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1
Schechter, Alan N. "Hemoglobin research and the origins of molecular medicine." Blood 112, no. 10 (November 15, 2008): 3927–38. http://dx.doi.org/10.1182/blood-2008-04-078188.
Анотація:
Abstract Much of our understanding of human physiology, and of many aspects of pathology, has its antecedents in laboratory and clinical studies of hemoglobin. Over the last century, knowledge of the genetics, functions, and diseases of the hemoglobin proteins has been refined to the molecular level by analyses of their crystallographic structures and by cloning and sequencing of their genes and surrounding DNA. In the last few decades, research has opened up new paradigms for hemoglobin related to processes such as its role in the transport of nitric oxide and the complex developmental control of the α-like and β-like globin gene clusters. It is noteworthy that this recent work has had implications for understanding and treating the prevalent diseases of hemoglobin, especially the use of hydroxyurea to elevate fetal hemoglobin in sickle cell disease. It is likely that current research will also have significant clinical implications, as well as lessons for other aspects of molecular medicine, the origin of which can be largely traced to this research tradition.
2
Quinlivan, Mark, and Judith Breuer. "Molecular and therapeutic aspects of varicella–zoster virus infection." Expert Reviews in Molecular Medicine 7, no. 15 (August 10, 2005): 1–24. http://dx.doi.org/10.1017/s146239940500966x.
Анотація:
Varicella–zoster virus (VZV) is a highly species-specific member of the Herpesviridae family. The virus exhibits multiple cell tropisms, infecting peripheral blood mononuclear cells and skin cells before establishing latency in sensory neurons. Such tropisms are essential both for primary infection, which manifests itself as chickenpox (varicella), and subsequent reactivation to cause herpes zoster (shingles). The highly cell-associated nature of the virus, coupled with its narrow host range, has resulted in the lack of an animal model that mimics its diseases in humans, thereby greatly hindering the study of events in VZV pathogenesis. Despite this, extensive studies both in vitro and in vivo in small-animal models have provided a fascinating insight into molecular events that govern VZV diseases. In addition, VZV has become the first human herpes virus for which a live attenuated vaccine has been developed.
3
Shperling, M. M., N. P. Tolokonskaya, N. V. Fomenko, and Ye V. Romanova. "The clinical aspects of Lyme borreliosis." Bulletin of Siberian Medicine 7 (December 30, 2008): 106–10. http://dx.doi.org/10.20538/1682-0363-2008-0-106-110.
Анотація:
The diagnosis of Lyme borreliosis is objective difficult. There are tendention of increasing of patients the age of 51 and older. The characteristics of disease, for example fever at acute time is connected to reactivity in acute diseases in general. On time antibodies detection of patients blood with suspicion of the cronical borreliosis is not criteria of proven disease.
4
Chen, Qijun, Martha Schlichtherle, and Mats Wahlgren. "Molecular Aspects of Severe Malaria." Clinical Microbiology Reviews 13, no. 3 (July 1, 2000): 439–50. http://dx.doi.org/10.1128/cmr.13.3.439.
Анотація:
SUMMARY Human infections with Plasmodium falciparum may result in severe forms of malaria. The widespread and rapid development of drug resistance in P. falciparum and the resistance of the disease-transmitting mosquitoes to insecticides make it urgent to understand the molecular background of the pathogenesis of malaria to enable the development of novel approaches to combat the disease. This review focuses on the molecular mechanisms of severe malaria caused by the P. falciparum parasite. The nature of severe malaria and the deleterious effects of parasite-derived toxins and host-induced cytokines are introduced. Sequestration, brought about by cytoadherence and rosetting, is linked to severe malaria and is mediated by multiple receptors on the endothelium and red blood cells. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is the ligand responsible for a majority of binding interactions, and the multiply adhesive features of this sticky molecule are presented. Antigenic variation is also a major feature of PfEMP1 and of the surface of the P. falciparum-infected erythrocyte. Possible mechanisms of P. falciparum antigenic variation in asexual stages are further discussed. We conclude this review with a perspective and suggestions of important aspects for future investigations.
5
Villar, M., J. M. Marimon, J. M. Garcia-Arenzana, A. G. de la Campa, M. J. Ferrandiz, and E. Perez-Trallero. "Epidemiological and molecular aspects of rifampicin-resistant Staphylococcus aureus isolated from wounds, blood and respiratory samples." Journal of Antimicrobial Chemotherapy 66, no. 5 (March 2, 2011): 997–1000. http://dx.doi.org/10.1093/jac/dkr059.
6
Vogler, Ingridt Hildegard, Anna Nishiya, Helena Kaminami Morimoto, Edna Maria Vissoci Reiche, André Luiz Bortoliero, Tiemi Matsuo, Ester Cerdeira Sabino, and Adelaide Jose Vaz. "Serological, epidemiological and molecular aspects of hepatitis C virus infection in a population from Londrina, PR, Brazil, 2001-2002." Revista do Instituto de Medicina Tropical de São Paulo 46, no. 6 (December 4, 2004): 303–8. http://dx.doi.org/10.1590/s0036-46652004000600002.
Анотація:
Serological, epidemiological and molecular aspects of hepatitis C virus (HCV) infection were evaluated in 183 subjects from Londrina, Paraná, Brazil, and adjacent areas. Serum samples which tested anti-HCV positive by microparticle enzyme immunoassay (MEIA) obtained from eight patients with chronic hepatitis C, 48 blood donors, and 127 patients infected with the human immunodeficiency virus (HIV) were submitted to another enzyme immunoassay (ELISA) and to the polymerase chain reaction (PCR). About 78.7% of samples were also reactive by ELISA, with the greater proportion (70.8%) of discordant results verified among blood donors. A similar finding was observed for HCV-RNA detection by PCR, with 111/165 (67.3%) positive samples, with higher rates among HIV-positive subjects and patients with chronic hepatitis than among blood donors. Sixty-one PCR-positive samples were submitted to HCV genotyping, with 77.1, 21.3 and 1.6% of the samples identified as types 1, 3 and 2, respectively. Finally, analysis of some risk factors associated with HCV infection showed that intravenous drug use was the most common risk factor among HIV/HCV co-infected patients, while blood transfusion was the most important risk factor in the group without HIV infection. The present study contributed to the knowledge regarding risk factors associated with HCV infection and the distribution of HCV genotypes in the population evaluated.
7
Riva, Giovanni, Mario Luppi, Patrizia Barozzi, Fabio Forghieri, and Leonardo Potenza. "How I treat HHV8/KSHV-related diseases in posttransplant patients." Blood 120, no. 20 (November 15, 2012): 4150–59. http://dx.doi.org/10.1182/blood-2012-04-421412.
Анотація:
Abstract Posttransplantation human herpesvirus-8 (HHV8)/Kaposi sarcoma herpesvirus (KSHV) primary infection and/or reactivations are associated with uncommon and sometimes fatal, neoplastic, and non-neoplastic diseases. HHV8-related clinical manifestations notably range from Kaposi sarcoma (KS) to either primary effusion lymphoma or multicentric Castleman disease B-cell malignancies, and from polyclonal HHV8-positive plasmacytic lymphoproliferative disorders to bone marrow failure and peripheral cytopenias, associated or not with hemophagocytic syndromes, and to acute hepatitis syndromes. We reviewed the patient series reported in the literature and summarized clinical management aspects, in terms of diagnosis, follow-up, and treatment. We described typical clinical presentations and histopathologic diagnostic features of these diseases, and we discussed the role of HHV8-specific serologic, molecular, and immunologic assays, particularly focusing on recent data from HHV8-specific T-cell monitoring in posttransplantation KS patients. We finally discussed actual therapeutic options, namely, the reduction or discontinuation of immunosuppressive therapy or the switch from calcineurin inhibitors to mTOR inhibitors, as alternatives to antineoplastic chemotherapy, along with the use of antiherpesvirus agents as prophylactic or therapeutic measures, and treatment with rituximab in posttrans-plantation multicentric Castleman disease patients and non-neoplastic HHV8-associated syndromes.
8
Artemenko, Yu S., M. B. Khamoshina, V. A. Ryabova, and Z. V. Zyukina. "Obesity in women: current aspects of reproductive health disorders." Meditsinskiy sovet = Medical Council, no. 5 (April 19, 2022): 32–39. http://dx.doi.org/10.21518/2079-701x-2022-16-5-32-39.
