Preface

Author(s): Nikolaos E. Labrou.

Journal Name: Recent Patents on Biotechnology

Volume 14 , Issue 1 , 2020

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VOLUME: 14
ISSUE: 1
Year: 2020
Page: [4 - 4]
Pages: 1
DOI: 10.2174/187220831401200121141703

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Meet Our Section Editor

Author(s): S.O. Dahunsi.

Journal Name: Recent Patents on Biotechnology

Volume 14 , Issue 1 , 2020

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VOLUME: 14
ISSUE: 1
Year: 2020
Page: [1 - 3]
Pages: 3
DOI: 10.2174/187220831401200121141549

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The Biological Impact Of Ulipristal Acetate On Cellular Networks Regulating Uterine Leiomyoma Growth.

(E-pub Abstract Ahead of Print)

Author(s): Andrea Tinelli*, Ioannis P Kosmas, Ospan A Mynbaev, Antonio Malvasi, Radmila Sparic, Daniele Vergara.

Journal Name: Current Pharmaceutical Design

Abstract:

Uterine UFs (UFs), or leiomyomas, represent the most frequent pelvic tumor in reproductive-aged women. Although of benign origin, UFs decrease fertility and cause significant reproductive dysfunctions. Compared to normal myometrium, UFs are characterized by a clinical and molecular heterogeneity as demonstrated by the presence of multiple genetic alterations and altered signaling pathways. Recently, selective progesteron-receptor modulators (SPRM), as ulipristal acetate (UPA), have demonstrated their clinical benefits by reducing tumor growth and extracellular matrix deposition. For these reasons, UPA is used in the clinical practice as an intermittent treatment for women symptomatic for UFs or, sometimes, before a myomectomy. However, drug effects on signaling pathways frequently upregulated in UFs remain largely unknown. In fact, the mechanisms of action of the UPA on UFs and on the surrounding areas are not yet understood. To learn more about UPA molecular mechanisms, UFs samples were treated ex vivo with UPA and profiled for drug effects on selected markers. During this preliminary ex vivo UPA administration, it was observed significant changes in the expression levels of proteins related to cell cycle regulation, cytoskeleton remodeling, and drug resistance. The UPA administration reduced cofilin, Erk and Src phosphorylation, p27 and ezrin protein levels, but not Akt phosphorylation and cyclin D1 and β-catenin levels. This preliminary ex vivo biological analysis provided new insights into the mechanism of action of UPA in the treatment of UFs, which could better explain the biological functioning of the drug on UFs.

Keywords: Uterine fibroids, Leiomyoma, Selective progesteron-receptor modulators, Ulipristal acetate, Progesteron

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DOI: 10.2174/1381612826666200121141533
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Recent Patents on Biotechnology

Editor-in-Chief:

Nikolaos Labrou
Laboratory of Enzyme Technology,
Department of Biotechnology
Agricultural University of Athens
Athens
Greece

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Plant Phenolics as Pathogen-Carrier Immunogenicity Modulator Haptens

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Author(s): Irais Castillo-Maldonado, María-de-la-Luz Sevilla-González, Dealmy Delgadillo-Guzmán, Agustina Ramírez-Moreno, Nidia Cabral-Hipólito, Mario-Alberto Rivera-Guillén, Luis-Benjamín Serrano-Gallardo, María-del-Carmen Vega-Menchaca, David Pedroza-Escobar*.

Journal Name: Current Pharmaceutical Biotechnology

Abstract:

Background: Pathogens use multiple mechanisms to disrupt cell functioning in their host and allow pathogenesis. These mechanisms involve communication between the pathogen and the host cell through protein-protein interactions. Protein-protein interactions chains referred to as signal transduction pathways are the processes by which a chemical or physical signal transmits through a cell as series of molecular events so the pathogen simply needs to intercept these molecular pathways at few positions to induce pathogenesis such as pathogen viability, infection or hypersensitivity. The pathogen nodes of interception are not necessary the most immunogenic; so that, novel immunogenicity-improvement strategies need to be developed thought a chemical conjugation of the pathogen-carrier nodes to develop an efficient immune response in order to block pathogenesis. On the other hand, if pathogen-carriers are immunogens; toleration ought to be induced by this conjugation avoiding hypersensitivity. Thus, this paper addresses the biological plausibility of plant-phenolics as pathogen-carrier immunogenicity modulator haptens.

Conclusion: The plant-phenolic compounds have in their structure functional groups such as hydroxyl, carbonyl, carboxyl, ester, or ether, capable of reacting with the amino or carbonyl groups of the amino acids of a pathogen-carrier to form conjugates. Besides, the varied carbon structures that these phenolic compounds have; it is possible to alter the pathogen-carrier related factors that determine the immunogenicity: 1) Structural complexity, 2) Molecular size, 3) Structural heterogeneity, 4) Accesibility to antigenic determinants or epitopes, 5) Optical configuration, 6) Physical state, or 7) Molecular rigidity.

Keywords: Plant phenolics, pathogen-carrier, immunogenicity, haptens, immunogen, toleragen.

