scholarly journals Potential Diagnostic and Prognostic Biomarkers of Epigenetic Drift within the Cardiovascular Compartment

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Robert G. Wallace ◽  
Laura C. Twomey ◽  
Marc-Antoine Custaud ◽  
Niall Moyna ◽  
Philip M. Cummins ◽  
...  

Biomarkers encompass a wide range of different measurable indicators, representing a tangible link to physiological changes occurring within the body. Accessibility, sensitivity, and specificity are significant factors in biomarker suitability. New biomarkers continue to be discovered, and questions over appropriate selection and assessment of their usefulness remain. If traditional markers of inflammation are not sufficiently robust in their specificity, then perhaps alternative means of detection may provide more information. Epigenetic drift (epigenetic modifications as they occur as a direct function with age), and its ancillary elements, including platelets, secreted microvesicles (MVs), and microRNA (miRNA), may hold enormous predictive potential. The majority of epigenetic drift observed in blood is independent of variations in blood cell composition, addressing concerns affecting traditional blood-based biomarker efficacy. MVs are found in plasma and other biological fluids in healthy individuals. Altered MV/miRNA profiles may also be found in individuals with various diseases. Platelets are also highly reflective of physiological and lifestyle changes, making them extremely sensitive biomarkers of human health. Platelets release increased levels of MVs in response to various stimuli and under a plethora of disease states, which demonstrate a functional effect on other cell types.

2020 ◽  
Vol 21 (15) ◽  
pp. 5404 ◽  
Author(s):  
Marco Quaglia ◽  
Guido Merlotti ◽  
Gabriele Guglielmetti ◽  
Giuseppe Castellano ◽  
Vincenzo Cantaluppi

New biomarkers of early and late graft dysfunction are needed in renal transplant to improve management of complications and prolong graft survival. A wide range of potential diagnostic and prognostic biomarkers, measured in different biological fluids (serum, plasma, urine) and in renal tissues, have been proposed for post-transplant delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction (CAD). This review investigates old and new potential biomarkers for each of these clinical domains, seeking to underline their limits and strengths. OMICs technology has allowed identifying many candidate biomarkers, providing diagnostic and prognostic information at very early stages of pathological processes, such as AR. Donor-derived cell-free DNA (ddcfDNA) and extracellular vesicles (EVs) are further promising tools. Although most of these biomarkers still need to be validated in multiple independent cohorts and standardized, they are paving the way for substantial advances, such as the possibility of accurately predicting risk of DGF before graft is implanted, of making a “molecular” diagnosis of subclinical rejection even before histological lesions develop, or of dissecting etiology of CAD. Identification of “immunoquiescent” or even tolerant patients to guide minimization of immunosuppressive therapy is another area of active research. The parallel progress in imaging techniques, bioinformatics, and artificial intelligence (AI) is helping to fully exploit the wealth of information provided by biomarkers, leading to improved disease nosology of old entities such as transplant glomerulopathy. Prospective studies are needed to assess whether introduction of these new sets of biomarkers into clinical practice could actually reduce the need for renal biopsy, integrate traditional tools, and ultimately improve graft survival compared to current management.


2018 ◽  
Vol 315 (4) ◽  
pp. G454-G463 ◽  
Author(s):  
Adam M. Lopez ◽  
Ryan D. Jones ◽  
Joyce J. Repa ◽  
Stephen D. Turley

Cholesteryl esters are generated at multiple sites in the body by sterol O-acyltransferase (SOAT) 1 or SOAT2 in various cell types and lecithin cholesterol acyltransferase in plasma. Esterified cholesterol and triacylglycerol contained in lipoproteins cleared from the circulation via receptor-mediated or bulk-phase endocytosis are hydrolyzed by lysosomal acid lipase within the late endosomal/lysosomal (E/L) compartment. Then, through the successive actions of Niemann-Pick C (NPC) 2 and NPC 1, unesterified cholesterol (UC) is exported from the E/L compartment to the cytosol. Mutations in either NPC1 or NPC2 lead to continuing entrapment of UC in all organs, resulting in multisystem disease, which includes hepatic dysfunction and in some cases liver failure. These studies investigated primarily whether elimination of SOAT2 in NPC1-deficient mice impacted hepatic UC sequestration, inflammation, and transaminase activities. Measurements were made in 7-wk-old mice fed a low-cholesterol chow diet or one enriched with cholesterol starting 2 wk before study. In the chow-fed mice, NPC1:SOAT2 double knockouts, compared with their littermates lacking only NPC1, had 20% less liver mass, 28% lower hepatic UC concentrations, and plasma alanine aminotransferase and aspartate aminotransferase activities that were decreased by 48% and 36%, respectively. mRNA expression levels for several markers of inflammation were all significantly lower in the NPC1 mutants lacking SOAT2. The existence of a new class of potent and selective SOAT2 inhibitors provides an opportunity for exploring if suppression of this enzyme could potentially become an adjunctive therapy for liver disease in NPC1 deficiency. NEW & NOTEWORTHY In Niemann-Pick type C1 (NPC1) disease, the entrapment of unesterified cholesterol (UC) in the endosomal/lysosomal compartment of all cells causes multiorgan disease, including neurodegeneration, pulmonary dysfunction, and liver failure. Some of this sequestered UC entered cells initially in the esterified form. When sterol O-acyltransferase 2, a cholesterol esterifying enzyme present in enterocytes and hepatocytes, is eliminated in NPC1-deficient mice, there is a reduction in their hepatomegaly, hepatic UC content, and cellular injury.


