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

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.

2021 ◽  
Author(s):  
Moataz Dowaidar

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.


2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Katia Rupel ◽  
Luisa Zupin ◽  
Giulia Ottaviani ◽  
Iris Bertani ◽  
Valentina Martinelli ◽  
...  

Abstract Resolution of bacterial infections is often hampered by both resistance to conventional antibiotic therapy and hiding of bacterial cells inside biofilms, warranting the development of innovative therapeutic strategies. Here, we report the efficacy of blue laser light in eradicating Pseudomonas aeruginosa cells, grown in planktonic state, agar plates and mature biofilms, both in vitro and in vivo, with minimal toxicity to mammalian cells and tissues. Results obtained using knock-out mutants point to oxidative stress as a relevant mechanism by which blue laser light exerts its anti-microbial effect. Finally, the therapeutic potential is confirmed in a mouse model of skin wound infection. Collectively, these data set blue laser phototherapy as an innovative approach to inhibit bacterial growth and biofilm formation, and thus as a realistic treatment option for superinfected wounds.


2021 ◽  
Vol 22 (19) ◽  
pp. 10436
Author(s):  
José Ramos-Vivas ◽  
Joshua Superio ◽  
Jorge Galindo-Villegas ◽  
Félix Acosta

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.


1998 ◽  
Vol 17 (5) ◽  
pp. 571-575 ◽  
Author(s):  
Amy L. Ellis

Drugs from a variety of chemical classes used for a wide range of therapeutic indications can be photosensitizers in humans. Several drugs are phototoxic in animal models as well; there are no nonclinical data for many. In vitro tests have been developed as predictors of phototoxicity and although they have been used as screens, none have replaced the in vivo tests done in rodents (usually mice or guinea pigs) since these have been good predictors of clinical phototoxicity. Some phototoxic drug classes are co-carcinogens with ultraviolet radiation (UVA and/or UVB) in hairless mice, specifically psoralens, retinoids, and fluo-roquinolones. Treatment with 8-methoxypsoralen and ultraviolet A radiation for psoriasis is also carcinogenic in humans. It has been suggested that in vitro photogenotoxicity assays using microorganisms or mammalian cells may be predictive of photo co-carcinogenicity. Some attractions of these in vitro assays, compared to the hairless mouse photo co-carcinogenicity assay, are their generally shorter duration and lower cost as well as reducing the number of animals used in research. Currently, personnel at the Food and Drug Administration (FDA) are examining the available data on phototoxicity, photogenotoxicity, and photo co-carcinogenicity to determine how this information can best be used toregulate and label drug products, and considering which assays should be recommended under specific circumstances.


2007 ◽  
Vol 114 (2) ◽  
pp. 99-108 ◽  
Author(s):  
Michael R. Loebinger ◽  
Susana Aguilar ◽  
Sam M. Janes

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.


Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1454
Author(s):  
Young-Kyung Jung ◽  
Dongyun Shin

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.


2020 ◽  
Vol 10 ◽  
Author(s):  
Ashish Vishwakarma ◽  
Poonam Arora ◽  
Mahaveer Dhobi

: 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.


Author(s):  
Prakash Nargatti ◽  
Sudhir Patil ◽  
Kiran Wadkar

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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rehana Parveen ◽  
Prasanta Kumar Maiti ◽  
Nabendu Murmu ◽  
Alokmay Datta

AbstractFollowing access into the cell, colloidal silver nanoparticles exhibit generalized cytotoxic properties, thus appear as omnipotent microbicidal, but not suitable for systemic use unless are free of toxic effects on host cells. The AgNP-Serum-18 when prepared from silver nitrate, using dextrose as reducing and group-matched homologous serum as a stabilizing agent, selective endocytosis, and oxidative stress-dependent bio-functional damages to the host are mostly eliminated. For their bio-mimicking outer coat, there is the least possibility of internalization into host cells or liberation of excess oxidants in circulation following interaction with erythrocytes or vascular endothelial cells. The presence of infection-specific antibodies in the serum can make such nano-conjugates more selective. A potent antimicrobial action and a wide margin of safety for mammalian cells in comparison with very similar PVA-capped silver nanoparticles have been demonstrated by the in-vitro challenge of such nanoparticles on different microbes, human liver cell-line, and in-vivo study on mice model. This may open up wide-range therapeutic prospects of colloidal nanoparticles.


2020 ◽  
Vol 26 (1) ◽  
pp. 110-128 ◽  
Author(s):  
Mahin Ramezani ◽  
Mohammad S. Amiri ◽  
Elaheh Zibaee ◽  
Zahra Boghrati ◽  
Zahra Ayati ◽  
...  

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.


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