Diabetes mellitus (DM) is a global metabolic disease with prevalence rates which have reached pandemic levels. This disease is strongly associated with vascular complications, even when the hyperglycemia is kept under control. The main complications of DM are stroke, myocardial infarction, and peripheral artery disease, and they often increase the risk of developing atherosclerosis, inflammatory angiopathy, and thrombosis. Angiopathy is commonly initiated by microvascular inflammation characterized by neutrophil extracellular traps (NETs) and metabolic abnormalities, and is controlled by (epi)-genetic events and immune / antigen-presenting cells. NETs play an important role in blood coagulation, activation of the innate and adaptive immune system, as well as vascular integrity and endothelial dysfunction. The aim of the review is to summarize the current knowledge about the role of NETs in the pathogenesis of vascular complications in DM.
{"title":"Challenging role of neutrophil extracellular traps in vascular complications of diabetes mellitus","authors":"A. Berezin","doi":"10.15761/IMM.1000330","DOIUrl":"https://doi.org/10.15761/IMM.1000330","url":null,"abstract":"Diabetes mellitus (DM) is a global metabolic disease with prevalence rates which have reached pandemic levels. This disease is strongly associated with vascular complications, even when the hyperglycemia is kept under control. The main complications of DM are stroke, myocardial infarction, and peripheral artery disease, and they often increase the risk of developing atherosclerosis, inflammatory angiopathy, and thrombosis. Angiopathy is commonly initiated by microvascular inflammation characterized by neutrophil extracellular traps (NETs) and metabolic abnormalities, and is controlled by (epi)-genetic events and immune / antigen-presenting cells. NETs play an important role in blood coagulation, activation of the innate and adaptive immune system, as well as vascular integrity and endothelial dysfunction. The aim of the review is to summarize the current knowledge about the role of NETs in the pathogenesis of vascular complications in DM.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75946136","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}
Mitochondria is an important cellular organelle. This organelle plays important role regarding intracellular energy. Of interest, this organelle has its specific set of genetic components. At present, several medical disorders, such as Parkinson disease, are proven for their rooted causes as mitochondrial disorders [1]. In mitochondrial disease, mutations in genes in the mitochondrial DNA (mtDNA) that encode structural mitochondrial proteins or proteins involved in mitochondrial function is observed and this is the basic rooted pathogenesis of the clinical problem [1].
{"title":"Mitochrondrial therapy: A new concept for therapeutic management for tropical diseases","authors":"V. Wiwanitkit","doi":"10.15761/imm.1000348","DOIUrl":"https://doi.org/10.15761/imm.1000348","url":null,"abstract":"Mitochondria is an important cellular organelle. This organelle plays important role regarding intracellular energy. Of interest, this organelle has its specific set of genetic components. At present, several medical disorders, such as Parkinson disease, are proven for their rooted causes as mitochondrial disorders [1]. In mitochondrial disease, mutations in genes in the mitochondrial DNA (mtDNA) that encode structural mitochondrial proteins or proteins involved in mitochondrial function is observed and this is the basic rooted pathogenesis of the clinical problem [1].","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75823209","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}
J. Greilberger, R. Wintersteiger, Ortner Astrid, M. Greilberger, R. Herwig
{"title":"Combination of 2-oxoglutarate/ascorbic acid/5-hydroxy-methyl-furfur-aldehyde/carnosine inhibits protein oxidation during radical exposure of cigarette smoke","authors":"J. Greilberger, R. Wintersteiger, Ortner Astrid, M. Greilberger, R. Herwig","doi":"10.15761/IMM.1000326","DOIUrl":"https://doi.org/10.15761/IMM.1000326","url":null,"abstract":"","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76228026","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}
Isabella Sabino Maceno, Samara Christina dos Santos, L. Tempest, I. Filho, C. Buchala
{"title":"Orthodontic traction technique: Clinical case report based on literature","authors":"Isabella Sabino Maceno, Samara Christina dos Santos, L. Tempest, I. Filho, C. Buchala","doi":"10.15761/IMM.1000323","DOIUrl":"https://doi.org/10.15761/IMM.1000323","url":null,"abstract":"","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89427128","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}
{"title":"Hadron spectroscopy, baryon spectroscopy and meson spectroscopy comparative study on malignant and benign human cancer cells and tissues under synchrotron radiation","authors":"A. Heidari","doi":"10.15761/imm.1000344","DOIUrl":"https://doi.org/10.15761/imm.1000344","url":null,"abstract":"","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90408531","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}
Heart failure (HF) is the final common pathway of many cardiovascular diseases (CVD). It imposes significant socio-economic and healthcare burden to both patients and healthcare systems. Although the most common cause of HF is ischemic heart diseases, other less common causes such as hyperthyroidism (thyrotoxicosis) should also be considered during diagnosis to improve overall clinical management of HF. Hyperthyroidism is a potentially reversible and curable cause of thyrotoxic HF (THF), which should be excluded in every new patient with HF especially in the absence of coronary artery disease and other structural heart diseases. However, the etiology of thyrotoxic HF remains partially understood – is it the consequence of hemodynamic insult, direct toxic effect or both? Its epidemiology is also difficult to assess because hypertensive, ischemic and other structural heart diseases have not been thoroughly excluded. The present review seeks to aggregate current published evidence on THF to provide a comprehensive understanding of its definition, prognosis, pathogenesis, manifestation, diagnosis and clinical management.
