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1
Grover, Casey, Justine How, and Reb Close. "Fentanyl, etizolam, and beyond: A feasibility study of a community partnership using handheld Raman spectrometry to identify substances in the local illicit drug supply." Journal of Public Health Research 12, no. 2 (2023): 227990362311663. http://dx.doi.org/10.1177/22799036231166313.
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Background: The United States is currently experiencing an unprecedented rise in fatal drug overdoses, which is in part due to the arrival of fentanyl, fentanyl analogs, and other synthetic drugs into the illicit drug supply. Traditional urine drug testing is often unable to detect fentanyl analogs and other novel synthetic drugs, which places physicians and first responders in the difficult position of treating patients who are intoxicated with or overdosing on unknown substances. Design and methods: We report, as a feasibility study, the development of a novel program to use a handheld Raman spectrometry device in our hospital’s Emergency Department to surveil our local illicit drug supply in terms of what substances are being sold and used. Results: Using our novel program, we were able to detect 27 substances in our illicit drug supply over a 10 month period, including fentanyl analogues. We shared, through our local opioid safety coalition, real-time information to first responders, substance use treatment programs, and physicians about the novel substances we detected using the handheld Raman spectrometer. Conclusions: A community partnership of using handheld Raman spectrometry in our hospital’s Emergency Department was successful in providing information to health care providers about novel substances in our illicit drug market. Additionally, the implementation of this program improved collaboration between local health care providers and local law enforcement.
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Maria, López‐Ramos, Figueroa‐Valverde Lauro, Díaz‐Cedillo Francisco, et al. "Synthesis of two 2,3,4,5‐tetrahydrooxepin‐7‐ylamino)benzoate derivatives as antibacterial agents against Escherichia coli and Staphylococcus aureus." Vietnam Journal of Chemistry 59, no. 6 (2021): 923–34. http://dx.doi.org/10.1002/vjch.202100095.
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AbstractSome protocols have been used to preparation of oxepine analogs using some substances which require special conditions such as higher‐temperatures or differences in the pH. The objective of this study was to synthesize two new oxepine‐derivatives from a Bicyclo[6.1.0]‐alkyne analog. Besides, the antibacterial effect against Escherichia coli and Staphylococcus aureus was determinate. The results showed that protocols used for synthesis of two oxepine analogs do not require special conditions to give a good yielding. Other data showed that oxepine analogs decreased the growth bacterial of Escherichia coli and Staphylococcus aureus. In conclusion, in this investigation a facile method for the synthesis of two oxepine derivatives is reported; in addition, these compounds could be good candidates as antibacterial reagents.
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Moriyama, Masako, Nobuhide Hayashi, Chinami Ohyabu, Masahiko Mukai, Seiji Kawano, and Shunichi Kumagai. "Performance Evaluation and Cross-Reactivity from Insulin Analogs with the ARCHITECT Insulin Assay,." Clinical Chemistry 52, no. 7 (2006): 1423–26. http://dx.doi.org/10.1373/clinchem.2005.065995.
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Abstract Background: Insulin measurement is used for the diagnosis of hypoglycemia and for insulin pharmacokinetic evaluations. We assessed the analytical and clinical performance of the ARCHITECT® insulin assay, a chemiluminescent immunoassay recently introduced for the ARCHITECT i2000 fully automated immunoassay analyzer (Abbott Laboratories). We also tested whether major insulin analogs cross-reacted with the immunoassay reagents. Methods: We used Clinical and Laboratory Standards Institute protocols to assess the analytical performance of the ARCHITECT insulin assay and compared its accuracy with that of the E-test TOSOH II (IRI) from TOSOH Corporation. We used 3 recombinant insulin analogs (lispro, aspart, and glargine) to evaluate the cross-reactivity of insulin analogs with the ARCHITECT immunoassay reagent. Results: The total CV for the ARCHITECT assay was <5%. Correlation between the ARCHITECT insulin assay and the E-test TOSOH II (IRI) was satisfactory in the measured range, but we detected a slope deviation between the assays. The ARCHITECT insulin assay showed low cross-reactivity to the insulin analog aspart, whereas it detected the other insulin analogs, lispro and glargine, in concentrations as high as the theoretical concentrations. Conclusions: The ARCHITECT insulin assay showed favorable basic performance, including reproducibility, dilution linearity, detection limit, and effects of interfering substances. When interpreting results, clinicians and laboratory pathologists should be aware of the cross-reactivity of the ARCHITECT and other immunoassays to specific insulin analogs prescribed to diabetes patients.
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Reznik, Oleg, Maksym Pochtovyi, Kateryna Yanishevska, and Andrii Butyrskyi. "Proof during the prejudicial inquiry of smugglingof narcotic drugs, psychotropic substances, their analogs, or precursors under the legislation of Ukraine." Revista Amazonia Investiga 10, no. 39 (2021): 159–68. http://dx.doi.org/10.34069/ai/2021.39.03.15.
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The object of the study is social relations regarding the prejudicial inquiry of smuggling narcotic drugs, psychotropic substances, their analogs or precursors. It has been found that there are scholars who choose different definitions for interpreting the nature of the proof, but are unanimous about the role of this process in proving a person’s guilt and choosing an adequate punishment. The authors use a set of scientific methods of modern epistemology as well as comparative, special legal, logical and other methods. We propose to analyze all the circumstances that are subject to proof during the prejudicial inquiry of smuggling of narcotic drugs, psychotropic substances, their analogs, or precursors. In this paper must identify the general grounds that must be proved in each crime and the specific circumstances that are important to prove only in the case of smuggling narcotic drugs, psychotropic substances, their analogs, or precursors. The conclusion is made about the importance of proper procedural support of criminal prosecution of persons who have committed a crime under Article 305 of the Criminal Code of Ukraine. Therefore, we propose to include in the subject of evidence for the prejudicial inquiry.
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Frisoni, Paolo, Erica Bacchio, Sabrine Bilel, et al. "Novel Synthetic Opioids: The Pathologist’s Point of View." Brain Sciences 8, no. 9 (2018): 170. http://dx.doi.org/10.3390/brainsci8090170.
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Background: New Psychoactive Substances (NPS) constitute a broad range of hundreds of natural and synthetic drugs, including synthetic opioids, synthetic cannabinoids, synthetic cathinones, and other NPS classes, which were not controlled from 1961 to 1971 by the United Nations drug control conventions. Among these, synthetic opioids represent a major threat to public health. Methods: A literature search was carried out using public databases (such as PubMed, Google Scholar, and Scopus) to survey fentanyl-, fentanyl analogs-, and other synthetic opioid-related deaths. Keywords including “fentanyl”, “fentanyl analogs”, “death”, “overdose”, “intoxication”, “synthetic opioids”, “Novel Psychoactive Substances”, “MT-45”, “AH-7921”, and “U-47700” were used for the inquiry. Results: From our literature examination, we inferred the frequent implication of fentanyls and synthetic opioids in side effects, which primarily affected the central nervous system and the cardiovascular and pulmonary systems. The data showed a great variety of substances and lethal concentrations. Multidrug-related deaths appeared very common, in most reported cases. Conclusions: The investigation of the contribution of novel synthetic opioid intoxication to death should be based on a multidisciplinary approach aimed at framing each case and directing the investigation towards targeted toxicological analyses.
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Kazir, Meital, and Yoav D. Livney. "Plant-Based Seafood Analogs." Molecules 26, no. 6 (2021): 1559. http://dx.doi.org/10.3390/molecules26061559.
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There is a growing global need to shift from animal- towards plant-based diets. The main motivations are environmental/sustainability-, human health- and animal welfare concerns. The aim is to replace traditional animal-based food with various alternatives, predominantly plant-based analogs. The elevated consumption of fish and seafood, leads to negative impacts on the ecosystem, due to dwindling biodiversity, environmental damage and fish diseases related to large-scale marine farming, and increased intake of toxic substances, particularly heavy metals, which accumulate in fish due to water pollution. While these facts lead to increased awareness and rising dietary shifts towards vegetarian and vegan lifestyles, still the majority of seafood consumers seek traditional products. This encourages the development of plant-based analogs for fish and seafood, mimicking the texture and sensorial properties of fish-meat, seafood, or processed fish products. Mimicking the internal structure and texture of fish or seafood requires simulating their nanometric fibrous-gel structure. Common techniques of structuring plant-based proteins into such textures include hydrospinning, electrospinning, extrusion, and 3D printing. The conditions required in each technique, the physicochemical and functional properties of the proteins, along with the use of other non-protein functional ingredients are reviewed. Trends and possible future developments are discussed.
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Tusiewicz, Kaja, Olga Wachełko, Marcin Zawadzki, and Paweł Szpot. "Forensic Aspects of Designer LSD Analogs Identification by GC–MS (EI) and UV Spectroscopy." Molecules 29, no. 23 (2024): 5717. https://doi.org/10.3390/molecules29235717.