2018 ◽  
Vol 62 (2) ◽  
pp. 193-204 ◽  
Author(s):  
Adam J. Poe ◽  
Anne A. Knowlton

Exosomes have become an important player in intercellular signaling. These lipid microvesicles can stably transfer miRNA, protein, and other molecules between cells and circulate throughout the body. Exosomes are released by almost all cell types and are present in most if not all biological fluids. The biologically active cargo carried by exosomes can alter the phenotype of recipient cells. Exosomes increasingly are recognized as having an important role in the progression and treatment of cardiac disease states. Injured cardiac cells can release exosomes with important pathological effects on surrounding tissue, in addition to effecting other organs. But of equal interest is the possible benefit(s) conferred by exosomes released from stem cells for use in treatment and possible repair of cardiac damage.


2019 ◽  
Vol 4 (33) ◽  
pp. eaau6085 ◽  
Author(s):  
Steven M. Lewis ◽  
Adam Williams ◽  
Stephanie C. Eisenbarth

The spleen is the largest secondary lymphoid organ in the body and, as such, hosts a wide range of immunologic functions alongside its roles in hematopoiesis and red blood cell clearance. The physical organization of the spleen allows it to filter blood of pathogens and abnormal cells and facilitate low-probability interactions between antigen-presenting cells (APCs) and cognate lymphocytes. APCs specific to the spleen regulate the T and B cell response to these antigenic targets in the blood. This review will focus on cell types, cell organization, and immunologic functions specific to the spleen and how these affect initiation of adaptive immunity to systemic blood-borne antigens. Potential differences in structure and function between mouse and human spleen will also be discussed.


Author(s):  
Vidya Y. Rao

wholesome management of disease states which include diet, habit and medicine for total reversal of disease. Skin is the largest part of the body which is the protective covering as well as a reflection of the internal system. In Ayurveda various dermatological diseases discussed with its etiopathogenesis, classification and management and also described the wide range of etiological factors for Skin diseases including dietary habits and psychosocial factors. Tvak is the reflection of rasa dhatu sarata, hence any derangement in rasa dhatu function directly implies vitiation of quality of skin. The review is to unveil the importance of rasa dhatu dushti assessment in tvak roga which can help in both treatment aspects i.e. nidana parivarjana and samprapti vighattana.


2013 ◽  
Vol 60 (2) ◽  
Author(s):  
Joanna Kałużna-Czaplińska ◽  
Ewa Żurawicz ◽  
Monika Michalska ◽  
Jacek Rynkowski

Homocysteine is an amino acid, which plays several important roles in human physiology. A wide range of disorders, including neuropsychiatric disorders and autism, are associated with increased homocysteine levels in biological fluids. Various B vitamins: B6 (pyridoxine), B12 (cobalamin), and B9 (folic acid) are required as co-factors by the enzymes involved in homocysteine metabolism. Therefore, monitoring of homocysteine levels in body fluids of autistic children can provide information on genetic and physiological diseases, improper lifestyle (including dietary habits), as well as a variety of pathological conditions. This review presents information on homocysteine metabolism, determination of homocysteine in biological fluids, and shows abnormalities in the levels of homocysteine in the body fluids of autistic children.


