Science contributes to globalization by creating new knowledge and technologies that can be shared and applied across different regions and cultures. The Regional Cooperation for Health, Science and Technology (RECOOP HST) Association combines the scientific output of partner organizations at the local and regional levels and uses it at the global level to prevent and eliminate major public health problems. Since research integrity (RI) varies among participating research organizations from the U.S.A. to Ukraine, RECOOP HST recognizes that high-quality research and outcomes, as measured by published papers, require a common understanding of scientific integrity and bioethics. During the last 15 years, RECOOP HST has organized workshops to educate scientists about the most devastating forms of research dishonesty: fabrication, falsification or plagiarism, which destroy trust and respect among scientists. Different types of research misconduct require different methods of detection and investigation. Now, with the rapid development of artificial intelligence (AI), various plagiarism-checking software has appeared. However, detecting fabrication and falsification is not so easy. In addition, AI should not be used to replace human reviewers, as there is currently insufficient evidence to support AI application in peer review. Two main approaches that RECOOP HST has taken to prevent misconduct and promote RI are evidence-based education and mentoring of students. Mentoring should take the form of informal discussions with students about responsible conduct of research and serving as a role model. Key strategies for promoting integrity include the development of institutional policies and the monitoring of activities with appropriate auditing of data. Keywords: fabrication, falsification, plagiarism, scientific and research integrity
{"title":"Scientific integrity in biomedical research is a global problem","authors":"S. Paryzhak, S. G. Vari","doi":"10.15407/ubj96.02.012","DOIUrl":"https://doi.org/10.15407/ubj96.02.012","url":null,"abstract":"Science contributes to globalization by creating new knowledge and technologies that can be shared and applied across different regions and cultures. The Regional Cooperation for Health, Science and Technology (RECOOP HST) Association combines the scientific output of partner organizations at the local and regional levels and uses it at the global level to prevent and eliminate major public health problems. Since research integrity (RI) varies among participating research organizations from the U.S.A. to Ukraine, RECOOP HST recognizes that high-quality research and outcomes, as measured by published papers, require a common understanding of scientific integrity and bioethics. During the last 15 years, RECOOP HST has organized workshops to educate scientists about the most devastating forms of research dishonesty: fabrication, falsification or plagiarism, which destroy trust and respect among scientists. Different types of research misconduct require different methods of detection and investigation. Now, with the rapid development of artificial intelligence (AI), various plagiarism-checking software has appeared. However, detecting fabrication and falsification is not so easy. In addition, AI should not be used to replace human reviewers, as there is currently insufficient evidence to support AI application in peer review. Two main approaches that RECOOP HST has taken to prevent misconduct and promote RI are evidence-based education and mentoring of students. Mentoring should take the form of informal discussions with students about responsible conduct of research and serving as a role model. Key strategies for promoting integrity include the development of institutional policies and the monitoring of activities with appropriate auditing of data. Keywords: fabrication, falsification, plagiarism, scientific and research integrity","PeriodicalId":23007,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"2 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140654871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Pokrovska, S. Mahiiovych, I. Fomenko, L. Biletska, H. Sklyarova, L. Kobylinska
Hypertension and type 2 diabetes mellitus (DM) remain widespread diseases that are becoming more prevalent. The role of visfatin and toll-like receptor (TLR) molecules in the pathogenesis of these diseases requires further research. Our aim was to study changes in visfatin and TLR levels in patients with hypertension and type 2 diabetes. Fifty-one patients were examined and divided into two groups: group 1 included 27 patients with hypertension and group 2 included 24 people with hypertension and type 2 DM. The control group included 18 practically healthy people. All individuals underwent general blood test, coagulogram, biochemical blood test, enzyme immunoassay to determine the level of visfatin and TLR in the blood serum and echocardiography. Hypertrophy of the walls of the left ventricle (LV) was observed in patients of two observed groups. The most common type of LV geometry was concentric hypertrophy (41.2%). The level of visfatin was significantly higher in patients of group 1, while in patients of group 2 it was decreased (P ˂ 0.05) and the level of TLR was increased (P ˂ 0.05). The elevated level of TLR in the serum of patients with hypertension can be considered a factor of low-grade inflammation, especially in combination with type 2 DM. The increase in the concentration of visfatin in hypertension serves as a more sensitive marker compared to TLR regarding the risk of developing comorbid cardiovascular pathology. The therapeutic treatments of patients with type 2 DM cause a reduction in the concentration of visfatin induced by hypertension. Keywords: hypertension, toll-like receptors, type 2 diabetes mellitus, visfatin
