Targeted chemical nucleases have a wide range of untapped applications in biological fields, including gene therapy

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Metal Complex ◽  
Dna Cleavage ◽  
Therapeutic Potential ◽  
Chemical Reactivity ◽  
Major Groove ◽  
Sequence Recognition ◽  
Wide Range ◽  
Chemical Nucleases

A feasible alternative to state-of-the-art enzymatic nucleases was created by regulating the cleavage activity of metal complexes using (covalent or non-covalent) homing agents. Targeted AMNs, unlike enzymatic nucleases, break DNA by an oxidative mechanism and can therefore permanently knock off genes. Compared to larger enzymatic nucleases, the modest size of the metal complex may aid cellular transfection. Furthermore, the painstaking construction of the sequence-specific probe permits a metal complex to be directed to dsDNA's minor or major groove. To direct the chemical reactivity of several small-molecule compounds to dsDNA's minor groove, covalently bonded polyamide samples were used. PNA and DNA were also used to construct antisense and antigen hybrids, with Watson–Crick or Hoogsteen base pairing with major groove nucleobases giving sequence recognition. Click chemistry created chimeric AMN-TFOs with desirable focused effects and negligible off-target cleavage. Clip-Phen-modified TFOs, 230 polypyridyl-modified TFOs, 232 and intercalating phenanthrene-modified TFOs are three contemporary instances of copper AMN–TFOs. All three systems have distinct advantages in maintaining the desired 2:1 phenthroline/copper ratio for DNA cleavage (clip-Phen TFOs), caging the copper center and facilitating efficient ROS-mediated strand scission (polypyridyl-modified TFO) and improving triplex stability (polypyridyl-modified TFO) (phenanthrene-TFOs). Cerium (IV)/EDTA complexes, recently shown to bind and hydrolytically cleave ssDNA/dsDNA junctions and used in conjunction with PNA to successfully introduce genome changes in vitro and in vivo, are another important class of targeted chemical nucleases. The chemical reactivity and wide flexibility of metal complex design, combined with their coupling to sequence specific samples for directed applications, show that these compounds have a wide range of untapped applications in biological fields such as chemotherapy, protein engineering, DNA footprinting, and gene editing. Parallel advancements in cell and tissue targeting will be essential to maximise their therapeutic potential, either by using specific ligands or creating new targeting modalities.

scholarly journals Phage Therapy as a Focused Management Strategy in Aquaculture

2021 ◽  
Vol 22 (19) ◽  
pp. 10436
Author(s):  
José Ramos-Vivas ◽  
Joshua Superio ◽  
Jorge Galindo-Villegas ◽  
Félix Acosta
Keyword(s):  
Bacterial Infections ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Control Strategies ◽  
Bacterial Species ◽  
Lytic Enzymes ◽  
Wide Range ◽  
Cultured Fish

Therapeutic bacteriophages, commonly called as phages, are a promising potential alternative to antibiotics in the management of bacterial infections of a wide range of organisms including cultured fish. Their natural immunogenicity often induces the modulation of a variated collection of immune responses within several types of immunocytes while promoting specific mechanisms of bacterial clearance. However, to achieve standardized treatments at the practical level and avoid possible side effects in cultivated fish, several improvements in the understanding of their biology and the associated genomes are required. Interestingly, a particular feature with therapeutic potential among all phages is the production of lytic enzymes. The use of such enzymes against human and livestock pathogens has already provided in vitro and in vivo promissory results. So far, the best-understood phages utilized to fight against either Gram-negative or Gram-positive bacterial species in fish culture are mainly restricted to the Myoviridae and Podoviridae, and the Siphoviridae, respectively. However, the current functional use of phages against bacterial pathogens of cultured fish is still in its infancy. Based on the available data, in this review, we summarize the current knowledge about phage, identify gaps, and provide insights into the possible bacterial control strategies they might represent for managing aquaculture-related bacterial diseases.

Therapeutic potential of stem cells in lung disease: progress and pitfalls

2007 ◽  
Vol 114 (2) ◽  
pp. 99-108 ◽  
Author(s):  
Michael R. Loebinger ◽  
Susana Aguilar ◽  
Sam M. Janes
Keyword(s):  
Stem Cells ◽  
Lung Disease ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Lung Parenchyma ◽  
Treatment Modalities ◽  
In Vivo Experiments ◽  
Wide Range

There has been increasing excitement over the last few years with the suggestion that exogenous stem cells may offer new treatment options for a wide range of diseases. Within respiratory medicine, these cells have been shown to have the ability to differentiate and function as both airway and lung parenchyma epithelial cells in both in vitro and increasingly in vivo experiments. The hypothesis is that these cells may actively seek out damaged tissue to assist in the local repair, and the hope is that their use will open up new cellular and genetic treatment modalities. Such is the promise of these cells that they are being rushed from the benchside to the bedside with the commencement of early clinical trials. However, important questions over their use remain and the field is presently littered with controversy and uncertainty. This review evaluates the progress made and the pitfalls encountered to date, and critically assesses the evidence for the use of stem cells in lung disease.

