Journal articles on the topic 'Medical molecular engineering of nucleic acids and proteins'
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Kim, Jinmyeong, Seungwoo Noh, Jeong Ah Park, Sang-Chan Park, Seong Jun Park, Jin-Ho Lee, Jae-Hyuk Ahn, and Taek Lee. "Recent Advances in Aptasensor for Cytokine Detection: A Review." Sensors 21, no. 24 (December 20, 2021): 8491. http://dx.doi.org/10.3390/s21248491.
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Cytokines are proteins secreted by immune cells. They promote cell signal transduction and are involved in cell replication, death, and recovery. Cytokines are immune modulators, but their excessive secretion causes uncontrolled inflammation that attacks normal cells. Considering the properties of cytokines, monitoring the secretion of cytokines in vivo is of great value for medical and biological research. In this review, we offer a report on recent studies for cytokine detection, especially studies on aptasensors using aptamers. Aptamers are single strand nucleic acids that form a stable three-dimensional structure and have been receiving attention due to various characteristics such as simple production methods, low molecular weight, and ease of modification while performing a physiological role similar to antibodies.
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Zhou, Qun. "Site-Specific Antibody Conjugation with Payloads beyond Cytotoxins." Molecules 28, no. 3 (January 17, 2023): 917. http://dx.doi.org/10.3390/molecules28030917.
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As antibody–drug conjugates have become a very important modality for cancer therapy, many site-specific conjugation approaches have been developed for generating homogenous molecules. The selective antibody coupling is achieved through antibody engineering by introducing specific amino acid or unnatural amino acid residues, peptides, and glycans. In addition to the use of synthetic cytotoxins, these novel methods have been applied for the conjugation of other payloads, including non-cytotoxic compounds, proteins/peptides, glycans, lipids, and nucleic acids. The non-cytotoxic compounds include polyethylene glycol, antibiotics, protein degraders (PROTAC and LYTAC), immunomodulating agents, enzyme inhibitors and protein ligands. Different small proteins or peptides have been selectively conjugated through unnatural amino acid using click chemistry, engineered C-terminal formylglycine for oxime or click chemistry, or specific ligation or transpeptidation with or without enzymes. Although the antibody protamine peptide fusions have been extensively used for siRNA coupling during early studies, direct conjugations through engineered cysteine or lysine residues have been demonstrated later. These site-specific antibody conjugates containing these payloads other than cytotoxic compounds can be used in proof-of-concept studies and in developing new therapeutics for unmet medical needs.
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Nazir, Gowhar, and Josee Amin. "Molecular tools for the diagnosis of periodontitis." International Journal of Dentistry Research 6, no. 3 (December 30, 2021): 81–88. http://dx.doi.org/10.31254/dentistry.2021.6304.
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Periodontitis is a multifactorial chronic inflammatory disease associated with dysbiotic biofilms and aberrant host inflammatory response. It is characterized by destruction of the tissues that support the teeth. Periodontitis is the major cause of tooth loss in adults significantly affecting the quality of life and is associated with many chronic non communicable diseases by contributing to systemic inflammatory burden. Early and accurate diagnosis is the key to the successful management of periodontitis as the entire treatment plan, prognosis, and maintenance directly depend on the quality of periodontal diagnosis. Traditionally the diagnosis of Periodontitis is based on recording medical and dental history, periodontal examination and radiographic findings. The current periodontal diagnostic process reveals only historical tissue destruction and does not provide any information regarding current disease activity, future progression or for monitoring response to therapy. For these reasons, new molecular diagnostic aids are being developed that allow an early detection of disease, determine the presence of current disease activity, predict sites at risk for future breakdown and monitor the response to periodontal therapy. Advanced molecular diagnostic techniques are a class of diagnostic tests that are used to detect and measure nucleic acids, proteins or metabolites in clinical samples to identify risk factors, screen asymptomatic patients, provide more accurate diagnosis and guide the process of development of an ideal therapeutic intervention. This paper provides a review of the molecular diagnostic tools that have the potential to be utilized for diagnosis and management of periodontitis.
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Gupta, Ms Veenu. "Microbial Production of Biopolymers and Polymer Precursors." International Journal for Research in Applied Science and Engineering Technology 10, no. 7 (July 31, 2022): 47–54. http://dx.doi.org/10.22214/ijraset.2022.45052.
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Abstract: Living organisms, namely, prokaryotes and eukaryotes, are able to synthesize a variety of polymers, such as nucleic acids, proteins, and other polyamides, polysaccharides, polyesters, polythioesters, polyanhydrides, polyisoprenoids, and lignin. Microorganisms provide a source of biopolymers and biopolysaccharides from renewable sources. Bacteria are capable of yielding biopolymers with properties comparable to plastics derived from petrochemicals, though more expensive. They have the additional advantage of being biodegradable. A wide range of microbial polysaccharides have been studied, and structure/function relationships for a number of these macromolecules have been determined. These biopolymers accomplish different essential and beneficial functions for the organisms. Among the biopolymers produced, many are used for various industrial applications. Currently, the biotechnological production of polymers has been mostly achieved by fermentation of microorganisms in stirred bioreactors. The biopolymers can be obtained as extracellular or intracellular compounds. Alternatively, biopolymers can also be produced by in vitro enzymatic processes. However, the largest amounts of biopolymers are still extracted from plant and animal sources. Biopolymers exhibit fascinating properties and play a major role in the food processing industry, e.g., modifying texture and other properties. Among the various biopolymers, polysaccharides and bioplastics are the most important in the food industry. This chapter will discuss the sources of polymers, their biosynthesis by different organisms, and their application in different fields. A huge variety of biopolymers, such as polysaccharides, polyesters, and polyamides, are naturally produced by microorganisms. These range from viscous solutions to plastics and their physical properties are dependent on the composition and molecular weight of the polymer. The genetic manipulation of microorganisms opens up an enormous potential for the biotechnological production of biopolymers with tailored properties suitable for highvalue medical application such as tissue engineering and drug delivery.
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Nishimura, Tomoki, and Kazunari Akiyoshi. "Artificial Molecular Chaperone Systems for Proteins, Nucleic Acids, and Synthetic Molecules." Bioconjugate Chemistry 31, no. 5 (April 26, 2020): 1259–67. http://dx.doi.org/10.1021/acs.bioconjchem.0c00133.
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Antropov, Denis N., and Grigory A. Stepanov. "Molecular Mechanisms Underlying CRISPR/Cas-Based Assays for Nucleic Acid Detection." Current Issues in Molecular Biology 45, no. 1 (January 10, 2023): 649–62. http://dx.doi.org/10.3390/cimb45010043.
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Applied to investigate specific sequences, nucleic acid detection assays can help identify novel bacterial and viral infections. Most up-to-date systems combine isothermal amplification with Cas-mediated detection. They surpass standard PCR methods in detection time and sensitivity, which is crucial for rapid diagnostics. The first part of this review covers the variety of isothermal amplification methods and describes their reaction mechanisms. Isothermal amplification enables fast multiplication of a target nucleic acid sequence without expensive laboratory equipment. However, researchers aim for more reliable results, which cannot be achieved solely by amplification because it is also a source of non-specific products. This motivated the development of Cas-based assays that use Cas9, Cas12, or Cas13 proteins to detect nucleic acids and their fragments in biological specimens with high specificity. Isothermal amplification yields a high enough concentration of target nucleic acids for the specific signal to be detected via Cas protein activity. The second part of the review discusses combinations of different Cas-mediated reactions and isothermal amplification methods and presents signal detection techniques adopted in each assay. Understanding the features of Cas-based assays could inform the choice of an optimal protocol to detect different nucleic acids.