{"title":"The levels of visfatin and toll-like receptors in arterial hypertension and type 2 diabetes mellitus","authors":"N. Pokrovska, S. Mahiiovych, I. Fomenko, L. Biletska, H. Sklyarova, L. Kobylinska","doi":"10.15407/ubj96.02.051","DOIUrl":"https://doi.org/10.15407/ubj96.02.051","url":null,"abstract":"Hypertension and type 2 diabetes mellitus (DM) remain widespread diseases that are becoming more prevalent. The role of visfatin and toll-like receptor (TLR) molecules in the pathogenesis of these diseases requires further research. Our aim was to study changes in visfatin and TLR levels in patients with hypertension and type 2 diabetes. Fifty-one patients were examined and divided into two groups: group 1 included 27 patients with hypertension and group 2 included 24 people with hypertension and type 2 DM. The control group included 18 practically healthy people. All individuals underwent general blood test, coagulogram, biochemical blood test, enzyme immunoassay to determine the level of visfatin and TLR in the blood serum and echocardiography. Hypertrophy of the walls of the left ventricle (LV) was observed in patients of two observed groups. The most common type of LV geometry was concentric hypertrophy (41.2%). The level of visfatin was significantly higher in patients of group 1, while in patients of group 2 it was decreased (P ˂ 0.05) and the level of TLR was increased (P ˂ 0.05). The elevated level of TLR in the serum of patients with hypertension can be considered a factor of low-grade inflammation, especially in combination with type 2 DM. The increase in the concentration of visfatin in hypertension serves as a more sensitive marker compared to TLR regarding the risk of developing comorbid cardiovascular pathology. The therapeutic treatments of patients with type 2 DM cause a reduction in the concentration of visfatin induced by hypertension. Keywords: hypertension, toll-like receptors, type 2 diabetes mellitus, visfatin","PeriodicalId":23007,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140656331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. V. Hrebenyk, S. M. Maslii, O. O. Shevchuk, M. M. Korda, S. G. Vari
COVID-19 has been associated with a wide range of cardiac sequelae after the acute phase. The goal of the study is to evaluate the spectrum of arrhythmias in the aspects of age, comorbidity and survival rate using ECG patterns in patients after COVID-19 during 2 months of recovery. ECG data of 758 patients were examined and analyzed, including 256 (33.6%) males and 503 (66.4%) females aged 15 to 90 (52.99 ± 11.68) years. A total of 848 ECGs were performed in acute period and recovery. ECG changes were classified according to the Minnesota code (MC) classes. It was found that age, sex, severity of COVID-19, presence of concomitant hypertension and diabetes mellitus have a significant impact on ECG changes. Age correlated with the severity of COVID-19 (r = 0.485, P < 0.001), concomitant hypertension (r = 0.471, P < 0.001), diabetes (r = 0.346, P < 0.001) and obesity (r = 0.179, P < 0.001). Correlations were established between age and the presence of baseline previous pathological ECGs (r = 0.290, P < 0.0001). We established that heart rhythm disorders related to the severity of the COVID course are significantly influenced by oxygen saturation (r = -0.211, P < 0.001) and, to a lesser extent, the percentage of lung damage according to CT data (r = 0.127, P = 0.060). The results of the arrhythmias screening in patients with COVID-19 demonstrate the association mainly with the severity of the disease, and comorbidity, especially diabetes mellitus. So, we may consider arrhythmogenesis in COVID-19 through the prism of inflammation, intoxication, hypoxia, metabolic disorders, and drug effects. Keywords: arrhythmias, electrocardiography, Minnesota code (MC) classes, post-COVID-19
{"title":"ECG patterns in post-COVID-19 patients","authors":"M. V. Hrebenyk, S. M. Maslii, O. O. Shevchuk, M. M. Korda, S. G. Vari","doi":"10.15407/ubj96.02.100","DOIUrl":"https://doi.org/10.15407/ubj96.02.100","url":null,"abstract":"COVID-19 has been associated with a wide range of cardiac sequelae after the acute phase. The goal of the study is to evaluate the spectrum of arrhythmias in the aspects of age, comorbidity and survival rate using ECG patterns in patients after COVID-19 during 2 months of recovery. ECG data of 758 patients were examined and analyzed, including 256 (33.6%) males and 503 (66.4%) females aged 15 to 90 (52.99 ± 11.68) years. A total of 848 ECGs were performed in acute period and recovery. ECG changes were classified according to the Minnesota code (MC) classes. It was found that age, sex, severity of COVID-19, presence of concomitant hypertension and diabetes mellitus have a significant impact on ECG changes. Age correlated with the severity of COVID-19 (r = 0.485, P < 0.001), concomitant hypertension (r = 0.471, P < 0.001), diabetes (r = 0.346, P < 0.001) and obesity (r = 0.179, P < 0.001). Correlations were established between age and the presence of baseline previous pathological ECGs (r = 0.290, P < 0.0001). We established that heart rhythm disorders related to the severity of the COVID course are significantly influenced by oxygen saturation (r = -0.211, P < 0.001) and, to a lesser extent, the percentage of lung damage according to CT data (r = 0.127, P = 0.060). The results of the arrhythmias screening in patients with COVID-19 demonstrate the association mainly with the severity of the disease, and comorbidity, especially diabetes mellitus. So, we may consider arrhythmogenesis in COVID-19 through the prism of inflammation, intoxication, hypoxia, metabolic disorders, and drug effects. Keywords: arrhythmias, electrocardiography, Minnesota code (MC) classes, post-COVID-19","PeriodicalId":23007,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"47 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140655760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Udovenko, Ye. Makogonenko, O. Hornytska, G. Gogolinska,, O. Yusova,, V. Chernyshenko
