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Item Glucoraphanin Triggers Rapid Antidepressant Responses in a Rat Model of Beta Amyloid-Induced Depressive-like Behaviour(MDPI, 2022) Tucci, P.; Bove, M.; Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Dimonte, S.; Morgese, M.G.; Schiavone, S.; Di Cesare Mannelli, L.; Ghelardini, C.; Trabace, L.Glucoraphanin (GRA) is a natural compound that has shown beneficial effects in chronic diseases and in central nervous system disorders. Moreover, GRA displayed antidepressant activity in preclinical models. We have previously demonstrated that a single intracerebroventricular administration of soluble amyloid-beta 1-42 (sAβ 1-42) in rat evokes a depressive-like phenotype by increasing immobility frequency in the forced swimming test (FST). The aim of this work was to investigate the effect of GRA in naïve and in sAβ-1-42-treated rats by using the FST. Behavioural analyses were accompanied by neurochemical and biochemical measurements in the prefrontal cortex (PFC), such as serotonin (5-HT), noradrenaline (NA), kynurenine (KYN), tryptophan (TRP), reactive oxygen species (ROS) and the transcription nuclear factor kappa B (NF-kB) levels. We reported that GRA administration in naïve rats at the dose of 50 mg/kg reduced the immobility frequency in the FST and increased 5-HT and NA levels in the PFC compared to controls. At the same dose, GRA reverted depressive-like effects of sAβ 1-42 administration, restored the 5-HT levels and reduced NF-kB, KYN and ROS levels in PFC. In conclusion, GRA rapidly reverting depressive-like behaviour, together with biochemical and neurochemical alterations, might represent a safe and natural candidate for the treatment of depression.Item Social isolation triggers oxidative status and impairs systemic and hepatic insulin sensitivity in normoglycemic rats(Elsevier, 2022) Bove, M.; Lama, A.; Schiavone, S.; Pirozzi, C.; Tucci, P.; Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Trinchese, G.; Corso, G.; Morgese, M.G.; Trabace, L.Drug-naïve psychotic patients show metabolic and hepatic dysfunctions. The rat social isolation model of psychosis allows to investigate mechanisms leading to these disturbances to which oxidative stress crucially contributes. Here, we investigated isolation-induced central and peripheral dysfunctions in glucose homeostasis and insulin sensitivity, along with redox dysregulation. Social isolation did not affect basal glycemic levels and the response to glucose and insulin loads in the glucose and insulin tolerance tests. However, HOMA-Index value were increased in isolated (ISO) rats. A hypothalamic reduction of AKT phosphorylation and a trend toward an increase in AMPK phosphorylation were observed following social isolation, accompanied by reduced GLUT-4 levels. Social isolation also induced a reduction of phosphorylation of the insulin receptor, of AKT and GLUT-2, and a decreased phosphorylation of AMPK in the liver. Furthermore, a significant reduction in hepatic CPT1 and PPAR-α levels was detected. ISO rats also showed significant elevations in hepatic ROS amount, lipid peroxidation and NOX4 expression, whereas no differences were detected in NOX2 and NOX1 levels. Expression of SOD2 in the mitochondrial fraction and SOD1 in the cytosolic fraction was not altered following social isolation, whereas SOD activity was increased. Furthermore, a decrease of hepatic CAT and GSH amount was observed in ISO rats compared to GRP animals. Our data suggest that the increased oxidant status and antioxidant capacity modifications may trigger hepatic and systemic insulin resistance, by altering signal hormone pathway and sustaining subsequent alteration of glucose homeostasis and metabolic impairment observed in the social isolation model of psychosis.Item Ketamine administration in early postnatal life as a tool for mimicking Autism Spectrum Disorders core symptoms(Elsevier Inc., 2022) Bove, M.; Schiavone, S.; Tucci, P.; Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Dimonte, S.; Colia, A.L.; Morgese, M.G.; Trabace, L.Autism Spectrum Disorders (ASD) core symptoms include deficits of social interaction, stereotyped behaviours, dysfunction in language and communication. Beyond them, several additional symptoms, such as cognitive impairment, anxiety-like states and hyperactivity are often occurring, mainly overlapping with other neuropsychiatric diseases. To untangle mechanisms underlying ASD etiology, and to identify possible