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Palermo, Giovanna, Kandammathe Valiyaveedu Sreekanth, Nicolò Maccaferri, Giuseppe Emanuele Lio, Giuseppe Nicoletta, Francesco De Angelis, Michael Hinczewski, and Giuseppe Strangi. "Hyperbolic dispersion metasurfaces for molecular biosensing." Nanophotonics 10, no. 1 (October 7, 2020): 295–314. http://dx.doi.org/10.1515/nanoph-2020-0466.
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AbstractSensor technology has become increasingly crucial in medical research and clinical diagnostics to directly detect small numbers of low-molecular-weight biomolecules relevant for lethal diseases. In recent years, various technologies have been developed, a number of them becoming core label-free technologies for detection of cancer biomarkers and viruses. However, to radically improve early disease diagnostics, tracking of disease progression and evaluation of treatments, today’s biosensing techniques still require a radical innovation to deliver high sensitivity, specificity, diffusion-limited transport, and accuracy for both nucleic acids and proteins. In this review, we discuss both scientific and technological aspects of hyperbolic dispersion metasurfaces for molecular biosensing. Optical metasurfaces have offered the tantalizing opportunity to engineer wavefronts while its intrinsic nanoscale patterns promote tremendous molecular interactions and selective binding. Hyperbolic dispersion metasurfaces support high-k modes that proved to be extremely sensitive to minute concentrations of ultralow-molecular-weight proteins and nucleic acids.
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Mojica, Wilfrido D., Ayesha Arshad, Sanjay Sharma, and Stephen P. Brooks. "Manual Exfoliation Plus Immunomagnetic Bead Separation as an Initial Step Toward Translational Research." Archives of Pathology & Laboratory Medicine 130, no. 1 (January 1, 2006): 74–79. http://dx.doi.org/10.5858/2006-130-74-mepibs.
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Abstract Context.—The development of biotechnologic platforms capable of high throughput analysis has ushered in a promising new era of translational medicine. However, most studies to date are based on in vitro cell lines or substitute models for human disease. Although these model systems have proven insightful, it is readily becoming apparent that human clinical tissue must be studied in order to fully understand all the nuances of human disease. Studies that are based on human tissue, however, are limited by qualitative and quantitative issues, factors often precluding their use in high throughput studies. Objective.—To develop a simple and rapid tissue procurement protocol for use in obtaining a homogeneous epithelial cell population from clinical tissue and the recovery of nucleic acids and proteins of high quality and quantity. Also, to determine if the technique preserves tissue, thereby allowing morphologic correlation with molecular findings. Design.—Performance of manual exfoliation to procure cells from clinical resection specimens and use of immunomagnetic beads embedded with the antibody ber-Ep4 for the positive enrichment of a homogeneous epithelial cell population. Nucleic acids and proteins are then separated using a phenol plus guanidine thiocyante solution. Nucleic acids and proteins are quantitated and qualitatively analyzed using standard laboratory techniques. Results.—Nucleic acids and proteins of high quality and quantity were recovered following manual exfoliation and immunomagnetic bead separation. Tissue architecture was not destroyed, thus permitting histologic and molecular correlation. Conclusions.—A simple and reproducible protocol is presented that may enable the molecular profiling of clinically resected tissue. Although the technique is currently limited to certain tissue and tumor types, further research will broaden its overall application.
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Wiebe, Leonard I. "Applications of nucleoside-based molecular probes for the in vivo assessment of tumour biochemistry using positron emission tomography (PET)." Brazilian Archives of Biology and Technology 50, no. 3 (May 2007): 445–59. http://dx.doi.org/10.1590/s1516-89132007000300011.
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Positron emission tomography (PET) is a non-invasive nuclear imaging technique. In PET, radiolabelled molecules decay by positron emission. The gamma rays resulting from positron annihilation are detected in coincidence and mapped to produce three dimensional images of radiotracer distribution in the body. Molecular imaging with PET refers to the use of positron-emitting biomolecules that are highly specific substrates for target enzymes, transport proteins or receptor proteins. Molecular imaging with PET produces spatial and temporal maps of the target-related processes. Molecular imaging is an important analytical tool in diagnostic medical imaging, therapy monitoring and the development of new drugs. Molecular imaging has its roots in molecular biology. Originally, molecular biology meant the biology of gene expression, but now molecular biology broadly encompasses the macromolecular biology and biochemistry of proteins, complex carbohydrates and nucleic acids. To date, molecular imaging has focused primarily on proteins, with emphasis on monoclonal antibodies and their derivative forms, small-molecule enzyme substrates and components of cell membranes, including transporters and transmembrane signalling elements. This overview provides an introduction to nucleosides, nucleotides and nucleic acids in the context of molecular imaging.
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Ye, Dekai, Xiaolei Zuo, and Chunhai Fan. "DNA Nanotechnology-Enabled Interfacial Engineering for Biosensor Development." Annual Review of Analytical Chemistry 11, no. 1 (June 12, 2018): 171–95. http://dx.doi.org/10.1146/annurev-anchem-061417-010007.
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Biosensors represent biomimetic analytical tools for addressing increasing needs in medical diagnosis, environmental monitoring, security, and biodefense. Nevertheless, widespread real-world applications of biosensors remain challenging due to limitations of performance, including sensitivity, specificity, speed, and reproducibility. In this review, we present a DNA nanotechnology-enabled interfacial engineering approach for improving the performance of biosensors. We first introduce the main challenges of the biosensing interfaces, especially under the context of controlling the DNA interfacial assembly. We then summarize recent progress in DNA nanotechnology and efforts to harness DNA nanostructures to engineer various biological interfaces, with a particular focus on the use of framework nucleic acids. We also discuss the implementation of biosensors to detect physiologically relevant nucleic acids, proteins, small molecules, ions, and other biomarkers. This review highlights promising applications of DNA nanotechnology in interfacial engineering for biosensors and related areas.
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Caraceni, P., N. De Maria, H. S. Ryu, A. Colantoni, L. Roberts, M. L. Maidt, Q. Pye, M. Bernardi, D. H. Van Thiel, and R. A. Floyd. "Proteins but not Nucleic Acids are Molecular Targets for the Free Radical Attack During Reoxygenation of Rat Hepatocytes." Free Radical Biology and Medicine 23, no. 2 (January 1997): 339–44. http://dx.doi.org/10.1016/s0891-5849(96)00571-0.
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Feng, Wei, Ashley M. Newbigging, Jeffrey Tao, Yiren Cao, Hanyong Peng, Connie Le, Jinjun Wu, et al. "CRISPR technology incorporating amplification strategies: molecular assays for nucleic acids, proteins, and small molecules." Chemical Science 12, no. 13 (2021): 4683–98. http://dx.doi.org/10.1039/d0sc06973f.
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Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) protein systems revolutionize genome engineering and advance analytical chemistry and diagnostic technology.
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Banerjee, Ashis Gopal, Sagar Chowdhury, Wolfgang Losert, and Satyandra K. Gupta. "Survey on indirect optical manipulation of cells, nucleic acids, and motor proteins." Journal of Biomedical Optics 16, no. 5 (2011): 051302. http://dx.doi.org/10.1117/1.3579200.