Based on the turbidimetric curve of formation and dissolution of a blood plasma clot initiated by the activated partial thromboplastin time reagent, a method for determining the coagulation component of thrombin activity and fibrinolytic activity of plasmin is proposed. The activity of thrombin was calculated by the value of the lag period, and plasmin by its amidase activity at the moment of complete dissolution of the clot. At the end of the lag period, about 0.45% of the available prothrombin was activated, and at the moment of complete dissolution of the clot 1.05% of the available plasminogen was activated. This method makes it possible to determine the ratio of the thrombin generation rate to that of plasmin, the time of clot formation to the time of its dissolution, as well as the overall hemostasis potential and coagulation and fibrinolytic components and their ratio. Keywords: coagulation, fibrinolysis, global hemostasis assay, plasmin generation, thrombin generation
{"title":"Determination of thrombin and plasmin activity using the turbidimetric analysis of clot formation and dissolution in human blood plasma","authors":"A. Udovenko, Ye. Makogonenko, O. Hornytska, G. Gogolinska,, O. Yusova,, V. Chernyshenko","doi":"10.15407/ubj96.02.019","DOIUrl":"https://doi.org/10.15407/ubj96.02.019","url":null,"abstract":"Based on the turbidimetric curve of formation and dissolution of a blood plasma clot initiated by the activated partial thromboplastin time reagent, a method for determining the coagulation component of thrombin activity and fibrinolytic activity of plasmin is proposed. The activity of thrombin was calculated by the value of the lag period, and plasmin by its amidase activity at the moment of complete dissolution of the clot. At the end of the lag period, about 0.45% of the available prothrombin was activated, and at the moment of complete dissolution of the clot 1.05% of the available plasminogen was activated. This method makes it possible to determine the ratio of the thrombin generation rate to that of plasmin, the time of clot formation to the time of its dissolution, as well as the overall hemostasis potential and coagulation and fibrinolytic components and their ratio. Keywords: coagulation, fibrinolysis, global hemostasis assay, plasmin generation, thrombin generation","PeriodicalId":23007,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"7 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140653751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. O. Labudzynskyi, E. Pasichna, O. I. Krynina, М. M. Veliky
Bisphosphonates (BPs) are primary agents in the current pharmacological arsenal against osteoclast-related bone loss due to osteoporosis, Paget’s disease and bone tumors. Due to the lack of complete understanding of the molecular mechanism of their action in bone tissue and the overlap of key properties between BPs of different generations, integral studies of BPs inhibitory and antiresorptive properties are relevant today. The present work was carried out to establish a comprehensive study of the inhibitory effects of methylene bisphosphonic acid (MBPA) on the mevalonate pathway, metabolic activity and cell death in vitro compared to zoledronic acid (Zol). Farnesyl pyrophosphate synthase activity of MBPA-treated J774A.1 cells was inhibited by 80%, compared with a 79% reduction in Zol-treated samples. The ability of MBPA to decrease the percentage of viable cells in culture is slightly lower compared with Zol. After 24 h of incubation with lowest concentration, the percentage of inhibition of metabolic activity was 10.6 and 25%, respectively. After 48 h, these values were 34.8 and 55.6%, respectively. The inhibitory effects of MBPA and Zol on the intensity of incorporation of radioactively labeled precursor [14C]-acetate to the cholesterol fraction were 76.2 and 59.1%, respectively. In the case of isoprenoid fraction, the inhibitory effects were 40.9% and 51.2%, respectively. MBPA and Zol differently induced apoptosis in the J774A.1 cells culture, increased count of apoptotic cells in 2.4 and 6.3 times, and also increased the number of propidium iodide-positive cells in 7.4 and 19 times, respectively. MBPA and Zol also increased the number of TUNEL-positive cells in macrophage culture in 2.6 and 5 times, respectively. Zoledronate significantly reduced carbonic anhydrase 2 and nuclear factor of activated T-cells 1 gene expression levels compared to the MBPA action. Thus, the use of MBPA in future research and therapy of both cancer and osteoporosis looks promising due to lower cytotoxicity, high efficiency of mevalonate pathway inhibition and the possibility of dosage variation. Keywords: cell death, cell viability, FPPS enzymatic activity, gene expression, J774A.1 macrophages, methylene bisphosphonic acid, radioisotopes., zoledronic acid