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Lysergic acid diethylamide (LSD) analogs, often referred to as new psychoactive substances, are synthesized to mimic controlled substances while evading drug regulations. This study emphasizes the challenges of identifying these compounds, particularly their isomeric forms. Gas chromatography–mass spectrometry (GC–MS) and UV spectroscopy were employed to analyze 13 LSD analogs. The effects of different solvents on the detection of these analogs were analyzed, demonstrating that solvents like diethyl ether, tert-butyl methyl ether, dichloromethane and acetone provided the best sensitivity and stability. Methanol, on the other hand, causes alcoholysis of many LSD analogs, which may lead to false results. Additionally, effective chromatographic separation of isomers was established, including LSD, MiPLA, LAMPA, 1P-LSD and 1P-MiPLA, as well as 1cP-LSD and 1cP-MiPLA, which is crucial for accurate identification. The elution order of the determined compounds with the use of developed chromatographic method was as follows: LSD, MiPLA, LAMPA, AL-LAD, LSZ, 2-Br-LSD, ALD-52, 1P-LSD, 1P-MiPLA, 1B-LSD, 1V-LSD, 1cP-LSD and 1cP-MiPLA. Differences in ion ratios observed in mass spectrometry (MS) were also analyzed to distinguish between closely related compounds. Several key ions for LSD analogs were able to be identified, including 221, 208, 207, 196, 194, 192, 181, 167, 154, 152 and 128 m/z. In analogs with an N-diethyl group (or variants like N-methyl-propyl in LAMPA or N-methyl-isopropyl in MiPLA), mass spectra showed fragments 100, 72 and 58 m/z. For LSZ, the cyclic group at R1 produces ions 98 and 70 m/z. Analogs with an N6 allyl group (e.g., AL-LAD) show a characteristic ion 247 m/z. This method allows for the correct differentiation of structural isomers based on their unique ion fragmentation patterns and relative intensities. UV spectroscopy was used as a supplementary tool for screening, though it has limitations in analyzing complex mixtures. This work contributes to the forensic identification of designer LSD analogs, ensuring reliable detection for legal and toxicological investigations.
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Xu, Hengwei, Zeyu Zhao, Shunsuke Kimura, Takeshi Onodera, and Kiyoshi Toko. "Molecular Structure Underlying the Allosteric Mechanism of Caffeine Detection in Taste Sensor." Chemosensors 11, no. 2 (2023): 97. http://dx.doi.org/10.3390/chemosensors11020097.
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The use of taste sensors with lipid/polymer membranes is one of the methods to evaluate taste. As previously reported, taste sensors can detect non-charged substances such as caffeine by modifying the lipid/polymer membranes with hydroxybenzoic acids (HBAs). The mechanism of caffeine detection by taste sensors was identified to be an allosteric one. Generally, the allosteric mechanism, defined as “regulation at distant sites”, is used to describe the regulation process for proteins. In this study, to improve the sensitivity of taste sensors to caffeine and its analogs using the allosteric mechanism, we used various modifiers of lipid/polymer membranes, and we detected caffeine using taste sensors with the modified membranes. The detection of the caffeine analogs theophylline and theobromine was also analyzed. The results of caffeine detection clarified that the molecular structure underlying the allosteric mechanism capable of effective caffeine detection involves both the carboxyl and hydroxyl groups, where the hydroxyl group can form intermolecular H bonds with caffeine. Furthermore, the taste sensors with a modifier, which has the molecular structure underlying the allosteric mechanism, showed high sensitivity to caffeine and caffeine analogs. The use of an allosteric mechanism may help improve the sensitivity of taste sensors to other non-charged pharmaceutical substances, such as dexamethasone and prednisolone, in the future.
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Choińska, Marta Katarzyna, Ivana Šestáková, Vojtěch Hrdlička, et al. "Electroanalysis of Fentanyl and Its New Analogs: A Review." Biosensors 12, no. 1 (2022): 26. http://dx.doi.org/10.3390/bios12010026.
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The review describes fentanyl and its analogs as new synthetic opioids and the possibilities of their identification and determination using electrochemical methods (e.g., voltammetry, potentiometry, electrochemiluminescence) and electrochemical methods combined with various separation methods. The review also covers the analysis of new synthetic opioids, their parent compounds, and corresponding metabolites in body fluids, such as urine, blood, serum, and plasma, necessary for a fast and accurate diagnosis of intoxication. Identifying and quantifying these addictive and illicit substances and their metabolites is necessary for clinical, toxicological, and forensic purposes. As a reaction to the growing number of new synthetic opioid intoxications and increasing fatalities observed over the past ten years, we provide thorough background for developing new biosensors, screen-printed electrodes, or other point-of-care devices.
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Longnecker, Stephen M. "Somatostatin and Octreotide: Literature Review and Description of Therapeutic Activity in Pancreatic Neoplasia." Drug Intelligence & Clinical Pharmacy 22, no. 2 (1988): 99–106. http://dx.doi.org/10.1177/106002808802200201.
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The somatostatins represent endogenous substances that serve a diversity of functions in the body. These activities are just beginning to be understood and could have major implications in the treatment of human disease. Their chief pharmacologic activities lie in the modification or modulation of protein hormone synthesis of the gastrointestinal system; a great many other systems may be involved as well. Since the discovery of the therapeutic potentials of naturally isolated somatostatins, attempts have been made to design newer analogs more conducive to practical use. Such an example is long-acting somatostatin analog octreotide. Literature has recently begun to appear describing the therapeutic activities of this and other similar compounds and the first steps to understanding their clinical pharmacology are being taken. Surprising activity has been found in the palliative treatment of a wide variety of formerly resistant gastrointestinal syndromes and endocrine tumors. These activities may have considerable future impact on the treatment of disease involving hormonal imbalance or inappropriate secretion.
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Petrou, S., R. W. Ordway, J. A. Hamilton, J. V. Walsh, and J. J. Singer. "Structural requirements for charged lipid molecules to directly increase or suppress K+ channel activity in smooth muscle cells. Effects of fatty acids, lysophosphatidate, acyl coenzyme A and sphingosine." Journal of General Physiology 103, no. 3 (1994): 471–86. http://dx.doi.org/10.1085/jgp.103.3.471.
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We determined the structural features necessary for fatty acids to exert their action on K+ channels of gastric smooth muscle cells. Examination of the effects of a variety of synthetic and naturally occurring lipid compounds on K+ channel activity in cell-attached and excised membrane patches revealed that negatively charged analogs of medium to long chain fatty acids (but not short chain analogs) as well as certain other negatively charged lipids activate the channels. In contrast, positively charged, medium to long chain analogs suppress activity, and neutral analogs are without effect. The key requirements for effective compounds seem to be a sufficiently hydrophobic domain and the presence of a charged group. Furthermore, those negatively charged compounds unable to "flip" across the bilayer are effective only when applied at the cytosolic surface of the membrane, suggesting that the site of fatty acid action is also located there. Finally, because some of the effective compounds, for example, the fatty acids themselves, lysophosphatidate, acyl Coenzyme A, and sphingosine, are naturally occurring substances and can be liberated by agonist-activated or metabolic enzymes, they may act as second messengers targeting ion channels.
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Imig, John D., Md Abdul Hye Khan, Anna Burkhan, Guan Chen, Adeniyi Michael Adebesin, and John R. Falck. "Kidney-Targeted Epoxyeicosatrienoic Acid Analog, EET-F01, Reduces Inflammation, Oxidative Stress, and Cisplatin-Induced Nephrotoxicity." International Journal of Molecular Sciences 22, no. 6 (2021): 2793. http://dx.doi.org/10.3390/ijms22062793.
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Although epoxyeicosatrienoic acid (EET) analogs have performed well in several acute and chronic kidney disease models, targeted delivery of EET analogs to the kidney can be reasonably expected to reduce the level of drug needed to achieve a therapeutic effect and obviate possible side effects. For EET analog kidney-targeted delivery, we conjugated a stable EET analog to folic acid via a PEG-diamine linker. Next, we compared the kidney targeted EET analog, EET-F01, to a well-studied EET analog, EET-A. EET-A or EET-F01 was infused i.v. and plasma and kidney tissue collected. EET-A was detected in the plasma but was undetectable in the kidney. On the other hand, EET-F01 was detected in the plasma and kidney. Experiments were conducted to compare the efficacy of EET-F01 and EET-A for decreasing cisplatin nephrotoxicity. Cisplatin was administered to WKY rats treated with vehicle, EET-A (10 mg/kg i.p.) or EET-F01 (20 mg/kg or 2 mg/kg i.p.). Cisplatin increased kidney injury markers, viz., blood urea nitrogen (BUN), N-acetyl-β-(D)-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1), and thiobarbituric acid reactive substances (TBARS). EET-F01 was as effective as EET-A in decreasing BUN, NAG, KIM-1, TBARS, and renal histological injury caused by cisplatin. Despite its almost 2×-greater molecular weight compared with EET-A, EET-F01 was comparably effective in decreasing renal injury at a 10-fold w/w lower dose. EET-F01 decreased cisplatin nephrotoxicity by reducing oxidative stress and inflammation. These data demonstrate that EET-F01 targets the kidney, allows for a lower effective dose, and combats cisplatin nephrotoxicity. In conclusion, we have developed a kidney targeted EET analog, EET-F01, that demonstrates excellent potential as a therapeutic for kidney diseases.
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Wang, Ling, Gustavo Murilo Alves, Sevde Dogruer Erkok, and Bruce McCord. "(Digital Presentation) Electrochemical and DFT Studies for Fentanyl and Fentanyl Analogs." ECS Meeting Abstracts MA2022-02, no. 64 (2022): 2390. http://dx.doi.org/10.1149/ma2022-02642390mtgabs.
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The abuse of opioids has been a critical issue to the public health for years. With the appearance of new fentanyl analogs, the overdose rates of opioids continue to bloom. Current screening methods, such as immunoassay, have difficulty detecting the full range of opioid analogues due to a wide variety of structural variations. We have been working on alternative screening methods, Electrochemical approaches, including square wave voltammetry and cyclic voltammetry, quickly distinguish the group of fentanyl analogs from other opioids with lower cost and easier operations. Both screening approaches are convenient for point-of-care analysis and laboratory tests. The electrochemical approaches utilize the SPE electrodes and PBS buffer. When the solid drugs were dissolved in the buffer solutions, then dropped on electrodes and analyzed via CHI instrument with an energy range of 0.5 – 1.8 eV. The SWV spectra identify fentanyl analogs from mixtures with the optimized condition for individual drugs, such as fentanyl, cocaine, heroin, opioids, amphetamines, and adulterants. Electrochemical approaches are less sensitive than instrumental methods, however, its operations and preparations are easier for un-trained staff. To understand the cross reaction of fentanyl analogs and impurities, as well as the metabolites, DFT calculations displayed the energy changes and pathways from parent drugs to metabolites. The electrochemical method permits a rapid, easily operated presumptive test for opioids in different benefits. When the method coupled with other screening methods, such as surface enhanced Raman spectroscopy our lab have done, the method can be orthogonal to mass spectrometry and sufficiently sensitive to detect compounds at toxicological levels. As a result it should be particularly useful for the screening of opioids and other novel psychoactive substances.