Анотація:
Obesity and overweight tend to increase in prevalence in the whole world. Obese people have a higher incidence of cardiovascular diseases, stroke, osteoarthritis, diabetes mellitus and reproductive system diseases. This is especially evident in women. Hormonal imbalances is developed among obese women in the hypothalamic-pituitary-ovarian axis, typically there are menstruation disorders, anovulation and female infertility. Adipose tissue is an endocrine organ, with an intricate role in bioactive molecules secrete, in particularly adipokines, which interact differently with a variety of molecular pathways, contribute to the development of insulin resistance, inflammation, hypertension, increased risk of cardiovascular events, disorders of blood clotting, differentiation and maturation of oocytes. In addition, women with obesity and metabolic syndrome have problems with conception at the endometrial level often, a significantly higher risk of having a miscarriage, and worse assisted reproductive technology outcomes. Obesity has negative effects on the endometrium in non-pregnant women, it is increasing the risk of abnormal uterine bleeding. Hormones derived from adipose tissue could be affected on the function of the uterus/endometrium and, consequently, affect the amount of menstrual blood loss. Contradictory results are observed in patients with endometriosis. The correlation of body mass index to the risk of endometriosis has not been proven in clinical studies, but there was a direct relationship between the severity of endometriosis and a high body mass index. The review presents possible relationships of diseases of the reproductive system with obesity and overweight, determining their development and pathogenesis of disorders of the formation of the functions of reproductive organs.
9
Eelen, Guy, Lucas Treps, Xuri Li, and Peter Carmeliet. "Basic and Therapeutic Aspects of Angiogenesis Updated." Circulation Research 127, no. 2 (July 3, 2020): 310–29. http://dx.doi.org/10.1161/circresaha.120.316851.
Анотація:
All organisms growing beyond the oxygen diffusion limit critically depend on a functional vasculature for survival. Yet blood vessels are far more than passive, uniform conduits for oxygen and nutrient supply. A remarkable organotypic heterogeneity is brought about by tissue-specific differentiated endothelial cells (lining the blood vessels’ lumen) and allows blood vessels to deal with organ-specific demands for homeostasis. On the flip side, when blood vessels go awry, they promote life-threatening diseases characterized by endothelial cells inappropriately adopting an angiogenic state (eg, tumor vascularization) or becoming dysfunctional (eg, diabetic microvasculopathies), calling respectively for antiangiogenic therapies and proangiogenic/vascular regenerative strategies. In solid tumors, despite initial enthusiasm, growth factor–based (mostly anti-VEGF [vascular endothelial growth factor]) antiangiogenic therapies do not sufficiently live up to the expectations in terms of efficiency and patient survival, in part, due to intrinsic and acquired therapy resistance. Tumors cunningly deploy alternative growth factors than the ones targeted by the antiangiogenic therapies to reinstigate angiogenesis or revert to other ways of securing blood flow, independently of the targeted growth factors. In trying to alleviate tissue ischemia and to repair dysfunctional or damaged endothelium, local in-tissue administration of (genes encoding) proangiogenic factors or endothelial (stem) cells harnessing regenerative potential have been explored. Notwithstanding evaluation in clinical trials, these approaches are often hampered by dosing issues and limited half-life or local retention of the administered agents. Here, without intending to provide an all-encompassing historical overview, we focus on some recent advances in understanding endothelial cell behavior in health and disease and identify novel molecular players and concepts that could eventually be considered for therapeutic targeting.
10
Łój, Magdalena, Magdalena Garncarz, and Michał Jank. "Genomic and genetic aspects of heart failure in dogs — A review." Acta Veterinaria Hungarica 60, no. 1 (March 1, 2012): 17–26. http://dx.doi.org/10.1556/avet.2012.002.
Анотація:
The most common causes of heart failure in dogs are valvular disease, predominantly endocardiosis, and myocardial disease, predominantly dilated cardiomyopathy. They are related to changes in the expression of several genes in the heart muscle and in peripheral blood nuclear cells which could be considered as prognostic or diagnostic markers of heart disease in dogs. Since many human genetic markers of heart failure have turned out to be useless in dogs, the screening for genomic markers of canine heart failure could give more insight into the molecular pathology of these diseases and aid the development of new treatment strategies.
11
Palomo, Laura, Pamela Acha, and Francesc Solé. "Genetic Aspects of Myelodysplastic/Myeloproliferative Neoplasms." Cancers 13, no. 9 (April 27, 2021): 2120. http://dx.doi.org/10.3390/cancers13092120.
Анотація:
Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are myeloid neoplasms characterized by the presentation of overlapping features from both myelodysplastic syndromes and myeloproliferative neoplasms. Although the classification of MDS/MPN relies largely on clinical features and peripheral blood and bone marrow morphology, studies have demonstrated that a large proportion of patients (~90%) with this disease harbor somatic mutations in a group of genes that are common across myeloid neoplasms. These mutations play a role in the clinical heterogeneity of these diseases and their clinical evolution. Nevertheless, none of them is specific to MDS/MPN and current diagnostic criteria do not include molecular data. Even when such alterations can be helpful for differential diagnosis, they should not be used alone as proof of neoplasia because some of these mutations may also occur in healthy older people. Here, we intend to review the main genetic findings across all MDS/MPN overlap syndromes and discuss their relevance in the management of the patients.
12
Moreira, Leonardo Marmo, and Juliana Pereira Lyon. "Heme Acquisition by trypanosomatids: Evaluation of the hemedependent behavior and its biochemical implications." Pubvet 14, no. 11 (November 2020): 1–7. http://dx.doi.org/10.31533/pubvet.v14n11a685.1-7.
Анотація:
The inability of some species to produce porphyrin-like compounds induces these species to search for blood to fulfill their heme requirement. The biological cycle of very relevant parasites, such as Leishmania sp. and Trypanossoma sp., is directly related to the search for heme. The understanding of this process in a chemical and biochemical approach is a pre-requisite to obtaining advancements regarding hemoprotein structureactivity relationships as well as molecular aspects of various pathological/physiological mechanisms associated with parasitary and/or blood diseases, between others. The present work presents an overview of the chemical/biochemical properties of porphyrin, heme, heme proteins, and parasitary diseases caused by Trypanossomatidae. We believe that this kind of discussion can contribute significantly to improve the understanding of the structure-function relation of these complex diseases
13
De Deurwaerdère, Philippe, and Giuseppe Di Giovanni. "Serotonin in Health and Disease." International Journal of Molecular Sciences 21, no. 10 (May 15, 2020): 3500. http://dx.doi.org/10.3390/ijms21103500.
Анотація:
The International Journal of Molecular Sciences Special Issue “Serotonin in health and diseases” covers several aspects of the multiple and still mysterious functions of serotonin (5-hydroxytryptamine; 5-HT). 5-HT is neurotransmitter acting in the central nervous system (CNS), blood factor, and neurohormone controlling the function of several peripheral organs. Beyond its widespread implication in physiology, the 5-HT system is involved in numerous diseases of the CNS (e.g., depression, anxiety, schizophrenia, obsessive-compulsive disorders, addiction, Parkinson’s disease) and peripheral organs (e.g., gastrointestinal disorders, cardiac arrhythmia, hypertension). The Special Issue includes 14 articles dealing with molecular and cellular effects of 5-HT in periphery and CNS, from functional aspects in lower animals to clinical practices. Beyond physiology, the Special Issue also covers the influence of 5-HT and its receptors in the mechanism of action of psychoactive molecules including antipsychotics, antidepressants, and drug of abuse. The recent progress made on the function and dysfunction of the 5-HT system will certainly increase the understanding of the widespread role of 5-HT ultimately leading to better apprehend its targeting in human diseases.
14
Kuchynka, Petr, Tomas Palecek, Martin Masek, Vladimir Cerny, Lukas Lambert, Ivana Vitkova, and Ales Linhart. "Current Diagnostic and Therapeutic Aspects of Eosinophilic Myocarditis." BioMed Research International 2016 (2016): 1–6. http://dx.doi.org/10.1155/2016/2829583.
Анотація:
Eosinophilic myocarditis (EM) represents a rare form of myocardial inflammation with very heterogeneous aetiology. In developed countries, the most prevalent causes of EM are hypersensitivity or allergic reactions, as well as hematological diseases leading to eosinophilia. The disease may have a variable clinical presentation, ranging from asymptomatic forms to life-threatening conditions. Most patients with EM have marked eosinophilia in peripheral blood. Endomyocardial biopsy needs to be performed in most cases in order to establish a definitive diagnosis of EM. The therapy depends on the underlying aetiology. Immunosuppressive therapy represents the treatment mainstay in the majority of EM forms.