{"title":"Inhibitory action of methylene bisphosphonic acid on metabolic activity and viability of J774A.1 cells","authors":"D. O. Labudzynskyi, E. Pasichna, O. I. Krynina, М. M. Veliky","doi":"10.15407/ubj96.02.108","DOIUrl":"https://doi.org/10.15407/ubj96.02.108","url":null,"abstract":"Bisphosphonates (BPs) are primary agents in the current pharmacological arsenal against osteoclast-related bone loss due to osteoporosis, Paget’s disease and bone tumors. Due to the lack of complete understanding of the molecular mechanism of their action in bone tissue and the overlap of key properties between BPs of different generations, integral studies of BPs inhibitory and antiresorptive properties are relevant today. The present work was carried out to establish a comprehensive study of the inhibitory effects of methylene bisphosphonic acid (MBPA) on the mevalonate pathway, metabolic activity and cell death in vitro compared to zoledronic acid (Zol). Farnesyl pyrophosphate synthase activity of MBPA-treated J774A.1 cells was inhibited by 80%, compared with a 79% reduction in Zol-treated samples. The ability of MBPA to decrease the percentage of viable cells in culture is slightly lower compared with Zol. After 24 h of incubation with lowest concentration, the percentage of inhibition of metabolic activity was 10.6 and 25%, respectively. After 48 h, these values were 34.8 and 55.6%, respectively. The inhibitory effects of MBPA and Zol on the intensity of incorporation of radioactively labeled precursor [14C]-acetate to the cholesterol fraction were 76.2 and 59.1%, respectively. In the case of isoprenoid fraction, the inhibitory effects were 40.9% and 51.2%, respectively. MBPA and Zol differently induced apoptosis in the J774A.1 cells culture, increased count of apoptotic cells in 2.4 and 6.3 times, and also increased the number of propidium iodide-positive cells in 7.4 and 19 times, respectively. MBPA and Zol also increased the number of TUNEL-positive cells in macrophage culture in 2.6 and 5 times, respectively. Zoledronate significantly reduced carbonic anhydrase 2 and nuclear factor of activated T-cells 1 gene expression levels compared to the MBPA action. Thus, the use of MBPA in future research and therapy of both cancer and osteoporosis looks promising due to lower cytotoxicity, high efficiency of mevalonate pathway inhibition and the possibility of dosage variation. Keywords: cell death, cell viability, FPPS enzymatic activity, gene expression, J774A.1 macrophages, methylene bisphosphonic acid, radioisotopes., zoledronic acid","PeriodicalId":23007,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"18 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140657841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Shymanskyi, O. Lisakovska, A. Khomenko, L. Yanitska, M. Veliky
Growing evidence suggests that vitamin D3 (D3, cholecalciferol) deficiency and impaired signaling of the hormonally active form of D3, 1α,25(OH)2D3 (1,25D3), through its cellular receptor (VDR) can be significant risk factors for the development of numerous multifactorial diseases, including diabetes. Our investigation was aimed at researching the D3 status in relation to the state of the D3 auto-/paracrine system in the brain and clarifying the effectiveness of the therapeutic use of D3 as a neuroprotective agent in experimental type 2 diabetes mellitus (T2DM). T2DM was induced in male Wistar rats by a combination of a high fat diet and a low dose of streptozotocin (25 mg/kg BW). Diabetic animals were treated with or without cholecalciferol (1,000 IU/kg BW, 30 days). The content of 25-hydroxyvitamin D3 (25D3) in blood serum and brain tissue was determined by ELISA. Analysis of mRNA expression of CYP24A1 and CYP27B1 genes was performed by RT-PCR. Protein levels of VDR, vitamin D3 binding protein (VDBP), CYP27B1 and CYP24A1 were investigated by Western blotting. A significant T2DM-associated decrease in the content of 25D3 in the blood serum was revealed, which correlated with a reduced content of this metabolite in the brain tissue. Impaired D3 status in animals with T2DM was accompanied by an increase in the levels of mRNA and protein of both 25D3 lα-hydroxylase (CYP27B1) and 1,25-hydroxyvitamin D3-24-hydroxylase (CYP24A1), which, respectively, provide local formation and degradation in the nervous tissue of the hormonally active form of D3 – 1,25D3. At the same time, a significant T2DM-induced down-regulation of the brain content of VDBP was shown. In addition, diabetes caused a slight increase in the protein expression of the VDR, through which the auto-/paracrine effects of 1,25D3 are realized in the brain. We have established a complete or partial corrective effect of cholecalciferol on D3 status, its bioavailability in the CNS and the level of protein expression of CYP27B1 and CYP24A1 in the brain of rats with T2DM. Abnormal D3 status in animals with T2DM was accompanied by compensatory changes in the expression of key components of the auto-/paracrine vitamin D3 system. Cholecalciferol was demonstrated to be partially effective in counteracting the impairments caused by T2DM. Keywords: 25-hydroxyvitamin D3, brain, type 2 diabetes, vitamin D3, vitamin D3 auto-/paracrine system
