scholarly journals Integrated diagnostics

2020 ◽  
Vol 30 (1) ◽  
pp. 18-30 ◽  
Author(s):  
Giuseppe Lippi ◽  
Mario Plebani
Keyword(s):  
Information Technology ◽  
Imaging Informatics ◽  
Human Diseases ◽  
Multidisciplinary Teams ◽  
Political Boundaries ◽  
In Vivo Diagnostics ◽  
Technical Advances ◽  
Integrated Diagnostics

The current scenario of in vitro and in vivo diagnostics can be summarized using the “silo metaphor”, where laboratory medicine, pathology and radiology are three conceptually separated diagnostic disciplines, which will increasingly share many comparable features. The substantial progresses in our understanding of biochemical-biological interplays that characterize many human diseases, coupled with extraordinary technical advances, are now generating important multidisciplinary convergences, leading the way to a new frontier, called integrated diagnostics. This new discipline, which is currently defined as convergence of imaging, pathology and laboratory tests with advanced information technology, has an enormous potential for revolutionizing diagnosis and therapeutic management of human diseases, including those causing the largest number of worldwide deaths (i.e. cardiovascular disease, cancer and infectious diseases). However, some important drawbacks should be overcome, mostly represented by insufficient information technology infrastructures, costs and enormous volume of different information that will be integrated and delivered. To overcome these hurdles, some specific strategies should be defined and implemented, such as planning major integration of exiting information systems or developing innovative ones, combining bioinformatics and imaging informatics, using health technology assessment for assessing cost and benefits, providing interpretative comments in integrated reports, developing and using expert systems and neural networks, overcoming cultural and political boundaries for generating multidisciplinary teams and integrated diagnostic algorithms.

scholarly journals Production and Application of Multicistronic Constructs for Various Human Disease Therapies

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 580 ◽  
Author(s):  
Alisa A. Shaimardanova ◽  
Kristina V. Kitaeva ◽  
Ilmira I. Abdrakhmanova ◽  
Vladislav M. Chernov ◽  
Catrin S. Rutland ◽  
...  
Keyword(s):  
Human Diseases ◽  
Cellular Biology ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
New Methods ◽  
In Vivo Experiments ◽  
Mutant Genes ◽  
Methods Of Treatment

The development of multicistronic vectors has opened up new opportunities to address the fundamental issues of molecular and cellular biology related to the need for the simultaneous delivery and joint expression of several genes. To date, the examples of the successful use of multicistronic vectors have been described for the development of new methods of treatment of various human diseases, including cardiovascular, oncological, metabolic, autoimmune, and neurodegenerative disorders. The safety and effectiveness of the joint delivery of therapeutic genes in multicistronic vectors based on the internal ribosome entry site (IRES) and self-cleaving 2A peptides have been shown in both in vitro and in vivo experiments as well as in clinical trials. Co-expression of several genes in one vector has also been used to create animal models of various inherited diseases which are caused by mutations in several genes. Multicistronic vectors provide expression of all mutant genes, which allows the most complete mimicking disease pathogenesis. This review comprehensively discusses multicistronic vectors based on IRES nucleotide sequence and self-cleaving 2A peptides, including its features and possible application for the treatment and modeling of various human diseases.

scholarly journals Oxidative Stress, Antioxidant Capabilities, and Bioavailability: Ellagic Acid or Urolithins?