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Periferakis, Argyrios, Georgios Tsigas, Aristodemos-Theodoros Periferakis, et al. "Antitumoral and Anti-inflammatory Roles of Somatostatin and Its Analogs in Hepatocellular Carcinoma." Analytical Cellular Pathology 2021 (November 27, 2021): 1–13. http://dx.doi.org/10.1155/2021/1840069.
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Hepatocellular carcinoma (HCC) is the most common primary liver cancer and affects about 8% of cirrhotic patients, with a recurrence rate of over 50%. There are numerous therapies available for the treatment of HCC, depending on cancer staging and condition of the patient. The complexity of the treatment is also justified by the unique pathogenesis of HCC that involves intricate processes such as chronic inflammation, fibrosis, and multiple molecular carcinogenesis events. During the last three decades, multiple in vivo and in vitro experiments have used somatostatin and its analogs (SSAs) to reduce the proliferative and metastatic potential of hepatoma cells by inducing their apoptosis and reducing angiogenesis and the inflammatory component of HCC. Most experiments have proven successful, revealing several different pathways and mechanisms corresponding to the aforementioned functions. Moreover, a correlation between specific effects and expression of somatostatin receptors (SSTRs) was observed in the studied cells. Clinical trials have tested either somatostatin or an analog, alone or in combination with other drugs, to explore the potential effects on HCC patients, in various stages of the disease. While the majority of these clinical trials exhibited minor to moderate success, some other studies were inconclusive or even reported negative outcomes. A complete evaluation of the efficacy of somatostatin and SSAs is still the matter of intense debate, and, if deemed useful, these substances may play a beneficial role in the management of HCC patients.
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Prieto-Rodríguez, Juliet A., Kevin P. Lévuok-Mena, Juan C. Cardozo-Muñoz та ін. "In Vitro and In Silico Study of the α-Glucosidase and Lipase Inhibitory Activities of Chemical Constituents from Piper cumanense (Piperaceae) and Synthetic Analogs". Plants 11, № 17 (2022): 2188. http://dx.doi.org/10.3390/plants11172188.
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Digestive enzymes are currently considered important therapeutic targets for the treatment of obesity and some associated metabolic diseases, such as type 2 diabetes. Piper cumanense is a species characterized by the presence of bioactive constituents, particularly prenylated benzoic acid derivatives. In this study, the inhibitory potential of chemical constituents from P. cumanense and some synthesized compounds was determined on digestive enzymes (pancreatic lipase (PL) and α-glucosidase (AG)). The methodology included isolating and identifying secondary metabolites from P. cumanense, synthesizing some analogs, and a molecular docking study. The chemical study allowed the isolation of four prenylated benzoic acid derivatives (1–4). Four analogs (5–8) were synthesized. Seven compounds were found to significantly inhibit the catalytic activity of PL with IC50 values between 28.32 and 55.8 µM. On the other hand, only two compounds (6 and 7) were active as inhibitors of AG with IC50 values lower than 155 µM, standing out as the potential multitarget of these chromane compounds. Enzyme kinetics and molecular docking studies showed that the bioactive compounds mainly interact with amino acids other than those of the catalytic site in both PL and AG. This work constitutes the first report on the antidiabetic and antiobesity potential of substances derived from P. cumanense.
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Marshall, Kenneth C., and Huangui Xiong. "Modulation of amino acid neurotransmitter actions by other neurotransmitters: some examples." Canadian Journal of Physiology and Pharmacology 69, no. 7 (1991): 1115–22. http://dx.doi.org/10.1139/y91-163.
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Developments in the field of central neurotransmission indicate that amino acids serve as important and widespread transmitters throughout the central nervous system. There are increasing indications from recent experimental studies that several of the other central neurotransmitters may exert potent effects on central neurons by modulating the actions of amino acids. Noradrenaline and serotonin have received particular attention as potential modulators, and a wide variety of actions has been reported for them. Modulatory actions have been reported at both pre- and post-synaptic levels, including both short- and long-term effects and facilitation or inhibition of amino acid actions. Selectivity has been found both for specific receptor subtypes of the neuromodulator and for specific effects of amino acids. Examples of such selectivity are modification of actions of an amino acid with little effect on spontaneous activity or membrane properties of the target cell, or in comparison to the actions of other neurotransmitters, or even other selective amino acid analogs. Modulatory actions on amino acids have also been reported for several other neurotransmitters including acetylcholine and various peptides. Recent studies of angiotensin II demonstrate that when iontophoretically applied, it can potently and selectively block the depolarizing action of glutamate on locus coeruleus neurons. It is possible that physiological influences of these various transmitter substances are expressed through modification of amino acid actions, rather than through direct effects on central neurons.Key words: neuromodulation, neurotransmitters, glutamic acid, noradrenaline, angiotensin II.
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Boo, Yong Chool. "Arbutin as a Skin Depigmenting Agent with Antimelanogenic and Antioxidant Properties." Antioxidants 10, no. 7 (2021): 1129. http://dx.doi.org/10.3390/antiox10071129.
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Arbutin is a compound of hydroquinone and D-glucose, and it has been over 30 years since there have been serious studies on the skin lightening action of this substance. In the meantime, there have been debates and validation studies about the mechanism of action of this substance as well as its skin lightening efficacy and safety. Several analogs or derivatives of arbutin have been developed and studied for their melanin synthesis inhibitory action. Formulations have been developed to improve the stability, transdermal delivery, and release of arbutin, and device usage to promote skin absorption has been developed. Substances that inhibit melanin synthesis synergistically with arbutin have been explored. The skin lightening efficacy of arbutin alone or in combination with other active ingredients has been clinically evaluated. Combined therapy with arbutin and laser could give enhanced depigmenting efficacy. The use of arbutin causes dermatitis rarely, and caution is recommended for the use of arbutin-containing products, especially from the viewpoint that hydroquinone may be generated during product use. Studies on the antioxidant properties of arbutin are emerging, and these antioxidant properties are proposed to contribute to the skin depigmenting action of arbutin. It is hoped that this review will help to understand the pros and cons of arbutin as a cosmetic ingredient, and will lead to future research directions for developing advanced skin lightening and protecting cosmetic products.
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Behling, Felix, Jürgen Honegger, Marco Skardelly, et al. "High Expression of Somatostatin Receptors 2A, 3, and 5 in Corticotroph Pituitary Adenoma." International Journal of Endocrinology 2018 (December 9, 2018): 1–12. http://dx.doi.org/10.1155/2018/1763735.
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The development of somatostatin analogs for the treatment of pituitary Cushing’s disease has been based on somatostatin receptor expression analyses of small cohorts of pituitary adenomas. Additionally, the classification of pituitary adenomas has recently changed. To enable progress with this treatment option, we assessed somatostatin receptors in a large cohort of corticotroph and other pituitary adenomas according to the new WHO classification of endocrine tumors. Paraffin-embedded tumor samples of 88 corticotroph pituitary adenomas and 30 nonadenomatous pituitary biopsies were analyzed after processing into tissue microarrays and immunohistochemical staining for SSTR 1, SSTR2A, SSTR3, SSTR4, and SSTR5. For comparison, 159 other noncorticotroph pituitary adenomas were analyzed. SSTR3 expression was higher in corticotroph adenomas compared to PIT-1-positive, gonadotroph, and nonfunctioning pituitary adenomas (p<0.0001, p=0.0280, and p<0.0001, respectively). This was also the case for the expression of SSTR5 (p=0.0003, p<0.0001, and p<0.0001, respectively). SSTR2A expression was higher compared to gonadotroph and nonfunctioning pituitary adenomas (p=0.0217 and 0.0126, respectively) while PIT-1-positive adenomas showed even higher SSTR2A expression (p<0.0001). SSTR2A and SSTR5 were both expressed higher in nonadenomatous pituitary biopsies than in pituitary adenomas (p=0.0126 and p=0.0008, respectively). There are marked expression differences of SSTR1-5 as well as changes in expression in recurrent disease that need to be addressed when looking for other possible substances for the treatment of Cushing’s disease. SSTR2A, SSTR3, and SSTR5 seem to be most suitable biomarkers for a targeted therapy with somatostatin analogs.
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dos Santos Cabrera, Marcia Perez, Marisa Rangel, João Ruggiero Neto та Katsuhiro Konno. "Chemical and Biological Characteristics of Antimicrobial α-Helical Peptides Found in Solitary Wasp Venoms and Their Interactions with Model Membranes". Toxins 11, № 10 (2019): 559. http://dx.doi.org/10.3390/toxins11100559.
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Solitary wasps use their stinging venoms for paralyzing insect or spider prey and feeding them to their larvae. We have surveyed bioactive substances in solitary wasp venoms, and found antimicrobial peptides together with some other bioactive peptides. Eumenine mastoparan-AF (EMP-AF) was the first to be found from the venom of the solitary eumenine wasp Anterhynchium flavomarginatum micado, showing antimicrobial, histamine-releasing, and hemolytic activities, and adopting an α-helical secondary structure under appropriate conditions. Further survey of solitary wasp venom components revealed that eumenine wasp venoms contained such antimicrobial α-helical peptides as the major peptide component. This review summarizes the results obtained from the studies of these peptides in solitary wasp venoms and some analogs from the viewpoint of (1) chemical and biological characterization; (2) physicochemical properties and secondary structure; and (3) channel-like pore-forming properties.
