10 results on '"Russian Academy of Sciences - Chernogolovka"'
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2. Evolution of the Bromate Electrolyte Composition in the Course of Its Electroreduction inside a Membrane-Electrode Assembly with a Proton-Exchange Membrane.
- Author
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Konev DV, Zader PA, and Vorotyntsev MA
- Subjects
- Bromates chemistry, Oxidation-Reduction, Electrodes, Bromine chemistry, Protons
- Abstract
The passage of cathodic current through the acidized aqueous bromate solution (catholyte) leads to a negative shift of the average oxidation degree of Br atoms. It means a distribution of Br-containing species in various oxidation states between -1 and +5, which are mutually transformed via numerous protonation/deprotonation, chemical, and redox/electrochemical steps. This process is also accompanied by the change in the proton (H
+ ) concentration, both due to the participation of H+ ions in these steps and due to the H+ flux through the cation-exchange membrane separating the cathodic and anodic compartments. Variations of the composition of the catholyte concentrations of all these components has been analyzed for various initial concentrations of sulfuric acid, cA (0.015-0.3 M), and two values of the total concentrations of Br atoms inside the system, c0 (0.1 or 1.0 M of Br atoms), as functions of the average Br-atom oxidation degree,tot , under the condition of the thermodynamic equilibrium of the above transformations. It is shown that during the exhaustion of the redox capacity of the catholyte ( x pass from 5 to -1), the pH value passes through a maximum. Its height and the corresponding average oxidation state of bromine atoms depend on the initial bromate/acid ratio. The constructed algorithm can be used to select the initial acid content in the bromate catholyte, which is optimal from the point of view of preventing the formation of liquid bromine at the maximum content of electroactive compounds.x pass from 5 to -1), the pH value passes through a maximum. Its height and the corresponding average oxidation state of bromine atoms depend on the initial bromate/acid ratio. The constructed algorithm can be used to select the initial acid content in the bromate catholyte, which is optimal from the point of view of preventing the formation of liquid bromine at the maximum content of electroactive compounds.- Published
- 2023
- Full Text
- View/download PDF
3. Beneficial Effects of Dinitrosyl Iron Complexes on Wound Healing Compared to Commercial Nitric Oxide Plasma Generator.
- Author
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Igrunkova A, Fayzullin A, Serejnikova N, Lipina T, Pekshev A, Vanin A, Zaborova V, Budanova E, Shestakov D, Kastyro I, and Shekhter A
- Subjects
- Rats, Animals, Iron chemistry, Wound Healing, Glutathione chemistry, Nitric Oxide chemistry, Nitrogen Oxides chemistry
- Abstract
Nitric oxide (NO) is a gaseous molecule which plays a key role in wound healing. Previously, we identified the optimal conditions for wound healing strategies using NO donors and an air plasma generator. The aim of this study was to compare the wound healing effects of binuclear dinitrosyl iron complexes with glutathione (B-DNIC-GSH) and NO-containing gas flow (NO-CGF) at their optimal NO doses (0.04 mmol for B-DNIC-GSH and 1.0 mmol for NO-CGF per 1 cm
2 ) in a rat full-thickness wound model over a 3-week period. Excised wound tissues were studied by light and transmission electron microscopy and immunohistochemical, morphometrical and statistical methods. Both treatments had an identical stimulating impact on wound healing, which indicated a higher dosage effectiveness of B-DNIC-GSH compared to the NO-CGF. B-DNIC-GSH spray application reduced inflammation and promoted fibroblast proliferation, angiogenesis and the growth of granulation tissue during the first 4 days after injury. However, prolonged NO spray effects were mild compared to NO-CGF. Future studies should determine the optimal B-DNIC-GSH solution course for a more effective wound healing stimulation.- Published
