Marker-Dependent Cleavage of RNA by Binary (split) DNAzyme (BiDz) and Binary DNA Machines (BiDM).

Oligonucleotide gene therapy (OGT) can be used to suppress specific RNA in cells and thus has been explored for gene therapy. Despite extensive effort, there is no clinically significant OGT for treating cancer. Low efficiency of OGT is one of the problems.

Evaluation of Nitric Oxide-Donating Properties of 11-indeno[1,2-]quinoxalin-11-one Oxime (IQ-1) by Electron Paramagnetic Resonance Spectroscopy.

IQ-1 (11-indeno[1,2-]quinoxalin-11-one oxime) is a specific c-Jun N-terminal kinase (JNK) inhibitor with anticancer and neuro- and cardioprotective properties. Because aryloxime derivatives undergo cytochrome P450-catalyzed oxidation to nitric oxide (NO) and ketones in liver microsomes, NO formation may be an additional mechanism of IQ-1 pharmacological action. In the present study, electron paramagnetic resonance (EPR) of the Fe complex with diethyldithiocarbamate (DETC) as a spin trap and hemoglobin (Hb) was used to detect NO formation from IQ-1 in the liver and blood of rats, respectively, after IQ-1 intraperitoneal administration (50 mg/kg).

Analysis of the Intensity of Nitric Oxide Production in Different Parts of the Spinal Cord after Modeling Combined Cerebral and Spinal Injury.

Using the method of electron paramagnetic resonance spectroscopy, we showed that NO production decreases by 60% (p<0.05) in the region located rostral to the spinal cord injury 7 days after combined injury to the brain and spinal cord. At the same time, NO production did not change in the site of spinal cord injury and caudal to the injury.

Recombinant Alpha-1 Antitrypsin-Fc Fusion Protein INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency: A Phase 1 Study.

Background: Alpha-1 antitrypsin deficiency (AATD) is characterized by low alpha-1 antitrypsin (AAT) levels, predisposing individuals to lung disease. The standard of care, plasma-derived AAT (pdAAT), is delivered as weekly infusions to maintain serum AAT concentrations ≥11µM (≈50% of those in healthy individuals). INBRX-101, a recombinant human AAT-Fc fusion protein, was designed to have a longer half-life and achieve higher AAT levels than pdAAT.

Investigation of NO Role in Neural Tissue in Brain and Spinal Cord Injury.

Nitric oxide (NO) production in injured and intact brain regions was compared by EPR spectroscopy in a model of brain and spinal cord injury in Wistar rats. The precentral gyrus of the brain was injured, followed by the spinal cord at the level of the first lumbar vertebra. Seven days after brain injury, a reduction in NO content of 84% in injured brain regions and 66% in intact brain regions was found.

Preclinical Characterization and Phase I Trial Results of INBRX-109, A Third-Generation, Recombinant, Humanized, Death Receptor 5 Agonist Antibody, in Chondrosarcoma.

Purpose: Patients with unresectable/metastatic chondrosarcoma have poor prognoses; conventional chondrosarcoma is associated with a median progression-free survival (PFS) of <4 months after first-line chemotherapy. No standard targeted therapies are available. We present the preclinical characterization of INBRX-109, a third-generation death receptor 5 (DR5) agonist, and clinical findings from a phase I trial of INBRX-109 in unresectable/metastatic chondrosarcoma (NCT03715933).

Aromatic sulphonamides of aziridine-2-carboxylic acid derivatives as novel PDIA1 and PDIA3 inhibitors.

In this study, we report a series of newly synthesised sulphonamides of aziridine-2-carboxylic acid (Az-COOH) ester and amide analogues as potent protein disulphide isomerase (PDI, EC 5.3.4.

Exploring Aspartic Protease Inhibitor Binding to Design Selective Antimalarials.

Selectivity is a major issue in the development of drugs targeting pathogen aspartic proteases. Here, we explore the selectivity-determining factors by studying specifically designed malaria aspartic protease (plasmepsin) open-flap inhibitors. Metadynamics simulations are used to uncover the complex binding/unbinding pathways of these inhibitors and describe the critical transition states in atomistic resolution.