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DOI: 10.2174/1389201021666200121130313
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Ferroptosis: a novel mechanism of artemisinin and its derivatives in cancer therapy

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Author(s): Shunqin Zhu, Qin Yu, Chunsong Huo, Yuanpeng Li, Linshen He, Botian Ran, Ji Chen, Yonghao Li, Wanhong Liu*.

Journal Name: Current Medicinal Chemistry

Abstract:

Background: Artemisinin is a sesquiterpene lactone compound with a special peroxide bridge that is tightly linked to the cytotoxicity involved in fighting malaria and cancer. Artemisinin and its derivatives (ARTs) are considered to be potential anticancer drugs that promote cancer cell apoptosis, induce cell cycle arrest and autophagy, inhibit cancer cell invasion and migration. Additionally, ARTs significantly increase intracellular reactive oxygen species (ROS) in cancer cells, which results in ferroptosis, a new form of cell death, depending on the ferritin concentration. Ferroptosis is regarded as a cancer suppressor and is considered a new mechanism for cancer therapy.

Methods: The anticancer activities of ARTs and reference molecules were compared by literature search and analysis. The latest research progress on ferroptosis was described, with a special focus on the molecular mechanism of artemisinin-induced ferroptosis.

Results: Artemisinin derivatives, artemisinin-derived dimers, hybrids and artemisinin-transferrin conjugates, could significantly improve anticancer activity, and their IC50 values are lower than those of reference molecules such as doxorubicin and paclitaxel. The biological activities of linkers in dimers and hybrids are an important consideration in the drug design processes. ARTs induce ferroptosis mainly by triggering intracellular ROS production, promoting the lysosomal degradation of ferritin and regulating the System Xc-/Gpx4 axis. Interestingly, ARTs also stimulate the feedback inhibition pathway.

Conclusion: Artemisinin and its derivatives could be used in the future as cancer therapies with broader application due to their induction of ferroptosis. Meanwhile, more attention should be paid to the development of novel artemisinin-related drugs based on the mechanism of artemisinin-induced ferroptosis.

Keywords: monoamine oxidase B, inhibitors, halogen, coumarin, chromone, thiazole, chalcone.

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DOI: 10.2174/0929867327666200121124404
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Neuronal Development-Related miRNAs as Biomarkers for Alzheimer's disease, Depression, Schizophrenia and Ionizing Radiation Exposure

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Author(s): Renu Chandra Segaran, Li Yun Chan, Hong Wang, Gautam Sethi*, Feng Ru Tang*.

Journal Name: Current Medicinal Chemistry

Abstract:

Radiation exposure may induce Alzheimer disease (AD), depression or schizophrenia. A number of experimental and clinical studies suggest the involvement of miRNA in the development of these diseases, and also in the neuropathological changes after brain radiation exposure. Current literature review indicated the involvement of 65 miRNAs in neuronal development in the brain. In the brain tissue, blood, or cerebral spinal fluid (CSF), 11, 55, or 28 miRNAs are involved in the development of AD respectively, 89, 50, 19 miRNAs in depression, and 102, 35, 8 miRNAs in schizophrenia. We compared miRNAs regulating neuronal development to those involved in genesis of AD, depression and schizophrenia and also those driving radiation-induced brain neuropathological changes by reviewing the available data. We found that 3, 11, or 8 neuronal development related miRNAs from the brain tissue, 13, 16 or 14 miRNAs from the blood of patient with AD, depression and schizophrenia respectively were also involved in radiation-induced brain pathological changes, suggesting a possibly specific involvement of these miRNAs in radiation-induced development of AD, depression and schizophrenia respectively. On the other hand, we noted that radiation-induced changes of two miRNAs, i.e., miR-132, miR-29 in the brain tissue, three miRNAs, i.e., miR-29c-5p, miR-106b-5p, miR-34a-5p in the blood were also involved in the development of AD, depression and schizophrenia, thereby suggesting that these miRNAs may be involved in the common brain neuropathological changes, such as impairment of neurogenesis and reduced learning memory ability observed in these three diseases and also after radiation exposure.

Keywords: miRNAs, brain tissue, cerebrospinal fluid, blood, Alzheimer disease, depression, schizophrenia and radiation, Venn diagram

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DOI: 10.2174/0929867327666200121122910
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Is Technical-grade Chlordane an Obesogen?

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Author(s): Juliana F. Silva, Bruno P. Moreira, Luís Rato, Maria de Lourdes Pereira, Pedro F. Oliveira, Marco G. Alves*.