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Vasile, Cornelia, Daniela Pamfil, Elena Stoleru, and Mihaela Baican. "New Developments in Medical Applications of Hybrid Hydrogels Containing Natural Polymers." Molecules 25, no. 7 (March 27, 2020): 1539. http://dx.doi.org/10.3390/molecules25071539.
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New trends in biomedical applications of the hybrid polymeric hydrogels, obtained by combining natural polymers with synthetic ones, have been reviewed. Homopolysaccharides, heteropolysaccharides, as well as polypeptides, proteins and nucleic acids, are presented from the point of view of their ability to form hydrogels with synthetic polymers, the preparation procedures for polymeric organic hybrid hydrogels, general physico-chemical properties and main biomedical applications (i.e., tissue engineering, wound dressing, drug delivery, etc.).
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Ye, Miaomiao, Jing Wang, Shuya Pan, Lihong Zheng, Zhi-Wei Wang, and Xueqiong Zhu. "Nucleic acids and proteins carried by exosomes of different origins as potential biomarkers for gynecologic cancers." Molecular Therapy - Oncolytics 25 (June 2022): 307. http://dx.doi.org/10.1016/j.omto.2022.05.006.
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Ye, Miaomiao, Jing Wang, Shuya Pan, Lihong Zheng, Zhi-Wei Wang, and Xueqiong Zhu. "Nucleic acids and proteins carried by exosomes of different origins as potential biomarkers for gynecologic cancers." Molecular Therapy - Oncolytics 24 (March 2022): 101–13. http://dx.doi.org/10.1016/j.omto.2021.12.005.
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Visca, Eva, Olav Lapaire, Irene Hösli, and Sinuhe Hahn. "Cell-free fetal nucleic acids as prenatal biomarkers." Expert Opinion on Medical Diagnostics 5, no. 2 (February 8, 2011): 151–60. http://dx.doi.org/10.1517/17530059.2011.554821.
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Li, Hanying, Thomas H. LaBean, and Kam W. Leong. "Nucleic acid-based nanoengineering: novel structures for biomedical applications." Interface Focus 1, no. 5 (June 28, 2011): 702–24. http://dx.doi.org/10.1098/rsfs.2011.0040.
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Nanoengineering exploits the interactions of materials at the nanometre scale to create functional nanostructures. It relies on the precise organization of nanomaterials to achieve unique functionality. There are no interactions more elegant than those governing nucleic acids via Watson–Crick base-pairing rules. The infinite combinations of DNA/RNA base pairs and their remarkable molecular recognition capability can give rise to interesting nanostructures that are only limited by our imagination. Over the past years, creative assembly of nucleic acids has fashioned a plethora of two-dimensional and three-dimensional nanostructures with precisely controlled size, shape and spatial functionalization. These nanostructures have been precisely patterned with molecules, proteins and gold nanoparticles for the observation of chemical reactions at the single molecule level, activation of enzymatic cascade and novel modality of photonic detection, respectively. Recently, they have also been engineered to encapsulate and release bioactive agents in a stimulus-responsive manner for therapeutic applications. The future of nucleic acid-based nanoengineering is bright and exciting. In this review, we will discuss the strategies to control the assembly of nucleic acids and highlight the recent efforts to build functional nucleic acid nanodevices for nanomedicine.
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Fonseca-Benitez, Angela, Consuelo Romero-Sánchez, and Sandra Janneth Perdomo Lara. "A Rapid and Simple Method for Purification of Nucleic Acids on Porous Membranes: Simulation vs. Experiment." Micromachines 13, no. 12 (December 16, 2022): 2238. http://dx.doi.org/10.3390/mi13122238.
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Paper-based microfluidic systems have emerged as one of the most promising technologies for developing point-of-care diagnostic platforms (POCT) for detecting and monitoring various diseases. Saliva is a non-invasive biofluid easily collected, transported, and stored. Due to its accessibility and connection to systemic diseases, saliva is one of the best candidates for medical advancement at the point of care, where people can easily monitor their health. However, saliva is a complex mixture of DNA, RNA, proteins, exosomes, and electrolytes. Thus, nucleic acid separation from the salivary components is essential for PCR applications. Paper membranes are a highly porous and foldable structure capable of transporting fluids without pumps and sophisticated systems. The current work presents an insight into simulations for nucleic acid extraction on three types of porous paper membranes for use in point-of-care devices. The flow fluid model is solved on a COMSOL Multiphysics 5.3 free version platform, and the results are compared with experimental assays. The results show that pore uniformity, wet strength, porosity, and functional groups of MF1™ and Fusion 5™ paper membranes are vital parameters affecting nucleic acid extraction and PCR amplification efficiency.
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Digel, I., P. Kayser, and G. M. Artmann. "Molecular Processes in Biological Thermosensation." Journal of Biophysics 2008 (May 12, 2008): 1–9. http://dx.doi.org/10.1155/2008/602870.
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Since thermal gradients are almost everywhere, thermosensation could represent one of the oldest sensory transduction processes that evolved in organisms. There are many examples of temperature changes affecting the physiology of living cells. Almost all classes of biological macromolecules in a cell (nucleic acids, lipids, proteins) can present a target of the temperature-related stimuli. This review discusses some features of different classes of temperature-sensing molecules as well as molecular and biological processes that involve thermosensation. Biochemical, structural, and thermodynamic approaches are applied in the paper to organize the existing knowledge on molecular mechanisms of thermosensation. Special attention is paid to the fact that thermosensitive function cannot be assigned to any particular functional group or spatial structure but is rather of universal nature. For instance, the complex of thermodynamic, structural, and functional features of hemoglobin family proteins suggests their possible accessory role as “molecular thermometers”.
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Bogomolova, E. G., P. M. Kopeykin, and A. A. Tagaev. "Genetic engineering approaches to the development of modern therapeutics." Medical academic journal 20, no. 3 (September 15, 2020): 49–60. http://dx.doi.org/10.17816/maj34092.
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The classic approach to production of protein-based therapeutics is their isolation from natural sources. This approach was associated with a number of difficulties, such as collecting the primary material from natural sources, isolating and purifying the protein, and its standardizing. With the development of recombinant DNA technology, itbecame possible to obtain large quantities of protein preparations lacking any contaminations. Human insulin produced using recombinant DNA technology is the first commercial therapeutic obtained by this way. Due to the rapid development of genetic engineering technologies, a large number of proteins have been obtained inEscherichia colicells. In recent years, the approach for the development of drugs based on DNA molecules containing genes encoding therapeutic proteins has been developing more actively. Today, many scientists believe in the prospects of application of DNA vaccines. The ease of production, stability, the ability to mimic natural infections and elicit appropriate immune responses make this vaccine platform extremely attractive. Delivery and targeting of immunologically relevant cells are major tasks for maximizing the immunogenicity of DNA vaccines. Several different approaches that are currently being used to achieve this goal are discussed in this review. Pharmaceuticals based on nucleic acids have a number of undeniable advantages. The main options for prophylactic RNA vaccines, the methods used to deliver RNA to the cell, and methods for increasing the effectiveness of RNA vaccines are discussed. Usage of therapeutic drugs based on protein molecules and low molecular weight compounds is complicated by the fact that they cannot be targeted at a specific gene or its protein product, responsible for the occurrence of the disease. Action of nucleic acids can be directly directed to a particular DNA region in order to edit its nucleotide sequence. This method allows to correct a genetic defect, eliminating the cause of the disease. The principles of gene therapy and the successes achieved in this area are discussed. This review summarizes current achievements in the development of drugs based on recombinant proteins and nucleic acids.
