THE INFLUENCE OF POLYPEPTIDE LIVER COMPLEX AND TETRAPEPTIDE ON ORGANISM PHYSIOLOGICAL FUNCTION IN NORM AND AGE-RELATED PATHOLOGY

2020 ◽  
pp. 159-164
Author(s):  
Б. И. Кузник ◽  
Н. В. Хасанова ◽  
Г. А. Рыжак ◽  
И. Е. Мещерякова ◽  
В. Х. Хавинсон
Keyword(s):  
Chronic Hepatitis ◽  
Antioxidant Status ◽  
High Efficiency ◽  
Physiological Function ◽  
Experimental Models ◽  
Old People ◽  
Age Related ◽  
Acute And Chronic Hepatitis ◽  
Elderly And Old People

Применение большого числа лекарственных средств у лиц пожилого и старческого возраста часто приводит к нарушению функции печени. При этом с возрастом повышается риск развития цирроза печени, острого и хронического гепатита, что обусловливает необходимость поиска эффективных и безопасных гепатопротекторов. В обзоре приведены данные исследования гепатопротекторных, иммуномодулирующих и геропротекторных свойств полипептидного комплекса, экстрагированного из печени телят (Вентвил) и тетрапептида KEDA ( Lys-Glu-Asp-Ala , Ливаген). В моделях экспериментальной патологии печени у животных (острый и хронический гепатит, цирроз) и исследованиях in vitro показана высокая эффективность Вентвила и пептида KEDA . Вентвил и пептид KEDA обладают сходными свойствами - приводят к норме иммунный и антиоксидантный статус, восстанавливают функции печени при гепатите. Показано, что наибольшее гепато-и иммунопротекторное действие пептидов проявляется при старении. The applying of many drugs in elderly and old people often is the reason of liver dysfunction. Thereat, the risk of liver fibroid induration, acute and chronic hepatitis increases during aging. It is the reason to find new, effective and harmless hepatoprotectors. In the review is shown the data of hepatoprotective, immunoprotective and antiageing properties of liver polypeptide complex (Ventvil) and KEDA tetrapeptide ( Lys-Glu-Asp-Ala , Livagen). In liver pathology experimental models (liver fibroid induration, acute and chronic hepatitis) in amimals and in vitro was shown high efficiency of Ventvil and KEDA peptide. Ventvil and KEDA peptide had concordant effects - normalized immune and antioxidant status, restored liver function during hepatitis. It was demonstrated, that maximal hepato- and immunoprotective effect of peptides verified in aging.

scholarly journals Experimental Models in Neovascular Age Related Macular Degeneration

2020 ◽  
Vol 21 (13) ◽  
pp. 4627
Author(s):  
Olivia Rastoin ◽  
Gilles Pagès ◽  
Maeva Dufies
Keyword(s):  
Macular Degeneration ◽  
Experimental Models ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
In Vivo Models ◽  
Age Related ◽  
Decoy Receptors ◽  
Endothelial Growth Factor

Neovascular age-related macular degeneration (vAMD), characterized by the neo-vascularization of the retro-foveolar choroid, leads to blindness within few years. This disease depends on angiogenesis mediated by the vascular endothelial growth factor A (VEGF) and to inflammation. The only available treatments consist of monthly intravitreal injections of antibodies directed against VEGF or VEGF/VEGFB/PlGF decoy receptors. Despite their relative efficacy, these drugs only delay progression to blindness and 30% of the patients are insensitive to these treatments. Hence, new therapeutic strategies are urgently needed. Experimental models of vAMD are essential to screen different innovative therapeutics. The currently used in vitro and in vivo models in ophthalmic translational research and their relevance are discussed in this review.

scholarly journals INFLAMM-AGING: THE HYPOTHESIS OF THE INFLAMMATION ROLE IN ALZHEIMER DISEASE PROGRESS

2019 ◽  
Vol 19 (1S) ◽  
pp. 88-91
Author(s):  
I M Kventoy ◽  
N S Linkova ◽  
A S Diatlova ◽  
V A Zuev ◽  
T V Kventaia
Keyword(s):  
Comparative Analysis ◽  
Alzheimer Disease ◽  
Chronic Inflammation ◽  
Control Group ◽  
Signal Molecules ◽  
Old People ◽  
Age Related ◽  
Neurodegenerative Pathology ◽  
Τ Protein ◽  
Elderly And Old People