Journal Name: Current Medicinal Chemistry

Abstract:

The prevalence of obesity has tripled in recent decades and is now considered an alarming public health problem. In recent years, a group of endocrine disruptors, known as obesogens, have been directly linked to the obesity epidemic. Its etiology is generally associated with a sedentary lifestyle, a high-fat diet and genetic predisposition, but environmental factors, such as obesogens, have also been reported as contributors for this pathology. In brief, obesogens are exogenous chemical compounds that alter metabolic processes and/or energy balance and appetite, thus predisposing to weight gain. Although this theory is still recent, the number of compounds with suspected obesogenic activity has steadily increased over the years, though much more remain a matter of debate. Technical-grade chlordane is an organochlorine pesticide widely present in the environment, albeit at low concentrations. Highly lipophilic, this compound can be metabolized by humans and animals into more toxic and stable compounds that are stored in fat tissue and consequently pose a danger to the human body, including the physiology of adipose tissue, which plays an important role in weight regulation. In addition, technical-grade chlordane is classified as a persistent organic pollutant, a group of chemicals whose epidemiological studies are associated with metabolic disorders, including obesity. Herein, we discuss the emerging roles of obesogens as threats to public health. We particularly discuss the relevance of chlordane persistence in the environment and how its effects on human and animal health provide evidence for its role as an endocrine disruptor with possible obesogenic activity.

Keywords: Obesity, Obesogens, Endocrine disruptor, Organochlorine, Persistent organic pollutant, Technical-grade chlordane.

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DOI: 10.2174/0929867327666200121122208
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Monoclonal antibodies carried in drug delivery nanosystems as a strategy for cancer treatment

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Author(s): Amanda Letícia Polli Silvestre, João Augusto Oshiro-Júnior*, Camila Garcia, Bruna Ortolani Turco, Joandra Maísa da Silva Leite, Bolivar Ponciano Goulart de Lima Damasceno, Jonas Corsino Maduro Soares, Marlus Chorilli*.

Journal Name: Current Medicinal Chemistry

Abstract:

Monoclonal antibodies carried in nanosystems have been extensively studied and reported as a promising tool for the treatment of various types of cancers. Monoclonal antibodies have great advantages for the treatment of cancer because their protein structure can bind to the target tissue; however, it has some challenges such as denaturation following heat exposure and extreme values of pH, temperature and solvents, the ability to undergo hydrolysis, oxidation and deamination and the formation of non-native aggregates, which totally compromises drug stability. In addition to these characteristics, they suffer rapid elimination when in the blood, which results in a short half-life and the production of neutralizing antibodies, rendering the doses ineffective. These challenges are overcome with encapsulation in nanosystems (liposomes, polymer nanoparticles, cyclodextrins, solid lipid nanoparticles, nanostructured lipid carriers, dendrimers and micelles) due to the characteristics of improving solubility, permeability, and selectivity only with tumor tissue; with that, there is a decrease in side effects beyond controlled release, which is critical to improving the therapeutic efficacy of cancer treatment. The article was divided into the different types of nanosystems, with a description of their definitions and applications in various types of cancers. Therefore, this review summarizes the use of monoclonal antibodies encapsulated in nanosystems and the description of clinical studies with biosimilars. Biosimilars are defined as products that are similar to monoclonal antibodies which are produced when the patent for the monoclonal antibodies expires.

Keywords: drug delivery nanosystems; biopharmaceuticals; cancer treatment; biosimilars; antibodies; new therapy.

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DOI: 10.2174/0929867327666200121121409
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Book Review on “Nanotechnology: Food and Environmental Paradigm”

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Author(s): Aditya Saran*, Ramyakrishna Pothu, Rajender Boddula.

Journal Name: Current Analytical Chemistry

Abstract:

Background: A Book Review on Nanotechnology: Food and environmental paradigm. Edited by Ram Prasad, Vivek Kumar and Manoj Kumar, Springer Nature Singapore, 2017, 340 Pages, ISBN 978-981-10-4677-3, DOI 10.1007/978-981-10-4678-0 This book is focused on the effects of nanomaterials in the environment and food. This book also emphasizes on the advantages gained through the application of nanotechnology in the broader area of food and environment.

Methods: Food web is the core of ecological balance and thus for sustainable environment. Presence of undesired nanomaterials in the food chain or web causes unwanted toxicity to the plants and animals of the food chain. In majority cases the presence of nanomaterials in food web causes toxicity, impairment of organs and/ or heavy loss to one or more population. Thus it is highly required to limit the release of nanomaterials in the environment. Also it is required to set the norms for the production, use and discard of nanomaterials.

Results: This book consists of 16 chapters which all together addresses a large dimension on the positive and negative effects of nanomaterials and the application of nanotechnology in various fields of food, agriculture and pharmaceutical industry. It is also important to evaluate the cost before implementing any new technology. It is not necessary that a good research which performed well in laboratory must also do well at industrial scale. Here a major barrier is cost which must be less to be implemented.

Conclusion: Application of desired nanomaterials is advantageous for many industries and quality life. Nano-fertilizers and nanopesticides enhance crop production. Nanotechnology plays significant role in food industry; from production, processing to packaging. Diagnostics is a field where nanotechnology is applied too much. New diagnostic methods using nanosensors, nanochips and nanocatalysts are evolving day by day.

Keywords: Nanotechnology, Food industry, Innovation, Nutrient management, Crop protection, Environmental issues

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DOI: 10.2174/1573411016666200121112657
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