scholarly journals Mitochondria Can Cross Cell Boundaries: An Overview of the Biological Relevance, Pathophysiological Implications and Therapeutic Perspectives of Intercellular Mitochondrial Transfer

2021 ◽  
Vol 22 (15) ◽  
pp. 8312
Author(s):  
Daniela Valenti ◽  
Rosa Anna Vacca ◽  
Loredana Moro ◽  
Anna Atlante
Keyword(s):  
Mammalian Cells ◽  
Therapeutic Potential ◽  
Cell Metabolism ◽  
Immunological Response ◽  
Biological Relevance ◽  
Mitochondrial Transfer ◽  
Response To Chemotherapy ◽  
Wide Range

Mitochondria are complex intracellular organelles traditionally identified as the powerhouses of eukaryotic cells due to their central role in bioenergetic metabolism. In recent decades, the growing interest in mitochondria research has revealed that these multifunctional organelles are more than just the cell powerhouses, playing many other key roles as signaling platforms that regulate cell metabolism, proliferation, death and immunological response. As key regulators, mitochondria, when dysfunctional, are involved in the pathogenesis of a wide range of metabolic, neurodegenerative, immune and neoplastic disorders. Far more recently, mitochondria attracted renewed attention from the scientific community for their ability of intercellular translocation that can involve whole mitochondria, mitochondrial genome or other mitochondrial components. The intercellular transport of mitochondria, defined as horizontal mitochondrial transfer, can occur in mammalian cells both in vitro and in vivo, and in physiological and pathological conditions. Mitochondrial transfer can provide an exogenous mitochondrial source, replenishing dysfunctional mitochondria, thereby improving mitochondrial faults or, as in in the case of tumor cells, changing their functional skills and response to chemotherapy. In this review, we will provide an overview of the state of the art of the up-to-date knowledge on intercellular trafficking of mitochondria by discussing its biological relevance, mode and mechanisms underlying the process and its involvement in different pathophysiological contexts, highlighting its therapeutic potential for diseases with mitochondrial dysfunction primarily involved in their pathogenesis.

scholarly journals Imperata cylindrica: A Review of Phytochemistry, Pharmacology, and Industrial Applications

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1454
Author(s):  
Young-Kyung Jung ◽  
Dongyun Shin
Keyword(s):  
Medicinal Plant ◽  
Therapeutic Potential ◽  
Chemical Constituents ◽  
Industrial Applications ◽  
Imperata Cylindrica ◽  
Pharmacological Activities ◽  
Wide Range ◽  
Pharmacological Studies

Imperata cylindrica is a medicinal plant native to southwestern Asia and the tropical and subtropical zones. To date, 72 chemical constituents have been isolated and identified from I. cylindrica Among these compounds, saponins, flavonoids, phenols, and glycosides are the major constituents. Investigations of pharmacological activities of I. cylindrica revealed that this edible medicinal herb exhibits a wide range of therapeutic potential including immunomodulatory, antibacterial, antitumor, anti-inflammatory, and liver protection activities both in vivo and in vitro. The purpose of this review is to provide an overview of I. cylindrica studies until 2019. This article also intends to review advances in the botanical, phytochemical, and pharmacological studies and industrial applications of I. cylindrica, which will provide a useful bibliography for further investigations and applications of I. cylindrica in medicines and foods.

Thespesia populnea: An Ethnomedicinal, Phytochemical and Pharmacological review

2020 ◽  
Vol 10 ◽  
Author(s):  
Ashish Vishwakarma ◽  
Poonam Arora ◽  
Mahaveer Dhobi
Keyword(s):  
Therapeutic Potential ◽  
Biological Activities ◽  
Experimental Studies ◽  
Bioactive Molecules ◽  
Chemical Components ◽  
Coastal Forests ◽  
Thespesia Populnea ◽  
Wide Range