2021 ◽  
Vol 3 (2) ◽  
pp. 89-98
Author(s):  
Andreea Cozea ◽  
◽  
Gheorghita Tanase ◽  
Mihaela Neagu ◽  

Complex studies were performed combining macroscopic and biochemical analyzes of selected biomonitors, exposed in exposure systems outdoor with mixtures of pollutants as well as controlled exposure with certain concentrations of pollutants in fumigation chambers. In this study, the following plant species were used as bioindicators: Nicotiana tabacum, Petunia hybrida, Ricinus comunis, Trifolium pretense. The exposure plant samples were compared with control samples of biomonitors maintained under standardized conditions in the climate chamber. Classical methods of biochemistry combined with those of exposure biomonitoring have led to the completion of knowledge about the ways of action of plants to pollution. The analysis of some of the antioxidant compounds that are representing a structural class of chemicals (enzymes) with a wide range of biological functions, with the role of free radical inhibition, was performed. Many of the constituent compounds in certain cell types, also called active compounds, in this case, polyphenols are present in the body of some plant species. Polyphenol's presence in organisms, that are not usually present or are in normal quantities, is caused by stress, (pollution being a stress factor). Large amounts of polyphenols in plants are also given by the presence of pollutants in the environment. Through these extensive combined studies, it has been demonstrated that pollution can be a degenerative factor at the biochemical and physiological level, at the plant tissue level, with irreversible effects.


2003 ◽  
Vol 178 (2) ◽  
pp. 177-193 ◽  
Author(s):  
R Zhou ◽  
D Diehl ◽  
A Hoeflich ◽  
H Lahm ◽  
E Wolf

IGFs have multiple functions regarding cellular growth, survival and differentiation under different physiological and pathological conditions. IGF effects are modulated systemically and locally by six high-affinity IGF-binding proteins (IGFBP-1 to -6). Despite their structural similarity, each IGFBP has unique properties and exhibits specific functions. IGFBP-4, the smallest IGFBP, exists in both non-glycosylated and N-glycosylated forms in all biological fluids. It is expressed by a wide range of cell types and tIssues, and its expression is regulated by different mechanisms in a cell type-specific manner. IGFBP-4 binds IGF-I and IGF-II with similar affinities and inhibits their actions under almost all in vitro and in vivo conditions. In this review, we summarize the available data regarding the following aspects of IGFBP-4: genomic organization, protein structure-function relationship, expression and its regulation, as well as IGF-dependent and -independent actions. The biological significance of IGFBP-4 for reproductive physiology, bone formation, renal pathophysiology and cancer is discussed.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mengrou Lu ◽  
Emma DiBernardo ◽  
Emily Parks ◽  
Hannah Fox ◽  
Si-Yang Zheng ◽  
...  

Extracellular vesicles (EVs) are important players in autoimmune diseases, both in disease pathogenesis and as potential treatments. EVs can transport autoimmune triggers throughout the body, facilitating the process of antigen presentation. Understanding the link between cellular stress and EV biogenesis and intercellular trafficking will advance our understanding of autoimmune diseases. In addition, EVs can also be effective treatments for autoimmune diseases. The diversity of cell types that produce EVs leads to a wide range of molecules to be present in EVs, and thus EVs have a wide range of physiological effects. EVs derived from dendritic cells or mesenchymal stem cells have been shown to reduce inflammation. Since many autoimmune treatments are focused only on symptom management, EVs present a promising avenue for potential treatments. This review looks at the different roles EVs can play in autoimmune diseases, from disease pathology to diagnosis and treatment. We also overview various methodologies in isolating or generating EVs and look to the future for possible applications of EVs in autoimmune diseases.


Electronics ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 150 ◽  
Author(s):  
Michele Dei ◽  
Joan Aymerich ◽  
Massimo Piotto ◽  
Paolo Bruschi ◽  
Francisco del Campo ◽  
...  

Smart wearables, among immediate future IoT devices, are creating a huge and fast growing market that will encompass all of the next decade by merging the user with the Cloud in a easy and natural way. Biological fluids, such as sweat, tears, saliva and urine offer the possibility to access molecular-level dynamics of the body in a non-invasive way and in real time, disclosing a wide range of applications: from sports tracking to military enhancement, from healthcare to safety at work, from body hacking to augmented social interactions. The term Internet of Wearables (IoW) is coined here to describe IoT devices composed by flexible smart transducers conformed around the human body and able to communicate wirelessly. In addition the biochemical transducer, an IoW-ready sensor must include a paired electronic interface, which should implement specific stimulation/acquisition cycles while being extremely compact and drain power in the microwatts range. Development of an effective readout interface is a key element for the success of an IoW device and application. This review focuses on the latest efforts in the field of Complementary Metal–Oxide–Semiconductor (CMOS) interfaces for electrochemical sensors, and analyses them under the light of the challenges of the IoW: cost, portability, integrability and connectivity.


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