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 707 ◽  
Author(s):  
Silvana Alfei ◽  
Barbara Marengo ◽  
Guendalina Zuccari
Keyword(s):  
Oxidative Stress ◽  
Ellagic Acid ◽  
Functional Foods ◽  
Fruits And Vegetables ◽  
Human Diseases ◽  
Natural Polyphenols ◽  
Extreme Variability ◽  
Therapeutic Alternatives

Oxidative stress (OS), triggered by overproduction of reactive oxygen and nitrogen species, is the main mechanism responsible for several human diseases. The available one-target drugs often face such illnesses, by softening symptoms without eradicating the cause. Differently, natural polyphenols from fruits and vegetables possess multi-target abilities for counteracting OS, thus representing promising therapeutic alternatives and adjuvants. Although in several in vitro experiments, ellagitannins (ETs), ellagic acid (EA), and its metabolites urolithins (UROs) have shown similar great potential for the treatment of OS-mediated human diseases, only UROs have demonstrated in vivo the ability to reach tissues to a greater extent, thus appearing as the main molecules responsible for beneficial activities. Unfortunately, UROs production depends on individual metabotypes, and the consequent extreme variability limits their potentiality as novel therapeutics, as well as dietary assumption of EA, EA-enriched functional foods, and food supplements. This review focuses on the pathophysiology of OS; on EA and UROs chemical features and on the mechanisms of their antioxidant activity. A discussion on the clinical applicability of the debated UROs in place of EA and on the effectiveness of EA-enriched products is also included.

scholarly journals Mouse models for inherited endocrine and metabolic disorders

2011 ◽  
Vol 211 (3) ◽  
pp. 211-230 ◽  
Author(s):  
Siân E Piret ◽  
Rajesh V Thakker
Keyword(s):  
Mouse Models ◽  
Metabolic Disorders ◽  
Human Diseases ◽  
Chemical Mutagenesis ◽  
Multiple Organs ◽  
Expression Of Genes ◽  
A Genome ◽  
New Treatments

In vivo models represent important resources for investigating the physiological mechanisms underlying endocrine and metabolic disorders, and for pre-clinical translational studies that may include the assessments of new treatments. In the study of endocrine diseases, which affect multiple organs, in vivo models provide specific advantages over in vitro models, which are limited to investigation of isolated systems. In recent years, the mouse has become the popular choice for developing such in vivo mammalian models, as it has a genome that shares ∼85% identity to that of man, and has many physiological systems that are similar to those in man. Moreover, methods have been developed to alter the expression of genes in the mouse, thereby generating models for human diseases, which may be due to loss- or gain-of-function mutations. The methods used to generate mutations in the mouse genome include: chemical mutagenesis; conventional, conditional and inducible knockout models; knockin models and transgenic models, and these strategies are often complementary. This review describes some of the different strategies that are utilised for generating mouse models. In addition, some mouse models that have been successfully generated by these methods for some human hereditary endocrine and metabolic disorders are reviewed. In particular, the mouse models generated for parathyroid disorders, which include: the multiple endocrine neoplasias; hyperparathyroidism-jaw tumour syndrome; disorders of the calcium-sensing receptor and forms of inherited hypoparathyroidism are discussed. The advances that have been made in our understanding of the mechanisms of these human diseases by investigations of these mouse models are described.

scholarly journals Generation of HLA Universal Megakaryocytes and Platelets by Genetic Engineering

2021 ◽  
Vol 12 ◽  
Author(s):  
Constanca Figueiredo ◽  
Rainer Blasczyk
Keyword(s):  
Genetic Engineering ◽  
New Technologies ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Genetically Engineered ◽  
Leukocyte Antigens ◽  
Cell Sources ◽  
Technical Advances

Patelet transfusion refractoriness remains a relevant hurdle in the treatment of severe alloimmunized thrombocytopenic patients. Antibodies specific for the human leukocyte antigens (HLA) class I are considered the major immunological cause for PLT transfusion refractoriness. Due to the insufficient availability of HLA-matched PLTs, the development of new technologies is highly desirable to provide an adequate management of thrombocytopenia in immunized patients. Blood pharming is a promising strategy not only to generate an alternative to donor blood products, but it may offer the possibility to optimize the therapeutic effect of the produced blood cells by genetic modification. Recently, enormous technical advances in the field of in vitro production of megakaryocytes (MKs) and PLTs have been achieved by combining progresses made at different levels including identification of suitable cell sources, cell pharming technologies, bioreactors and application of genetic engineering tools. In particular, use of RNA interference, TALEN and CRISPR/Cas9 nucleases or nickases has allowed for the generation of HLA universal PLTs with the potential to survive under refractoriness conditions. Genetically engineered HLA-silenced MKs and PLTs were shown to be functional and to have the capability to survive cell- and antibody-mediated cytotoxicity using in vitro and in vivo models. This review is focused on the methods to generate in vitro genetically engineered MKs and PLTs with the capacity to evade allogeneic immune responses.