{"title":"Thyrotoxic heart failure: A review of clinical status and meta-analysis of electrocardiogram diagnosis and medical clinical management methods","authors":"Aref Albakri","doi":"10.15761/IMM.1000350","DOIUrl":"https://doi.org/10.15761/IMM.1000350","url":null,"abstract":"Heart failure (HF) is the final common pathway of many cardiovascular diseases (CVD). It imposes significant socio-economic and healthcare burden to both patients and healthcare systems. Although the most common cause of HF is ischemic heart diseases, other less common causes such as hyperthyroidism (thyrotoxicosis) should also be considered during diagnosis to improve overall clinical management of HF. Hyperthyroidism is a potentially reversible and curable cause of thyrotoxic HF (THF), which should be excluded in every new patient with HF especially in the absence of coronary artery disease and other structural heart diseases. However, the etiology of thyrotoxic HF remains partially understood – is it the consequence of hemodynamic insult, direct toxic effect or both? Its epidemiology is also difficult to assess because hypertensive, ischemic and other structural heart diseases have not been thoroughly excluded. The present review seeks to aggregate current published evidence on THF to provide a comprehensive understanding of its definition, prognosis, pathogenesis, manifestation, diagnosis and clinical management.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73248992","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}
Yuzo Nakagawa-Yag, H. Hara, Chisato Kanai, Masashi Sato, A. Hara
Medical treatment using high-voltage electric potential (HELP) devices to generate an electric field (EF) is an alternative therapy commonly used in Japan. However, the mechanisms underlying potential health benefits of this therapy are still unclear. Therefore, we investigated the effect of HELP exposure (9 kV/electrode+9 kV/ electrode, 30 min) on several cytokines and hormones using enzyme-linked immunosorbent assays in plasma samples obtained from healthy human subjects before and after a single treatment session. Immunoreactive interleukin (IL)-1β and IL-6 levels were significantly downregulated following HELP exposure. Under these treatment conditions, HELP exposure did not exert on immunoreactive IL-10, IL-18, transforming growth factor-beta 1 (TGF-β1), tumor necrosis factor-alpha (TNF-α) adrenaline, serotonin, histamine, neuropeptide Y, somatostatin, insulin, or dehydroepiandrosterone sulfate (DHEAS) levels. The activation of transient receptor potential melastatin 8 (TRPM8) induces the suppression of the levels of inflammatory markers. Therefore, we further examined the in silico docking simulation of lysoPC-22:4, lysoPE-20:4, and lysoPE-22:6 with TRPM8 using a homology model. The binding energies were -10.8, -10.4, and -11.4 kcal/mol for lysoPC-22:4, lysoPE-20:4, and lysoPE-22:6, respectively. Our findings provide new insights into the molecular mechanisms underlying pain control and sleep quality alleviation following EF therapy. Abbreviations: CRP: C-reactive protein; DHEAS: dehydroepiandrosterone sulfate; EF: electric field; HELP: high-voltage electric potential; HODE: hydroxyoctadecadienoic acid; IL: interleukin; lysoPC: lysophosphatidylcholine; lysoPC-22:4: (2-{[(2R)-3-[(7Z,10Z,13Z,16Z)docosa-7,10,13,16-tetraenoyloxy]-2-hydropropyl phosphonato]oxy} ethyl)trimethylazanium; lysoPE: lysophosphatidylethanolamine; lysoPE-22:6: (2-aminoethoxy)[(2R)-2-[(4Z, 7Z, 10Z, 13Z, 16Z, 19Z)docosa-4,7,10,13,16-hexaenoyloxy]-3-hydroxypropoxy]phosphinic acid; lysoPE-20:4: (2-aminoethoxy) [(2R)-2-hydroxy-3-[(5Z, 8Z, 11Z, 14Z)-icosa-5,8,11,14-tetraenoyloxy] propoxy] phosphinic acid; OEA: Oleoylethanolamide; TGF-β: transforming growth factor beta; TNF-α: tumor necrosis factor alpha; TRPM8: transient receptor potential melastatin 8; TRPV1: transient receptor potential vanilloid 1.