15
Weisel, John W., and Rustem I. Litvinov. "Mechanisms of fibrin polymerization and clinical implications." Blood 121, no. 10 (March 7, 2013): 1712–19. http://dx.doi.org/10.1182/blood-2012-09-306639.
Анотація:
Abstract Research on all stages of fibrin polymerization, using a variety of approaches including naturally occurring and recombinant variants of fibrinogen, x-ray crystallography, electron and light microscopy, and other biophysical approaches, has revealed aspects of the molecular mechanisms involved. The ordered sequence of fibrinopeptide release is essential for the knob-hole interactions that initiate oligomer formation and the subsequent formation of 2-stranded protofibrils. Calcium ions bound both strongly and weakly to fibrin(ogen) have been localized, and some aspects of their roles are beginning to be discovered. Much less is known about the mechanisms of the lateral aggregation of protofibrils and the subsequent branching to yield a 3-dimensional network, although the αC region and B:b knob-hole binding seem to enhance lateral aggregation. Much information now exists about variations in clot structure and properties because of genetic and acquired molecular variants, environmental factors, effects of various intravascular and extravascular cells, hydrodynamic flow, and some functional consequences. The mechanical and chemical stability of clots and thrombi are affected by both the structure of the fibrin network and cross-linking by plasma transglutaminase. There are important clinical consequences to all of these new findings that are relevant for the pathogenesis of diseases, prophylaxis, diagnosis, and treatment.
16
Hühmer, Andreas F., Roger G. Biringer, Heidi Amato, Alfred N. Fonteh, and Michael G. Harrington. "Protein Analysis in Human Cerebrospinal Fluid: Physiological Aspects, Current Progress and Future Challenges." Disease Markers 22, no. 1-2 (2006): 3–26. http://dx.doi.org/10.1155/2006/158797.
Анотація:
The introduction of lumbar puncture into clinical medicine over 100 years ago marks the beginning of the study of central nervous system diseases using the human cerebrospinal fluid (CSF). Ever since, CSF has been analyzed extensively to elucidate the physiological and biochemical bases of neurological disease. The proximity of CSF to the brain makes it a good target for studying the pathophysiology of brain functions, but the barrier function of the CSF also impedes its diagnostic value. Today, measurements to determine alterations in the composition of CSF are central in the differential diagnosis of specific diseases of the central nervous system (CNS). In particular, the analysis of the CSF protein composition provides crucial information in the diagnosis of CNS diseases. This enables the assessment of the physiology of the blood-CSF barrier and of the immunology of intrathecial responses. Besides those routine measurements, protein compositional studies of CSF have been extended recently to many other proteins in the expectation that comprehensive analysis of lower abundance CSF proteins will lead to the discovery of new disease markers. Disease marker discovery by molecular profiling of the CSF tissue has the enormous potential of providing many new disease relevant molecules. New developments in protein profiling techniques hold promise for the discovery and validation of relevant disease markers. In this review, we summarize the current efforts and progress in CSF protein profiling measurements using conventional and current protein analysis tools. We also discuss necessary development in methodology in order to have the highest impact on the study of the molecular composition of CSF proteins.
17
Nii, Takenobu, Tomotoshi Marumoto, and Kenzaburo Tani. "Roles of p53 in Various Biological Aspects of Hematopoietic Stem Cells." Journal of Biomedicine and Biotechnology 2012 (2012): 1–10. http://dx.doi.org/10.1155/2012/903435.
Анотація:
Hematopoietic stem cells (HSCs) have the capacity to self-renew as well as to differentiate into all blood cell types, and they can reconstitute hematopoiesis in recipients with bone marrow ablation. In addition, transplantation therapy using HSCs is widely performed for the treatment of various incurable diseases such as hematopoietic malignancies and congenital immunodeficiency disorders. For the safe and successful transplantation of HSCs, their genetic and epigenetic integrities need to be maintained properly. Therefore, understanding the molecular mechanisms that respond to various cellular stresses in HSCs is important. The tumor suppressor protein, p53, has been shown to play critical roles in maintenance of “cell integrity” under stress conditions by controlling its target genes that regulate cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. In this paper, we summarize recent reports that describe various biological functions of HSCs and discuss the roles of p53 associated with them.
18
Presta, Ivan, Marco Vismara, Fabiana Novellino, Annalidia Donato, Paolo Zaffino, Elisabetta Scali, Krizia Caterina Pirrone, Maria Francesca Spadea, Natalia Malara, and Giuseppe Donato. "Innate Immunity Cells and the Neurovascular Unit." International Journal of Molecular Sciences 19, no. 12 (December 3, 2018): 3856. http://dx.doi.org/10.3390/ijms19123856.
Анотація:
Recent studies have clarified many still unknown aspects related to innate immunity and the blood-brain barrier relationship. They have also confirmed the close links between effector immune system cells, such as granulocytes, macrophages, microglia, natural killer cells and mast cells, and barrier functionality. The latter, in turn, is able to influence not only the entry of the cells of the immune system into the nervous tissue, but also their own activation. Interestingly, these two components and their interactions play a role of great importance not only in infectious diseases, but in almost all the pathologies of the central nervous system. In this paper, we review the main aspects in the field of vascular diseases (cerebral ischemia), of primitive and secondary neoplasms of Central Nervous System CNS, of CNS infectious diseases, of most common neurodegenerative diseases, in epilepsy and in demyelinating diseases (multiple sclerosis). Neuroinflammation phenomena are constantly present in all diseases; in every different pathological state, a variety of innate immunity cells responds to specific stimuli, differentiating their action, which can influence the blood-brain barrier permeability. This, in turn, undergoes anatomical and functional modifications, allowing the stabilization or the progression of the pathological processes.
19
Stakhneva, E. M., E. V. Kashtanova, Ya V. Polonskaya, V. S. Shramko, and Yu I. Ragino. "Mechanisms of vascular aging." Bulletin of Siberian Medicine 21, no. 2 (July 18, 2022): 186–94. http://dx.doi.org/10.20538/1682-0363-2022-2-186-194.
Анотація:
Vascular aging plays a key role in morbidity and mortality in the elderly. With age, the vasculature undergoes changes characterized by endothelial dysfunction, wall thickening, decreased elongation, and arterial stiffness. The review focuses on the main cellular and molecular mechanisms of aging, including oxidative stress, endothelial dysfunction, inflammation, increased arterial stiffness, and molecular genetic aspects. Their role in the pathogenesis of diseases associated with aging is considered. Some of the molecular mechanisms underlying these processes include increased expression and activation of matrix metalloproteinases, activation of transforming growth factor β1 signaling, increased levels of C-reactive protein, interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)α, and N-terminal pro B-type natriuretic peptide (NT-pro-BNP), and activation of proinflammatory signaling pathways. These events can be caused by vasoactive agents, such as angiotensin II and endothelin-1, the levels of which increase with aging. For prevention of cardiovascular diseases, it is important to understand the mechanisms underlying age-related pathophysiological changes in the blood vessels.
20
Erickson, Michelle A., and William A. Banks. "Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease." Journal of Cerebral Blood Flow & Metabolism 33, no. 10 (August 7, 2013): 1500–1513. http://dx.doi.org/10.1038/jcbfm.2013.135.
Анотація:
The blood–brain barrier (BBB) plays critical roles in the maintenance of central nervous system (CNS) homeostasis. Dysfunction of the BBB occurs in a number of CNS diseases, including Alzheimer's disease (AD). A prevailing hypothesis in the AD field is the amyloid cascade hypothesis that states that amyloid-β (Aβ) deposition in the CNS initiates a cascade of molecular events that cause neurodegeneration, leading to AD onset and progression. In this review, the participation of the BBB in the amyloid cascade and in other mechanisms of AD neurodegeneration will be discussed. We will specifically focus on three aspects of BBB dysfunction: disruption, perturbation of transporters, and secretion of neurotoxic substances by the BBB. We will also discuss the interaction of the BBB with components of the neurovascular unit in relation to AD and the potential contribution of AD risk factors to aspects of BBB dysfunction. From the results discussed herein, we conclude that BBB dysfunction contributes to AD through a number of mechanisms that could be initiated in the presence or absence of Aβ pathology.
21
Da Costa, Lydie, Thierry Leblanc, and Narla Mohandas. "Diamond-Blackfan anemia." Blood 136, no. 11 (September 10, 2020): 1262–73. http://dx.doi.org/10.1182/blood.2019000947.
