overview of recent developments in the pyrrole derivatives as anticancer agents, with a main focus towards the key moieties required for the anti-tumor activities. Pyrrole molecules comprising prominent targeting capacities against microtubule polymerization, tyrosine kinases, cytochrome p450 family 1, histone deacetylase and bcl-2 proteins were reported. In addition, several mechanisms of action, such as apoptosis, cell cycle arrest, inhibiting kinases, angiogenesis, disruption of cell migration, modulation of nuclear receptor responsiveness and others were analyzed. Furthermore, in most of the discussed cases we provided synthesis schemes of the mentioned molecules. Overall, the utilization of pyrrole scaffold for the design and synthesis of novel anticancer drugs could be a promising approach for future investigations.

/pdf/pyrrole-as-an-important-scaffold-of-anticancer-drugs-recent-13cb96ej.pdf

Pyrrole as an Important Scaffold of Anticancer Drugs: Recent Advances.

https://hal.science/hal-03834587/document

SOD mimics: From the tool box of the chemists to cellular studies.

Radiotherapy is an essential and effective treatment modality for cancer. Excessive levels of reactive oxygen species (ROS) induced by ionizing radiation disrupt the redox homeostasis and lead to oxidative stress that may result in cell death. However, the tumor cell microenvironment is dynamic and responds to radiotherapy by activating numerous cellular signaling pathways. By scavenging excess ROS, the activity levels of the endogenous antioxidant enzymes result in radioresistance and worsen the clinical outcomes. To assess the full potential of radiotherapy, it is essential to explore the underlying mechanisms of oxidative stress in radiotherapy for potential target identification. The present review article summarized recent data demonstrating nuclear factor-erythroid factor 2-related factor 2 (Nrf2) as a powerful transcription factor and one of the major cellular defense mechanisms that protect against oxidative stress in response to radiotherapy; the glutathione (GSH) and thioredoxin (Trx) systems complement each other and are effective antioxidant mechanisms associated with the protection of cancer cells from radiation damage. In addition, it is suggested that dual targeting to inhibit GSH and Trx enzymes may be a potential strategy for the development of radiosensitive and radioprotective drugs.

/pdf/molecular-pathways-associated-with-oxidative-stress-and-kw76pp4f.pdf

Molecular pathways associated with oxidative stress and their potential applications in radiotherapy (Review)

Hyperspectral estimation of wheat stripe rust using fractional order differential equations and Gaussian process methods

Addressing validation challenges for TROPOMI solar-induced chlorophyll fluorescence products using tower-based measurements and an NIRv-scaled approach

The wheat canopy reflectance spectrum is affected by many internal and external factors such as diseases and growth stage. Separating the effects of disease stress on the crop from the observed mixed signals is crucial for increasing the precision of remote sensing monitoring of wheat stripe rust. The canopy spectrum of winter wheat infected by stripe rust was processed with the difference-in-differences (DID) algorithm used in econometrics. The monitoring accuracies of wheat stripe rust before and after processing with the DID algorithm were compared in the presence of various external factors, disease severity, and several simulated satellite sensors. The correlation between the normalized difference vegetation index processed by the DID algorithm (NDVI- DID ) and the disease severity level (SL) increased in comparison with the NDVI before processing. The increase in precision in the natural disease area in the field in the presence of large differences in growth stage, growth, planting, and management of the crop was greater than that in the controlled experiment. For low disease levels (SL < 20%), the R 2 of the regression of NDVI- DID on SL was 38.8% higher than that of the NDVI and the root mean square error (RMSE) was reduced by 11.1%. The increase in precision was greater than that for the severe level (SL > 40%). According to the measured hyperspectral data, the spectral reflectance of three satellite sensor levels was simulated. The wide-band NDVI was calculated. Compared with the wide-band NDVI and vegetation indexes (VI S ) before DID processing, there were increases in the correlation between SL and the various types of VI S - DID , as well as in the correlation between SL and NDVI- DID . It is feasible to apply the DID algorithm to multispectral satellite data and diverse types of VI S for monitoring wheat stripe rust. Our results improve the quantification of independent effects of stripe rust infection on canopy reflectance spectrum, increase the precision of remote sensing monitoring of wheat stripe rust, and provide a reference for remote sensing monitoring of other crop diseases. 

Quantifying the effects of stripe rust disease on wheat canopy spectrum based on eliminating non-physiological stresses

MnTnBuOE-2-PyP5+ Ascorbate in the Treatment of Ovarian Cancer

Most cardiac arrest (CA) survivors experience varying degrees of neurologic deficits. To understand the mechanisms that underpin CA-induced brain injury and, subsequently, develop effective treatments, experimental CA research is essential. To this end, a few mouse CA models have been established. In most of these models, the mice are placed in the supine position in order to perform chest compression for cardiopulmonary resuscitation (CPR). However, this resuscitation procedure makes the real-time imaging/monitoring of brain physiology during CA and resuscitation challenging. To obtain such critical knowledge, the present protocol presents a mouse asphyxia CA model that does not require the chest compression CPR step. This model allows for the study of dynamic changes in blood flow, vascular structure, electrical potentials, and brain tissue oxygen from the pre-CA baseline to early post-CA reperfusion. Importantly, this model applies to aged mice. Thus, this mouse CA model is expected to be a critical tool for deciphering the impact of CA on brain physiology.

Mouse Cardiac Arrest Model for Brain Imaging and Brain Physiology Monitoring During Ischemia and Resuscitation.

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