pharmacological approaches, different factors, such as environmental, immunological and genetic ones, need to be considered. In this context, ASD animal models, aiming to reproduce the wide range of behavioural phenotypes of this uniquely human disorder, represent a very useful tool. Ketamine administration in early postnatal life of mice has already been studied as a suitable animal model resembling psychotic-like symptoms. Here, we investigated whether ketamine administration, at postnatal days 7, 9 and 11, might induce behavioural features able to mimic ASD typical symptoms in adult mice. To this aim, we developed a 4-days behavioural tests battery, including Marble Burying, Hole Board, Olfactory and Social tests, to assess repetitive and stereotyped behaviour, social deficits and anxiety-like symptoms. Moreover, by using this mouse model, we performed neurochemical and biomolecular analyses, quantifying neurotransmitters belonging to excitatory-inhibitory pathways, such as glutamate, glutamine and gamma-aminobutyric acid (GABA), as well as immune activation biomarkers related to ASD, such as CD11b and glial fibrillary acidic protein (GFAP), in the hippocampus and amygdala. Possible alterations in levels of brain-derived neurotrophic factor (BDNF) expression in the hippocampus and amygdala were also evaluated. Our results showed an increase in stereotyped behaviours, together with social impairments and anxiety-like behaviour in adult mice, receiving ketamine administration in early postnatal life. In addition, we found decreased BDNF and enhanced GFAP hippocampal expression levels, accompanied by elevations in glutamate amount, as well as reduction in GABA content in amygdala and hippocampus. In conclusion, early ketamine administration may represent a suitable animal model of ASD, exhibiting face validity to mimic specific ASD symptoms, such as social deficits, repetitive repertoire and anxiety-like behaviour.Item Precision Medicine in Alzheimer’s Disease: Investigating Comorbid Common Biological Substrates in the Rat Model of Amyloid Beta-Induced Toxicity(Frontiers Media S.A., 2022) Morgese, M.G.; Bove, M.; Di Cesare Mannell, L.; Schiaone, S.; Coli, A.L.; Dimonte, S.; Mhillaj, E.; Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Tucci, P.; Ghelardini, C.; Traace, L.Alzheimer’s disease (AD), one of the most widespread neurodegenerative disorder, is a fatal global burden for the elder population. Although many efforts have been made, the search of a curative therapy is still ongoing. Individuating phenotypic traits that might help in investigating treatment response is of growing interest in AD research. AD is a complex pathology characterized by many comorbidities, such as depression and increased susceptibility to pain perception, leading to postulate that these conditions may rely on common biological substrates yet to be determined. In order to investigate those biological determinants to be associable with phenotypic traits, we used the rat model of amyloid beta-induced toxicity. This established model of early phase of AD is obtained by the intracerebroventricular injection of soluble amyloid beta1-42 (Aβ) peptide 7 days before performing experiments. In this model, we have previously reported increased immobility in the forced swimming test, reduced cortical serotonin levels and subtle alterations in the cognitive domain a depressive-like phenotype associated with subtle alteration in memory processes. In light of evaluating pain perception in this animal model, we performed two different behavioral tests commonly used, such as the paw pressure test and the cold plate test, to analyze mechanical hyperalgesia and thermal allodynia, respectively. Behavioural outcomes confirmed the memory impairment in the social recognition test and, compared to sham, Aβ-injected rats showed an increased selective susceptibility to mechanical but not to thermal stimulus. Behavioural data were then corroborated by neurochemical and biochemical biomarker analyses either at central or peripheral level. Data showed that the peptide injection evoked a significant increase in hypothalamic glutamate, kynurenine and dopamine content, while serotonin levels were reduced. Plasma Cystatin-C, a cysteine protease, was increased while serotonin and melatonin levels were decreased in Aβ-injected rats. Urinary levels paralleled plasma quantifications, indicating that Aβ-induced deficits in pain perception, mood and cognitive domain may also depend on