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Egorov, O. S., N. Yu Borisova, E. Ya Borisova, M. L. Rezhabbaev, E. Yu Afanas’eva, and E. V. Arzamastsev. "Structure and biological action of analogs and derivatives of biogenic polyamines." Fine Chemical Technologies 16, no. 4 (2021): 287–306. http://dx.doi.org/10.32362/2410-6593-2021-16-4-287-306.
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Objectives. Biogenic polyamines are widely present in nature. They are characteristic of both protozoan cells and multicellular organisms. These compounds have a wide range of biological functions and are necessary for normal growth and development of cells. Violation of polyamine homeostasis can cause significant abnormalities in cell functioning, provoking various pathological processes, including oncological and neuropsychiatric diseases. The impact on the “polyamine pathway” is an attractive basis for the creation of many pharmacological agents with a diverse spectrum of action. The purpose of this review is to summarize the results of the studies devoted to understanding the biological activity of compounds of the polyamine series, comparing their biological action with action on certain molecular targets. Due to the structural diversity of this group of substances, it is impossible to fully reflect the currently available data in one review. Therefore, in this work, the main attention is paid to the derivatives, acyclic saturated polyamines.Results. The following aspects are considered: biological functionality, biosynthesis and catabolism, cell transport, and localization of biogenic polyamines in the living systems. Structural analogs and derivatives of biogenic polyamines with antitumor, neuroprotective, antiarrhythmic, antiparasitic, antibacterial, and other biological activities are represented; the relationship between biological activity and the target of exposure is reflected. It was found that the nature of the substituent, the number of cationic centers, and the length of the polyamine chain have a great influence on the nature of the effect.Conclusions. At present, the use of polyamine structures is restrained by cytotoxicity and nonspecific toxic effects on the central nervous system. Further research in the field of biochemistry, cell transport, and a deeper understanding of receptor interaction mechanisms will help making polyamines as the basis for potential drug formulation.
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Fiume, Monice M., Wilma F. Bergfeld, Donald V. Belsito, et al. "Safety Assessment of Monosaccharides, Disaccharides, and Related Ingredients as Used in Cosmetics." International Journal of Toxicology 38, no. 1_suppl (2019): 5S—38S. http://dx.doi.org/10.1177/1091581818814189.
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The Cosmetic Ingredient Review Expert Panel (Panel) assessed the safety of 25 monosaccharides, disaccharides, and related ingredients and concluded these are safe in the present practices of use and concentration described in the safety assessment. Many of these ingredients are common dietary sugars, dietary sugar replacements, or very closely related analogs and salts; 7 of the ingredients are listed by the Food and Drug Administration as generally recognized as safe food substances. The most commonly reported cosmetic function is as a skin-conditioning agent; other commonly reported functions are use as a humectant or as a flavoring agent. The Panel reviewed the animal and clinical data included in this assessment, acknowledged that the oral safety of many of these ingredients has been well established, and found it appropriate to extrapolate the existing information to conclude on the safety of all the monosaccharides, disaccharides, and related ingredients.
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Chen, Shanshan, Wenhua Zhou, and Miaojun Lai. "Synthetic Cathinones: Epidemiology, Toxicity, Potential for Abuse, and Current Public Health Perspective." Brain Sciences 14, no. 4 (2024): 334. http://dx.doi.org/10.3390/brainsci14040334.
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Synthetic cathinones, derived from cathinone found in the plant Catha edulis, represent the second largest and most frequently seized group of new psychoactive substances. They are considered as β-keto analogs of amphetamine, sharing pharmacological effects with amphetamine and cocaine. This review describes the neurotoxic properties of synthetic cathinones, encompassing their capacity to induce neuroinflammation, dysregulate neurotransmitter systems, and alter monoamine transporters and receptors. Additionally, it discusses the rewarding and abuse potential of synthetic cathinones drawing from findings obtained through various preclinical animal models, contextualized with other classical psychostimulants. The review also offers an overview of current abuse trends of synthetic cathinones on the illicit drug market, specifying the aspects covered, and underscores the risks they pose to public health. Finally, the review discusses public health initiatives and efforts to reduce the hazards of synthetic cathinones, including harm reduction methods, education, and current clinical management strategies.
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Prasolov, Mikhail Alexeyevich. "The Existence of God and the Resources of Metaphysical Personalism." Philosophy of Religion: Analytic Researches 4, no. 2 (2020): 71–90. http://dx.doi.org/10.21146/2587-683x-2020-4-2-71-90.
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The article analyses and assesses metaphysical personalism – a group of personalists including both Russian (L.M. Lopatin, A.A. Kozlov, P.E. Astaf’ev, S.A. Askol’dov, E.A. Bobrov) and German (G. Teichmüller) philosophers – in the context of modern discussions about the existence of God. The importance and potential of metaphysical personalism stems from its specific features: a conscious task of creating a personalistic metaphysics as a system, understanding of metaphysics as a rational philosophy, critical attitude to its own methods, use of rational controversial arguments in polemics, pursuance of metaphysical substantiation of the Christian theism. The article studies how metaphysical personalism sets and solves the problem of the reality of substance as the concept required to substantiate the existence of God. The concept of substance is given within the Aristotelian tradition as a real self-identical unity, the source and centre of active power. Personalism is particularly focused on proving the equal reality of both the substance and its actions. The concept of substance is substantiated based on the grounds of immediate consciousness (“inner experience”). Only the reality of spiritual, self-conscious individual substances is accepted. Other substances can be conceived by the analogy with the substance of a human subject. However, the criterion of differentiation of the substances of various ontological statuses remains unclear. The ontological argument requires to analyse the concept of being, which is also based on the structure of consciousness, including the substance of the self, its activity and the content of the activity. The immediate consciousness of a man is an archetype of any being. A man can directly access the reality of God in the consciousness of the own being. Therefore, the evidence of the existence of God results from the self-evidence of the consciousness of a substantial subject. Metaphysical personalism using the resources of the rational metaphysics has substantiated the existence of God through the structures and immediate experience of the consciousness of the subject.
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Bessler, W. G., M. Cox, A. Lex, B. Suhr, K. H. Wiesmüller, and G. Jung. "Synthetic lipopeptide analogs of bacterial lipoprotein are potent polyclonal activators for murine B lymphocytes." Journal of Immunology 135, no. 3 (1985): 1900–1905. http://dx.doi.org/10.4049/jimmunol.135.3.1900.
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Abstract The lipoprotein from the outer membrane of Escherichia coli and other Enterobacteriaceae is a potent polyclonal activator for B lymphocytes. To determine the molecular structure responsible for the biologic activity of lipoprotein, a well-defined series of analogs of its N-terminal part was synthesized: S-(2,3-bis(palmitoyloxy)-(2-RS)-propyl)-N-palmitoyl-(R)-cysteine, -cysteine methyl ester, -cysteinyl-serine, -cysteinyl-seryl-serine, -cysteinyl-seryl-seryl-asparagine, and -cysteinyl-seryl-seryl-asparaginyl-alanine. All compounds were tested for mitogenic activity toward spleen cells from BALB/c, LPS-non-responder C3H/HeJ, and congenitally athymic C3H/Tif/Bom/nu/nu mice, measuring the incorporation of [3H]thymidine into DNA. Lymphocyte activation was confirmed by determination of the incorporation of [3H]uridine into RNA and [3H]leucine into protein. The synthetic lipopeptides were also investigated for their ability to stimulate B lymphocytes into immunoglobulin secretion, as shown by a hemolytic plaque assay. Throughout our studies, the compounds carrying two to five amino acids exhibited strong stimulation activity toward B lymphocytes comparable to native lipoprotein. In contrast, products containing only one amino acid, cysteine or cysteine methyl ester, were only marginally active, indicating that to obtain full biologic activity the presence of the hydrophilic dipeptide structure is necessary. All compounds exhibited only a marginal effect on thymocytes. Thus, a series of defined synthetic fragments of a bacterial outer membrane component exhibits a pronounced mitogenic and polyclonally stimulating activity towards B lymphocytes. The substances will be valuable tools for more detailed investigations on the molecular mechanisms of B cell activation.
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Roeb, Elke. "Diagnostic and Therapy of Nonalcoholic Fatty Liver Disease: A Narrative Review." Visceral Medicine 38, no. 2 (2021): 126–32. http://dx.doi.org/10.1159/000519611.
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<b><i>Background:</i></b> The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing and strongly associated with the metabolic syndrome, especially with obesity. A subtype, nonalcoholic steatohepatitis (NASH), might progress to advanced fibrosis and cirrhosis. NASH patients have an increased all-cause mortality. First and foremost are malignancies, followed by cardiovascular diseases. <b><i>Summary:</i></b> The NAFLD fibrosis score and noninvasive liver stiffness measurement (transient hepatic elastography) are essential components for the diagnostic risk assessment of NAFLD patients. Other steatoses (alcohol, genetic disorders, drugs, toxins, malnutrition, etc.) must be considered in the differential diagnosis. So far, there is no approved liver-specific drug therapy with a proven effect on NAFLD for patients without diabetes mellitus. Obeticholic acid (FXR agonist), cenicriviroc (a dual inhibitor of the chemokine receptors (CCR), CCR2 and CCR5), acetyl-CoA carboxylase inhibitors, and several thyroid hormone analogs are the most advanced substances in clinical development in ongoing phase 2 and 3 studies. <b><i>Key Messages:</i></b> Weight loss, physical training, and the screening and treatment of risk factors represent the cornerstones of NAFLD therapy. Treatment with glucagon-like peptide 1 analogs (e.g., liraglutide, semaglutide) and sodium-dependent glucose transporter 2 inhibitors can be recommended in patients with diabetes and NASH.
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Dolinak, David. "Opioid Toxicity." Academic Forensic Pathology 7, no. 1 (2017): 19–35. http://dx.doi.org/10.23907/2017.003.