: Thespesia populnea, family, Malvaceae, commonly known as paras pipal and Indian tulip tree, is widely distributed in coastal forests of India and south-eastern areas. The plant is medicinally used for the treatment of numerous diseases including cutaneous infections, brain and liver disorders.The review summarizes all the information related to botanical characteristics, traditional uses, chemical components and biological activities of T. populnea, in order to exploit therapeutic potential of this plant.x.The available information about T. populnea was collected through the online search on Web of Science, PubMed, Science Direct, Springer and Google Scholar. T. populnea is widely explored concerning its phytochemistry and biological activities. Amongst all phytoconstituents present in Thespesia, sesquiterpenes and phenolic compounds are major bioactive ingredients in plant. Experimental studies show that these compounds exhibit a wide range of biological activities including anti-inflammatory, antidiabetic, analgesic, wound healing, anti-alzheimer, anti-ulcer and anti-psoriasis in in vitro and in vivo animal studies.To sum up, the plant, T. populnea, possess high medicinal and social value, that deserves further investigation. T. populnea is promising plant to be utilized in the development of pharmaceutical drug products. However, there is a lack of scientific studies to confirm its ethnopharmcological uses. In addition, further studies on isolation of bioactive molecules and their pharmacological studies are recommended that could be of great significance towards clinical application of this plant.

scholarly journals Phytochemical Profile and Pharmacological Aspects of Achyranthes aspera Linn- An Overview

2021 ◽  
pp. 187-206
Author(s):  
Prakash Nargatti ◽  
Sudhir Patil ◽  
Kiran Wadkar
Keyword(s):  
Therapeutic Potential ◽  
Perennial Herb ◽  
African Countries ◽  
In Vivo Models ◽  
Achyranthes Aspera ◽  
Beneficial Effects ◽  
Folk Remedy ◽  
Wide Range

Background: Achyranthes asperaLinn, commonly known as Apamarga in Ayurveda (Prickly Chaff flower in English, Aghara in Hindi, Aghada in Marathi), is aannual, perennial herb that belong to Family Amaranthaceae and Genus Achyranthes consisting of several species which are popular as folk remedies. Certain ayurvedic and Unani practitioners use various parts of plant to treat various diseases.The present review aims to provide up-to-date information on different aspects of plant involving its botanical description, phytochemistry and bioactivities of different extractsto assess its therapeutic potential as a valuable source of natural compounds with beneficial effects on human health. Methodology: Systematic search of scientific databases like Google, Google scholar, PubMed, Web of Science, Science Direct, SciFinder, Springer link were used to find potentially significant scientific research and reports of Achyranthes asperaLinnusing combination of relevant keywords. Results: Achyranthes aspera Linn is a popular folk remedy in the traditional medicinal system in all tropical Asian and African countries. So far,58 important compounds have been isolated and identified from various parts of plant. These isolated constituents are mainly flavonoids, tannins, terpenoids, saponins, phytosterols; phenolic compounds etc which posseses activities like anti-inflammatory, antimicrobial, anti-oxidant, hypoglycemic, antihyperlipidemic, spermicidal and other various important medicinal properties. Conclusion: Even though this plant consists of a wide range of phytochemicals and evaluated forbiological activities using various in-vitro and in-vivo models but they are limited. More attention should be paid to identify mechanisms that underlie beneficial therapeutic potential.It is essential to conduct the next level of research, by extending pharmacological to design novel drugs.

A Review on the Phytochemistry, Ethnobotanical Uses and Pharmacology of Borago Species

2020 ◽  
Vol 26 (1) ◽  
pp. 110-128 ◽  
Author(s):  
Mahin Ramezani ◽  
Mohammad S. Amiri ◽  
Elaheh Zibaee ◽  
Zahra Boghrati ◽  
Zahra Ayati ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Scientific Information ◽  
Modern Medicine ◽  
Point Of View ◽  
African Countries ◽  
Traditional Uses ◽  
Wide Range ◽  
Ethnobotanical Uses

Ethnopharmacological Relevance: Borago L., (family Boraginaceae) is a small genus of annual or perennial herbs with branched flowers, which is commonly found in the Mediterranean region. Some species known as Gavzabȃn in Asian and some African countries are traditionally used instead of Borago. Aims of the Review: The purpose of this study was to provide comprehensive scientific information on phytochemistry, traditional uses and pharmacological activities of Borago species to provide an insight into further research on the therapeutic potential of these plants. In many studies, it has been shown that different parts of Borago species, including leaves, flowers, seeds, roots and aerial parts possess numerous ethnobotanical values. Materials and Methods: All ethnobotanical, phytochemical, pharmacological, and clinical data were collected from online journals, magazines and books (all of which were published in English, Arabic, and Persian) from 1968 to 2018. Electronic databases such as Google, Google Scholar, PubMed, Science Direct, Researchgate, and other online collections were used. Results: The phytochemical studies on five species showed a wide range of phytochemicals belonging to different classes of secondary metabolites. From a pharmacological point of view, different extracts and fractions, essential oils, and pure compounds isolated from various Borago species have shown diverse activities in in vitro, in vivo, and clinical studies confirming various traditional uses of Borago genus. Conclusions: Considering the reported activities of the Borago genus both in traditional and modern medicine, further studies on biological aspects and identification of the mechanism of action for drug discovery are highly required.