The influence of an external magnetic field on the dynamics of magnetite reduction with hydrogen.

The kinetics of hydrogen reduction of magnetite was investigated in different magnetic fields. The magnetic moment measurements were used for the control of the reaction. A strong difference in the magnetic properties of the reaction results was obtained for applied strong and weak magnetic fields.

The Effects of Repeated Administration of the Micellar Complex of Methylprednisolone on the Locomotor Activity of a Terrestrial Snails.

We studied the effects of repeated injections of methylprednisolone and its micellar complex with block-copolymer on locomotor activity of a terrestrial snail. It was shown that methylprednisolone solution injected into the hemolymph of the animal produced a direct effect on the muscle system of the animal as soon as 1 h after administration: it slowed down snail locomotion and reduced contractile activity of the foot muscles. The micellar complex of methylprednisolone with block-copolymer prevented this effect during the first 2 days of injection and negatively affected locomotion only in 2 days after injection, the decrease in locomotion in this case was not accompanied by a decrease in contractile activity of the foot muscle.

Identification of BBOX1 as a Therapeutic Target in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease. Because of its heterogeneity and lack of hormone receptors or HER2 expression, targeted therapy is limited. Here, by performing a functional siRNA screening for 2-OG-dependent enzymes, we identified gamma-butyrobetaine hydroxylase 1 () as an essential gene for TNBC tumorigenesis.

Changes in Membrane and Threshold Potentials of Command Neurons in Terrestrial Snail during Development of a Conditioned Situational Defensive Reflex.

Changes of the electrical characteristics of command neurons of defensive behavior caused by the development of a conditioned situational defensive reflex were studied experimentally under in vitro conditions on preparations of the nervous system of snails. After learning, the membrane and threshold potentials of command neurons LPa3 and RPa3 significantly decreased and excitability of the studied neurons increased.

Effects of Thryptophan Hydroxylase Blockade by P-Chlorophenylalanine on Contextual Memory Reconsolidation after Training of Different Intensity.

The processes of memory formation and its storage are extremely dynamic. Therefore, the determination of the nature and temporal evolution of the changes that underlie the molecular mechanisms of retrieval and cause reconsolidation of memory is the key to understanding memory formation. Retrieval induces the plasticity, which may result in reconsolidation of the original memory and needs critical molecular events to stabilize the memory or its extinction.

Spermine Induces Autophagy in Plants: Possible Role of NO and Reactive Oxygen Species.

This is the first study to show that polyamine spermine, a low-molecular-weight nitrogen-containing compound, can induce autophagy in plants. This process is accompanied by an increased generation of reactive oxygen species and nitric oxide, which play a signal role and are required for triggering autophagy.

Evaluation of butorphanol-azaperone-medetomidine in captive cheetah (Acinonyx jubatus) immobilization.

Objective: The butorphanol-azaperone-medetomidine fixed-dose combination (BAM, respectively, 30-12-12 mg mL) with subsequent antagonism by naltrexone-atipamezole was evaluated for reversible immobilization of captive cheetahs (Acinonyx jubatus).

Study Design: Prospective, clinical trial.

Animals: Twelve cheetahs (six males and six females, weighing 37-57 kg) housed in enclosures, were immobilized at Hoedspruit Endangered Species Centre in the Republic of South Africa.

A month in a horse's life: healing process of a fractured third metatarsal bone from medieval Viljandi, Estonia.

The remains of a horse's hind foot - a third metatarsal bone and three phalanges - were found in a presumed waste pit of a prosperous medieval household in Viljandi, Estonia, dated from the second half of the 13 to the beginning of the 15 century. The metatarsal bone had been broken during the horse's lifetime and showed evidence of partial healing. Using archaeological, zooarchaeological, morphological, microscopic, densitometric and radiographic analyses, we investigated the bones and the healing process in order to understand animal treatment in a medieval urban context.

Impairing of Serotonin Synthesis by P-Chlorphenylanine Prevents the Forgetting of Contextual Memory After Reminder and the Protein Synthesis Inhibition.