{"title":"Acute electric field downregulates human plasma immunoreactive interleukin-6 and -1β levels: Molecular mechanisms underlying inflammation alleviation through electric field therapy","authors":"Yuzo Nakagawa-Yag, H. Hara, Chisato Kanai, Masashi Sato, A. Hara","doi":"10.15761/IMM.1000333","DOIUrl":"https://doi.org/10.15761/IMM.1000333","url":null,"abstract":"Medical treatment using high-voltage electric potential (HELP) devices to generate an electric field (EF) is an alternative therapy commonly used in Japan. However, the mechanisms underlying potential health benefits of this therapy are still unclear. Therefore, we investigated the effect of HELP exposure (9 kV/electrode+9 kV/ electrode, 30 min) on several cytokines and hormones using enzyme-linked immunosorbent assays in plasma samples obtained from healthy human subjects before and after a single treatment session. Immunoreactive interleukin (IL)-1β and IL-6 levels were significantly downregulated following HELP exposure. Under these treatment conditions, HELP exposure did not exert on immunoreactive IL-10, IL-18, transforming growth factor-beta 1 (TGF-β1), tumor necrosis factor-alpha (TNF-α) adrenaline, serotonin, histamine, neuropeptide Y, somatostatin, insulin, or dehydroepiandrosterone sulfate (DHEAS) levels. The activation of transient receptor potential melastatin 8 (TRPM8) induces the suppression of the levels of inflammatory markers. Therefore, we further examined the in silico docking simulation of lysoPC-22:4, lysoPE-20:4, and lysoPE-22:6 with TRPM8 using a homology model. The binding energies were -10.8, -10.4, and -11.4 kcal/mol for lysoPC-22:4, lysoPE-20:4, and lysoPE-22:6, respectively. Our findings provide new insights into the molecular mechanisms underlying pain control and sleep quality alleviation following EF therapy. Abbreviations: CRP: C-reactive protein; DHEAS: dehydroepiandrosterone sulfate; EF: electric field; HELP: high-voltage electric potential; HODE: hydroxyoctadecadienoic acid; IL: interleukin; lysoPC: lysophosphatidylcholine; lysoPC-22:4: (2-{[(2R)-3-[(7Z,10Z,13Z,16Z)docosa-7,10,13,16-tetraenoyloxy]-2-hydropropyl phosphonato]oxy} ethyl)trimethylazanium; lysoPE: lysophosphatidylethanolamine; lysoPE-22:6: (2-aminoethoxy)[(2R)-2-[(4Z, 7Z, 10Z, 13Z, 16Z, 19Z)docosa-4,7,10,13,16-hexaenoyloxy]-3-hydroxypropoxy]phosphinic acid; lysoPE-20:4: (2-aminoethoxy) [(2R)-2-hydroxy-3-[(5Z, 8Z, 11Z, 14Z)-icosa-5,8,11,14-tetraenoyloxy] propoxy] phosphinic acid; OEA: Oleoylethanolamide; TGF-β: transforming growth factor beta; TNF-α: tumor necrosis factor alpha; TRPM8: transient receptor potential melastatin 8; TRPV1: transient receptor potential vanilloid 1.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"104 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79217940","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}
Jinyao Liu, Ayako Himemiya-Hakucho, Xu Liu, K. Yoshimura, T. Fujimiya
The effects of stress on the atherosclerosis are complex. Here we discuss how the chronic complex stress (CCS), when combined with an atherogenic diet (AD), leads to the development of atherosclerosis in mice. The CCS mouse model consisted of physical and psychosocial stressors of different types and intensities presented in a random order. Eighty-seven mice were divided into a standard chow diet (n=44) and AD (n=43) groups and bred for 4 months. Both groups were subdivided into groups without and with CCS treatment. The CCS was performed during the last month of the study. Ultrasound bio microscopy, histopathological and fluorescence immunohistochemical examinations, ELISA, PCR, and flow cytometry were used. We showed that CCS, when combined with atherogenic diet, resulted in accelerated process of the atherosclerosis, as measured by the maximum intima media thickness and hypoechoic plaque formation in the ultrasound bio microscopy, mean aortic well area in the hematoxylin and eosin staining, max Oil-Red-O content in the Oil Red O staining, and the aortic triglyceride level. These changes were accompanied by endothelial dysfunction and excessive inflammation based on down-regulation of aortic Nos3 mRNA expression, up-regulation of aortic syndecan-1 (Sdc1) and thrombomodulin (Thbd) mRNA expressions, and an increased percentage of CD45-positive cells in the aorta. Stressed mice had upregulation of aortic tumor necrosis factor-alpha (Tnf-α) gene expression, co-up-regulation of aortic nuclear receptor subfamily 3, group C, member 1 (Nr3c1) and Nfkb1 mRNA expressions, and hyperactivity of adrenal gland function based on increased phenyl ethanolamine-N-methyltransferase (PNMT) and NR3C1-positive cells, up-regulation of Nr3c1 and Pnmt mRNA expressions in the adrenal gland. These observations may demonstrate that CCS, via hyperactivity of the adrenal gland and aortic proinflammatory cytokine (Tnf-α)-related co-up-regulation of aortic Nr3c1 and Nfkb1 gene expressions, accelerated the atherosclerosis development in mice, especially when combined with atherogenic diet.