scholarly journals Naringenin Nano-Delivery Systems and Their Therapeutic Applications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 291
Author(s):  
Mohammed Bhia ◽  
Mahzad Motallebi ◽  
Banafshe Abadi ◽  
Atefeh Zarepour ◽  
Miguel Pereira-Silva ◽  
...  
Keyword(s):  
Skin Diseases ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Delivery Systems ◽  
In Vivo Models ◽  
Wide Range

Naringenin (NRG) is a polyphenolic phytochemical belonging to the class of flavanones and is widely distributed in citrus fruits and some other fruits such as bergamot, tomatoes, cocoa, and cherries. NRG presents several interesting pharmacological properties, such as anti-cancer, anti-oxidant, and anti-inflammatory activities. However, the therapeutic potential of NRG is hampered due to its hydrophobic nature, which leads to poor bioavailability. Here, we review a wide range of nanocarriers that have been used as delivery systems for NRG, including polymeric nanoparticles, micelles, liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanosuspensions, and nanoemulsions. These nanomedicine formulations of NRG have been applied as a potential treatment for several diseases, using a wide range of in vitro, ex vivo, and in vivo models and different routes of administration. From this review, it can be concluded that NRG is a potential therapeutic option for the treatment of various diseases such as cancer, neurological disorders, liver diseases, ocular disorders, inflammatory diseases, skin diseases, and diabetes when formulated in the appropriate nanocarriers.

scholarly journals Cardamonin Attenuates Experimental Colitis and Associated Colorectal Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 661
Author(s):  
Shirley James ◽  
Jayasekharan S. Aparna ◽  
Anu Babu ◽  
Aswathy Mary Paul ◽  
Manendra Babu Lankadasari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Experimental Colitis ◽  
Tumor Formation ◽  
Raw 264.7 Cells ◽  
Wide Range ◽  
Nitrous Oxide Production ◽  
Anti Inflammatory

Cardamonin is a naturally occurring chalcone, majorly from the Zingiberaceae family, which includes a wide range of spices from India. Herein, we investigated the anti-inflammatory property of cardamonin using different in vitro and in vivo systems. In RAW 264.7 cells, treatment with cardamonin showed a reduced nitrous oxide production without affecting the cell viability and decreased the expression of iNOS, TNF-α, and IL-6, and inhibited NF-kB signaling which emphasizes the role of cardamonin as an anti-inflammatory molecule. In a mouse model of dextran sodium sulfate (DSS)-induced colitis, cardamonin treatment protected the mice from colitis. Subsequently, we evaluated the therapeutic potential of this chalcone in a colitis-associated colon cancer model. We performed microRNA profiling in the different groups and observed that cardamonin modulates miRNA expression, thereby inhibiting tumor formation. Together, our findings indicate that cardamonin has the potential to be considered for future therapy against colorectal cancer.

scholarly journals Programmable DNA cleavage by Ago nucleases from mesophilic bacteria Clostridium butyricum and Limnothrix rosea

2019 ◽  
Author(s):  
Anton Kuzmenko ◽  
Denis Yudin ◽  
Sergei Ryazansky ◽  
Andrey Kulbachinskiy ◽  
Alexei A. Aravin
Keyword(s):  
Dna Cleavage ◽  
Elevated Temperatures ◽  
Biochemical Characterization ◽  
Clostridium Butyricum ◽  
Seed Region ◽  
Mesophilic Bacteria ◽  
Highly Active ◽  
Wide Range

ABSTRACTArgonaute (Ago) proteins are the key players in RNA interference in eukaryotes, where they function as RNA-guided RNA endonucleases. Prokaryotic Argonautes (pAgos) are much more diverse than their eukaryotic counterparts but their cellular functions and mechanisms of action remain largely unknown. Some pAgos were shown to use small DNA guides for endonucleolytic cleave of complementary DNA in vitro. However, previously studied pAgos from thermophilic prokaryotes function at elevated temperatures which limits their potential use as a tool in genomic applications. Here, we describe two pAgos from mesophilic bacteria, Clostridium butyricum (CbAgo) and Limnothrix rosea (LrAgo), that act as DNA-guided DNA nucleases at physiological temperatures. In contrast to previously studied pAgos, CbAgo and LrAgo can use not only 5’-phosphorylated but also 5’-hydroxyl DNA guides, with diminished precision of target cleavage. Both LrAgo and CbAgo can tolerate guide/target mismatches in the seed region, but are sensitive to mismatches in the 3’-guide region. CbAgo is highly active under a wide range of conditions and can be used for programmable endonucleolytic cleavage of both single-stranded and double-stranded DNA substrates at moderate temperatures. The biochemical characterization of mesophilic pAgo proteins paths the way for their use for DNA manipulations both in vitro and in vivo.

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