The injection of p-chlorophenylalanine, specific blocker of 5-HT synthesis 3 days before reminder with anisomycin administration prevented forgetting. It is known that the reminder cause reactivation of the long-term memory and it leads to reconsolidation of memory. We showed earlier that the disruption of the reconsolidation of contextual memory in terrestrial snail was caused by anisomycin, the inhibitor of protein syntheses (Gainutdinova et al.

Evaluation of butorphanol-azaperone-medetomidine (BAM) in captive blesbok immobilization (Damaliscus pygargus phillipsi).

Objective: The fixed-dose combination of butorphanol, azaperone and medetomidine (BAM; 30, 12 and 12 mg mL, respectively) with subsequent antagonism by naltrexone-atipamezole was evaluated for reversible immobilization of captive blesbok (Damaliscus pygargus phillipsi).

Study Design: Prospective, clinical trial.

Animals: Sixteen blesbok (four males and twelve females), weighing 52.

Responses of Withdrawal Interneurons to Serotonin Applications in Naïve and Learned Snails Are Different.

Long-term changes in membrane potential after associative training were described previously in identified premotor interneurons for withdrawal of the terrestrial snail . Serotonin was shown to be a major transmitter involved in triggering the long-term changes in mollusks. In the present study we compared the changes in electrophysiological characteristics of identifiable premotor interneurons for withdrawal in response to bath applications of serotonin (5-HT) or serotonin precursor 5-hydroxytryptophan (5-HTP) in preparations from naïve, neurotoxin-injected or associatively trained snails.

Molecular Bases of Brain Preconditioning.

Preconditioning of the brain induces tolerance to the damaging effects of ischemia and prevents cell death in ischemic penumbra. The development of this phenomenon is mediated by mitochondrial adenosine triphosphate-sensitive potassium ([Formula: see text]) channels and nitric oxide signaling (NO). The aim of this study was to investigate the dynamics of molecular changes in mitochondria after ischemic preconditioning (IP) and the effect of pharmacological preconditioning (PhP) with the [Formula: see text]-channels opener diazoxide on NO levels after ischemic stroke in rats.

Evaluation of BAM (butorphanol-azaperone-medetomidine) in captive African lion (Panthera leo) immobilization.

Objective: The combination of butorphanol, azaperone and medetomidine (BAM) with subsequent antagonism by naltrexone-yohimbine or naltrexone-atipamezole was evaluated for reversible immobilization of captive African lions (Panthea leo).

Study Design: Prospective, clinical trial.

Animals: Twenty lions, 11 males and nine females, weighing 38-284 kg were immobilized in South Africa.

Effects of NO Synthase Blocker L-NAME on Functional State of the Neuromotor System during Traumatic Disease of the Spinal Cord.

Functional state of the neuromotor system after administration of a nonspecific NO synthase blocker L-NAME was studied on the model of experimental contusion of the spinal cord. Electron paramagnetic resonance measurements of NO production in the damaged segment of the spinal cord were performed for estimation of the dynamics of intensity of NO production during traumatic disease of the spinal cord and selection of optimal period for L-NAME administration. The status of the neuromotor system was evaluated by stimulation electromyography.

[The role of ATP-dependent potassium channels and nitric oxide system in the neuroprotective effect of preconditioning].

Aim: To study a role of ATP-dependent potassium channels (K+ATP) in the neuroprotective effect of ischemic (IP) and pharmacological (PP) preconditioning and evaluate the dynamics of blood nitric oxide (NO) metabolites in cerebral ischemia.

Material And Methods: A model of ischemic stroke induced by the electrocoagulation of a middle cerebral artery (MCA) branch was used in male rats (n=86). Glibenclamide, a selective inhibitor of ATP-sensitive K+ channels, and diazoxide, a potassium channel activator, were used.

Effects of NO Donors and Inhibitors of NO Synthase and Guanylate Cyclase on the Acquisition of a Conditioned Defense Food Aversion Response in Edible Snails.

Experiments on edible snails revealed that NO synthase blockade with a nonspecific neuronal NO synthase inhibitor L-NAME before defense food aversion conditioning is followed by a decrease in the rate of learning. Exogenous NO donors, sodium nitroprusside and dinitrosyl iron complex, were shown to improve learning. Chronic administration of a specific soluble guanylate cyclase inhibitor ODQ also increased the rate of learning.