Анотація:
Abstract Diamond-Blackfan anemia (DBA) was the first ribosomopathy described and is a constitutional inherited bone marrow failure syndrome. Erythroblastopenia is the major characteristic of the disease, which is a model for ribosomal diseases, related to a heterozygous allelic variation in 1 of the 20 ribosomal protein genes of either the small or large ribosomal subunit. The salient feature of classical DBA is a defect in ribosomal RNA maturation that generates nucleolar stress, leading to stabilization of p53 and activation of its targets, resulting in cell-cycle arrest and apoptosis. Although activation of p53 may not explain all aspects of DBA erythroid tropism, involvement of GATA1/HSP70 and globin/heme imbalance, with an excess of the toxic free heme leading to reactive oxygen species production, account for defective erythropoiesis in DBA. Despite significant progress in defining the molecular basis of DBA and increased understanding of the mechanistic basis for DBA pathophysiology, progress in developing new therapeutic options has been limited. However, recent advances in gene therapy, better outcomes with stem cell transplantation, and discoveries of putative new drugs through systematic drug screening using large chemical libraries provide hope for improvement.
22
Bambauer, Rolf. "Therapeutic Apheresis in Neurology." Journal of Clinical Research and Reports 5, no. 5 (November 21, 2020): 01–09. http://dx.doi.org/10.31579/2690-1919/118.
Анотація:
Therapeutic plasma exchange (TPE) remove harmful plasma constituents from patient’s blood and replacing the extracted plasma with replacement solutions. The advantages of TPE with hollow fiber membranes are a complete separation of the corpuscular components from the plasma and due to increased blood flow rate higher efficacy. Therapeutic apheresis (TA) is used more and more throughout the world. The development of new, more sophisticated membranes and new adsorption technologies allow the most selective separation of plasma components. TA has been successfully introduced in a variety of autoantibody-mediated diseases. TA is the first- or second-line therapy in the treatment of neurological disorders. The updated information on immunology and molecular biology of different neurological diseases are discussed in relation to the rationale for apheresis therapy and its place in combination with other modern treatments. The different neurological diseases can be treated by various apheresis methods. Pathogenetical aspects are demonstrated in these diseases, in which they are clarified. TA has been shown to effectively remove the autoantibodies, immune complexes, inflammatory moderators, paraproteins, and other toxins from blood and lead to rapid clinical improvement. For the neurological diseases, which can be treated with TA, the guidelines of the Apheresis Application Committee (AAC) of the American Society for Apheresis (ASFA) are cited.
23
Al-Koussa, Houssam, Ibrahim AlZaim, and Marwan E. El-Sabban. "Pathophysiology of Coagulation and Emerging Roles for Extracellular Vesicles in Coagulation Cascades and Disorders." Journal of Clinical Medicine 11, no. 16 (August 22, 2022): 4932. http://dx.doi.org/10.3390/jcm11164932.
Анотація:
The notion of blood coagulation dates back to the ancient Greek civilization. However, the emergence of innovative scientific discoveries that started in the seventeenth century formulated the fundamentals of blood coagulation. Our understanding of key coagulation processes continues to evolve, as novel homeostatic and pathophysiological aspects of hemostasis are revealed. Hemostasis is a dynamic physiological process, which stops bleeding at the site of injury while maintaining normal blood flow within the body. Intrinsic and extrinsic coagulation pathways culminate in the homeostatic cessation of blood loss, through the sequential activation of the coagulation factors. Recently, the cell-based theory, which combines these two pathways, along with newly discovered mechanisms, emerged to holistically describe intricate in vivo coagulation mechanisms. The complexity of these mechanisms becomes evident in coagulation diseases such as hemophilia, Von Willebrand disease, thrombophilia, and vitamin K deficiency, in which excessive bleeding, thrombosis, or unnecessary clotting, drive the development and progression of diseases. Accumulating evidence implicates cell-derived and platelet-derived extracellular vesicles (EVs), which comprise microvesicles (MVs), exosomes, and apoptotic bodies, in the modulation of the coagulation cascade in hemostasis and thrombosis. As these EVs are associated with intercellular communication, molecular recycling, and metastatic niche creation, emerging evidence explores EVs as valuable diagnostic and therapeutic approaches in thrombotic and prothrombotic diseases.
24
Khaw, Kay-Tee. "Epidemiological aspects of ageing." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 352, no. 1363 (December 29, 1997): 1829–35. http://dx.doi.org/10.1098/rstb.1997.0168.
Анотація:
A major societal challenge is to improve quality of life and prevent or reduce disability and dependency in an ageing population. Increasing age is associated with increasing risk of disability and loss of independence, due to functional impairments such as loss of mobility, hearing and vision; a major issue must be how far disability can be prevented. Ageing is associated with loss of bone tissue, reduction in muscle mass, reduced respiratory function, decline in cognitive function, rise in blood pressure and macular degeneration which predispose to disabling conditions such as osteoporosis, heart disease, dementia and blindness. However, there are considerable variations in different communities in terms of the rate of age–related decline. Large geographic and secular variations in the age–adjusted incidence of major chronic diseases such as stroke, hip fracture, coronary heart disease, cancer, visual loss from cataract, glaucoma and macular degeneration suggest strong environmental determinants in diet, physical activity and smoking habit. The evidence suggests that a substantial proportion of chronic disabling conditions associated with ageing are preventable, or at least postponable and not an inevitable accompaniment of growing old. Postponement or prevention of these conditions may not only increase longevity, but, more importantly, reduce the period of illnesses such that the majority of older persons may live high–quality lives, free of disability, until very shortly before death. We need to understand better the factors influencing the onset of age–related disability in the population, so that we have appropriate strategies to maintain optimal health in an ageing population.
25
Bilska-Wilkosz, Anna, Małgorzata Iciek, and Magdalena Górny. "Chemistry and Biochemistry Aspects of the 4-Hydroxy-2,3-trans-nonenal." Biomolecules 12, no. 1 (January 16, 2022): 145. http://dx.doi.org/10.3390/biom12010145.
Анотація:
4-hydroxy-2,3-trans-nonenal (C9H16O2), also known as 4-hydroxy-2E-nonenal (C9H16O2; HNE) is an α,β-unsaturated hydroxyalkenal. HNE is a major aldehyde, formed in the peroxidation process of ω-6 polyunsaturated fatty acids (ω-6 PUFAs), such as linoleic and arachidonic acid. HNE is not only harmful but also beneficial. In the 1980s, the HNE was regarded as a “toxic product of lipid peroxidation” and the “second toxic messenger of free radicals”. However, already at the beginning of the 21st century, HNE was perceived as a reliable marker of oxidative stress, growth modulating factor and signaling molecule. Many literature data also indicate that an elevated level of HNE in blood plasma and cells of the animal and human body is observed in the course of many diseases, including cancer. On the other hand, it is currently proven that cancer cells divert to apoptosis if they are exposed to supraphysiological levels of HNE in the cancer microenvironment. In this review, we briefly summarize the current knowledge about the biological properties of HNE.
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Sambanthamurthi, Ravigadevi, YewAi Tan, Kalyana Sundram, Kenneth C. Hayes, Mahinda Abeywardena, Soon-Sen Leow, Shamala Devi Sekaran, et al. "Positive outcomes of oil palm phenolics on degenerative diseases in animal models." British Journal of Nutrition 106, no. 11 (June 7, 2011): 1664–75. http://dx.doi.org/10.1017/s0007114511002133.
Анотація:
It is well established that plant phenolics elicit various biological activities, with positive effects on health. Palm oil production results in large volumes of aqueous by-products containing phenolics. In the present study, we describe the effects of oil palm phenolics (OPP) on several degenerative conditions using various animal models. OPP reduced blood pressure in a NO-deficient rat model, protected against ischaemia-induced cardiac arrhythmia in rats and reduced plaque formation in rabbits fed an atherogenic diet. In Nile rats, a spontaneous model of the metabolic syndrome and type 2 diabetes, OPP protected against multiple aspects of the syndrome and diabetes progression. In tumour-inoculated mice, OPP protected against cancer progression. Microarray studies on the tumours showed differential transcriptome profiles that suggest anti-tumour molecular mechanisms involved in OPP action. Thus, initial studies suggest that OPP may have potential against several chronic disease outcomes in mammals.
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Kondoh, Hiroshi, Masahiro Kameda, and Mitsuhiro Yanagida. "Whole Blood Metabolomics in Aging Research." International Journal of Molecular Sciences 22, no. 1 (December 26, 2020): 175. http://dx.doi.org/10.3390/ijms22010175.