应激对动脉粥样硬化的影响是复杂的。在这里，我们讨论了慢性复杂应激(CCS)与致动脉粥样硬化饮食(AD)联合如何导致小鼠动脉粥样硬化的发展。CCS小鼠模型由不同类型和强度的生理和心理应激源按随机顺序呈现。将87只小鼠分为标准饲料组(n=44)和AD组(n=43)，饲养4个月。两组再分为未接受CCS治疗组和接受CCS治疗组。CCS在研究的最后一个月进行。采用超声生物显微镜、组织病理学和荧光免疫组织化学检查、ELISA、PCR和流式细胞术。我们发现，当CCS与致动脉粥样硬化饮食结合时，通过超声生物显微镜测量内膜中膜最大厚度和低回声斑块形成，苏木精和伊红染色的平均主动脉孔面积，Oil-Red-O染色的最大Oil-Red-O含量和主动脉甘油三酯水平来测量动脉粥样硬化过程。主动脉Nos3 mRNA表达下调，主动脉syndecan-1 (Sdc1)和血栓调节素(Thbd) mRNA表达上调，主动脉中cd45阳性细胞比例增加，这些变化伴随着内皮功能障碍和过度炎症。应激小鼠主动脉肿瘤坏死因子-α (Tnf-α)基因表达上调，主动脉核受体亚家族3、C组、成员1 (Nr3c1)和Nfkb1 mRNA表达上调，肾上腺功能亢进(基于苯乙醇胺- n -甲基转移酶(PNMT)和Nr3c1阳性细胞增加，肾上腺Nr3c1和PNMT mRNA表达上调)。这些观察结果可能表明，CCS通过肾上腺亢进和主动脉促炎细胞因子(Tnf-α)相关的主动脉Nr3c1和Nfkb1基因表达的共同上调，加速了小鼠动脉粥样硬化的发展，特别是与致动脉粥样硬化饮食结合使用时。
{"title":"The chronic complex stress combined atherogenic diet accelerates the process of atherosclerosis in mice","authors":"Jinyao Liu, Ayako Himemiya-Hakucho, Xu Liu, K. Yoshimura, T. Fujimiya","doi":"10.15761/imm.1000338","DOIUrl":"https://doi.org/10.15761/imm.1000338","url":null,"abstract":"The effects of stress on the atherosclerosis are complex. Here we discuss how the chronic complex stress (CCS), when combined with an atherogenic diet (AD), leads to the development of atherosclerosis in mice. The CCS mouse model consisted of physical and psychosocial stressors of different types and intensities presented in a random order. Eighty-seven mice were divided into a standard chow diet (n=44) and AD (n=43) groups and bred for 4 months. Both groups were subdivided into groups without and with CCS treatment. The CCS was performed during the last month of the study. Ultrasound bio microscopy, histopathological and fluorescence immunohistochemical examinations, ELISA, PCR, and flow cytometry were used. We showed that CCS, when combined with atherogenic diet, resulted in accelerated process of the atherosclerosis, as measured by the maximum intima media thickness and hypoechoic plaque formation in the ultrasound bio microscopy, mean aortic well area in the hematoxylin and eosin staining, max Oil-Red-O content in the Oil Red O staining, and the aortic triglyceride level. These changes were accompanied by endothelial dysfunction and excessive inflammation based on down-regulation of aortic Nos3 mRNA expression, up-regulation of aortic syndecan-1 (Sdc1) and thrombomodulin (Thbd) mRNA expressions, and an increased percentage of CD45-positive cells in the aorta. Stressed mice had upregulation of aortic tumor necrosis factor-alpha (Tnf-α) gene expression, co-up-regulation of aortic nuclear receptor subfamily 3, group C, member 1 (Nr3c1) and Nfkb1 mRNA expressions, and hyperactivity of adrenal gland function based on increased phenyl ethanolamine-N-methyltransferase (PNMT) and NR3C1-positive cells, up-regulation of Nr3c1 and Pnmt mRNA expressions in the adrenal gland. These observations may demonstrate that CCS, via hyperactivity of the adrenal gland and aortic proinflammatory cytokine (Tnf-α)-related co-up-regulation of aortic Nr3c1 and Nfkb1 gene expressions, accelerated the atherosclerosis development in mice, especially when combined with atherogenic diet.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79430511","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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