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Zheng, Chao, Hong Ying Jia, Li Yuan Liu, Qi Wang, Hong Chuan Jiang, Li Song Teng, Cui Zhi Geng, et al. "Molecular fingerprint of precancerous lesions in breast atypical hyperplasia." Journal of International Medical Research 48, no. 6 (June 2020): 030006052093161. http://dx.doi.org/10.1177/0300060520931616.
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Objective To identify atypical hyperplasia (AH) of the breast by shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS), and to explore the molecular fingerprinting characteristics of breast AH. Methods Breast hyperplasia was studied in 11 hospitals across China from January 2015 to December 2016. All patients completed questionnaires on women’s health. The differences between patients with and without breast AH were compared. AH breast lesions were detected by Raman spectroscopy followed by the SHINERS technique. Results There were no significant differences in clinical features and risk-related factors between patients with breast AH (n = 37) and the control group (n = 2576). Fifteen cases of breast AH lesions were detected by Raman spectroscopy. The main different Raman peaks in patients with AH appeared at 880, 1001, 1086, 1156, 1260, and 1610 cm−1, attributed to the different vibrational modes of nucleic acids, β-carotene, and proteins. Shell-isolated nanoparticles had different enhancement effects on the nucleic acid, protein, and lipid components in AH. Conclusion Raman spectroscopy can detect characteristic molecular changes in breast AH lesions, and may thus be useful for the non-invasive early diagnosis and for investigating the mechanism of tumorigenesis in patients with breast AH.
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Privalov, Peter L. "Thermodynamic problems in structural molecular biology." Pure and Applied Chemistry 79, no. 8 (January 1, 2007): 1445–62. http://dx.doi.org/10.1351/pac200779081445.
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The most essential feature of living biological systems is their high degree of structural organization. The key role is played by two linear heteropolymers, the proteins and nucleic acids. Under environmental conditions close to physiological, these biopolymers are folded into unique native conformations, genetically determined by the arrangement of their standard building blocks. In their native conformation, biological macromolecules recognize their partners and associate with them, forming specific, higher-order complexes, the "molecular machines". Folding of biopolymers into their native conformation and their association with partners is in principle a reversible, thermodynamically driven process. Investigation of the thermodynamics of these basic biological processes has prime importance for understanding the mechanisms of forming these supra-macromolecular constructions and their functioning.
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Crnković, Ana, Marija Srnko, and Gregor Anderluh. "Biological Nanopores: Engineering on Demand." Life 11, no. 1 (January 5, 2021): 27. http://dx.doi.org/10.3390/life11010027.
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Nanopore-based sensing is a powerful technique for the detection of diverse organic and inorganic molecules, long-read sequencing of nucleic acids, and single-molecule analyses of enzymatic reactions. Selected from natural sources, protein-based nanopores enable rapid, label-free detection of analytes. Furthermore, these proteins are easy to produce, form pores with defined sizes, and can be easily manipulated with standard molecular biology techniques. The range of possible analytes can be extended by using externally added adapter molecules. Here, we provide an overview of current nanopore applications with a focus on engineering strategies and solutions.
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Zhang, Zhenjiang, Jenna A. Dombroski, and Michael R. King. "Engineering of Exosomes to Target Cancer Metastasis." Cellular and Molecular Bioengineering 13, no. 1 (December 23, 2019): 1–16. http://dx.doi.org/10.1007/s12195-019-00607-x.
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AbstractAs a nanoscale subset of extracellular vehicles, exosomes represent a new pathway of intercellular communication by delivering cargos such as proteins and nucleic acids to recipient cells. Importantly, it has been well documented that exosome-mediated delivery of such cargo is involved in many pathological processes such as tumor progression, cancer metastasis, and development of drug resistance. Innately biocompatible and possessing ideal structural properties, exosomes offer distinct advantages for drug delivery over artificial nanoscale drug carriers. In this review, we summarize recent progress in methods for engineering exosomes including isolation techniques and exogenous cargo encapsulation, with a focus on applications of engineered exosomes to target cancer metastasis.
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Ruigrok, Vincent J. B., Mark Levisson, Michel H. M. Eppink, Hauke Smidt, and John van der Oost. "Alternative affinity tools: more attractive than antibodies?" Biochemical Journal 436, no. 1 (April 27, 2011): 1–13. http://dx.doi.org/10.1042/bj20101860.
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Antibodies are the most successful affinity tools used today, in both fundamental and applied research (diagnostics, purification and therapeutics). Nonetheless, antibodies do have their limitations, including high production costs and low stability. Alternative affinity tools based on nucleic acids (aptamers), polypeptides (engineered binding proteins) and inorganic matrices (molecular imprinted polymers) have received considerable attention. A major advantage of these alternatives concerns the efficient (microbial) production and in vitro selection procedures. The latter approach allows for the high-throughput optimization of aptamers and engineered binding proteins, e.g. aiming at enhanced chemical and physical stability. This has resulted in a rapid development of the fields of nucleic acid- and protein-based affinity tools and, although they are certainly not as widely used as antibodies, the number of their applications has steadily increased in recent years. In the present review, we compare the properties of the more conventional antibodies with these innovative affinity tools. Recent advances of affinity tool developments are described, both in a medical setting (e.g. diagnostics, therapeutics and drug delivery) and in several niche areas for which antibodies appear to be less attractive. Furthermore, an outlook is provided on anticipated future developments.
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Stripp, B. R., J. A. Whitsett, and D. L. Lattier. "Strategies for analysis of gene expression: pulmonary surfactant proteins." American Journal of Physiology-Lung Cellular and Molecular Physiology 259, no. 4 (October 1, 1990): L185—L197. http://dx.doi.org/10.1152/ajplung.1990.259.4.l185.
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Gene transcription is regulated by the formation of protein-DNA complexes that influence the rate of specific initiation of transcription by RNA polymerase. Recent experimental advances allowing the identification of cis regulatory sequences that specify the binding of trans acting protein factors have made significant contributions to our understanding of the mechanistic complexities of transcriptional regulation. These methodologies have prompted the use of similar strategies to elucidate transcriptional control mechanisms involved in the tissue specific and developmental regulation of pulmonary surfactant protein gene expression. The purpose of this review is to describe various methodologies by which molecular biologists identify and subsequently assay regions of nucleic acids presumed to be integral in gene regulation at the level of transcription. It is well established that genes encoding surfactant proteins are subject to regulation by hormones, cytokines, and a variety of biologically active reagents. Perhaps future studies utilizing molecular tools outlined in this review will be valuable in identification of DNA sequences and protein factors required for the regulation of lung surfactant genes.
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Varotsis, Constantinos, Marios Papageorgiou, Charalampos Tselios, Konstantinos A. Yiannakkos, Anastasia Adamou, and Antonis Nicolaides. "Bacterial Colonization on the Surface of Copper Sulfide Minerals Probed by Fourier Transform Infrared Micro-Spectroscopy." Crystals 10, no. 11 (November 5, 2020): 1002. http://dx.doi.org/10.3390/cryst10111002.