Анотація:
Diversity is observed in the wave of global aging because it is a complex biological process exhibiting individual variability. To assess aging physiologically, markers for biological aging are required in addition to the calendar age. From a metabolic perspective, the aging hypothesis includes the mitochondrial hypothesis and the calorie restriction (CR) hypothesis. In experimental models, several compounds or metabolites exert similar lifespan-extending effects, like CR. However, little is known about whether these metabolic modulations are applicable to human longevity, as human aging is greatly affected by a variety of factors, including lifestyle, genetic or epigenetic factors, exposure to stress, diet, and social environment. A comprehensive analysis of the human blood metabolome captures complex changes with individual differences. Moreover, a non-targeted analysis of the whole blood metabolome discloses unexpected aspects of human biology. By using such approaches, markers for aging or aging-relevant conditions were identified. This information should prove valuable for future diagnosis or clinical interventions in diseases relevant to aging.
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Chen, Cen, Feng-Qing Yang, Qian Zhang, Feng-Qin Wang, Yuan-Jia Hu, and Zhi-Ning Xia. "Natural Products for Antithrombosis." Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–17. http://dx.doi.org/10.1155/2015/876426.
Анотація:
Thrombosis is considered to be closely related to several diseases such as atherosclerosis, ischemic heart disease and stroke, as well as rheumatoid arthritis, hyperuricemia, and various inflammatory conditions. More and more studies have been focused on understanding the mechanism of molecular and cellular basis of thrombus formation as well as preventing thrombosis for the treatment of thrombotic diseases. In reality, there is considerable interest in the role of natural products and their bioactive components in the prevention and treatment of thrombosis related disorders. This paper briefly describes the mechanisms of thrombus formation on three aspects, including coagulation system, platelet activation, and aggregation, and change of blood flow conditions. Furthermore, the natural products for antithrombosis by anticoagulation, antiplatelet aggregation, and fibrinolysis were summarized, respectively.
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Kandarakov, Oleg, and Alexander Belyavsky. "Clonal Hematopoiesis, Cardiovascular Diseases and Hematopoietic Stem Cells." International Journal of Molecular Sciences 21, no. 21 (October 24, 2020): 7902. http://dx.doi.org/10.3390/ijms21217902.
Анотація:
Cardiovascular diseases and cancer, the leading causes of morbidity and mortality in the elderly, share some common mechanisms, in particular inflammation, contributing to their progression and pathogenesis. However, somatic mutagenesis, a driving force in cancer development, has not been generally considered as an important factor in cardiovascular disease pathology. Recent studies demonstrated that during normal aging, somatic mutagenesis occurs in blood cells, often resulting in expansion of mutant clones that dominate hematopoiesis at advanced age. This clonal hematopoiesis is primarily associated with mutations in certain leukemia-related driver genes and, being by itself relatively benign, not only increases the risks of subsequent malignant hematopoietic transformation, but, unexpectedly, has a significant impact on progression of atherosclerosis and cardiovascular diseases. In this review, we discuss the phenomenon of clonal hematopoiesis, the most important genes involved in it, its impact on cardiovascular diseases, and relevant aspects of hematopoietic stem cell biology.
30
Mursch-Edlmayr, Anna-Sophie, Matthias Bolz, and Clemens Strohmaier. "Vascular Aspects in Glaucoma: From Pathogenesis to Therapeutic Approaches." International Journal of Molecular Sciences 22, no. 9 (April 28, 2021): 4662. http://dx.doi.org/10.3390/ijms22094662.
Анотація:
Glaucomatous optic neuropathies have been regarded as diseases caused by high intraocular pressure for a long time, despite the concept of vascular glaucoma dating back to von Graefe in 1854. Since then, a tremendous amount of knowledge about the ocular vasculature has been gained; cohort studies have established new vascular risk factors for glaucoma as well as identifying protective measures acting on blood vessels. The knowledge about the physiology and pathophysiology of the choroidal, retinal, as well as ciliary and episcleral circulation has also advanced. Only recently have novel drugs based on that knowledge been approved for clinical use, with more to follow. This review provides an overview of the current vascular concepts in glaucoma, ranging from novel pathogenesis insights to promising therapeutic approaches, covering the supply of the optic nerve head as well as the aqueous humor production and drainage system.
31
Tatzber, Franz, Sieglinde Zelzer, Barbara Obermayer-Pietsch, Stefan Rinnerhofer, Michael Kundi, Gerhard Cvirn, Georg Wultsch, et al. "Occupational Health Aspects with Special Focus on Physiological Differences between Office and Metalworkers." Antioxidants 11, no. 4 (March 25, 2022): 633. http://dx.doi.org/10.3390/antiox11040633.
Анотація:
Physical workload adversely impacts inflammation, oxidative stress and mood in heavy workers. We compared these risk parameters between metalworkers (n = 20) and office workers (n = 30), including gender differences. Blood samples were analyzed with thirty parameters to overview endocrinology, inflammation, and psychological and oxidative stress. Despite an adequate antioxidative supply, oxidative stress occurred in metalworkers, as indicated by significantly increased peroxide and homocysteine (Hcy) levels. Moreover, increased concentrations were observed in this group regarding psychological stress and diet-related parameters. Sex-specific differences were determined for physical dimensions, dehydroepiandrosterone sulfate (DHEAS), Hcy, uric acid, triglycerides, osmolality, anti-Mullerian hormone (AMH) and testosterone. Age-associated differences were observed for DHEAS, glycosylated hemoglobin, adrenaline, AMH and testosterone. In male office workers, the body mass index was associated with increased LDL-HDL, cholesterol-HDL and homeostatic model assessment of insulin resistance (HOMA-IR). In conclusion, these results indicate increased oxidative stress and psychological stress in heavy workers independently of adequate antioxidant sustenance. The sedentary occupation of office workers, in turn, favored diseases of affluence. This might be particularly relevant for long-term occupied persons and older workers due to a hormonal shift coming along, given the risk for oxidative stress-related diseases such as cardiovascular disease, particularly in the case of males, based on their lifestyle habits.
32
Russo, Annamaria, Ester Tellone, Davide Barreca, Silvana Ficarra, and Giuseppina Laganà. "Implication of COVID-19 on Erythrocytes Functionality: Red Blood Cell Biochemical Implications and Morpho-Functional Aspects." International Journal of Molecular Sciences 23, no. 4 (February 16, 2022): 2171. http://dx.doi.org/10.3390/ijms23042171.
Анотація:
Several diseases (such as diabetes, cancer, and neurodegenerative disorders) affect the morpho-functional aspects of red blood cells, sometimes altering their normal metabolism. In this review, the hematological changes are evaluated, with particular focus on the morphology and metabolic aspects of erythrocytes. Changes in the functionality of such cells may, in fact, help provide important information about disease severity and progression. The viral infection causes significant damage to the blood cells that are altered in size, rigidity, and distribution width. Lower levels of hemoglobin and anemia have been reported in several studies, and an alteration in the concentration of antioxidant enzymes has been shown to promote a dangerous state of oxidative stress in red blood cells. Patients with severe COVID-19 showed an increase in hematological changes, indicating a progressive worsening as COVID-19 severity progressed. Therefore, monitored hematological alterations in patients with COVID-19 may play an important role in the management of the disease and prevent the risk of a severe course of the disease. Finally, monitored changes in erythrocytes and blood, in general, may be one of the causes of the condition known as Long COVID.
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Tain, You-Lin, and Chien-Ning Hsu. "Developmental and Early Life Origins of Hypertension: Preventive Aspects of Melatonin." Antioxidants 11, no. 5 (May 8, 2022): 924. http://dx.doi.org/10.3390/antiox11050924.
Анотація:
Hypertension represents a major disease burden worldwide. Abundant evidence suggests that hypertension can originate in early life. Adverse programming processes can be prevented by early life intervention—namely, reprogramming—to avoid developing chronic diseases later in life. Melatonin is an endogenously produced hormone with a multifaceted biological function. Although melatonin supplementation has shown benefits for human health, less attention has been paid to exploring its reprogramming effects on the early life origins of hypertension. In this review, first, we discuss the physiological roles of melatonin in pregnancy, fetal development, and the regulation of blood pressure. Then, we summarize the epidemiological and experimental evidence for the early life origins of hypertension. This is followed by a description of the animal models used to examine early melatonin therapy as a reprogramming strategy to protect against the early life origins of hypertension. A deeper understanding of the developmental programming of hypertension and recent advances in early melatonin intervention might provide a path forward in reducing the global burden of hypertension.