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In recent years, there has been a substantial increase in opioid use and abuse, and in opioid-related fatal overdoses. The increase in opioid use has resulted at least in part from individuals transitioning from prescribed opioids to heroin and fentanyl, which can cause significant respiratory depression that can progress to apnea and death. Heroin and fentanyl may be used individually, together, or in combination with other substances such as ethanol, benzodiazepines, or other drugs that can have additional deleterious effects on respiration. Suspicion that a death is drug-related begins with the decedent's medical and social history, and scene investigation, where drugs and drug paraphernalia may be encountered, and examination of the decedent, which may reveal needle punctures and needle track marks. At autopsy, the most significant internal finding that is reflective of opioid toxicity is pulmonary edema and congestion, and frothy watery fluid is often present in the airways. Various medical ailments such as heart and lung disease and obesity may limit an individual's physiologic reserve, rendering them more susceptible to the toxic effects of opioids and other drugs. Although many opioids will be detected on routine toxicology testing, more specialized testing may be warranted for opioid analogs, or other uncommon, synthetic, or semisynthetic drugs.
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Salomone, A., R. Bigiarini, J. J. Palamar, et al. "Toward the Interpretation of Positive Testing for Fentanyl and Its Analogs in Real Hair Samples: Preliminary Considerations." Journal of Analytical Toxicology 44, no. 4 (2020): 362–69. http://dx.doi.org/10.1093/jat/bkz102.
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Abstract The detection of new psychoactive substances (NPS) in hair has become extensively researched in recent years. Although most NPS fall into the classes of synthetic cannabinoids and designer cathinones, novel synthetic opioids (NSO) have appeared with increasing frequency in the illicit drug supply. While the detection of NSO in hair is now well documented, interpretation of results presents several controversial issues, as is quite common in hair analysis. In this study, an ultra-high-performance liquid chromatography-tandem mass spectrometry method able to detect 13 synthetic opioids (including fentanyl analogs) and metabolites in hair was applied to 293 real samples. Samples were collected in the USA between November 2016 and August 2018 from subjects who had reported heroin use in the past year or had already tested positive to hair testing for common opiates. The range, mean and median concentrations were calculated for each analyte, in order to draw a preliminary direction for a possible cut-off to discriminate between exposure to either low or high quantities of the drug. Over two-thirds (68%) of samples tested positive for fentanyl at concentrations between LOQ and 8600 pg/mg. The mean value was 382 pg/mg and the median was 95 pg/mg. The metabolites norfentanyl and 4-ANPP were also quantified and were found between LOQ and 320 pg/mg and between LOQ and 1400 pg/mg, respectively. The concentration ratios norfentanyl/fentanyl, 4-ANPP/fentanyl and norfentanyl/4-ANPP were also tested as potential markers of active use and to discriminate the intake of fentanyl from other analogs. The common occurrence of samples positive for multiple drugs may suggest that use is equally prevalent among consumers, which is not the case, as correlations based on quantitative results demonstrated. We believe this set of experimental observations provides a useful starting point for a wide discussion aimed to better understand positive hair testing for fentanyl and its analogs in hair samples.
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Marasco, Matteo, Elena Romano, Giulia Arrivi, et al. "Exploring Carcinoid Syndrome in Neuroendocrine Tumors: Insights from a Multidisciplinary Narrative Review." Cancers 16, no. 22 (2024): 3831. http://dx.doi.org/10.3390/cancers16223831.
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Carcinoid syndrome (CS) is a rare condition associated with neuroendocrine tumors (NETs), particularly those originating in the gastrointestinal tract, which secrete bioactive substances like serotonin. The management of CS requires a multidisciplinary approach due to its complex clinical manifestations, including flushing, diarrhea, bronchospasm, and carcinoid heart disease. Optimal care involves collaboration between several professional figures like oncologists, endocrinologists, gastroenterologists, surgeons, and dietitians. Currently, a wide range of treatments are available, focused on both symptom control and tumor burden reduction. Somatostatin analogs (SSAs) are the first-line therapy for symptom relief. Still, in patients with progressive disease or refractory CS, other options include targeted therapies, peptide receptor radionuclide therapy (PRRT), liver-directed therapies, and surgical resection, when feasible. Furthermore, management of complications related to prolonged serotonin release and malnutrition as a result of exocrine pancreatic insufficiency, post-surgical conditions, vitamin deficit, and chronic diarrhea often requires early detection to mitigate symptoms and improve the quality of life in these patients. The complexity of CS necessitates individualized care and continuous coordination among specialists to optimize outcomes and enhance patient well-being.
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Callahan, H. L., C. Kelley, T. Pereira, and M. Grogl. "Microtubule inhibitors: structure-activity analyses suggest rational models to identify potentially active compounds." Antimicrobial Agents and Chemotherapy 40, no. 4 (1996): 947–52. http://dx.doi.org/10.1128/aac.40.4.947.
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Trifluralin, a dinitroaniline microtubule inhibitor currently in use as an herbicide, has been shown to inhibit the proliferation of Plasmodium falciparum, Trypanosoma brucei, and several species of Leishmania, in vitro. As a topical formulation, trifluralin is also effective in vivo (in BALB/c mice) against Leishmania major and Leishmania mexicana. Although trifluralin and other dinitroaniline herbicides show significant activity as antiparasitic compounds, disputed indications of potential carcinogenicity will probably limit advanced development of these substances. However, researchers have suggested that the activity of trifluralin is due to an impurity or contaminant, not to trifluralin itself. We have pursued this lead and identified the structure of the active impurity. This compound, chloralin, is 100 times more active than trifluralin. On the basis of its structure, we developed a rational structure-activity model for chloralin. Using this model, we have successfully predicted and tested active analogs in a Leishmania promastigote assay; thus, we have identified the putative mechanism of action of this class of drugs in Leishmania species. Potentially, this will allow the design of noncarcinogenic, active drugs.
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Efremenko, Elena, Aysel Aslanli, Nikolay Stepanov, Olga Senko, and Olga Maslova. "Various Biomimetics, Including Peptides as Antifungals." Biomimetics 8, no. 7 (2023): 513. http://dx.doi.org/10.3390/biomimetics8070513.
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Biomimetics, which are similar to natural compounds that play an important role in the metabolism, manifestation of functional activity and reproduction of various fungi, have a pronounced attraction in the current search for new effective antifungals. Actual trends in the development of this area of research indicate that unnatural amino acids can be used as such biomimetics, including those containing halogen atoms; compounds similar to nitrogenous bases embedded in the nucleic acids synthesized by fungi; peptides imitating fungal analogs; molecules similar to natural substrates of numerous fungal enzymes and quorum-sensing signaling molecules of fungi and yeast, etc. Most parts of this review are devoted to the analysis of semi-synthetic and synthetic antifungal peptides and their targets of action. This review is aimed at combining and systematizing the current scientific information accumulating in this area of research, developing various antifungals with an assessment of the effectiveness of the created biomimetics and the possibility of combining them with other antimicrobial substances to reduce cell resistance and improve antifungal effects.
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Rasmussen, Henrik Berg, Gesche Jürgens, Ragnar Thomsen, et al. "Cellular Uptake and Intracellular Phosphorylation of GS-441524: Implications for Its Effectiveness against COVID-19." Viruses 13, no. 7 (2021): 1369. http://dx.doi.org/10.3390/v13071369.
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GS-441524 is an adenosine analog and the parent nucleoside of the prodrug remdesivir, which has received emergency approval for treatment of COVID-19. Recently, GS-441524 has been proposed to be effective in the treatment of COVID-19, perhaps even being superior to remdesivir for treatment of this disease. Evaluation of the clinical effectiveness of GS-441524 requires understanding of its uptake and intracellular conversion to GS-441524 triphosphate, the active antiviral substance. We here discuss the potential impact of these pharmacokinetic steps of GS-441524 on the formation of its active antiviral substance and effectiveness for treatment of COVID-19. Available protein expression data suggest that several adenosine transporters are expressed at only low levels in the epithelial cells lining the alveoli in the lungs, i.e., the alveolar cells or pneumocytes from healthy lungs. This may limit uptake of GS-441524. Importantly, cellular uptake of GS-441524 may be reduced during hypoxia and inflammation due to decreased expression of adenosine transporters. Similarly, hypoxia and inflammation may lead to reduced expression of adenosine kinase, which is believed to convert GS-441524 to GS-441524 monophosphate, the perceived rate-limiting step in the intracellular formation of GS-441524 triphosphate. Moreover, increases in extracellular and intracellular levels of adenosine, which may occur during critical illnesses, has the potential to competitively decrease cellular uptake and phosphorylation of GS-441524. Taken together, tissue hypoxia and severe inflammation in COVID-19 may lead to reduced uptake and phosphorylation of GS-441524 with lowered therapeutic effectiveness as a potential outcome. Hypoxia may be particularly critical to the ability of GS-441524 to eliminate SARS-CoV-2 from tissues with low basal expression of adenosine transporters, such as alveolar cells. This knowledge may also be relevant to treatments with other antiviral adenosine analogs and anticancer adenosine analogs as well.
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Rizzuti, Bruno, Fedora Grande, Filomena Conforti, et al. "Rutin Is a Low Micromolar Inhibitor of SARS-CoV-2 Main Protease 3CLpro: Implications for Drug Design of Quercetin Analogs." Biomedicines 9, no. 4 (2021): 375. http://dx.doi.org/10.3390/biomedicines9040375.