{"title":"Vitamin D(3) auto-/paracrine system in rat brain relating to vitamin D(3) status in experimental type 2 diabetes mellitus","authors":"I. Shymanskyi, O. Lisakovska, A. Khomenko, L. Yanitska, M. Veliky","doi":"10.15407/ubj96.02.038","DOIUrl":"https://doi.org/10.15407/ubj96.02.038","url":null,"abstract":"Growing evidence suggests that vitamin D3 (D3, cholecalciferol) deficiency and impaired signaling of the hormonally active form of D3, 1α,25(OH)2D3 (1,25D3), through its cellular receptor (VDR) can be significant risk factors for the development of numerous multifactorial diseases, including diabetes. Our investigation was aimed at researching the D3 status in relation to the state of the D3 auto-/paracrine system in the brain and clarifying the effectiveness of the therapeutic use of D3 as a neuroprotective agent in experimental type 2 diabetes mellitus (T2DM). T2DM was induced in male Wistar rats by a combination of a high fat diet and a low dose of streptozotocin (25 mg/kg BW). Diabetic animals were treated with or without cholecalciferol (1,000 IU/kg BW, 30 days). The content of 25-hydroxyvitamin D3 (25D3) in blood serum and brain tissue was determined by ELISA. Analysis of mRNA expression of CYP24A1 and CYP27B1 genes was performed by RT-PCR. Protein levels of VDR, vitamin D3 binding protein (VDBP), CYP27B1 and CYP24A1 were investigated by Western blotting. A significant T2DM-associated decrease in the content of 25D3 in the blood serum was revealed, which correlated with a reduced content of this metabolite in the brain tissue. Impaired D3 status in animals with T2DM was accompanied by an increase in the levels of mRNA and protein of both 25D3 lα-hydroxylase (CYP27B1) and 1,25-hydroxyvitamin D3-24-hydroxylase (CYP24A1), which, respectively, provide local formation and degradation in the nervous tissue of the hormonally active form of D3 – 1,25D3. At the same time, a significant T2DM-induced down-regulation of the brain content of VDBP was shown. In addition, diabetes caused a slight increase in the protein expression of the VDR, through which the auto-/paracrine effects of 1,25D3 are realized in the brain. We have established a complete or partial corrective effect of cholecalciferol on D3 status, its bioavailability in the CNS and the level of protein expression of CYP27B1 and CYP24A1 in the brain of rats with T2DM. Abnormal D3 status in animals with T2DM was accompanied by compensatory changes in the expression of key components of the auto-/paracrine vitamin D3 system. Cholecalciferol was demonstrated to be partially effective in counteracting the impairments caused by T2DM. Keywords: 25-hydroxyvitamin D3, brain, type 2 diabetes, vitamin D3, vitamin D3 auto-/paracrine system","PeriodicalId":23007,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"60 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140656199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I built research capacity and networks for the first ten years in the RECOOP Research Consortium from 2002 to 2012. The RECOOP HST Consortium, with the financial support of Cedars–Sinai Medical Center (CSMC), applied for the International Visegrad Fund (IVF) grants. We applied for 20 Standard Grants and won 14 Standard Grants to support forming and managing research networks and multinational–multidisciplinary research projects. The IVF grants won by CSMC – RECOOP helped move toward the 21st Century and broaden the scope of activities in RECOOP. Also, the IVF grants helped to build support networks for biosafety and biosecurity, animal use in research, clinical research management, and research and Innovation management training. RECOOP HST Association implemented the Common Mechanism of Diseases (CMD) research program for innovative life science research in member countries. The objectives were to increase the number of young scientists participating in creative research. Knowledge sharing is the most essential element of collaborative research. Within the context of RECOOP, my final endeavor will focus on investigating the diagnosis and management of Post-Traumatic Stress Disorder (PTSD) in Ukraine. As of January 2024, an estimated 6.3 million people have been forced to flee Ukraine, with 94 percent of them hosted in European countries, representing 5.9 million refugees. In Ukraine, an estimated 7.8 million people need health assistance, and 11.5 million need protection assistance and services. Studies of PTSD report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. We, as researchers, must continually share our research findings and diligently replicate established methods and protocols. These tasks can often feel akin to the labor of Sisyphus. Moreover, within the scientific community, integrity is paramount; dishonesty is swiftly met with consequences akin to the justice administered by Zeus. Therefore, we researchers must roll a boulder up a hill again and again, and after we have proved that the published scientific work is sound, the “boulder” and the scientist will stay on top of the hill. Keywords: burden of Sisyphus, define research strategy, funding opportunities, Post Traumatic Stress Disorder (PTSD) in Ukraine, RECOOP HST Association, research capacity building and networks, sciences and arts