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Biofilm formation is a molecular assembly process occurring at interfaces, such as in bioleaching processes. The real time monitoring of the marker bands of amide I/amide II by FTIR microspectroscopy during Acidithiobacillus ferrooxidans colonization on chalcopyrite surfaces revealed the central role of lipids, proteins and nucleic acids in bacterial cell attachment to copper sulfide surfaces. The Raman and FTIR spectra of the interactions of Acidithiobacillus ferrooxidans with bornite are also reported.
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Benhal, Prateek, David Quashie, Yoontae Kim, and Jamel Ali. "Insulator Based Dielectrophoresis: Micro, Nano, and Molecular Scale Biological Applications." Sensors 20, no. 18 (September 7, 2020): 5095. http://dx.doi.org/10.3390/s20185095.
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Insulator based dielectrophoresis (iDEP) is becoming increasingly important in emerging biomolecular applications, including particle purification, fractionation, and separation. Compared to conventional electrode-based dielectrophoresis (eDEP) techniques, iDEP has been demonstrated to have a higher degree of selectivity of biological samples while also being less biologically intrusive. Over the past two decades, substantial technological advances have been made, enabling iDEP to be applied from micro, to nano and molecular scales. Soft particles, including cell organelles, viruses, proteins, and nucleic acids, have been manipulated using iDEP, enabling the exploration of subnanometer biological interactions. Recent investigations using this technique have demonstrated a wide range of applications, including biomarker screening, protein folding analysis, and molecular sensing. Here, we review current state-of-art research on iDEP systems and highlight potential future work.
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Jaekel, Stegemann, and Saccà. "Manipulating Enzymes Properties with DNA Nanostructures." Molecules 24, no. 20 (October 14, 2019): 3694. http://dx.doi.org/10.3390/molecules24203694.
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Nucleic acids and proteins are two major classes of biopolymers in living systems. Whereas nucleic acids are characterized by robust molecular recognition properties, essential for the reliable storage and transmission of the genetic information, the variability of structures displayed by proteins and their adaptability to the environment make them ideal functional materials. One of the major goals of DNA nanotechnology—and indeed its initial motivation—is to bridge these two worlds in a rational fashion. Combining the predictable base-pairing rule of DNA with chemical conjugation strategies and modern protein engineering methods has enabled the realization of complex DNA-protein architectures with programmable structural features and intriguing functionalities. In this review, we will focus on a special class of biohybrid structures, characterized by one or many enzyme molecules linked to a DNA scaffold with nanometer-scale precision. After an initial survey of the most important methods for coupling DNA oligomers to proteins, we will report the strategies adopted until now for organizing these conjugates in a predictable spatial arrangement. The major focus of this review will be on the consequences of such manipulations on the binding and kinetic properties of single enzymes and enzyme complexes: an interesting aspect of artificial DNA-enzyme hybrids, often reported in the literature, however, not yet entirely understood and whose full comprehension may open the way to new opportunities in protein science.
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Campbell, Jack, Georgia Kastania, and Dmitry Volodkin. "Encapsulation of Low-Molecular-Weight Drugs into Polymer Multilayer Capsules Templated on Vaterite CaCO3 Crystals." Micromachines 11, no. 8 (July 24, 2020): 717. http://dx.doi.org/10.3390/mi11080717.
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Polyelectrolyte multilayer capsules (PEMCs) templated onto biocompatible and easily degradable vaterite CaCO3 crystals via the layer-by-layer (LbL) polymer deposition process have served as multifunctional and tailor-made vehicles for advanced drug delivery. Since the last two decades, the PEMCs were utilized for effective encapsulation and controlled release of bioactive macromolecules (proteins, nucleic acids, etc.). However, their capacity to host low-molecular-weight (LMW) drugs (<1–2 kDa) has been demonstrated rather recently due to a limited retention ability of multilayers to small molecules. The safe and controlled delivery of LMW drugs plays a vital role for the treatment of cancers and other diseases, and, due to their tunable and inherent properties, PEMCs have shown to be good candidates for smart drug delivery. Herein, we summarize recent progress on the encapsulation of LMW drugs into PEMCs templated onto vaterite CaCO3 crystals. The drug loading and release mechanisms, advantages and limitations of the PEMCs as LMW drug carriers, as well as bio-applications of drug-laden capsules are discussed based upon the recent literature findings.
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Marwicka, Justyna, and Anna Zięba. "Antioxidants as a defence against reactive oxygen species." Aesthetic Cosmetology and Medicine 10, no. 6 (December 2021): 271–76. http://dx.doi.org/10.52336/acm.2021.10.6.02.
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Reactive oxygen species are formed as a natural product of metabolic processes occurring in the organism or under the influence of external factors. Under homeostasis, they play an important role as a cellular signaling device. During oxidative stress, when they are produced in excess, they can cause damages to proteins, lipids, carbohydrates or nucleic acids. Exposure of cells and extracellular structures to free radicals activate natural mechanisms to eliminate free radicals and their derivatives. The aim of the article was to present what antioxidants are, and how they protect cells against the free radicals. The protective system against the free radicals consists of antioxidant enzymes: superoxide dismutase, catalase, glutathione peroxidases, and reductase. Low-molecular antioxidants such as vitamin C, E, carotenoids, coenzyme Q10, flavonoids, glutathione and melatonin also play an important role.
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Poghossian, Arshak, and Michael J. Schöning. "Capacitive Field-Effect EIS Chemical Sensors and Biosensors: A Status Report." Sensors 20, no. 19 (October 2, 2020): 5639. http://dx.doi.org/10.3390/s20195639.
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Electrolyte-insulator-semiconductor (EIS) field-effect sensors belong to a new generation of electronic chips for biochemical sensing, enabling a direct electronic readout. The review gives an overview on recent advances and current trends in the research and development of chemical sensors and biosensors based on the capacitive field-effect EIS structure—the simplest field-effect device, which represents a biochemically sensitive capacitor. Fundamental concepts, physicochemical phenomena underlying the transduction mechanism and application of capacitive EIS sensors for the detection of pH, ion concentrations, and enzymatic reactions, as well as the label-free detection of charged molecules (nucleic acids, proteins, and polyelectrolytes) and nanoparticles, are presented and discussed.
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Meroni, Gabriele, Simona Panelli, Gianvincenzo Zuccotti, Claudio Bandi, Lorenzo Drago, and Dario Pistone. "Probiotics as Therapeutic Tools against Pathogenic Biofilms: Have We Found the Perfect Weapon?" Microbiology Research 12, no. 4 (December 6, 2021): 916–37. http://dx.doi.org/10.3390/microbiolres12040068.
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Bacterial populations inhabiting a variety of natural and human-associated niches have the ability to grow in the form of biofilms. A large part of pathological chronic conditions, and essentially all the bacterial infections associated with implanted medical devices or prosthetics, are caused by microorganisms embedded in a matrix made of polysaccharides, proteins, and nucleic acids. Biofilm infections are generally characterized by a slow onset, mild symptoms, tendency to chronicity, and refractory response to antibiotic therapy. Even though the molecular mechanisms responsible for resistance to antimicrobial agents and host defenses have been deeply clarified, effective means to fight biofilms are still required. Lactic acid bacteria (LAB), used as probiotics, are emerging as powerful weapons to prevent adhesion, biofilm formation, and control overgrowth of pathogens. Hence, using probiotics or their metabolites to quench and interrupt bacterial communication and aggregation, and to interfere with biofilm formation and stability, might represent a new frontier in clinical microbiology and a valid alternative to antibiotic therapies. This review summarizes the current knowledge on the experimental and therapeutic applications of LAB to interfere with biofilm formation or disrupt the stability of pathogenic biofilms.