Inflamm-aging - the term, describes the development of chronic inflammation during aging without the infection pathology. It is supposed, that inflamm-aging is one of the reason of age-related pathology, partially, Alzheimer disease (AD). There were done comparative analysis of AD (Аβ42, τ-protein, р16) and inflammation (IL-6, TGFα, NF-kB) markers in hippocamp and blood lymphocytes in elderly and old people. It was shown, that expression of investigated signal molecules in hippocamp and lymphocytes of elderly and old AD people increased in comparison with people of control group (without neurodegenerative pathology). Thus, inflammation mediators play important role in AD pathogenesis and can be the potential target for neuropathology therapy.

scholarly journals The Antioxidative, Antiaging, and Hepatoprotective Effects of Alkali-Extractable Polysaccharides by Agaricus bisporus

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Shangshang Li ◽  
Juan Li ◽  
Jianjun Zhang ◽  
Wenshuai Wang ◽  
Xiuxiu Wang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Enzyme Activities ◽  
Agaricus Bisporus ◽  
Antioxidant Status ◽  
Reducing Power ◽  
Hepatic Enzyme ◽  
Age Related ◽  
Hepatoprotective Effects

The aim of this work was designed to investigate the antioxidant, antiaging, and hepatoprotective effects of alkali-extractable polysaccharides (AlAPS) and their three purified fractions (AlAPS-1, AlAPS-2, and AlAPS-3) from Agaricus bisporus in D-galactose induced aging mice. For in vitro antioxidant analysis, both AlAPS and its fractions exhibited moderate reducing power, Fe2+-chelating activities, and potent scavenging activities on hydroxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. The in vivo results demonstrated that the polysaccharides, especially AlAPS-2, showed potential antiaging and hepatoprotective effects by enhancing the antioxidant status, decreasing serum hepatic enzyme activities, and improving the lipid metabolism. This study suggested that the polysaccharides extracted and purified from A. bisporus could be exploited as a potent dietary supplement to attenuate aging and prevent age-related diseases.

scholarly journals Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 824
Author(s):  
Andrea Capucciati ◽  
Fabio A. Zucca ◽  
Enrico Monzani ◽  
Luigi Zecca ◽  
Luigi Casella ◽  
...  
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Brain Aging ◽  
Experimental Models ◽  
Test Tube ◽  
Age Related ◽  
And Function ◽  
Endogenous Metabolites ◽  
High Degree

Neuromelanin (NM) accumulates in catecholamine long-lived brain neurons that are lost in neurodegenerative diseases. NM is a complex substance made of melanic, peptide and lipid components. NM formation is a natural protective process since toxic endogenous metabolites are removed during its formation and as it binds excess metals and xenobiotics. However, disturbances of NM synthesis and function could be toxic. Here, we review recent knowledge on NM formation, toxic mechanisms involving NM, go over NM binding substances and suggest experimental models that can help identifying xenobiotic modulators of NM formation or function. Given the high likelihood of a central NM role in age-related human neurodegenerative diseases such as Parkinson’s and Alzheimer’s, resembling such diseases using animal models that do not form NM to a high degree, e.g., mice or rats, may not be optimal. Rather, use of animal models (i.e., sheep and goats) that better resemble human brain aging in terms of NM formation, as well as using human NM forming stem cellbased in vitro (e.g., mid-brain organoids) models can be more suitable. Toxicants could also be identified during chemical synthesis of NM in the test tube.

scholarly journals Inflammaging: Role in pathogenesis and molecular diagnostics of age-related dilated cardiomyopathy

2021 ◽  
pp. 67-72
Author(s):  
И.М. Кветной ◽  
Н.С. Линькова ◽  
А.Э. Пухальская ◽  
К.Л. Козлов ◽  
Г.И. Гурко ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Molecular Diagnostics ◽  
Molecular Medicine ◽  
Signal Molecules ◽  
Old People ◽  
Melatonin Synthesis ◽  
Age Related ◽  
Klotho Protein ◽  
Salivary Concentration ◽  
Elderly And Old People