{"title":"Research capacity building, networks, define research strategy, and funding opportunities in RECOOP HST Association","authors":"S. G. Vari","doi":"10.15407/ubj96.02.005","DOIUrl":"https://doi.org/10.15407/ubj96.02.005","url":null,"abstract":"I built research capacity and networks for the first ten years in the RECOOP Research Consortium from 2002 to 2012. The RECOOP HST Consortium, with the financial support of Cedars–Sinai Medical Center (CSMC), applied for the International Visegrad Fund (IVF) grants. We applied for 20 Standard Grants and won 14 Standard Grants to support forming and managing research networks and multinational–multidisciplinary research projects. The IVF grants won by CSMC – RECOOP helped move toward the 21st Century and broaden the scope of activities in RECOOP. Also, the IVF grants helped to build support networks for biosafety and biosecurity, animal use in research, clinical research management, and research and Innovation management training. RECOOP HST Association implemented the Common Mechanism of Diseases (CMD) research program for innovative life science research in member countries. The objectives were to increase the number of young scientists participating in creative research. Knowledge sharing is the most essential element of collaborative research. Within the context of RECOOP, my final endeavor will focus on investigating the diagnosis and management of Post-Traumatic Stress Disorder (PTSD) in Ukraine. As of January 2024, an estimated 6.3 million people have been forced to flee Ukraine, with 94 percent of them hosted in European countries, representing 5.9 million refugees. In Ukraine, an estimated 7.8 million people need health assistance, and 11.5 million need protection assistance and services. Studies of PTSD report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. We, as researchers, must continually share our research findings and diligently replicate established methods and protocols. These tasks can often feel akin to the labor of Sisyphus. Moreover, within the scientific community, integrity is paramount; dishonesty is swiftly met with consequences akin to the justice administered by Zeus. Therefore, we researchers must roll a boulder up a hill again and again, and after we have proved that the published scientific work is sound, the “boulder” and the scientist will stay on top of the hill. Keywords: burden of Sisyphus, define research strategy, funding opportunities, Post Traumatic Stress Disorder (PTSD) in Ukraine, RECOOP HST Association, research capacity building and networks, sciences and arts","PeriodicalId":23007,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"15 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140658205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Atrial fibrillation (AF) is the most common abnormal type of heart rhythm (cardiac arrhythmia), which is considered the leading cause of stroke. There have been limited studies on the prognostic markers for atrial disease and AF-associated ischemic stroke, despite the high demand for this procedure in daily clinical practice to monitor disease course and assess risk of stroke in patients with AF and chronic heart failure (CHF). Thus, the aim of the present study was to evaluate the levels of serum biomarkers related to ischemic stroke in CHF patients with the different forms of AF. Forty-six patients with various types of AF (paroxysmal, persistent and permanent) with or without ischemic stroke were enrolled in the study, 36 clinically healthy donors served as a control. The levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and angiostatins (AS) were evaluated by western blot analysis in the serum. The levels of active matrix metalloproteinases (MMPs) were analysed by gelatin zymography. Elevated levels of iNOS were shown in patients with all AF forms as compared with control, but iNOS levels in post-ischemic patients were significantly higher than that in paroxysmal AF individuals. However, the levels of VEGF and AS did not differ from the baseline value in patients with paroxysmal AF, while dramatic increase of their contents was shown in post-stroke patients with persistent and permanent types of AF. Elevated active MMP-9 levels were shown to be associated with the diagnosis of all AF forms, regardless of the occurrence of stroke. Taken together, our findings demonstrate that tested proteins can be considered as valuable biomarkers of AF forms transformation and potentially useful for ischemic stroke risk stratification in patients with AF and CHF. Observed changes in regulatory protein levels may expand our understanding of pathological roles of endothelial function dysregulation, disrupted angiogenesis balance and abnormal tissue remodeling in AF and associated ischemic events. Keywords: angiostatins, atrial fibrillation, biomarkers, iNOS, ischemic stroke, MMP-9, VEGF
心房颤动（房颤）是最常见的心律异常类型（心律失常），被认为是导致中风的主要原因。尽管在日常临床实践中监测心房颤动和慢性心力衰竭（CHF）患者的病程和评估中风风险对这一程序的需求很高，但有关心房疾病和心房颤动相关缺血性中风的预后标志物的研究却很有限。因此，本研究旨在评估患有不同形式房颤的慢性心力衰竭患者与缺血性中风相关的血清生物标志物水平。研究共纳入 46 名伴有或不伴有缺血性中风的不同类型房颤（阵发性、持续性和永久性）患者，36 名临床健康供体作为对照。血清中诱导型一氧化氮合酶（iNOS）、血管内皮生长因子（VEGF）和血管紧张素（AS）的水平通过 Western 印迹分析进行了评估。明胶酶谱分析了活性基质金属蛋白酶（MMPs）的水平。与对照组相比，各种房颤患者的 iNOS 水平均升高，但缺血后患者的 iNOS 水平明显高于阵发性房颤患者。然而，在阵发性房颤患者中，血管内皮生长因子和 AS 的水平与基线值没有差异，而在脑卒中后的持续性和永久性房颤患者中，其含量则急剧增加。无论是否发生中风，活性 MMP-9 水平的升高都与所有房颤形式的诊断有关。综上所述，我们的研究结果表明，测试的蛋白质可被视为房颤形式转变的重要生物标志物，并有可能用于房颤和慢性心力衰竭患者缺血性中风风险分层。所观察到的调节蛋白水平的变化可能会拓展我们对内皮功能失调、血管生成平衡紊乱和组织重塑异常在心房颤动及相关缺血性事件中的病理作用的认识。关键词：血管紧张素；心房颤动；生物标志物；iNOS；缺血性中风；MMP-9；血管内皮生长因子