these biomarkers. In conclusion, in the present study, we demonstrated that this animal model can mimic several comorbid conditions typical of the early phase of AD. Therefore, in the perspective of generating novel therapeutic strategies relevant to precision medicine in AD, this animal model and the biomarkers evaluated herein may represent an advantageous approach.Item Precision Medicine in Alzheimer’s Disease: Investigating Comorbid Common Biological Substrates in the Rat Model of Amyloid Beta-Induced Toxicity(Frontiers Media S.A., 2021) Morgese, M.G.; Bove, M.; Di Cesare Mannelli, L.; Schiavone, S.; Colia, A.L.; Dimonte, S.; Mhillaj, E.; Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Tucci, P.; Ghelardini, C.; Trabace, L.Alzheimer’s disease (AD), one of the most widespread neurodegenerative disorder, is a fatal global burden for the elder population. Although many efforts have been made, the search of a curative therapy is still ongoing. Individuating phenotypic traits that might help in investigating treatment response is of growing interest in AD research. AD is a complex pathology characterized by many comorbidities, such as depression and increased susceptibility to pain perception, leading to postulate that these conditions may rely on common biological substrates yet to be determined. In order to investigate those biological determinants to be associable with phenotypic traits, we used the rat model of amyloid beta-induced toxicity. This established model of early phase of AD is obtained by the intracerebroventricular injection of soluble amyloid beta1-42 (Aβ) peptide 7 days before performing experiments. In this model, we have previously reported increased immobility in the forced swimming test, reduced cortical serotonin levels and subtle alterations in the cognitive domain a depressive-like phenotype associated with subtle alteration in memory processes. In light of evaluating pain perception in this animal model, we performed two different behavioral tests commonly used, such as the paw pressure test and the cold plate test, to analyze mechanical hyperalgesia and thermal allodynia, respectively. Behavioural outcomes confirmed the memory impairment in the social recognition test and, compared to sham, Aβ-injected rats showed an increased selective susceptibility to mechanical but not to thermal stimulus. Behavioural data were then corroborated by neurochemical and biochemical biomarker analyses either at central or peripheral level. Data showed that the peptide injection evoked a significant increase in hypothalamic glutamate, kynurenine and dopamine content, while serotonin levels were reduced. Plasma Cystatin-C, a cysteine protease, was increased while serotonin and melatonin levels were decreased in Aβ-injected rats. Urinary levels paralleled plasma quantifications, indicating that Aβ-induced deficits in pain perception, mood and cognitive domain may also depend on these biomarkers. In conclusion, in the present study, we demonstrated that this animal model can mimic several comorbid conditions typical of the early phase of AD. Therefore, in the perspective of generating novel therapeutic strategies relevant to precision medicine in AD, this animal model and the biomarkers evaluated herein may represent an advantageous approach.Item Morphological Peculiarities of Parasitic (Trichosomoides crassicauda) Infection in Rat Urinary Bladder(Sciendo, 2021) Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Линдін, Микола Сергійович; Лындин, Николай Сергеевич; Lyndin, Mykola Serhiiovych; Гирявенко, Наталія Іванівна; Гирявенко, Наталья Ивановна; Hyriavenko, Nataliia Ivanivna; Москаленко, Роман Андрійович; Москаленко, Роман Андреевич; Moskalenko, Roman Andriiovych; Линдіна, Юлія Миколаївна; Лындина, Юлия Николаевна; Lyndina, Yuliia Mykolaivna; Сікора, Катерина Олексіївна; Сикора, Екатерина Алексеевна; Sikora, Kateryna Oleksiivna; Чижма, Руслана Анатоліївна; Чижма, Руслана Анатольевна; Chyzhma, Ruslana Anatoliivna; Дяченко, Олена Олегівна; Дяченко, Елена Олеговна; Diachenko, Olena Olehivna; Романюк, Анатолій Миколайович; Романюк, Анатолий Николаевич; Romaniuk, Anatolii MykolaiovychTrichosomoides crassicauda (T. crassicauda) is a parasite commonly localized in the urinary bladder (UB) of laboratory and wild rats. The presence of these helminths can influence the prediction of pathological changes in the UB. Therefore, the purpose of this research was to make a comprehensive study of the features of the morphological