- 2023
- Full Text
- View/download PDF
4. Conjugates of Tacrine and Salicylic Acid Derivatives as New Promising Multitarget Agents for Alzheimer's Disease.
- Author
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Makhaeva GF, Kovaleva NV, Rudakova EV, Boltneva NP, Grishchenko MV, Lushchekina SV, Astakhova TY, Serebryakova OG, Timokhina EN, Zhilina EF, Shchegolkov EV, Ulitko MV, Radchenko EV, Palyulin VA, Burgart YV, Saloutin VI, Bachurin SO, and Richardson RJ
- Subjects
- Animals, Mice, Acetylcholinesterase metabolism, Amyloid beta-Peptides metabolism, Antioxidants pharmacology, Butyrylcholinesterase metabolism, Cholinesterase Inhibitors chemistry, Molecular Docking Simulation, Salicylamides, Structure-Activity Relationship, Salicylic Acid chemistry, Alzheimer Disease drug therapy, Alzheimer Disease metabolism, Tacrine pharmacology, Tacrine chemistry
- Abstract
A series of previously synthesized conjugates of tacrine and salicylamide was extended by varying the structure of the salicylamide fragment and using salicylic aldehyde to synthesize salicylimine derivatives. The hybrids exhibited broad-spectrum biological activity. All new conjugates were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity toward BChE. The structure of the salicylamide moiety exerted little effect on anticholinesterase activity, but AChE inhibition increased with spacer elongation. The most active conjugates were salicylimine derivatives: IC
50 values of the lead compound 10c were 0.0826 µM (AChE) and 0.0156 µM (BChE), with weak inhibition of the off-target carboxylesterase. The hybrids were mixed-type reversible inhibitors of both cholinesterases and displayed dual binding to the catalytic and peripheral anionic sites of AChE in molecular docking, which, along with experimental results on propidium iodide displacement, suggested their potential to block AChE-induced β -amyloid aggregation. All conjugates inhibited Aβ42 self-aggregation in the thioflavin test, and inhibition increased with spacer elongation. Salicylimine 10c and salicylamide 5c with (CH2 )8 spacers were the lead compounds for inhibiting Aβ42 self-aggregation, which was corroborated by molecular docking to Aβ42 . ABTS•+ -scavenging activity was highest for salicylamides 5a-c , intermediate for salicylimines 10a-c , low for F-containing salicylamides 7 , and non-existent for methoxybenzoylamides 6 and difluoromethoxybenzoylamides 8 . In the FRAP antioxidant (AO) assay, the test compounds displayed little or no activity. Quantum chemical analysis and molecular dynamics (MD) simulations with QM/MM potentials explained the AO structure-activity relationships. All conjugates were effective chelators of Cu2+ , Fe2+ , and Zn2+ , with molar compound/metal (Cu2+ ) ratios of 2:1 ( 5b ) and ~1:1 ( 10b ). Conjugates exerted comparable or lower cytotoxicity than tacrine on mouse hepatocytes and had favorable predicted intestinal absorption and blood-brain barrier permeability. The overall results indicate that the synthesized conjugates are promising new multifunctional agents for the potential treatment of AD.- Published
- 2023
- Full Text
- View/download PDF
5. Water-Soluble Salts Based on Benzofuroxan Derivatives-Synthesis and Biological Activity.
- Author
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Chugunova E, Matveeva V, Tulesinova A, Iskanderov E, Akylbekov N, Dobrynin A, Khamatgalimov A, Appazov N, Boltayeva L, Duisembekov B, Zhanakov M, Aleksandrova Y, Sashenkova T, Klimanova E, Allayarova U, Balakina A, Mishchenko D, Burilov A, and Neganova M
- Subjects
- Animals, Mice, Seeds, Salts, Dose-Response Relationship, Drug, Water, Germination, Benzoxazoles pharmacology, Antineoplastic Agents pharmacology
- Abstract
A series of novel water-soluble salts of benzofuroxans was achieved via aromatic nucleophilic substitution reaction of 4,6-dichloro-5-nitrobenzofuroxan with various amines. The salts obtained showed good effectiveness of the pre-sowing treatment of seeds of agricultural crops at concentrations of 20-40 mmol. In some cases, the seed treatment with salts leads not only to improved seed germination, but also to the suppression of microflora growth. Additionally, their anti-cancer activityin vitrohas been researched. The compounds with morpholine fragments or a fragment of N -dimethylpropylamine, demonstrated the highest cytotoxic activity, which is in good correlation with the ability to inhibit the glycolysis process in tumor cells. Two compounds 4e and 4g were selected for further experiments using laboratory animals. It was found that the lethal dose of 50% (LD
50 ) is 22.0 ± 1.33 mg/kg for 4e and 13.75 ± 1.73 mg/kg for 4g , i.e., compound 4e is two times less toxic than 4g, according to the mouse model in vivo. It was shown that the studied compounds exhibit antileukemia activity after a single intraperitoneal injection at doses from 1.25 to 5 mg/kg, as a result of which the average lifespan of animals with a P388 murine leukemia tumor increases from 20 to 28%. Thus, the water-soluble salts of benzofuroxans can be considered as promisingcandidates for further development, both as anti-cancer agents and as stimulants for seed germination and regulators of microflora crop growth.- Published
- 2022
- Full Text
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6. Bis(Benzofuran-1,3- N , N -heterocycle)s as Symmetric and Synthetic Drug Leads against Yellow Fever Virus.