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Steenbeke, Mieke, Sander De Bruyne, Jerina Boelens, Matthijs Oyaert, Griet Glorieux, Wim Van Biesen, Jere Linjala, Joris R. Delanghe, and Marijn M. Speeckaert. "Exploring the possibilities of infrared spectroscopy for urine sediment examination and detection of pathogenic bacteria in urinary tract infections." Clinical Chemistry and Laboratory Medicine (CCLM) 58, no. 10 (September 25, 2020): 1759–67. http://dx.doi.org/10.1515/cclm-2020-0524.
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AbstractObjectivesIn this study, the possibilities of Fourier-transformed infrared spectroscopy (FTIR) for analysis of urine sediments and for detection of bacteria causing urinary tract infections (UTIs) were investigated.MethodsDried urine specimens of control subjects and patients presenting with various nephrological and urological conditions were analysed using mid-infrared spectroscopy (4,000–400 cm−1). Urine samples from patients with a UTI were inoculated on a blood agar plate. After drying of the pure bacterial colonies, FTIR was applied and compared with the results obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Chemometric data analysis was used to classify the different species.ResultsDue to the typical molecular assignments of lipids, proteins, nucleic acids and carbohydrates, FTIR was able to identify bacteria and showed promising results in the detection of proteins, lipids, white and red blood cells, as well as in the identification of crystals. Principal component analysis (PCA) allowed to differentiate between Gram-negative and Gram-positive species and soft independent modelling of class analogy (SIMCA) revealed promising classification ratios between the different pathogens.ConclusionsFTIR can be considered as a supplementary method for urine sediment examination and for detection of pathogenic bacteria in UTI.
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Park, Goeun, Hanbin Park, Sang-Chan Park, Moonbong Jang, Jinho Yoon, Jae-Hyuk Ahn, and Taek Lee. "Recent Developments in DNA-Nanotechnology-Powered Biosensors for Zika/Dengue Virus Molecular Diagnostics." Nanomaterials 13, no. 2 (January 16, 2023): 361. http://dx.doi.org/10.3390/nano13020361.
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Zika virus (ZIKV) and dengue virus (DENV) are highly contagious and lethal mosquito-borne viruses. Global warming is steadily increasing the probability of ZIKV and DENV infection, and accurate diagnosis is required to control viral infections worldwide. Recently, research on biosensors for the accurate diagnosis of ZIKV and DENV has been actively conducted. Moreover, biosensor research using DNA nanotechnology is also increasing, and has many advantages compared to the existing diagnostic methods, such as polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). As a bioreceptor, DNA can easily introduce a functional group at the 5′ or 3′ end, and can also be used as a folded structure, such as a DNA aptamer and DNAzyme. Instead of using ZIKV and DENV antibodies, a bioreceptor that specifically binds to viral proteins or nucleic acids has been fabricated and introduced using DNA nanotechnology. Technologies for detecting ZIKV and DENV can be broadly divided into electrochemical, electrical, and optical. In this review, advances in DNA-nanotechnology-based ZIKV and DENV detection biosensors are discussed.
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Liskova, Alena, Marek Samec, Lenka Koklesova, Erik Kudela, Peter Kubatka, and Olga Golubnitschaja. "Mitochondriopathies as a Clue to Systemic Disorders—Analytical Tools and Mitigating Measures in Context of Predictive, Preventive, and Personalized (3P) Medicine." International Journal of Molecular Sciences 22, no. 4 (February 18, 2021): 2007. http://dx.doi.org/10.3390/ijms22042007.
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The mitochondrial respiratory chain is the main site of reactive oxygen species (ROS) production in the cell. Although mitochondria possess a powerful antioxidant system, an excess of ROS cannot be completely neutralized and cumulative oxidative damage may lead to decreasing mitochondrial efficiency in energy production, as well as an increasing ROS excess, which is known to cause a critical imbalance in antioxidant/oxidant mechanisms and a “vicious circle” in mitochondrial injury. Due to insufficient energy production, chronic exposure to ROS overproduction consequently leads to the oxidative damage of life-important biomolecules, including nucleic acids, proteins, lipids, and amino acids, among others. Different forms of mitochondrial dysfunction (mitochondriopathies) may affect the brain, heart, peripheral nervous and endocrine systems, eyes, ears, gut, and kidney, among other organs. Consequently, mitochondriopathies have been proposed as an attractive diagnostic target to be investigated in any patient with unexplained progressive multisystem disorder. This review article highlights the pathomechanisms of mitochondriopathies, details advanced analytical tools, and suggests predictive approaches, targeted prevention and personalization of medical services as instrumental for the overall management of mitochondriopathy-related cascading pathologies.
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Glickman, Michael H., and Aaron Ciechanover. "The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction." Physiological Reviews 82, no. 2 (April 1, 2002): 373–428. http://dx.doi.org/10.1152/physrev.00027.2001.
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Between the 1960s and 1980s, most life scientists focused their attention on studies of nucleic acids and the translation of the coded information. Protein degradation was a neglected area, considered to be a nonspecific, dead-end process. Although it was known that proteins do turn over, the large extent and high specificity of the process, whereby distinct proteins have half-lives that range from a few minutes to several days, was not appreciated. The discovery of the lysosome by Christian de Duve did not significantly change this view, because it became clear that this organelle is involved mostly in the degradation of extracellular proteins, and their proteases cannot be substrate specific. The discovery of the complex cascade of the ubiquitin pathway revolutionized the field. It is clear now that degradation of cellular proteins is a highly complex, temporally controlled, and tightly regulated process that plays major roles in a variety of basic pathways during cell life and death as well as in health and disease. With the multitude of substrates targeted and the myriad processes involved, it is not surprising that aberrations in the pathway are implicated in the pathogenesis of many diseases, certain malignancies, and neurodegeneration among them. Degradation of a protein via the ubiquitin/proteasome pathway involves two successive steps: 1) conjugation of multiple ubiquitin moieties to the substrate and 2) degradation of the tagged protein by the downstream 26S proteasome complex. Despite intensive research, the unknown still exceeds what we currently know on intracellular protein degradation, and major key questions have remained unsolved. Among these are the modes of specific and timed recognition for the degradation of the many substrates and the mechanisms that underlie aberrations in the system that lead to pathogenesis of diseases.
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Scognamiglio, Viviana, and Amina Antonacci. "Structural Changes as a Tool for Affinity Recognition: Conformational Switch Biosensing." Crystals 12, no. 9 (August 27, 2022): 1209. http://dx.doi.org/10.3390/cryst12091209.
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Biosensors draw inspiration from natural chemosensing based on molecular switches between different bond-induced conformational states. Proteins and nucleic acids can be adapted into switch-based biosensors with a wide plethora of different configurations, taking advantage of the variety of transduction systems, from optical to electrochemical or electrochemiluminescence, as well as from nanomaterials for signal augmentation. This review reports the latest trends in conformational switch biosensors reported in the literature in the last 10 years, focusing on the main representative and recent examples of protein-based switching biosensors, DNA nanomachines, and structure-switched aptamers being applied for the detection of a wide range of target analytes with interest in biomedical and agro-environmental sectors.