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The pandemic, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has stimulated the search for antivirals to tackle COVID-19 infection. Molecules with known pharmacokinetics and already approved for human use have been demonstrated or predicted to be suitable to be used either directly or as a base for a scaffold-based drug design. Among these substances, quercetin is known to be a potent in vitro inhibitor of 3CLpro, the SARS-CoV-2 main protease. However, its low in vivo bioavailability calls for modifications to its molecular structure. In this work, this issue is addressed by using rutin, a natural flavonoid that is the most common glycosylated conjugate of quercetin, as a model. Combining experimental (spectroscopy and calorimetry) and simulation techniques (docking and molecular dynamics simulations), we demonstrate that the sugar adduct does not hamper rutin binding to 3CLpro, and the conjugated compound preserves a high potency (inhibition constant in the low micromolar range, Ki = 11 μM). Although showing a disruption of the pseudo-symmetry in the chemical structure, a larger steric volume and molecular weight, and a higher solubility compared to quercetin, rutin is able to associate in the active site of 3CLpro, interacting with the catalytic dyad (His41/Cys145). The overall results have implications in the drug-design of quercetin analogs, and possibly other antivirals, to target the catalytic site of the SARS-CoV-2 3CLpro.
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Tri Cahyadi, N. Indra, and Paul Steven. "Hypertonic dextrose compare with other substances for knee osteoarthritis: a meta-analysis of randomized control trial." International Surgery Journal 12, no. 1 (2024): 72–79. https://doi.org/10.18203/2349-2902.isj20243988.
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Background: Globally, osteoarthritis (OA) highly prevalent in the elderly more than 80% of those over 55 years old. At least 151 million people worldwide are afflicted. The knees, hips and spine are the joint areas that are most frequently affected. For the treatment of knee OA, intra-articular injection like stem cells, platelet rich plasma (PRP), and hypertonic dextrose (HD) the most used prolotherapy fluid is HD. It is widely accessible, reasonably inexpensive priced and reportedly safe. The aim of this meta-analysis is to thoroughly assess and compare the results of intra articular dextrose prolotherapy with hyaluronic acid and normal saline, with a focus on visual analog scale (VAS) and WOMAC score. Methods: A comprehensive search was conducted across major electronic databases for relevant studies published from 2014 to 2024. Studies that compare intra articular dextrose prolotherapy with hyaluronic acid and normal saline for knee OA were included. We recorded the first author, year, study design, sample number, age, sex, Kellgren Lawrence grade, VAS and WOMAC score were extracted and analyzed using appropriate statistical methods. Results: The initial search yielded a total of 2371 studies, of which 7 studies met the inclusion criteria, consisting of a total of 372 patients of intra articular dextrose prolotherapy with hyaluronic acid and normal saline for knee OA. It shows that there is no significant difference in VAS score between two groups (MD=-0.72, 95% CI:-1.74 to 0.31, p=0.17). There was no difference in WOMAC score between two groups. Conclusions: Our results show that both methods provide similar outcome in pain scale and WOMAC score. More over to enhance the efficacy of prolotherapy in comparison to alternative treatments like HA or saline injections, it is suggested that a multicenter clinical trial with a larger number of participants be carried out.
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Thomas, Andreas, Lukas Benzenberg, Lia Bally, and Mario Thevis. "Facilitated Qualitative Determination of Insulin, Its Synthetic Analogs, and C-Peptide in Human Urine by Means of LC–HRMS." Metabolites 11, no. 5 (2021): 309. http://dx.doi.org/10.3390/metabo11050309.
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The increasing importance to determine bioactive peptide hormones such as insulin, its synthetic analogs, and C-peptide in urine samples represents an analytical challenge. The physiological concentrations of insulin in urine are commonly found at sub-ng/mL levels and thus represent a complex analytical task. C-peptide concentrations, on the other hand, tend to be in the moderate ng/mL range and are hence much easier to determine. Insulin and C-peptide are important in the diagnostics and management of metabolic disorders such as diabetes mellitus and are also particularly relevant target analytes in professional sports and forensics. All insulins are classified on the World Anti-Doping Agency’s (WADA) list of prohibited substances and methods in sports with a minimum required performance level (MRPL) of 50 pg/mL. Until now, methods combining immunoextraction and subsequent mass spectrometric detection have mostly been used for this purpose. With the method developed here, sample preparation has been simplified considerably and does not require an antibody-based sample purification. This was achieved by a sophisticated mixed-mode solid-phase extraction and subsequent separation with liquid chromatography coupled to high-resolution mass spectrometry. Included target insulins were human, lispro, glulisine, aspart, glargine metabolite, degludec, and additionally, human C-peptide. The method was validated for the synthetic insulin analogs considering WADA requirements including specificity, limit of detection (10–25 pg/mL), limit of identification, recovery (25–100%), robustness, carry over (<2%), and matrix effects. All sample preparation steps were controlled by two stable isotope-labeled internal standards, namely, [[2H10] LeuB6, B11, B15, B17]-insulin and [[13C6] Leu26, 30] C-peptide. Finally, the method was applied to samples from patients with diabetes mellitus treated with synthetic insulins.
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Andres-Mach, Marta, Mirosław Zagaja, Joanna Szala-Rycaj, et al. "In Vivo and In Vitro Characterization of Close Analogs of Compound KA-11, a New Antiseizure Drug Candidate." International Journal of Molecular Sciences 24, no. 9 (2023): 8302. http://dx.doi.org/10.3390/ijms24098302.
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Epilepsy is a neurological disorder involving a number of disease syndromes with a complex etiology. A properly matched antiseizure drug (ASD) gives remission in up to 70% of patients. Nevertheless, there is still a group of about 30% of patients suffering from drug-resistant epilepsy. Consequently, the development of new more effective and/or safer ASDs is still an unmet clinical need. Thus, our current studies were focused on the structural optimization/modifications of one of the leading compounds, KA-11, aiming at the improvement of its antiseizure activity. As a result, we designed and synthesized two close analogs with highly pronounced drug-like physicochemical properties according to in silico predictions, namely KA-228 and KA-232, which were subsequently tested in a panel of animal seizure models, i.e., MES, 6 Hz (32 mA), scPTZ and ivPTZ. Among these compounds, KA-232, which was designed as a water-soluble salt, was distinctly more effective than KA-228 and assured similar antiseizure protection as its chemical prototype KA-11. With the aim of a more detailed characterization of both new molecules, in vitro binding tests were performed to evaluate the potential mechanisms of action. Furthermore, KA-232 was also evaluated in several ADME-Tox studies, and the results obtained strongly supported its drug-like potential. The proposed chemical modification of KA-11 enabled the identification of new pharmacologically active chemotypes, particularly water-soluble KA-232, which, despite the lack of better efficacy than the leading compound, may be used as a chemical prototype for the development of new ASDs, as well as substances potentially active in other neurological or neurodegenerative conditions.
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Utyanov, D. A., N. L. Vostrikova, E. R. Vasilevskaya, A. V. Kulikovskii, and S. Yu Karabanov. "Chemical contaminants entering food products from polymer packaging. Review." Food systems 8, no. 1 (2025): 29–35. https://doi.org/10.21323/2618-9771-2025-8-1-29-35.
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The paper presents a review of scientific literature devoted to the problem of food product contamination with various types of substances from packaging materials. The problem under consideration is large-scale — there are many types of compounds that can enter food products from packaging. Food product contamination can occur due to migration of substances used for production of packaging materials. Plastic polymer packages represent the highest risk of food product contamination. The interest of the scientific community and the need for studying the described theme are determined by the fact that the prevailing proportion of all compounds that migrate into a food product from packaging possesses toxic or carcinogenic activity, and thus, presents the potential risk for human health. Bisphenols are most studied among all contaminants described in this paper. Many studies on their migration into food products have shown that bisphenols were found practically in all types of food products: meat, dairy, fish, fruit and vegetable. The significant migration of bisphenols has been observed in juice products and bottled water. Due to the adverse effect of bisphenol A on the human body, its use in the production of packaging materials for food products is forbidden. However, this ban has led to distribution of analogs, namely, bisphenols B, C, F, AF and others, which are found in food products. The performed review has shown that the problem of food product contamination with contaminants from packaging materials requires serious attention of the scientific community.
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Peña-Morán, Omar Aristeo, Jesús Jiménez-Pérez, Litzia Cerón-Romero, and Maribel Rodríguez-Aguilar. "In Silico Conformation of the Drug Colchicine into Tubulin Models and Acute Phytotoxic Activity on Cucumis sativus Radicles." Plants 11, no. 14 (2022): 1805. http://dx.doi.org/10.3390/plants11141805.
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Many tests are used to determine the toxic activity of miscellaneous substances, and those that are simple, fast, and inexpensive are useful for screening compounds with applications in different fields. The Cucumis sativus root growth inhibition test is an example of acute toxicity determinations. On the other hand, colchicine has been used as a herbicide to generate polyploids in plant species finally reaching the environment; for this reason, colchicine could become a point of attention in ecotoxicology. This work established that Cucumis sativus, at the colchicine binding site (CBS) in tubulin, shares 100% similarity with humans. Colchicine was docked on seven Cucumis sativus computational models of the αβ-tubulin heterodimer, allowing us to understand a possible conformation in tubulin to trigger its antimitotic effect. Furthermore, an in vitro phytotoxicity assay of colchicine-treated cucumber radicles indicated a hormetic-type concentration-dependent response with macroscopic changes in radicles and hypocotyl. These results support the highly preserved grade of tubulins in several species, and using microtubule inhibitors could require attention in ecotoxicological issues. The Cucumis sativus root growth test could help evaluate small molecules (colchicine analogs), chiefly by CBS interactions, a known druggable site, still a target in the search for antimitotic compounds.
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Bednarska, Katarzyna, and Izabela Fecka. "Potential of Vasoprotectives to Inhibit Non-Enzymatic Protein Glycation, and Reactive Carbonyl and Oxygen Species Uptake." International Journal of Molecular Sciences 22, no. 18 (2021): 10026. http://dx.doi.org/10.3390/ijms221810026.