scholarly journals Functional Difference of Mitochondrial Genome and Its Association with Traits of Common Complex Diseases in Humans

2017 ◽  
Author(s):  
Young Min Cho ◽  
Kyong Soo Park ◽  
Youngmi Kim Pak ◽  
Masashi Tanaka ◽  
Hong Kyu Lee
Keyword(s):  
Metabolic Syndrome ◽  
Mitochondrial Genome ◽  
Serum Triglyceride ◽  
Complex Diseases ◽  
Human Diseases ◽  
Dna Polymorphisms ◽  
Mitochondrial Genomes ◽  
Functional Difference

AbstractRecent evidence suggests that mitochondrial genomes harboring common mitochondrial DNA polymorphisms might have functional difference and could be associated with common complex human diseases such as metabolic syndrome and cancer that are related to mitochondrial dysfunction. However, there has been no report examining the functional difference of mitochondrial genome in the pathogenesis of such diseases at the cellular or molecular level. In order to examine the effect of mitochondrial genome on metabolic syndrome or cancer without interference from nuclear genes, we analyzed trans-mitochondrial cytoplasmic hybrid cells (cybrids) with common Asian mtDNA haplogroups A, B, D, and F from healthy volunteers. The mitochondrial oxygen consumption rates of cybrids were associated with multiple components of metabolic syndrome such as body mass index, waist circumference, serum triglyceride levels and high-density lipoprotein cholesterol levels. In addition, the cybrids showed varying degree of tumorigenicity both in vitro and in vivo. Especially, the cybrids harboring mtDNA haplogroup D had a significantly slower growth rate. These findings suggest that the phenotypes of common complex diseases in humans can be determined by their mitochondrial genomes. Therefore, not only nuclear genome but also mitochondrial genome should be considered in explaining the genetic pathogenesis of common complex human diseases.

scholarly journals Resveratrol Nanoparticles: A Promising Therapeutic Advancement over Native Resveratrol

Processes ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 458
Author(s):  
Ill-Min Chung ◽  
Umadevi Subramanian ◽  
Prabhu Thirupathi ◽  
Baskar Venkidasamy ◽  
Ramkumar Samynathan ◽  
...  
Keyword(s):  
Human Diseases ◽  
Physiological System ◽  
Research Publications ◽  
Research Findings ◽  
By Products

The importance of fruit-derived resveratrol (RES) in the treatment of various diseases has been discussed in various research publications. Those research findings have indicated the ability of the molecule as therapeutic in the context of in vitro and in vivo conditions. Mostly, the application of RES in in vivo conditions, encapsulation processes have been carried out using various nanoparticles that are made of biocompatible biomaterials, which are easily digested or metabolized, and RES is absorbed effectively. These biomaterials are non-toxic and are safe to be used as components in the biotherapeutics. They are made from naturally available by-products of food materials like zein or corn or components of the physiological system as with lipids. The versatility of the RES nanoparticles in their different materials, working range sizes, specificity in their targeting in various human diseases, and the mechanisms associated with them are discussed in this review.

scholarly journals Radioisotopes Used as Radiotracers for in vitro and in vivo Diagnostics

2016 ◽  
Vol 28 (2) ◽  
pp. 235-241 ◽  
Author(s):  
Vesna Kuntic ◽  
Jasmina Brboric ◽  
Zorica Vujic ◽  
Snezana Uskokovic-Markovic
Keyword(s):  
In Vivo Diagnostics

scholarly journals Manganese is a Physiologically Relevant TORC1 Activator in Yeast and Mammals.