34
Hansson, Elisabeth, and Lars Rönnbäck. "Astroglial Receptors as Putative Targets for Neurotoxic Agents." Alternatives to Laboratory Animals 16, no. 3 (March 1989): 270–73. http://dx.doi.org/10.1177/026119298901600311.
Анотація:
Astrocytes respond to neurotoxins and play a crucial role in metabolic and structural nerve tissue dysfunction in diseases, such as epilepsy, degenerative diseases, hepatic encephalopathy, and in other toxic states. The cells make up part of the blood/brain barrier, thus being “aware of” blood-borne substances which can penetrate into the nervous tissue. The cells also extend processes into the synaptic regions and probably regulate neuronal activity. Cells respond to changes in their environment by means of specific receptors that detect incoming signals and translate the information into a form that can be recognised by intracellular effector systems. Aspects of astrocyte receptors for neurotransmitters and neuromodulators, receptor interactions, second messenger systems and automodulation of genes after receptor activation are summarised as a basis for studies on the evaluation of the effects of neurotoxic substances and drugs.
35
Nollet, Lukas, Matthias Van Gils, Shana Verschuere, and Olivier Vanakker. "The Role of Vitamin K and Its Related Compounds in Mendelian and Acquired Ectopic Mineralization Disorders." International Journal of Molecular Sciences 20, no. 9 (April 30, 2019): 2142. http://dx.doi.org/10.3390/ijms20092142.
Анотація:
Ectopic mineralization disorders comprise a broad spectrum of inherited or acquired diseases characterized by aberrant deposition of calcium crystals in multiple organs, such as the skin, eyes, kidneys, and blood vessels. Although the precise mechanisms leading to ectopic calcification are still incompletely known to date, various molecular targets leading to a disturbed balance between pro- and anti-mineralizing pathways have been identified in recent years. Vitamin K and its related compounds, mainly those post-translationally activated by vitamin K-dependent carboxylation, may play an important role in the pathogenesis of ectopic mineralization as has been demonstrated in studies on rare Mendelian diseases, but also on highly prevalent disorders, like vascular calcification. This narrative review compiles and summarizes the current knowledge regarding the role of vitamin K, its metabolism, and associated compounds in the pathophysiology of both monogenic ectopic mineralization disorders, like pseudoxanthoma elasticum or Keutel syndrome, as well as acquired multifactorial diseases, like chronic kidney disease. Clinical and molecular aspects of the various disorders are discussed according to the state-of-the-art, followed by a comprehensive literature review regarding the role of vitamin K in molecular pathophysiology and as a therapeutic target in both human and animal models of ectopic mineralization disorders.
36
Hernández, Carolina, Aníbal Teherán, Carolina Flórez, and Juan David Ramírez. "Comparison of parasite loads in serum and blood samples from patients in acute and chronic phases of Chagas disease." Parasitology 145, no. 14 (April 17, 2018): 1837–43. http://dx.doi.org/10.1017/s0031182018000598.
Анотація:
AbstractMolecular methods have been developed for the detection and quantification ofTrypanosoma cruziDNA in blood samples from patients with Chagas disease. However, aspects of sample processing necessary for quantitative real-time PCR (qPCR), such as the addition of guanidine hydrochloride to whole blood samples, may limit timely access to molecular diagnosis. We analysed 169 samples from serum and guanidine-EDTA blood (GEB) obtained from patients in acute and chronic phases of Chagas disease. We applied qPCR targeted to the satellite DNA region. Finally, we compared the parasite loads and cycle of threshold values of the qPCR. The results confirmed the usefulness of serum samples for the detection and quantification of parasite DNA in patients with Chagas disease, especially in the acute phase. However, the parasite loads detected in serum samples from patients in the chronic phase were lower than those detected in GEB samples. The epidemiological implications of the findings are herein discussed.
37
Pintilie, Sebastian Romeo, Alice D. Condrat, Adriana Fodor, Adela-Viviana Sitar-Tăut, Marc Damian, Cezar Login, Lucia Lotrean, et al. "Neuroprotective effects of physical exercise: Implications in health and disease." Romanian Medical Journal 68, no. 3 (September 30, 2021): 383–89. http://dx.doi.org/10.37897/rmj.2021.3.9.
Анотація:
Physical exercises have long been linked to numerous health improvements, ranging from cardiovascular to psychiatric. In this review, we take a closer look on its anatomical, physiological and chemical effects on the brain. Starting from the clinical to the cellular level, we will analyze the neurogenesis, anti-inflammatory effects on Brain-Blood Barrier and synaptic plasticity, outlining known molecular aspects that are influenced by physical activity, such as: gene expression, changes of growth factors and neurotransmitter levels and means of reverting molecular mechanisms of ageing. The brain derived neurotrophic factor (BDNF) is one of the central molecules that links the physical exercise to neurogenesis, neuroprotection, cognitive functions, dendritic growth, memory formation and many more. We indicate the correlation between physical activity and mental health in diseases like depression, Alzheimer’s dementia and Parkinson’s disease.
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Hirai, Nobuyasu, Kei Kasahara, Yoshihiko Ogawa, Yuki Suzuki, Naokuni Hishiya, Ryuichi Nakano, Hisakazu Yano, Masahide Yoshikawa, and Keiichi Mikasa. "130. Clinical Presentation and Molecular Epidemiology Characterization of Invasive GBS Infection in Nara, Japan from 2007 to 2016." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S94. http://dx.doi.org/10.1093/ofid/ofz360.205.
Анотація:
Abstract Background Streptococcus agalactiae (GBS), a leading cause of neonatal infections, also occurs as an invasive infection in elderly people. The aim of this study was to evaluate the clinical aspect of invasive infections and the phenotypic and genetic diversity of GBS isolates to develop better antibiotics treatment and curb the increasing rate of antibiotic resistance in Nara, Japan. Methods GBS strains sequentially collected from blood and cerebrospinal fluid cultures between 2007 and 2016 were identified and evaluated for capsular types, multilocus sequence typing (MLST), antibiotic susceptibility, resistant gene, and pulsed-field gel electrophoresis (PFGE). Clinical characteristics were retrospectively collected. Results A total of 42 GBS isolates (12 from children and 30 from adults) were collected. In adults, common underlying conditions were malignancy and diabetes, and primary bacteremia was the most common source of infection. In children, 6 were early-onset diseases, 4 were late-onset diseases, and 2 were school children. Overall, the mortality rate was 0% in children and 17% in adults. The serotypes and main clonal complex are summarized in Table 1. Minimum inhibitory concentrations of the antibiotics were also determined (Table 2). The serotypes and resistant genes are shown in Table 3. PFGE revealed serotypes V and VI belonging to ST1, and serotype III belonging to ST335 were highly identical. Conclusion In clinical aspects, neonates with early-onset diseases experienced certain disorders during the perinatal period. In adults, serotype Ib, which tends to exhibit levofloxacin resistance, was the most common, followed by serotypes V and VI belonging to ST1; however, they were not observed in children. Contrastingly, serotype III belonging to ST335, which tends to exhibit macrolide resistance, was mainly observed in children. Quinolone among adults and macrolide among the younger generation are widely used as oral antibiotics in Japan. A tendency to use antibiotics affects bacterial flora and induces selectivity of specific clones, thereby causing diseases in the local community. Continuous surveillance is warranted in local areas for appropriate antibiotics treatment and prevent increasing antibiotic-resistant isolates. Disclosures All authors: No reported disclosures.
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Yang, Guangrui, Jiayang Zhang, Tingting Jiang, James Monslow, Soon Yew Tang, Leslie Todd, Ellen Puré, Lihong Chen, and Garret A. FitzGerald. "Bmal1 Deletion in Myeloid Cells Attenuates Atherosclerotic Lesion Development and Restrains Abdominal Aortic Aneurysm Formation in Hyperlipidemic Mice." Arteriosclerosis, Thrombosis, and Vascular Biology 40, no. 6 (June 2020): 1523–32. http://dx.doi.org/10.1161/atvbaha.120.314318.