changes in the UB wall of white laboratory rats as a result of T. crassicauda infestation. The study was performed on male rats using histological (Hematoxyline-Eosin and Alcian Blue staining) and immunohistochemical (Ki-67, Hsp70, Hsp90α, CD3 and CD20) methods. T. crassicauda was detected in both urine and UB samples. Morphological changes were observed as disruption in urothelial cell stratification and insignificant proliferative and immune responses in the UB. Increased heat shock protein levels were observed which may suggest a natural body’s resistance to this parasite.Item The role of psammoma bodies in the ovarian serous adenocarcinoma(Sumy State University, 2020) Chizhma, R.A.; Soloviov N.O.; Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Піддубний, Артем Михайлович; Поддубный, Артем Михайлович; Piddubnyi, Artem MykhailovychOne of the current problems among women’s reproductive system diseases is ovarian tumors. Each year the risk of this disease shows a tendency to increase. The pathognomonic feature of the morphological diagnostic of ovarian cancer is Psammoma bodies (PBs), which are represented by plasticized calcium structures and are placed in the form of concentration circles. Should be noted, that the process of pathological biomineralization is most common in serous papillary carcinoma, but the mechanism of PBs formation is not fully understood yet.Item Reparative processes features in trophic ulcers caused by diabetes mellitus with the use of platelet-rich plasma(ALUNA, 2020) Дужий, Ігор Дмитрович; Дужий, Игорь Дмитриевич; Duzhyi, Ihor Dmytrovych; Ніколаєнко, Андрій Сергійович; Николаенко, Андрей Сергеевич; Nikolaienko, Andrii Serhiiovych; Попадинець, Василь Миронович; Попадинець, Василий Миронович; Popadynets, Vasyl Myronovych; Кравець, Олександр Валерійович; Кравец, Александр Валерьевич; Kravets, Oleksandr Valeriiovych; Гресько, Ігор Яремович; Гресько, Игорь Еремеевич; Hresko, Ihor Yaremovych; Голубничий, Станіслав Олександрович; Голубничий, Станислав Александрович; Holubnychyi, Stanislav Oleksandrovych; Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Линдін, Микола Сергійович; Лындин, Николай Сергеевич; Lyndin, Mykola Serhiiovych; Романюк, Анатолій Миколайович; Романюк, Анатолий Николаевич; Romaniuk, Anatolii MykolaiovychThe improvement of the treatment results of the lower limbs ulcers, caused by the diabetes mellitus by using our technique of the platelet-rich plasma application; the study of the features of the morphological and immunohistochemical changes, and the effect of the growth factors of the platelet-rich plasma on the regeneration and healing of the ulcers. 38 patients with the trophic ulcers of the lower limbs, caused by diabetes mellitus were involved in the study. To assess the morphological features of the reparative processes before and after the treatment with PRP, the histological and immunohystochemical studies of the biopsy specimen of ulcers were carried out.Item Histological features of testicular seminoma(Sumy State University, 2020) Брусовцов, Дмитро Олегович; Брусовцов, Дмитрий Олегович; Brusovtsov, Dmytro Olehovych; Линдін, Микола Сергійович; Лындин, Николай Сергеевич; Lyndin, Mykola Serhiiovych; Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Гирявенко, Наталія Іванівна; Гирявенко, Наталья Ивановна; Hyriavenko, Nataliia IvanivnaTumors occupy one of the leading positions among the diseases, and annually its indicators continue growing. Testicular neoplasias are not an exemption. This pathology occurs in 3 % of young men of working age (15-45 years old) among all malignant neoplasms that worsen the reproductive health indicators. It underlines the importance of the detailed study of the testicle tumor features that will contribute to therapy individualization and increase the patient's overall survival rate.Item Prostatic сalculi сauses reduction of heat shock proteins expression in prostate cancer(The Romanian National Library, 2020) Abdul-Rahman, T.; Піддубний, Артем Михайлович; Поддубный, Артем Михайлович; Piddubnyi, Artem Mykhailovych; Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Москаленко, Роман Андрійович; Москаленко, Роман Андреевич; Moskalenko, Roman AndriiovychHeat shock proteins (Hsp) have an important role in tumor cells. Unfortunately, there is no data on the effect of intraluminal inclusions (IIn) on the expression of Hsp in prostate cancer (PCa) cells. The aim of our study was to detect the association between IIn and expression of Hsp in PCa tissue.