{"title":"Circulating levels of potential markers of ischemic stroke in patients with the different forms of atrial fibrillation and chronic heart failure","authors":"A. O. Tykhomyrov, O. Yu. Sirenko, O. Kuryata","doi":"10.15407/ubj96.02.062","DOIUrl":"https://doi.org/10.15407/ubj96.02.062","url":null,"abstract":"Atrial fibrillation (AF) is the most common abnormal type of heart rhythm (cardiac arrhythmia), which is considered the leading cause of stroke. There have been limited studies on the prognostic markers for atrial disease and AF-associated ischemic stroke, despite the high demand for this procedure in daily clinical practice to monitor disease course and assess risk of stroke in patients with AF and chronic heart failure (CHF). Thus, the aim of the present study was to evaluate the levels of serum biomarkers related to ischemic stroke in CHF patients with the different forms of AF. Forty-six patients with various types of AF (paroxysmal, persistent and permanent) with or without ischemic stroke were enrolled in the study, 36 clinically healthy donors served as a control. The levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and angiostatins (AS) were evaluated by western blot analysis in the serum. The levels of active matrix metalloproteinases (MMPs) were analysed by gelatin zymography. Elevated levels of iNOS were shown in patients with all AF forms as compared with control, but iNOS levels in post-ischemic patients were significantly higher than that in paroxysmal AF individuals. However, the levels of VEGF and AS did not differ from the baseline value in patients with paroxysmal AF, while dramatic increase of their contents was shown in post-stroke patients with persistent and permanent types of AF. Elevated active MMP-9 levels were shown to be associated with the diagnosis of all AF forms, regardless of the occurrence of stroke. Taken together, our findings demonstrate that tested proteins can be considered as valuable biomarkers of AF forms transformation and potentially useful for ischemic stroke risk stratification in patients with AF and CHF. Observed changes in regulatory protein levels may expand our understanding of pathological roles of endothelial function dysregulation, disrupted angiogenesis balance and abnormal tissue remodeling in AF and associated ischemic events. Keywords: angiostatins, atrial fibrillation, biomarkers, iNOS, ischemic stroke, MMP-9, VEGF","PeriodicalId":23007,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"2 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140654313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nonalcoholic fatty liver disease (NAFLD), which can progress to nonalcoholic steatohepatitis (NASH), is a significant health concern affecting a substantial portion of the population. This study investigates the role of neutrophil extracellular traps (NETs) in liver inflammation induced by high-fat high-cholesterol diet (HFHCD) and high-fructose diet (HFD). The chronic nature of NAFLD involves low-grade inflammation with cytokine elevation. The research aims to visualize neutrophil elastase (NE) activity during HFHCD and HFD representing conditions of low-grade activation and assess neutrophil functional status. The study employs a mouse model subjecting animals to HFHCD, HFD or a standard diet (SD) for six weeks. Various analyses were used including histological evaluations, in vivo imaging of NE activity using a fluorescent probe, fluorescent microscopy, flow cytometry and assessment of neutrophil function through reactive oxygen species (ROS) levels. Mice on HFHCD and HFD display liver damage consistent with NASH, which was validated pathohistologically. NE activity in blood significantly increases after six weeks indicating systemic NETs involvement. In vivo imaging confirms NE activity in multiple organs. Cellular localization reveals NETs persistence even after neutrophil destruction in splenocytes indicating systemic involvement. Neutrophils under HFHCD exhibit a functional phenotype associated with low-grade inflammation, higher basal ROS levels and reduced activation potential. This study establishes the systemic impact of NETs in HFHCD- and HFD-induced liver inflammation, providing insights into the functional state of neutrophils. The findings contribute to understanding the mechanisms underlying chronic liver conditions and may inform future therapeutic strategies. Keywords: high fat diet, in vivo imaging, low-grade inflammation, NASH, neutrophil elastase, neutrophil extracellular traps, neutrophils
非酒精性脂肪肝（NAFLD）可发展为非酒精性脂肪性肝炎（NASH），是影响相当一部分人健康的重大问题。本研究调查了中性粒细胞胞外捕获物（NET）在高脂高胆固醇饮食（HFHCD）和高果糖饮食（HFD）诱导的肝脏炎症中的作用。非酒精性脂肪肝的慢性性质包括细胞因子升高的低度炎症。该研究旨在观察高脂高胆固醇饮食（HFHCD）和高果糖饮食（HFD）期间代表低度激活状态的中性粒细胞弹性蛋白酶（NE）活性，并评估中性粒细胞的功能状态。研究采用了一种小鼠模型，对动物进行为期六周的高频高密度脂蛋白胆固醇饮食（HFHCD）、高频高密度脂蛋白胆固醇饮食（HFD）或标准饮食（SD）。研究采用了多种分析方法，包括组织学评估、使用荧光探针对中性粒细胞活性进行体内成像、荧光显微镜、流式细胞术以及通过活性氧（ROS）水平评估中性粒细胞功能。服用高密度脂蛋白胆固醇和高密度脂蛋白胆固醇饮食的小鼠显示出与 NASH 一致的肝损伤，病理组织学对此进行了验证。血液中的 NE 活性在六周后明显增加，表明有全身性 NETs 参与。体内成像证实了 NE 在多个器官中的活性。细胞定位显示，即使脾细胞中的中性粒细胞被破坏，NETs 仍会持续存在，这表明NETs 涉及全身。高频高密度脂蛋白血症患者的中性粒细胞表现出与低度炎症、较高的基础 ROS 水平和较低的活化潜能相关的功能表型。这项研究确定了NET在HFHCD和HFD诱导的肝脏炎症中的系统性影响，为深入了解中性粒细胞的功能状态提供了依据。这些发现有助于了解慢性肝病的发病机制，并为未来的治疗策略提供参考。关键词：高脂饮食；体内成像；低度炎症；NASH；中性粒细胞弹性蛋白酶；中性粒细胞胞外捕获器；中性粒细胞
{"title":"Neutrophil activation at high-fat high-cholesterol and high-fructose diets induces low-grade inflammation in mice","authors":"G. Bila, O. Vishchur, V. Vovk, S. Vari, R. Bilyy","doi":"10.15407/ubj96.02.027","DOIUrl":"https://doi.org/10.15407/ubj96.02.027","url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD), which can progress to nonalcoholic steatohepatitis (NASH), is a significant health concern affecting a substantial portion of the population. This study investigates the role of neutrophil extracellular traps (NETs) in liver inflammation induced by high-fat high-cholesterol diet (HFHCD) and high-fructose diet (HFD). The chronic nature of NAFLD involves low-grade inflammation with cytokine elevation. The research aims to visualize neutrophil elastase (NE) activity during HFHCD and HFD representing conditions of low-grade activation and assess neutrophil functional status. The study employs a mouse model subjecting animals to HFHCD, HFD or a standard diet (SD) for six weeks. Various analyses were used including histological evaluations, in vivo imaging