Анотація:
Objective: Although the molecular components of circadian rhythms oscillate in discrete cellular components of the vasculature and many aspects of vascular function display diurnal variation, the cellular connections between the molecular clock and inflammatory cardiovascular diseases remain to be elucidated. Previously we have shown that pre- versus postnatal deletion of Bmal1 (brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1), the nonredundant core clock gene has contrasting effects on atherogenesis. Here we investigated the effect of myeloid cell Bmal1 deletion on atherogenesis and abdominal aortic aneurysm formation in mice. Approach and Results: Mice lacking Bmal1 in myeloid cells were generated by crossing Bmal1 flox/flox mice with lysozyme 2 promoter-driven Cre recombinase mice on a hyperlipidemic low-density lipoprotein receptor-deficient background and were fed on a high-fat diet to induce atherosclerosis. Atherogenesis was restrained, concomitant with a reduction of aortic proinflammatory gene expression in myeloid cell Bmal1 knockout mice. Body weight, blood pressure, blood glucose, triglycerides, and cholesterol were unaltered. Similarly, myeloid cell depletion of Bmal1 also restrained Ang II (angiotensin II) induced formation of abdominal aortic aneurysm in hyperlipidemic mice. In vitro, RNA-Seq analysis demonstrated a proinflammatory response in cultured macrophages in which there was overexpression of Bmal1. Conclusions: Myeloid cell Bmal1 deletion retards atherogenesis and restrains the formation of abdominal aortic aneurysm and may represent a potential therapeutic target for inflammatory cardiovascular diseases.
40
Yao, Pei-Li, Jeremy Peavey, and Goldis Malek. "Leveraging Nuclear Receptors as Targets for Pathological Ocular Vascular Diseases." International Journal of Molecular Sciences 21, no. 8 (April 21, 2020): 2889. http://dx.doi.org/10.3390/ijms21082889.
Анотація:
Vasculogenesis and angiogenesis are physiological mechanisms occurring throughout the body. Any disruption to the precise balance of blood vessel growth necessary to support healthy tissue, and the inhibition of abnormal vessel sprouting has the potential to negatively impact stages of development and/or healing. Therefore, the identification of key regulators of these vascular processes is critical to identifying therapeutic means by which to target vascular-associated compromises and complications. Nuclear receptors are a family of transcription factors that have been shown to be involved in modulating different aspects of vascular biology in many tissues systems. Most recently, the role of nuclear receptors in ocular biology and vasculopathies has garnered interest. Herein, we review studies that have used in vitro assays and in vivo models to investigate nuclear receptor-driven pathways in two ocular vascular diseases associated with blindness, wet or exudative age-related macular degeneration, and proliferative diabetic retinopathy. The potential therapeutic targeting of nuclear receptors for ocular diseases is also discussed.
41
Rubattu, Speranza, and Massimo Volpe. "Natriuretic Peptides in the Cardiovascular System: Multifaceted Roles in Physiology, Pathology and Therapeutics." International Journal of Molecular Sciences 20, no. 16 (August 16, 2019): 3991. http://dx.doi.org/10.3390/ijms20163991.
Анотація:
The natriuretic peptides (NPs) family includes a class of hormones and their receptors needed for the physiological control of cardiovascular functions. The discovery of NPs provided a fundamental contribution into our understanding of the physiological regulation of blood pressure, and of heart and kidney functions. NPs have also been implicated in the pathogenesis of several cardiovascular diseases (CVDs), including hypertension, atherosclerosis, heart failure, and stroke. A fine comprehension of the molecular mechanisms dependent from NPs and underlying the promotion of cardiovascular damage has contributed to improve our understanding of the molecular basis of all major CVDs. Finally, the opportunity to target NPs in order to develop new therapeutic tools for a better treatment of CVDs has been developed over the years. The current Special Issue of the Journal covers all major aspects of the molecular implications of NPs in physiology and pathology of the cardiovascular system, including NP-based therapeutic approaches.
42
Bridle, Tristen G., Premkumari Kumarathasan, and Jürgen Gailer. "Toxic Metal Species and ‘Endogenous’ Metalloproteins at the Blood–Organ Interface: Analytical and Bioinorganic Aspects." Molecules 26, no. 11 (June 4, 2021): 3408. http://dx.doi.org/10.3390/molecules26113408.
Анотація:
Globally, human exposure to environmental pollutants causes an estimated 9 million deaths per year and it could also be implicated in the etiology of diseases that do not appear to have a genetic origin. Accordingly, there is a need to gain information about the biomolecular mechanisms that causally link exposure to inorganic environmental pollutants with distinct adverse health effects. Although the analysis of blood plasma and red blood cell (RBC) cytosol can provide important biochemical information about these mechanisms, the inherent complexity of these biological matrices can make this a difficult task. In this perspective, we will examine the use of metalloentities that are present in plasma and RBC cytosol as potential exposure biomarkers to assess human exposure to inorganic pollutants. Our primary objective is to explore the principal bioinorganic processes that contribute to increased or decreased metalloprotein concentrations in plasma and/or RBC cytosol. Furthermore, we will also identify metabolites which can form in the bloodstream and contain essential as well as toxic metals for use as exposure biomarkers. While the latter metal species represent useful biomarkers for short-term exposure, endogenous plasma metalloproteins represent indicators to assess the long-term exposure of an individual to inorganic pollutants. Based on these considerations, the quantification of metalloentities in blood plasma and/or RBC cytosol is identified as a feasible research avenue to better understand the adverse health effects that are associated with chronic exposure of various human populations to inorganic pollutants. Exposure to these pollutants will likely increase as a consequence of technological advances, including the fast-growing applications of metal-based engineering nanomaterials.
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Tanaka, Masashi, Satoshi Saito, Takayuki Inoue, Noriko Satoh-Asahara та Masafumi Ihara. "Novel Therapeutic Potentials of Taxifolin for Amyloid-β-associated Neurodegenerative Diseases and Other Diseases: Recent Advances and Future Perspectives". International Journal of Molecular Sciences 20, № 9 (30 квітня 2019): 2139. http://dx.doi.org/10.3390/ijms20092139.
Анотація:
Amyloid-β (Aβ) has been closely implicated in the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer’s disease (AD), the major causes of dementia. Thus, Aβ could be a target for the treatment of these diseases, for which, currently, there are no established effective treatments. Taxifolin is a bioactive catechol-type flavonoid present in various plants, such as herbs, and it exhibits pleiotropic effects including anti-oxidant and anti-glycation activities. Recently, we have demonstrated that taxifolin inhibits Aβ fibril formation in vitro and have further shown that it improves cerebral blood flow, facilitating Aβ clearance in the brain and suppressing cognitive decline in a mouse model of CAA. These findings suggest the novel therapeutic potentials of taxifolin for CAA. Furthermore, recent extensive studies have reported several novel aspects of taxifolin supporting its potential as a therapeutic drug for AD and metabolic diseases with a high risk for dementia as well as for CAA. In this review, we have summarized the recent advances in taxifolin research based on in vitro, in vivo, and in silico approaches. Furthermore, we have discussed future research directions on the potential of taxifolin for use in novel therapeutic strategies for CAA, AD, and metabolic diseases with an increased risk for dementia.
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Kaczmarek, Radoslaw, Pawel Gajdzis, and Malgorzata Gajdzis. "Eph Receptors and Ephrins in Retinal Diseases." International Journal of Molecular Sciences 22, no. 12 (June 8, 2021): 6207. http://dx.doi.org/10.3390/ijms22126207.
Анотація:
Retinal diseases are the leading cause of irreversible blindness. They affect people of all ages, from newborns in retinopathy of prematurity, through age-independent diabetic retinopathy and complications of retinal detachment, to age-related macular degeneration (AMD), which occurs mainly in the elderly. Generally speaking, the causes of all problems are disturbances in blood supply, hypoxia, the formation of abnormal blood vessels, and fibrosis. Although the detailed mechanisms underlying them are varied, the common point is the involvement of Eph receptors and ephrins in their pathogenesis. In our study, we briefly discussed the pathophysiology of the most common retinal diseases (diabetic retinopathy, retinopathy of prematurity, proliferative vitreoretinopathy, and choroidal neovascularization) and collected available research results on the role of Eph and ephrins. We also discussed the safety aspect of the use of drugs acting on Eph and ephrin for ophthalmic indications.
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Kuzmin, I. V., and S. V. Kuzmina. "Anticholinergic therapy of an overactive bladder: clinical practice aspects." Russian Medical Inquiry 5, no. 5 (2021): 273–79. http://dx.doi.org/10.32364/2587-6821-2021-5-5-273-279.