Актуальность. В патогенезе дилатационной кардиомиопатии (ДКМП) у лиц старших возрастных групп важную роль играет инфламэйджинг и нарушение мелатонинобразующей функции эпифиза. Важной задачей молекулярной медицины является поиск сигнальных молекул - маркеров ДКМП. Цель работы - провести сравнительную оценку концентрации IL-1β, IL-6, Klotho, Sirt3, FGF23 и мелатонина в слюне у пациентов старших возрастных групп с ДКМП и без неё. Методы. Определение концентрации сигнальных молекул в слюне осуществляли методом иммуноферментного анализа с последующей статистической обработкой полученных данных. Результаты. У пациентов с ДКМП пожилого и старческого возраста концентрация маркеров инфламэйджинга (IL-1β, IL-6) в слюне повышалась в 8,6-19,1 раза по сравнению с этими показателями у лиц без ДКМП. Концентрация белка Klotho, ингибирующего синтез провоспалительных цитокинов, в слюне пациентов с ДКМП пожилого и старческого возраста была в 4,2-7,6 раза ниже по сравнению с этим показателем у лиц без ДКМП. У пациентов с ДКМП пожилого и старческого возраста концентрация в слюне мелатонина и регулируемого им Sirt3 была в 2,1-4,3 раза ниже по сравнению с этим показателем у лиц без ДКМП. Концентрация FGF23 в слюне не зависела от возраста пациентов и наличия ДКМП. Заключение. В патогенезе ДКМП у лиц старших возрастных групп важную роль играет инфламэйджинг. Об этом свидетельствует снижение синтеза белка Klotho и повышение уровня провоспалительных цитокинов IL-1β и IL-6. Другим звеном патогенеза ДКМП является снижение синтеза мелатонина и, как следствие, нарушение функции сигнального пути Mst1/Sirt3. Исследование концентрации IL-1β, IL-6, Klotho, SIRT3 и мелатонина в слюне может применяться для молекулярной диагностики ДКМП у лиц пожилого и старческого возраста. Background. Inflammaging and disorder of melatonin synthesis in the pineal gland play an important role in the pathogenesis of dilated cardiomyopathy (DC) in elderly and old people. An important objective of molecular medicine is searching for signal molecules, markers of DC. The aim of this work was to compare concentrations of IL-1β, IL-6, Klotho, Sirt3, FGF23, and melatonin in saliva of elderly and old DC patients and persons without DC. Methods. Concentrations of signal molecules were measured in saliva by ELISA. Results. Salivary concentrations of inflammaging markers (IL-1β, IL-6) in elderly and old DC patients were 8.6-19.1 times higher than in persons without DC. Salivary concentration of Klotho protein, an inhibitor of pro-inflammatory cytokine synthesis, was increased 4.2-7.6 times in elderly and old DC patients compared to the values in persons without DC. Salivary concentrations of melatonin and melatonin-regulated Sirt3 were decreased 2.1-4.3 times in elderly and old DC patients compared to the values in persons without DC. Salivary concentration of FGF23 did not depend on the age or presence of DC. Conclusion. Inflammaging plays in important role in the pathogenesis of DC in elderly and old people as evidenced by decreased synthesis of Klotho and increased levels of the pro-inflammatory cytokines IL-1β and IL-6. Another step in the DC pathogenesis is decreased melatonin synthesis and the resultant dysregulation of the Mst1/Sirt3 signaling way. Measuring concentrations of IL-1β, IL-6, Klotho, SIRT3, and melatonin in saliva can be used for molecular diagnostics of DC in elderly and old people.

scholarly journals Mesenchymal Stem Cell-Based Therapy for Retinal Degenerative Diseases: Experimental Models and Clinical Trials

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 588
Author(s):  
Vladimir Holan ◽  
Katerina Palacka ◽  
Barbora Hermankova
Keyword(s):  
Clinical Trials ◽  
Experimental Studies ◽  
Experimental Models ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
Retinal Cells ◽  
Cell Based Therapy ◽  
Age Related ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy or glaucoma, represent the main causes of a decreased quality of vision or even blindness worldwide. However, despite considerable efforts, the treatment possibilities for these disorders remain very limited. A perspective is offered by cell therapy using mesenchymal stem cells (MSCs). These cells can be obtained from the bone marrow or adipose tissue of a particular patient, expanded in vitro and used as the autologous cells. MSCs possess potent immunoregulatory properties and can inhibit a harmful inflammatory reaction in the diseased retina. By the production of numerous growth and neurotrophic factors, they support the survival and growth of retinal cells. In addition, MSCs can protect retinal cells by antiapoptotic properties and could contribute to the regeneration of the diseased retina by their ability to differentiate into various cell types, including the cells of the retina. All of these properties indicate the potential of MSCs for the therapy of diseased retinas. This view is supported by the recent results of numerous experimental studies in different preclinical models. Here we provide an overview of the therapeutic properties of MSCs, and their use in experimental models of retinal diseases and in clinical trials.

scholarly journals A Peptide-Based Nanocarrier for an Enhanced Delivery and Targeting of Flurbiprofen into the Brain for the Treatment of Alzheimer’s Disease: An In Vitro Study