of NE activity using a fluorescent probe, fluorescent microscopy, flow cytometry and assessment of neutrophil function through reactive oxygen species (ROS) levels. Mice on HFHCD and HFD display liver damage consistent with NASH, which was validated pathohistologically. NE activity in blood significantly increases after six weeks indicating systemic NETs involvement. In vivo imaging confirms NE activity in multiple organs. Cellular localization reveals NETs persistence even after neutrophil destruction in splenocytes indicating systemic involvement. Neutrophils under HFHCD exhibit a functional phenotype associated with low-grade inflammation, higher basal ROS levels and reduced activation potential. This study establishes the systemic impact of NETs in HFHCD- and HFD-induced liver inflammation, providing insights into the functional state of neutrophils. The findings contribute to understanding the mechanisms underlying chronic liver conditions and may inform future therapeutic strategies. Keywords: high fat diet, in vivo imaging, low-grade inflammation, NASH, neutrophil elastase, neutrophil extracellular traps, neutrophils","PeriodicalId":23007,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"68 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140655815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Kramar, I. Andriichuk, N. Ohinska, Yu. V. Soroka, Z. Nebesna, S. Dybkova, L. Rieznichenko, N. Lisnychuk
One of the properties of nanoparticles is their ability to correct manifestations of oxidative stress and endotoxemia, which are critical factors in cancer development. Therefore, the work aimed to investigate the effect of the usage of Au/Ag/Fe nanoparticles on oxidative stress indicators and endotoxemia parameters in experimental colon carcinogenesis. The study was performed on 90 white male rats kept in standard vivarium conditions. The division into groups: I – intact animals; II – intact animals with 21 days NPs administration; III – animals injected with N,N-dimethylhydrazine dihydrochloride for 30 weeks; ІV – animals to which Au/Ag/Fe nanoparticles were intragastrically administered daily for 21 days after induced adenocarcinoma. According to our results, the concentration of oxidative stress indicators significantly increases under DMH-induced carcinogenesis conditions. It was established that the 21-day intragastric administration of NP Au/Ag/Fe composition caused a significant (P < 0.001) decrease in the concentration of TBARS in the blood serum by 1.33 times, in the content of diene and triene conjugates by 1.63 and 1.98 times, respectively compared to the third experimental group. The introduction of NPs in the fourth experimental group reduces the concentration of the Schiff bases by 1.34 times (P < 0.001), decreases the content of POMP370 and POMP430 by 1.25 (P < 0.001) and 1.37 times (P < 0.001), respectively, compared to the third experimental group. We also observed the reduction of endotoxemia levels in a fourth experimental animal group based on a significant decrease in MMM indexis and EII percentage. Keywords: Au/Ag/Fe nanoparticles, endotoxemia, induced colon carcinogenesis, N‚N-dimethylhydrazine dihydrochloride, oxidative stress
{"title":"Effect of metal nanoparticles usage on oxidative stress indicators and endotoxemia parameters under DMH-induced carcinogenesis","authors":"S. Kramar, I. Andriichuk, N. Ohinska, Yu. V. Soroka, Z. Nebesna, S. Dybkova, L. Rieznichenko, N. Lisnychuk","doi":"10.15407/ubj96.02.075","DOIUrl":"https://doi.org/10.15407/ubj96.02.075","url":null,"abstract":"One of the properties of nanoparticles is their ability to correct manifestations of oxidative stress and endotoxemia, which are critical factors in cancer development. Therefore, the work aimed to investigate the effect of the usage of Au/Ag/Fe nanoparticles on oxidative stress indicators and endotoxemia parameters in experimental colon carcinogenesis. The study was performed on 90 white male rats kept in standard vivarium conditions. The division into groups: I – intact animals; II – intact animals with 21 days NPs administration; III – animals injected with N,N-dimethylhydrazine dihydrochloride for 30 weeks; ІV – animals to which Au/Ag/Fe nanoparticles were intragastrically administered daily for 21 days after induced adenocarcinoma. According to our results, the concentration of oxidative stress indicators significantly increases under DMH-induced carcinogenesis conditions. It was established that the 21-day intragastric administration of NP Au/Ag/Fe composition caused a significant (P < 0.001) decrease in the concentration of TBARS in the blood serum by 1.33 times, in the content of diene and triene conjugates by 1.63 and 1.98 times, respectively compared to the third experimental group. The introduction of NPs in the fourth experimental group reduces the concentration of the Schiff bases by 1.34 times (P < 0.001), decreases the content of POMP370 and POMP430 by 1.25 (P < 0.001) and 1.37 times (P < 0.001), respectively, compared to the third experimental group. We also observed the reduction of endotoxemia levels in a fourth experimental animal group based on a significant decrease in MMM indexis and EII percentage. Keywords: Au/Ag/Fe nanoparticles, endotoxemia, induced colon carcinogenesis, N‚N-dimethylhydrazine dihydrochloride, oxidative stress","PeriodicalId":23007,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"11 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140653789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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