- Author
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Gupta NK, Jayakumar S, Huang WC, Leyssen P, Neyts J, Bachurin SO, Hwu JR, and Tsay SC
- Subjects
- Animals, Yellow fever virus, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Benzimidazoles pharmacology, Synthetic Drugs pharmacology, Yellow Fever Vaccine, Benzofurans pharmacology, Benzofurans therapeutic use
- Abstract
The yellow fever virus (YFV) is an emerging RNA virus and has caused large outbreaks in Africa and Central and South America. The virus is often transmitted through infected mosquitoes and spreads from area to area because of international travel. Being an acute viral hemorrhagic disease, yellow fever can be prevented by an effective, safe, and reliable vaccine, but not be eliminated. Currently, there is no antiviral drug available for its cure. Thus, two series of novel bis(benzofuran−1,3-imidazolidin-4-one)s and bis(benzofuran−1,3-benzimidazole)s were designed and synthesized for the development of anti-YFV lead candidates. Among 23 new bis-conjugated compounds, 4 of them inhibited YFV strain 17D (Stamaril) on Huh-7 cells in the cytopathic effect reduction assays. These conjugates exhibited the most compelling efficacy and selectivity with an EC50 of <3.54 μM and SI of >15.3. The results are valuable for the development of novel antiviral drug leads against emerging diseases.
- Published
- 2022
- Full Text
- View/download PDF
7. MiRNAs as Noninvasive Biomarkers and Therapeutic Agents of Pituitary Adenomas.
- Author
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Beylerli O, Beeraka NM, Gareev I, Pavlov V, Yang G, Liang Y, and Aliev G
- Subjects
- Apoptosis genetics, Cell Proliferation genetics, Gene Expression Regulation, Neoplastic, Humans, Pituitary Neoplasms drug therapy, Pituitary Neoplasms pathology, Biomarkers, Tumor genetics, MicroRNAs genetics, Molecular Targeted Therapy, Pituitary Neoplasms genetics
- Abstract
Pituitary adenoma (PA) accounts for 10-15% of all intracranial neoplasms. Even though most pituitary adenomas are benign, it is known that almost 35% of them exhibit an aggressive clinical course, including rapid proliferative activity and invasion of neighboring tissues. MicroRNAs (miRNAs) are short single-stranded RNA molecules that can influence post-transcriptional regulation by controlling target genes. Based on research data on miRNAs over the past 20 years, more than 60% of genes encoding human proteins are regulated by miRNAs, which ultimately control basic cellular mechanisms, including cell proliferation, differentiation, and apoptosis. Dysregulation of miRNAs has been observed in a number of diseases, especially tumors like PA. A majority of miRNAs are expressed within the cells themselves. However, the circulating miRNAs can be detected in several biological fluids of the human body. The identification of circulating miRNAs as new molecular markers may increase the ability to detect a tumor, predict the course of a disease, plan to choose suitable treatment, and diagnose at the earliest signs of impending neoplastic transformation. Therapy of PAs with aggressive behavior is a complex task. When surgery and chemotherapy fail, radiotherapy becomes the treatment of choice against PAs. Therefore, the possibility of implementing circulating miRNAs as innovative diagnostic and therapeutic agents for PA is one of the main exciting ideas.
- Published
- 2020
- Full Text
- View/download PDF
8. Exosomes: Insights from Retinoblastoma and Other Eye Cancers.
- Author
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Lande K, Gupta J, Ranjan R, Kiran M, Torres Solis LF, Solís Herrera A, Aliev G, and Karnati R
- Subjects
- Cell Line, Eye Neoplasms diagnosis, Eye Neoplasms metabolism, Gene Expression Regulation, Neoplastic, Humans, Retina pathology, Exosomes metabolism, MicroRNAs metabolism, Retina metabolism, Retinal Neoplasms diagnosis, Retinal Neoplasms metabolism, Retinoblastoma diagnosis, Retinoblastoma metabolism
- Abstract
Exosomes, considered as cell debris or garbage bags, have been later characterized as nanometer-sized extracellular double-membrane lipid bilayer bio-vesicles secreted by the fusion of vesicular bodies with the plasma membrane. The constituents and the rate of exosomes formation differ in different pathophysiological conditions. Exosomes are also observed and studied in different parts of the eye, like the retina, cornea, aqueous, and vitreous humor. Tear fluid consists of exosomes that are shown to regulate various cellular processes. The role of exosomes in eye cancers, especially retinoblastoma (RB), is not well explored, although few studies point towards their presence. Retinoblastoma is an intraocular tumor that constitutes 3% of cases of cancer in children. Diagnosis of RB may require invasive procedures, which might lead to the spread of the disease to other parts. Due to this reason, better ways of diagnosis are being explored. Studies on the exosomes in RB tumors and serum might help designing better diagnostic approaches for RB. In this article, we reviewed studies on exosomes in the eye, with a special emphasis on RB. We also reviewed miRNAs expressed in RB tumor, serum, and cell lines and analyzed the targets of these miRNAs from the proteins identified in the RB tumor exosomes. hsa-miR-494 and hsa-miR-9, upregulated and downregulated, respectively in RB, have the maximum number of targets. Although oppositely regulated, they share the same targets in the proteins identified in RB tumor exosomes. Overall this review provides the up-to-date progress in the area of eye exosome research, with an emphasis on RB.