2021 ◽  
Author(s):  
Raffaele Nicastro ◽  
Helene Gaillard ◽  
Laura Zarzuela ◽  
Elisabet Fernandez-Garcia ◽  
Mercedes Tome ◽  
...  
Keyword(s):  
Metal Ion ◽  
Human Diseases ◽  
Natural Resistance ◽  
Homeostatic Process ◽  
Downstream Effectors ◽  
Mtorc1 Signaling ◽  
The Family ◽  
Macrophage Protein

The essential biometal manganese (Mn) functions as a cofactor for several enzymatic activities that are critical for the prevention of human diseases. Whether intracellular Mn levels may also modulate signaling events has so far remained largely unexplored. The target of rapamycin complex 1 (TORC1, mTORC1 in mammals) is a conserved protein kinase complex that requires metal co-factors to phosphorylate its downstream effectors as part of a central, homeostatic process that coordinates cell growth and metabolism in response to nutrient and/or growth factor availability. Using genetic and biochemical approaches, we show here that TORC1 activity is exquisitely sensitive to stimulation by Mn both in vivo and in vitro. Mn-mediated control of TORC1 depends on Smf1 and Smf2, two members of the family of natural resistance-associated macrophage protein (NRAMP) metal ion transporters, the turnover of which is subjected to feedback control by TORC1 activity. Notably, increased Mn levels and consequent activation of TORC1 cause retrograde dysregulation and antagonize the rapamycin-induced gene expression and autophagy programs in yeast. Because Mn also activates mTORC1 signaling in aminoacid starved human cells, our data indicate that intracellular Mn levels may constitute an evolutionary conserved physiological cue that modulates eukaryotic TORC1/mTORC1 signaling. Our findings therefore reveal a hitherto elusive connection between intracellular Mn levels, mTORC1 activity, and human diseases.

Detection and Validation of Native Plants Traditionally Used as Medicine in Guatemala

2019 ◽  
Vol 5 (1) ◽  
pp. 5-30 ◽  
Author(s):  
Armando Cáceres ◽  
Sully M. Cruz
Keyword(s):  
Native Species ◽  
Clinical Evidence ◽  
Multidisciplinary Teams ◽  
Medicinal Species ◽  
Primary Health ◽  
Comprehensive Literature Review ◽  
International Projects ◽  
Potential Use

Guatemala as part of Mesoamerica, is a region of high biological and cultural diversity, where several cultures have flourished. Since 1976, a project started for the detection, validation, production, and utilization of medicinal species for primary health care. It included several ethnobotanical surveys conducted among ten Guatemalan ethnical groups. The objective of this paper is to summarize the ethnobotanical surveys conducted in the country and review the literature validating the use of the most promising native species. From these surveys, more than 650 plant species used for medicinal purposes were detected and cultivation activities were conducted for some of these species. Initially, in cooperation with the multidisciplinary teams in Guatemala, and later with other academic institutions in Brazil, Costa Rica, Italy, Mexico, Panama, Spain and United States, in vitro and in vivo validation activities were performed, such as biocidal, anti-inflammatory, spasmolytic, immunomodulatory, antioxidant and other activities. A comprehensive literature review of the most relevant species was performed. Based on the traditional utilization and preclinical or clinical evidence, several national and international projects were conducted. The most interesting results include anti-candida (Solanum nigrescens), antimicrobial (Tagetes lucida), immunomodulator (Phlebodium pseudoaureum), anti-protozoal (Neurolaena lobata), sedative (Valeriana prionophylla), anti-menopause (Piper hispidum) activities and others. With this information and the reviewed literature, specific formulas were prepared for the treatment of different pathologies, leading to several products registered as phytotherapic in Guatemala. Concise updated information is integrated into mini-reviews for 15 species in order to inform about the properties, chemistry and potential use of these species.

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