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Zhu, Mengxi, Shan Li, Sanqiang Li, Haojie Wang, Juanjuan Xu, Yili Wang, and Gaofeng Liang. "Strategies for Engineering Exosomes and Their Applications in Drug Delivery." Journal of Biomedical Nanotechnology 17, no. 12 (December 1, 2021): 2271–97. http://dx.doi.org/10.1166/jbn.2021.3196.
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Exosomes are representative of a promising vehicle for delivery of biomolecules. Despite their discovery nearly 40 years, knowledge of exosomes and extracellular vesicles (EVs) and the role they play in etiology of disease and normal cellular physiology remains in its infancy. EVs are produced in almost all cells, containing nucleic acids, lipids, and proteins delivered from donor cells to recipient cells. Consequently, they act as mediators of intercellular communication and molecular transfer. Recent studies have shown that, exosomes are associated with numerous physiological and pathological processes as a small subset of EVs, and they play a significant role in disease progression and treatment. In this review, we discuss several key questions: what are exosomes, why do they matter, and how do we repurpose them in their strategies and applications in drug delivery systems. In addition, opportunities and challenges of exosome-based theranostics are also described and directions for future research are presented.
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Han, Guoliang, Ziqi Qiao, Yuxia Li, Chengfeng Wang, and Baoshan Wang. "The Roles of CCCH Zinc-Finger Proteins in Plant Abiotic Stress Tolerance." International Journal of Molecular Sciences 22, no. 15 (August 3, 2021): 8327. http://dx.doi.org/10.3390/ijms22158327.
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Zinc-finger proteins, a superfamily of proteins with a typical structural domain that coordinates a zinc ion and binds nucleic acids, participate in the regulation of growth, development, and stress adaptation in plants. Most zinc fingers are C2H2-type or CCCC-type, named after the configuration of cysteine (C) and histidine (H); the less-common CCCH zinc-finger proteins are important in the regulation of plant stress responses. In this review, we introduce the domain structures, classification, and subcellular localization of CCCH zinc-finger proteins in plants and discuss their functions in transcriptional and post-transcriptional regulation via interactions with DNA, RNA, and other proteins. We describe the functions of CCCH zinc-finger proteins in plant development and tolerance to abiotic stresses such as salt, drought, flooding, cold temperatures and oxidative stress. Finally, we summarize the signal transduction pathways and regulatory networks of CCCH zinc-finger proteins in their responses to abiotic stress. CCCH zinc-finger proteins regulate the adaptation of plants to abiotic stress in various ways, but the specific molecular mechanisms need to be further explored, along with other mechanisms such as cytoplasm-to-nucleus shuttling and post-transcriptional regulation. Unraveling the molecular mechanisms by which CCCH zinc-finger proteins improve stress tolerance will facilitate the breeding and genetic engineering of crops with improved traits.
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Morales-García, A. L., R. G. Bailey, S. Jana, and J. G. Burgess. "The role of polymers in cross-kingdom bioadhesion." Philosophical Transactions of the Royal Society B: Biological Sciences 374, no. 1784 (September 9, 2019): 20190192. http://dx.doi.org/10.1098/rstb.2019.0192.
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The secretion of extracellular polymeric substances provides an evolutionary advantage found in many organisms that can adhere to surfaces and cover themselves in a protective matrix. This ability is found in prokaryotes, archaea and eukaryotes, all of which use functionally similar polysaccharides, proteins and nucleic acids to form extracellular matrices, mucus and bioadhesive substances. These macromolecules have been investigated from the perspective of polymer biophysics, and theories to help understand adhesion, viscosity and gelling have been developed. These properties can be measured experimentally using straightforward methods such as cell counting as well as more advanced techniques such as atomic force microscopy and rheometry. An integrated understanding of the properties and uses of adhesive macromolecules across kingdoms is also important and can provide the basis for a range of biotechnological and medical applications. This article is part of the theme issue ‘Transdisciplinary approaches to the study of adhesion and adhesives in biological systems’.
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Kim, Seohyun, Sangmin Ji, and Hye Ran Koh. "CRISPR as a Diagnostic Tool." Biomolecules 11, no. 8 (August 6, 2021): 1162. http://dx.doi.org/10.3390/biom11081162.
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Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system has recently gained growing attention as a diagnostic tool due to its capability of specific gene targeting. It consists of Cas enzymes and a guide RNA (gRNA) that can cleave the target DNA or RNA based on the sequence of the gRNA, making it an attractive genetic engineering technique. In addition to the target-specific binding and cleavage, the trans-cleavage activity was reported for some Cas proteins, including Cas12a and Cas13a, which is to cleave the surrounding single-stranded DNA or RNA upon the target binding of Cas-gRNA complex. All these activities of the CRISPR-Cas system are based on its target-specific binding, making it applied to develop diagnostic methods by detecting the disease-related gene as well as microRNAs and the genetic variations such as single nucleotide polymorphism and DNA methylation. Moreover, it can be applied to detect the non-nucleic acids target such as proteins. In this review, we cover the various CRISPR-based diagnostic methods by focusing on the activity of the CRISPR-Cas system and the form of the target. The CRISPR-based diagnostic methods without target amplification are also introduced briefly.
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Hwang, Hee Sook, Hyosuk Kim, Geonhee Han, Jong Won Lee, Kwangmeyung Kim, Ick Chan Kwon, Yoosoo Yang, and Sun Hwa Kim. "Extracellular Vesicles as Potential Therapeutics for Inflammatory Diseases." International Journal of Molecular Sciences 22, no. 11 (May 22, 2021): 5487. http://dx.doi.org/10.3390/ijms22115487.
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Extracellular vesicles (EV) deliver cargoes such as nucleic acids, proteins, and lipids between cells and serve as an intercellular communicator. As it is revealed that most of the functions associated to EVs are closely related to the immune response, the important role of EVs in inflammatory diseases is emerging. EVs can be functionalized through EV surface engineering and endow targeting moiety that allows for the target specificity for therapeutic applications in inflammatory diseases. Moreover, engineered EVs are considered as promising nanoparticles to develop personalized therapeutic carriers. In this review, we highlight the role of EVs in various inflammatory diseases, the application of EV as anti-inflammatory therapeutics, and the current state of the art in EV engineering techniques.
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Unruh, Colin, Nicolas Van Bavel, Max Anikovskiy, and Elmar J. Prenner. "Benefits and Detriments of Gadolinium from Medical Advances to Health and Ecological Risks." Molecules 25, no. 23 (December 7, 2020): 5762. http://dx.doi.org/10.3390/molecules25235762.
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Gadolinium (Gd)-containing chelates have been established as diagnostics tools. However, extensive use in magnetic resonance imaging has led to increased Gd levels in industrialized parts of the world, adding to natural occurrence and causing environmental and health concerns. A vast amount of data shows that metal may accumulate in the human body and its deposition has been detected in organs such as brain and liver. Moreover, the disease nephrogenic systemic fibrosis has been linked to increased Gd3+ levels. Investigation of Gd3+ effects at the cellular and molecular levels mostly revolves around calcium-dependent proteins, since Gd3+ competes with calcium due to their similar size; other reports focus on interaction of Gd3+ with nucleic acids and carbohydrates. However, little is known about Gd3+ effects on membranes; yet some results suggest that Gd3+ interacts strongly with biologically-relevant lipids (e.g., brain membrane constituents) and causes serious structural changes including enhanced membrane rigidity and propensity for lipid fusion and aggregation at much lower concentrations than other ions, both toxic and essential. This review surveys the impact of the anthropogenic use of Gd emphasizing health risks and discussing debilitating effects of Gd3+ on cell membrane organization that may lead to deleterious health consequences.