Full textAbstract:
Reactive carbonyl species (RCS) such as methylglyoxal (MGO) or glyoxal (GO) are the main precursors of the formation of advanced glycation end products (AGEs). AGEs are a major factor in the development of vascular complications in diabetes. Vasoprotectives (VPs) exhibit a wide range of activities beneficial to cardiovascular health. The present study aimed to investigate selected VPs and their structural analogs for their ability to trap MGO/GO, inhibit AGE formation, and evaluate their antioxidant potential. Ultra-high-performance liquid chromatography coupled with an electrospray ionization mass spectrometer (UHPLC-ESI-MS) and diode-array detector (UHPLC-DAD) was used to investigate direct trapping capacity and kinetics of quenching MGO/GO, respectively. Fluorimetric and colorimetric measurements were used to evaluate antiglycation and antioxidant action. All tested substances showed antiglycative effects, but hesperetin was the most effective in RCS scavenging. We demonstrated that rutin, diosmetin, hesperidin, and hesperetin could trap both MGO and GO by forming adducts, whose structures we proposed. MGO-derived AGE formation was inhibited the most by hesperetin, and GO-derived AGEs by diosmetin. High reducing and antiradical activity was confirmed for quercetin, rutin, hesperetin, and calcium dobesilate. Therefore, in addition to other therapeutic applications, some VPs could be potential candidates as antiglycative agents to prevent AGE-related complications of diabetes.
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Urban, Laurent, Félicie Lauri, Douae Ben Hdech, and Jawad Aarrouf. "Prospects for Increasing the Efficacy of Plant Resistance Inducers Stimulating Salicylic Acid." Agronomy 12, no. 12 (2022): 3151. http://dx.doi.org/10.3390/agronomy12123151.
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Systemic acquired resistance is a powerful mechanism, based on the salicylic acid (SA) signaling pathway, which allows plants to resist to a wide range of pathogens. High SA, moreover, plays a key role in plant tolerance to abiotic stress. It seems, therefore, desirable to supply analogs of SA or stimulate the production of endogenous SA. Unfortunately, the chemical substances or physical means used for this effect often display a variable efficacy. After providing a review of them, we defend three major ideas: (i) plant resistance inducers (PRIs) must be combined for higher efficacy, notably for exploiting synergic effects between the SA and other signaling pathways, (ii) disease pressure can be reduced by exploiting the fungicidal properties displayed by some PRIs, (iii) biostimulants and crop management techniques should be used to ensure that plants have the resources they need to synthesize the compounds and structures required for efficient and lasting resistance. Some PRIs could also be used for their biostimulant effects in stress conditions. It could be concluded that holistic approaches which jointly address the issues of defense and tolerance stimulation, disease pressure and resource availability in plants are the ones that will allow for substantial reduction in fungicide use without sacrificing crop performance.
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Ivanova, Elizaveta, Margarita Osipova, Tatyana Vasilieva, et al. "The Recycling of Substandard Rocket Fuel N,N-Dimethylhydrazine via the Involvement of Its Hydrazones Derived from Glyoxal, Acrolein, Metacrolein, Crotonaldehyde, and Formaldehyde in Organic Synthesis." International Journal of Molecular Sciences 24, no. 24 (2023): 17196. http://dx.doi.org/10.3390/ijms242417196.
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“Heptil” (unsymmetrical dimethylhydrazine—UDMH) is extensively employed worldwide as a propellant for rocket engines. However, UDMH constantly loses its properties as a result of its continuous and uncontrolled absorption of moisture, which cannot be rectified. This situation threatens its long-term usability. UDMH is an exceedingly toxic compound (Hazard Class 1), which complicates its transportation and disposal. Incineration is currently the only method used for its disposal, but this process generates oxidation by-products that are even more toxic than the original UDMH. A more benign approach involves its immediate reaction with a formalin solution to form 1,1–dimethyl-2-methylene hydrazone (MDH), which is significantly less toxic by an order of magnitude. MDH can then be polymerized under acidic conditions, and the resulting product can be burned, yielding substantial amounts of nitrogen oxides. This review seeks to shift the focus of MDH from incineration towards its application in the synthesis of relatively non-toxic and readily available analogs of various pharmaceutical substances. We aim to bring the attention of the international chemical community to the distinctive properties of MDH, as well as other hydrazones (such as glyoxal, acrolein, crotonal, and meta-crolyl), wherein each structural fragment can initiate unique transformations that have potential applications in molecular design, pharmaceutical research, and medicinal chemistry.
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Chandak, Raman R., and Nachiket S. Dighe. "A Review on Phytochemical & Pharmacological Profile of Pergularia Daemia linn." Journal of Drug Delivery and Therapeutics 9, no. 4-s (2019): 809–14. http://dx.doi.org/10.22270/jddt.v9i4-s.3426.
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Many indigenous Indian medicinal plants have been found to be successfully used to manage diabetes and some of them have been tested and active principles isolated. However, search for new antidiabetic drugs for effective treatment is on. The vast majority of people on this planet still rely on their traditional material medica (medicinal plants and other materials) for their everyday health care needs. It is also a fact that one quarter of all medical prescriptions are formulations based on substances derived from plants or plant-derived synthetic analogs. The herbal drug from tribal region is selected for the study which is used for diabetes andliver diseases. Pergularia daemia (Asclepiadaceae) is a perennial herb growing widely along the road sides of India. It has been used in folk medicine for the treatment of Dibetis mellitus &liver disorders. It is widely distributed in the tropical and sub tropicalregions of the world. Various phytochemical including terpenoid, flavonoids, sterols and cardenolids have been isolated andidentified from the various parts of the plant (leaves, stems, shoots, roots, seeds and fruits whole plant). P. daemia widely used by various tribal communities in Western Ghats of India for the treatment of variety of ailments, while predominantly the roots of theplant have been used to treat liver disease and jaundice.The present review article aims towards medicinal Pharmacological potential, Bioactive remedies, Phytochemical profile and other important aspects of P. daemia.
 Keywords: Ethnobotanical uses, Pergularia daemia, Pharmacological Profile, Phytochemical Profile
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Ye, R., J. K. Keller, Q. Jin, B. J. M. Bohannan, and S. D. Bridgham. "Mechanisms for the suppression of methane production in peatland soils by a humic substance analog." Biogeosciences Discussions 11, no. 1 (2014): 1739–71. http://dx.doi.org/10.5194/bgd-11-1739-2014.
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Abstract. Methane (CH4) production is often impeded in many northern peatland soils, although inorganic terminal electron acceptors (TEAs) are usually present in low concentrations in these soils. Recent studies suggest that humic substances in wetland soils can be utilized as organic TEAs for anaerobic respiration and may directly inhibit CH4 production. Here we utilize the humic analog anthraquinone-2, 6-disulfonate (AQDS) to explore the importance of humic substances, and their effects on the temperature sensitivity of anaerobic decomposition, in two peatland soils. In a bog peat, AQDS was not instantly utilized as a TEA, but greatly inhibited the fermentative production of acetate, carbon dioxide (CO2), and hydrogen (H2), as well as CH4 production. When added together with glucose, AQDS was partially reduced after a lag period of 5 to 10 days. In contrast, no inhibitory effect of AQDS on fermentation was found in a fen peat and AQDS was readily reduced as an organic TEA. The addition of glucose and AQDS to both bog and fen peats caused complicated temporal dynamics in the temperature sensitivity of CH4 production, reflecting temporal changes in the temperature responses of other carbon processes with effects on methanogenesis. Our results show that the humic analog AQDS can act both as an inhibitory agent and a TEA in peatland soils. The high concentrations of humic substances in northern peatlands may greatly influence the effect of climate change on soil carbon cycling in these ecosystems.
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Ivanov, L. V., O. Р. Bezugla, O. V. Shcherbak, L. V. Derymedvid, and V. G. Kravchenko. "Soft dosage forms as interfaces." News of Pharmacy, no. 2(102) (October 19, 2021): 25–29. http://dx.doi.org/10.24959/nphj.21.57.
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Aim. To analyze data on combined drugs in soft dosage forms as potential drug interfaces. Materials and methods. The bibliosemantic research method was used in the work. Results and discussion. By analogy with foreign interfaces of carbon nanotubes with neurons it has been proposed to consider a number of soft dosage forms as interfaces between inanimate organic structures of dosage forms and living cells of the skin tissue or the mucous membrane. A number of soft dosage forms, which can be considered as interfaces between the inanimate organics of dosage forms and living cells of the skin tissue and mucosa, has been studied and analyzed. Interfaces are polymer matrices made of polyethylene glycols, high molecular weight polysaccharides, carbomers, etc. A carbomer can be considered as the basis of plastic, conformationally mobile interfaces between the general dosage form and living cells of the skin and mucosa. It has been shown that the mechanism of increasing biocompatibility with the help of polyethylene glycols is the ability of PEG molecules due to compaction (spiralization) or expansion of the molecules to accept the optimal conformation, giving their hydrophobic or polar groups for the optimal binding, on the one hand, with medicinal substances (drugs), and, on the other hand, with bioobjects. It has been shown that the affinity for PEG-400 phosphatidylcholine liposomes is 6 times greater than that of propylene glycol, and the affinity for PEG-1500 liposomes is 24 times higher than that of propylene glycol. Upon contact with the skin or the mucosa the interface structure may be destroyed as the components of the dosage form have different affinities for membranes of cells of biological surfaces – surface active substances that quickly bind to the lipid bilayer of the membranes of the skin or mucous membranes are the first ones that leave the dosage forms. Then, other auxiliary substances of the interface bind to the cell membranes at different speeds and in different ways. Conclusions. Therefore, a dosage form as an interface is a dynamic matrix that can rebuild and, as it contacts the membranes of skin cells or mucous membranes, promote absorption of the drug substance according to a specific program.
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Martinovich, V. P., and K. U. Baradzina. "Peptide Hormones in Medicine: A 100-Year History." Russian Journal of Bioorganic Chemistry 48, no. 2 (2022): 221–32. http://dx.doi.org/10.1134/s1068162022020157.