Анотація:
The review presents data on the epidemiology, clinical course and modern methods to the treatment of overactive bladder. It also describes the pharmacological bases of anticholinergic drug use, which are first-line in the treatment of this disease. The pharmacological and clinical aspects of the new M-holinoblocker, fesoterodine, are considered. The drug belongs to the competitive blockers of M2-and M3-cholinergic receptors. The conducted studies have shown the high clinical efficacy of fesoterodine. Due to the low lipophilicity and large molecular weight, the drug’s ability to penetrate the blood-brain barrier is minimal, which causes a low frequency of adverse events from the central nervous system. The pharmacokinetic and pharmacodynamic properties of fesoterodine allow it to be prescribed to "vulnerable" groups of patients — the elderly, patients with CNS diseases and cognitive disorders. According to the FORTA system, fesoterodine is the only antimuscarinic drug classified in category B. The results of a multiple-criteria decision-making showed a favorable benefit-risk profile of fesoterodine, prescribed according to a flexible dosage regimen of 4 mg and 8 mg. Important benefits of fesoterodine are the convenience of intake, the possibility of dose titration, as well as the ratio of treatment costs and its efficacy. The practical issues of using fesoterodine in various clinical cases are considered. KEYWORDS: overactive bladder, anticholinergic therapy, fesoterodine, multiple-criteria decision-making, FORTA classification. FOR CITATION: Kuzmin I.V., Kuzmina S.V. Anticholinergic therapy of an overactive bladder: clinical practice aspects. Russian Medical Inquiry. 2021;5(5):273–279 (in Russ.). DOI: 10.32364/2587-6821-2021-5-5-273-279.
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Yolken, R. H., and E. F. Torrey. "Viruses, schizophrenia, and bipolar disorder." Clinical Microbiology Reviews 8, no. 1 (January 1995): 131–45. http://dx.doi.org/10.1128/cmr.8.1.131.
Анотація:
The hypothesis that viruses or other infectious agents may cause schizophrenia or bipolar disorder dates to the 19th century but has recently been revived. It could explain many clinical, genetic, and epidemiologic aspects of these diseases, including the winter-spring birth seasonality, regional differences, urban birth, household crowding, having an older sibling, and prenatal exposure to influenza as risk factors. It could also explain observed immunological changes such as abnormalities of lymphocytes, proteins, autoantibodies, and cytokines. However, direct studies of viral infections in individuals with these psychiatric diseases have been predominantly negative. Most studies have examined antibodies in blood or cerebrospinal fluid, and relatively few studies have been done on viral antigens, genomes, cytopathic effect on cell culture, and animal transmission experiments. Viral research on schizophrenia and bipolar disorder is thus comparable to viral research on multiple sclerosis and Parkinson's disease: an attractive hypothesis with scattered interesting findings but no clear proof. The application of molecular biological techniques may allow the identification of novel infectious agents and the associations of these novel agents with serious mental diseases.
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Atiakshin, Dmitrii A., Andrey A. Kostin, Ivan D. Trotsenko, Victoria V. Shishkina, Markus Tiemann, and Igor B. Buchwalow. "Carboxypeptidase A3 in the structure of the protease phenotype of mast cells: cytophysiological aspects." RUDN Journal of Medicine 26, no. 1 (March 21, 2022): 9–33. http://dx.doi.org/10.22363/2313-0245-2022-26-1-9-33.
Анотація:
Carboxypeptidase A3 (CPA3) is a specific protease of mast cells (MC) with variable expression and appears to be one of the preformed components of the secretome. CPA3 is involved in regulation of the state of a specifi tissue microenvironment and components of the integrative-buffer metabolic environment in adaptive and pathological processes; it affects implementation of the innate immunity, mechanisms of angiogenesis, processes of the extracellular matrix remodeling, etc. CPA3 identification using protocols of multiplex immunohistochemistry allows specifying details of the organ-specific mast cell population features, including the protease phenotype, mechanisms of biogenesis with cytoand histotopographic criteria, and features of secretory pathways. Numerous biological effects of CPA3, including participation in the regulation of the pulmonary parenchyma and systemic blood flow, in biogenesis and remodeling of the fibrous component of the extracellular matrix, in epigenetic reprogramming, determine the importance of fundamental investigation of the physiological activity of protease and its involvement in the implementation of pathological processes. Further studies will contribute to the detection of the translational value of the mast cell CPA3 expression features as a prognostic factor and a promising molecular target for treatment of socially significant diseases.
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Atiakshin, Dmitrii A., Andrey A. Kostin, Ivan D. Trotsenko, Victoria V. Shishkina, Markus Tiemann, and Igor B. Buchwalow. "Carboxypeptidase A3 in the structure of the protease phenotype of mast cells: cytophysiological aspects." RUDN Journal of Medicine 26, no. 1 (March 3, 2022): 9–32. http://dx.doi.org/10.22363/2313-0245-2022-26-1-9-32.
Анотація:
Carboxypeptidase A3 (CPA3) is a specific protease of mast cells (MC) with variable expression and appears to be one of the preformed components of the secretome. CPA3 is involved in regulation of the state of a specifi tissue microenvironment and components of the integrative-buffer metabolic environment in adaptive and pathological processes; it affects implementation of the innate immunity, mechanisms of angiogenesis, processes of the extracellular matrix remodeling, etc. CPA3 identification using protocols of multiplex immunohistochemistry allows specifying details of the organ-specific mast cell population features, including the protease phenotype, mechanisms of biogenesis with cyto- and histotopographic criteria, and features of secretory pathways. Numerous biological effects of CPA3, including participation in the regulation of the pulmonary parenchyma and systemic blood flow, in biogenesis and remodeling of the fibrous component of the extracellular matrix, in epigenetic reprogramming, determine the importance of fundamental investigation of the biological activity and regulation of pathological processes of CPA3. Further studies will contribute to the detection of the true value of the mast cell CPA3 expression features as a prognostic factor and a promising molecular target for treatment of socially significant diseases.
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Veluswamy, Priya, Max Wacker, Dimitrios Stavridis, Thomas Reichel, Hendrik Schmidt, Maximilian Scherner, Jens Wippermann, and Guido Michels. "The SARS-CoV-2/Receptor Axis in Heart and Blood Vessels: A Crisp Update on COVID-19 Disease with Cardiovascular Complications." Viruses 13, no. 7 (July 12, 2021): 1346. http://dx.doi.org/10.3390/v13071346.
Анотація:
The SARS-CoV-2 virus causing COVID-19 disease has emerged expeditiously in the world and has been declared pandemic since March 2020, by World Health Organization (WHO). The destructive effects of SARS-CoV-2 infection are increased among the patients with pre-existing chronic conditions and, in particular, this review focuses on patients with underlying cardiovascular complications. The expression pattern and potential functions of SARS-CoV-2 binding receptors and the attributes of SARS-CoV-2 virus tropism in a physio-pathological state of heart and blood vessel are precisely described. Of note, the atheroprotective role of ACE2 receptors is reviewed. A detailed description of the possible detrimental role of SARS-CoV-2 infection in terms of vascular leakage, including endothelial glycocalyx dysfunction and bradykinin 1 receptor stimulation is concisely stated. Furthermore, the potential molecular mechanisms underlying SARS-CoV-2 induced clot formation in association with host defense components, including activation of FXIIa, complements and platelets, endothelial dysfunction, immune cell responses with cytokine-mediated action are well elaborated. Moreover, a brief clinical update on patient with COVID-19 disease with underlying cardiovascular complications and those who had new onset of cardiovascular complications post-COVID-19 disease was also discussed. Taken together, this review provides an overview of the mechanistic aspects of SARS-CoV-2 induced devastating effects, in vital organs such as the heart and vessels.
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Xu, Jie, Xin Yu, and Zhimin Wang. "The Risk and Clinical Treatment of Hypertensive Diseases in Pregnant Women." BioMed Research International 2022 (September 5, 2022): 1–13. http://dx.doi.org/10.1155/2022/8480106.
Анотація:
Hypertensive disorders of pregnancy are a group of pregnancy-related diseases characterized by the coexistence of pregnancy and elevated blood pressure, which seriously endanger the health of mothers and infants, and are one of the main causes of maternal and perinatal deaths. The purpose of this paper is to investigate the clinical analysis of vitamin E and astragalus in the adjuvant treatment of hypertensive disorders in pregnancy and to describe the learning model. This paper puts forward the problem of clinical treatment, which is established on the basis of adjuvant therapy, then narrates around the clinical characteristics of gestational hypertension, and designs and analyzes the experimental design and analysis of adjuvant therapy with vitamin E and astragalus. The experimental results showed that the delivery methods of the three groups of patients were compared P < 0.05 . Compared with the traditional Chinese medicine control group and the vitamin E control group, there were more vaginal births in the experimental group, 36 patients in total. It shows that astragalus and vitamin E can alleviate the disease in different aspects and can effectively intervene in gestational hypertension.