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Mehta, Piyush. "Dry Powder Inhalers: A Focus on Advancements in Novel Drug Delivery Systems." Journal of Drug Delivery 2016 (October 27, 2016): 1–17. http://dx.doi.org/10.1155/2016/8290963.
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Administration of drug molecules by inhalation route for treatment of respiratory diseases has the ability to deliver drugs, hormones, nucleic acids, steroids, proteins, and peptides, particularly to the site of action, improving the efficacy of the treatment and consequently lessening adverse effects of the treatment. Numerous inhalation delivery systems have been developed and studied to treat respiratory diseases such as asthma, COPD, and other pulmonary infections. The progress of disciplines such as biomaterials science, nanotechnology, particle engineering, molecular biology, and cell biology permits further improvement of the treatment capability. The present review analyzes modern therapeutic approaches of inhaled drugs with special emphasis on novel drug delivery system for treatment of various respiratory diseases.
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Bardhan, Jaydeep P. "Gradient models in molecular biophysics: progress, challenges, opportunities." Journal of the Mechanical Behavior of Materials 22, no. 5-6 (December 1, 2013): 169–84. http://dx.doi.org/10.1515/jmbm-2013-0024.
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AbstractIn the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g., molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding nonlocal dielectric response. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain, and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost 40 years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The review concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics.
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Keysberg, Christoph, Oliver Hertel, Louise Schelletter, Tobias Busche, Chiara Sochart, Jörn Kalinowski, Raimund Hoffrogge, Kerstin Otte, and Thomas Noll. "Exploring the molecular content of CHO exosomes during bioprocessing." Applied Microbiology and Biotechnology 105, no. 9 (May 2021): 3673–89. http://dx.doi.org/10.1007/s00253-021-11309-8.
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Abstract In biopharmaceutical production, Chinese hamster ovary (CHO) cells derived from Cricetulus griseus remain the most commonly used host cell for recombinant protein production, especially antibodies. Over the last decade, in-depth multi-omics characterization of these CHO cells provided data for extensive cell line engineering and corresponding increases in productivity. However, exosomes, extracellular vesicles containing proteins and nucleic acids, are barely researched at all in CHO cells. Exosomes have been proven to be a ubiquitous mediator of intercellular communication and are proposed as new biopharmaceutical format for drug delivery, indicator reflecting host cell condition and anti-apoptotic factor in spent media. Here we provide a brief overview of different separation techniques and subsequently perform a proteome and regulatory, non-coding RNA analysis of exosomes, derived from lab-scale bioreactor cultivations of a CHO-K1 cell line, to lay out reference data for further research in the field. Applying bottom-up orbitrap shotgun proteomics and next-generation small RNA sequencing, we detected 1395 proteins, 144 micro RNA (miRNA), and 914 PIWI-interacting RNA (piRNA) species differentially across the phases of a batch cultivation process. The exosomal proteome and RNA data are compared with other extracellular fractions and cell lysate, yielding several significantly exosome-enriched species. Key points • First-time comprehensive protein and miRNA characterization of CHO exosomes. • Isolation protocol and time point of bioprocess strongly affect quality of extracellular vesicles. • CHO-derived exosomes also contain numerous piRNA species of yet unknown function.
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Ito, Kentaro, Hideo Takakusa, Masayo Kakuta, Akira Kanda, Nana Takagi, Hiroyuki Nagase, Nobuaki Watanabe, et al. "Renadirsen, a Novel 2′OMeRNA/ENA® Chimera Antisense Oligonucleotide, Induces Robust Exon 45 Skipping for Dystrophin In Vivo." Current Issues in Molecular Biology 43, no. 3 (September 25, 2021): 1267–81. http://dx.doi.org/10.3390/cimb43030090.
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Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease caused by out-of-frame or nonsense mutation in the dystrophin gene. It begins with a loss of ambulation between 9 and 14 years of age, followed by various other symptoms including cardiac dysfunction. Exon skipping of patients’ DMD pre-mRNA induced by antisense oligonucleotides (AOs) is expected to produce shorter but partly functional dystrophin proteins, such as those possessed by patients with the less severe Becker muscular dystrophy. We are working on developing modified nucleotides, such as 2′-O,4′-C-ethylene-bridged nucleic acids (ENAs), possessing high nuclease resistance and high affinity for complementary RNA strands. Here, we demonstrate the preclinical characteristics (exon-skipping activity in vivo, stability in blood, pharmacokinetics, and tissue distribution) of renadirsen, a novel AO modified with 2′-O-methyl RNA/ENA chimera phosphorothioate designed for dystrophin exon 45 skipping and currently under clinical trials. Notably, systemic delivery of renadirsen sodium promoted dystrophin exon skipping in cardiac muscle, skeletal muscle, and diaphragm, compared with AOs with the same sequence as renadirsen but conventionally modified by PMO and 2′OMePS. These findings suggest the promise of renadirsen sodium as a therapeutic agent that improves not only skeletal muscle symptoms but also other symptoms in DMD patients, such as cardiac dysfunction.
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Yim, Seok W., Taiho Kim, Ted A. Laurence, Steve Partono, Dongsik Kim, Younggyu Kim, Shimon Weiss, and Armin Reitmair. "Four-Color Alternating-Laser Excitation Single-Molecule Fluorescence Spectroscopy for Next-Generation Biodetection Assays." Clinical Chemistry 58, no. 4 (April 1, 2012): 707–16. http://dx.doi.org/10.1373/clinchem.2011.176958.
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Abstract BACKGROUND Single-molecule detection (SMD) technologies are well suited for clinical diagnostic applications by offering the prospect of minimizing precious patient sample requirements while maximizing clinical information content. Not yet available, however, is a universal SMD-based platform technology that permits multiplexed detection of both nucleic acid and protein targets and that is suitable for automation and integration into the clinical laboratory work flow. METHODS We have used a sensitive, specific, quantitative, and cost-effective homogeneous SMD method that has high single-well multiplexing potential and uses alternating-laser excitation (ALEX) fluorescence-aided molecule sorting extended to 4 colors (4c-ALEX). Recognition molecules are tagged with different-color fluorescence dyes, and coincident confocal detection of ≥2 colors constitutes a positive target-detection event. The virtual exclusion of the majority of sources of background noise eliminates washing steps. Sorting molecules with multidimensional probe stoichiometries (S) and single-molecule fluorescence resonance energy transfer efficiencies (E) allows differentiation of numerous targets simultaneously. RESULTS We show detection, differentiation, and quantification—in a single well—of (a) 25 different fluorescently labeled DNAs; (b) 8 bacterial genetic markers, including 3 antibiotic drug–resistance determinants found in 11 septicemia-causing Staphylococcus and Enterococcus strains; and (c) 6 tumor markers present in blood. CONCLUSIONS The results demonstrate assay utility for clinical molecular diagnostic applications by means of multiplexed detection of nucleic acids and proteins and suggest potential uses for early diagnosis of cancer and infectious and other diseases, as well as for personalized medicine. Future integration of additional technology components to minimize preanalytical sample manipulation while maximizing throughput should allow development of a user-friendly (“sample in, answer out”) point-of-care platform for next-generation medical diagnostic tests that offer considerable savings in costs and patient sample.