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Abstract This review is devoted to the 100-year history of the investigation of peptide hormones and the creation of drugs on their basis, starting from the insulin discovery and its introduction into a medical practice in 1921. The basic groups of the peptide hormones are discussed: neurohypophyseal hormones, hypothalamic releasing hormones, incretins, insulin, adrenocorticotropic hormone (ACTH), and calcitonin. The first therapeutic agents based on the peptide hormones were created by a traditional approach that involved the isolation of peptides from animal tissues, their purification to individual compounds, determination of their primary structure, their chemical synthesis or their deep purification, and the creation of a pharmaceutical substance. A modern approach to creation of peptide hormone drugs is based on their consideration as ligands of the corresponding cellular receptors and the use of computer modeling, efficient synthesis methods, and high-throughput screening. The combination of these methods enabled the development of analogs which would be more active than the corresponding natural compounds, exhibit other activities in addition to the hormonal regulation, and be resistant to biodegradation. Such therapeutic agents have been designed on the basis of agonistic and antagonistic analogs of somatostatin and luliberin, and have found wide application in hormonal regulation and cancer treatment. Over the past two decades, the glucagon-like peptide (GLP-1) has been intensively investigated as a potential therapeutic agent. In our review, we describe modifications which resulted in the most highly effective long-acting drugs. Now, natural hormones and their analogs are widely present in the pharmaceutical market.
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Apostolopoulos, Vasso, Joanna Bojarska, Tsun-Thai Chai, et al. "A Global Review on Short Peptides: Frontiers and Perspectives." Molecules 26, no. 2 (2021): 430. http://dx.doi.org/10.3390/molecules26020430.
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Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide “drugs” initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.
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Jeznach-Steinhagen, Anna, Joanna Ostrowska, Aneta Czerwonogrodzka-Senczyna, Iwona Boniecka, Urszula Shahnazaryan, and Alina Kuryłowicz. "Dietary and Pharmacological Treatment of Nonalcoholic Fatty Liver Disease." Medicina 55, no. 5 (2019): 166. http://dx.doi.org/10.3390/medicina55050166.
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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the developed world. Simple hepatic steatosis is mild, but the coexistence of steatohepatitis (NASH) and fibrosis increases the risk of hepatocellular carcinoma. Proper dietary and pharmacological treatment is essential for preventing NAFLD progression. The first-line treatment should include dietary intervention and increased physical activity. The diet should be based on the food pyramid, with a choice of products with low glycemic index, complex carbohydrates in the form of low-processed cereal products, vegetables, and protein-rich products. Usage of insulin-sensitizing substances, pro- and prebiotics, and vitamins should also be considered. Such a therapeutic process is intended to support both liver disease and obesity-related pathologies, including insulin resistance, diabetes, dyslipidemia, and blood hypertension. In the pharmacological treatment of NAFLD, apart from pioglitazone, there are new classes of antidiabetic drugs that are of value, such as glucagon-like peptide 1 analogs and sodium/glucose cotransporter 2 antagonists, while several other compounds that target different pathogenic pathways are currently being tested in clinical trials. Liver biopsies should only be considered when there is a lack of decline in liver enzymes after 6 months of the abovementioned treatment. Dietary intervention is recommended in all patients with NAFLD, while pharmacological treatment is recommended especially for those with NASH and showing significant fibrosis in a biopsy.
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Diak, Douglass M., Brian E. Crucian, Mayra Nelman-Gonzalez, and Satish K. Mehta. "Saliva Diagnostics in Spaceflight Virology Studies—A Review." Viruses 16, no. 12 (2024): 1909. https://doi.org/10.3390/v16121909.
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Many biological markers of normal and disease states can be detected in saliva. The benefits of saliva collection for research include being non-invasive, ease of frequent sample collection, saving time, and being cost-effective. A small volume (≈1 mL) of saliva is enough for these analyses that can be collected in just a few minutes. For “dry” saliva paper matrices, additional drying times (about 30 min) may be needed, but this can be performed at room temperature without the need for freezers and specialized equipment. Together, these make saliva an ideal choice of body fluid for many clinical studies from diagnosis to monitoring measurable biological substances in hospital settings, remote, and other general locations including disaster areas. For these reasons, we have been using saliva (dry as well as wet) from astronauts participating in short- and long-duration space missions for over two decades to conduct viral, stress, and immunological studies. We have also extended the use of saliva to space analogs including bed rest, Antarctica, and closed-chamber studies. Saliva is a biomarker-rich and easily accessible body fluid that could enable larger and faster public health screenings, earlier disease detection, and improved patient outcomes. This review summarizes our lessons learned from utilizing saliva in spaceflight research and highlights the advantages and disadvantages of saliva in clinical diagnostics.
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Alaa, AL TIMIMI, OBEIDAT Saleh, EJJEBLI Samia, AMRI MERYEM, HABOUB Meryem, and HABBAL Rachida. "Carcinoid Syndrome-induced Multi-valvular Heart Disease: A Rare Cause of Heart Failure in a 45-Year-Old Woman." Cardiology and Angiology: An International Journal 14, no. 2 (2025): 17–23. https://doi.org/10.9734/ca/2025/v14i2483.
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Background: Carcinoid syndrome, a rare neuroendocrine disorder, can lead to progressive valvular fibrosis due to the excessive secretion of serotonin and other vasoactive substances. This typically affects the right-sided cardiac valves and rarely the left side. The resulting carcinoid heart disease represents an uncommon but serious cause of heart failure. Presentation of Case: We report the case of a 45-year-old woman admitted for progressive heart failure symptoms, including dyspnea, peripheral edema, and fatigue. She also experienced flushing and diarrhea suggestive of carcinoid syndrome. Transthoracic echocardiography revealed severe tricuspid, mitral, and aortic valve involvement, with biatrial dilation and features of severe stenosis and regurgitation. Work-up revealed elevated urinary 5-HIAA and chromogranin A levels, and imaging identified a hyper vascular ileocecal mass consistent with a neuroendocrine tumor. The diagnosis of carcinoid syndrome with multivalvular carcinoid heart disease was established. Discussion: This case illustrates the diagnostic challenge of distinguishing carcinoid heart disease from other etiologies such as rheumatic heart disease. The rare left-sided valvular involvement, likely due to high circulating serotonin levels, underscores the severity of tumor burden. Early identification through echocardiography and biochemical markers is crucial. Management requires both symptomatic treatment of heart failure and control of the underlying tumor through somatostatin analogs and surgical or oncologic intervention. Conclusion: Carcinoid-induced multivalvular heart disease is a rare but critical diagnosis in patients with neuroendocrine tumors. Optimal care requires a multidisciplinary approach combining cardiology, oncology, and cardiac surgery to improve outcomes and manage complex systemic involvement.
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Pochuev, P. V., N. G. Romanova, and E. L. Malankina. "Efficiency of joint glycine and auxin analogs foliar treatment on coriander seeds yield and essential oil quality." Vegetable crops of Russia, no. 5 (September 26, 2022): 76–81. http://dx.doi.org/10.18619/2072-9146-2022-5-76-81.
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Coriander is the leading essential oil crop and occupies vast areas, both in our country and abroad, and is be used to produce linalool, with subsequent processing into other aromatic substances. Increasing its yield and quality of raw materials with the help of modern preparations is an urgent problem of essential oil production.Purpose of the work: increasing the productivity of coriander with combined use of foliar treatments with glycine and auxin-containing preparations for directed control production process in coriander seed.Material and methods. As objects for studying the effect of the drug, varieties of coriander sowing Yantar and Avangard were chosen. Plants were sown in the first or third decade of April, depending on the conditions of the year, using a SZT-3.6 seeder with row spacing of 15 cm. The seeding rate was 25 kg/ha, the seeding depth was 2 cm. concentration 10 mg/l. Drug concentrations: IAA-glycol phosphate – 25, 50 and 100 mg/l, DvaU - 2 ml/l. Treatment with a solution of IUKGF and DvaU was carried out in the phase of budding-beginning of flowering. The cutting was carried out during the period of browning of seeds on the central umbrella. The content of essential oil was determined according to SP XIV method 1.Results. As a result of the research, a positive effect of foliar treatments with glycine was revealed, both on the yield and on the content of essential oil in the raw material of coriander seed varieties Yantar and Avangard. Based on the results obtained, the effective concentration of the drug is determined not only by the characteristics of the variety, but also by weather conditions, when, depending on the conditions during the processing period and the previous harvest, different aspects of the drug action appear. The maximum increase in the collection of essential oil of coriander variety Yantar (11.1 kg/ha) was noted during the combined treatment of plants with glycine at a rate of 10 mg/l in the leaf rosette phase and IAA-GF at a rate of 50 mg/l in the budding phase; varieties Avangard (8.6 kg/ha) - with combined treatment of plants with glycine at a rate of 10 mg/l in the leaf rosette phase and DvaU at a rate of 2 ml/l in the budding phase.
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Tuinen, Sjoerd van. "Michelangelo, Leibniz and the Serpentine Figure." Deleuze Studies 5, no. 1 (2011): 63–72. http://dx.doi.org/10.3366/dls.2011.0007.
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In his lectures from 1987, Deleuze draws an analogy between Michelangelo's figures and Leibnizian substances by claiming that neither are essences but rather sources of modifications or manners of being. The best way to explore this analogy, I argue, is by focusing on Michelangelo's preference for serpentine shapes. By putting key passages from The Logic of Sensation, The Fold: Leibniz and the Baroque and What is Philosophy? in resonance with the Leibnizian accounts of corporeal aggregates and possible worlds on the one hand and art history on the other, I will try to develop a Deleuzian concept for the typically Mannerist ideal of the serpentine figure. Although Deleuze usually prefers to speak in musical terms of refrains and counterpoints by which various blocs of sensation resonate with each other, in the visual arts it is the serpentine figure that renders visible sensory becoming as a rhythmic counter-positioning of possible worlds within a single body without organs.