- Published
- 2020
- Full Text
- View/download PDF
9. Updated Understanding of Cancer as a Metabolic and Telomere-Driven Disease, and Proposal for Complex Personalized Treatment, a Hypothesis.
- Author
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Muresanu C, Somasundaram SG, Vissarionov SV, Torres Solis LF, Solís Herrera A, Kirkland CE, and Aliev G
- Subjects
- Cell Division, Cellular Senescence genetics, DNA Damage genetics, DNA Damage physiology, DNA, Mitochondrial genetics, Holistic Health, Humans, Mitochondria metabolism, Neoplasms genetics, Neoplasms therapy, Oxidative Stress, Precision Medicine methods, Telomerase metabolism, Telomere genetics, Telomere Homeostasis genetics, Neoplasms metabolism, Telomere metabolism, Telomere Homeostasis physiology
- Abstract
In this review, we propose a holistic approach to understanding cancer as a metabolic disease. Our search for relevant studies in medical databases concludes that cancer cells do not evolve directly from normal healthy cells. We hypothesize that aberrant DNA damage accumulates over time-avoiding the natural DNA controls that otherwise repair or replace the rapidly replicating cells. DNA damage starts to accumulate in non-replicating cells, leading to senescence and aging. DNA damage is linked with genetic and epigenetic factors, but the development of cancer is favored by telomerase activity. Evidence indicates that telomere length is affected by chronic inflammations, alterations of mitochondrial DNA, and various environmental factors. Emotional stress also influences telomere length. Chronic inflammation can cause oxidative DNA damage. Oxidative stress, in turn, can trigger mitochondrial changes, which ultimately alter nuclear gene expression. This vicious cycle has led several scientists to view cancer as a metabolic disease. We have proposed complex personalized treatments that seek to correct multiple changes simultaneously using a psychological approach to reduce chronic stress, immune checkpoint therapy with reduced doses of chemo and radiotherapy, minimal surgical intervention, if any, and mitochondrial metabolic reprogramming protocols supplemented by intermittent fasting and personalized dietary plans without interfering with the other therapies.
- Published
- 2020
- Full Text
- View/download PDF
10. Application of Acyzol in the Context of Zinc Deficiency and Perspectives.
- Author
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Aliev G, Li Y, Chubarev VN, Lebedeva SA, Parshina LN, Trofimov BA, Sologova SS, Makhmutova A, Avila-Rodriguez MF, Klochkov SG, Galenko-Yaroshevsky PA, and Tarasov VV
- Subjects
- Animals, Clinical Studies as Topic, Drug Evaluation, Preclinical, Humans, Imidazoles chemistry, Mice, Nutrition Disorders diagnosis, Nutrition Disorders prevention & control, Treatment Outcome, Zinc Acetate chemistry, Zinc Acetate pharmacology, Nutrition Disorders drug therapy, Nutrition Disorders etiology, Trace Elements deficiency, Zinc deficiency, Zinc Acetate therapeutic use
- Abstract
Zinc is one of the most important essential trace elements. It is involved in more than 300 enzyme systems and is an indispensable participant in many biochemical processes. Zinc deficiency causes a number of disorders in the human body, the main ones being the delay of growth and puberty, immune disorders, and cognitive dysfunctions. There are over two billion people in the world suffering from zinc deficiency conditions. Acyzol, a zinc-containing medicine, developed as an antidote against carbon monoxide poisoning, demonstrates a wide range of pharmacological activities: Anti-inflammatory, reparative, detoxifying, immunomodulatory, bacteriostatic, hepatoprotective, adaptogenic, antioxidant, antihypoxic, and cardioprotective. The presence of zinc in the composition of Acyzol suggests the potential of the drug in the treatment and prevention of zinc deficiency conditions, such as Prasad's disease, immune system pathology, alopecia, allergodermatoses, prostate dysfunction, psoriasis, stomatitis, periodontitis, and delayed mental and physical development in children. Currently, the efficiency of Acyzol in the cases of zinc deficiency is shown in a large number of experimental studies. So, Acyzol can be used as a highly effective drug for pharmacologic therapy of a wide range of diseases and conditions and it opens up new perspectives in the treatment and prevention of zinc deficiency conditions.
- Published
- 2019
- Full Text
- View/download PDF
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