Nanomaterials ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1590
Author(s):  
Shafq Al-azzawi ◽  
Dhafir Masheta ◽  
Anna Guildford ◽  
Gary Phillips ◽  
Matteo Santin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Efficiency ◽  
Solid Phase ◽  
Amyloid Β ◽  
In Vitro Study ◽  
Target Cells ◽  
Age Related ◽  
The Brain

Alzheimer’s disease (AD) is an age-related disease caused by abnormal accumulation of amyloid-β in the brain leading to progressive tissue degeneration. Flurbiprofen (FP), a drug used to mitigate the disease progression, has low efficacy due to its limited permeability across the blood–brain barrier (BBB). In a previous work, FP was coupled at the uppermost branching of an ε-lysine-based branched carrier, its root presenting a phenylalanine moiety able to increase the hydrophobicity of the complex and enhance the transport across the BBB by adsorptive-mediated transcytosis (AMT). The present study explores a different molecular design of the FP-peptide delivery system, whereby its root presents an ApoE-mimicking peptide, a targeting ligand that could enhance transport across the BBB by receptor-mediated transcytosis (RMT). The functionalised complex was synthesised using a solid-phase peptide synthesis and characterised by mass spectrometry and FTIR. Cytotoxicity and permeability of this complex across an in vitro BBB model were analysed. Moreover, its activity and degradation to release the drug were investigated. The results revealed successful synthesis and grafting of FP molecules at the uppermost molecular branches of the lysine terminal without observed cytotoxicity. When covalently linked to the nanocarrier, FP was still active on target cells, albeit with a reduced activity, and was released as a free drug upon hydrolysis in a lysosome-mimicking medium. Noticeably, this work shows the high efficiency of RMT-driven FP delivery over delivery systems relying on AMT.

Ultrastructure of Choriocarcinoma in Vitro

1969 ◽  
Vol 27 ◽  
pp. 362-363
Author(s):  
John C. Garancis ◽  
R. A. Pattillo
Keyword(s):  
Cell Line ◽  
Physiological Function ◽  
Cell System ◽  
Bewo Cell ◽  
Bewo Cells ◽  
Gestational Choriocarcinoma ◽  
Bewo Cell Line

Growth of cell system (BeWo-cell line) derived from human gestational choriocarcinoma has been established and continuously maintained in-vitro. Furthermore, it is evident from the previous studies that this cell line has retained the physiological function of the placental trophoblasts, namely the synthesis of human chorionic gonadotrophil(HCG).The BeWo cells were relatively small and possessed single nuclei, thus indicating that this cell line consists exclusively of cytotrophoblasts. In some instances cells appeared widely separated and their lateral surfaces were provided with numerous microvilli (Fig.1).

Neutralization of a Low Molecular Weight Heparin (LHN-1) and Conventional Heparin by Protamine Sulfate in Rats

1986 ◽  
Vol 56 (03) ◽  
pp. 318-322 ◽  
Author(s):  
V Diness ◽  
P B Østergaard
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Thrombus Formation ◽  
Experimental Models ◽  
Protamine Sulfate ◽  
Low Molecular Weight ◽  
Antithrombotic Effect ◽  
Higher Doses

SummaryThe neutralization of a low molecular weight heparin (LHN-1) and conventional heparin (CH) by protamine sulfate has been studied in vitro and in vivo. In vitro, the APTT activity of CH was completely neutralized in parallel with the anti-Xa activity. The APTT activity of LHN-1 was almost completely neutralized in a way similar to the APTT activity of CH, whereas the anti-Xa activity of LHN-1 was only partially neutralized.In vivo, CH 3 mg/kg and LHN-1 7.2 mg/kg was given intravenously in rats. The APTT and anti-Xa activities, after neutralization by protamine sulfate in vivo, were similar to the results in vitro. In CH treated rats no haemorrhagic effect in the rat tail bleeding test and no antithrombotic effect in the rat stasis model was found at a protamine sulfate to heparin ratio of about 1, which neutralized APTT and anti-Xa activities. In LHN-1 treated rats the haemorrhagic effect was neutralized when APTT was close to normal whereas higher doses of protamine sulfate were required for neutralization of the antithrombotic effect. This probably reflects the fact that in most experimental models higher doses of heparin are needed to induce bleeding than to prevent thrombus formation. Our results demonstrate that even if complete neutralization of APTT and anti-Xa activities were not seen in LHN-1 treated rats, the in vivo effects of LHN-1 could be neutralized as efficiently as those of conventional heparin. The large fall in blood pressure caused by high doses of protamine sulfate alone was prevented by the prior injection of LHN-1.

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