scholarly journals Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5608
Author(s):  
Jilan A. Nazeam ◽  
Ghada M. Ragab ◽  
Amira A. El-Gazar ◽  
Shereen S. El-Mancy ◽  
Lina Jamil ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Acne Vulgaris ◽  
In Vivo Model ◽  
Biofilm Inhibition ◽  
Behavioral Alteration ◽  
Antibiotic Development ◽  
Ppar Γ

Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes’ pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an acne vulgaris model. A nano-emulgel of thyme/clove EOs (NEG8) was designed, standardized, and its antimicrobial activity was screened in vitro and in vivo against genetically identified skin bacterial clinical isolates (Pseudomonas stutzeri, Enterococcus faecium and Bacillus thuringiensis). As per our findings, NEG8 exhibited bacteriostatic and potent biofilm inhibition activities. An in vivo model was also established using the commercially available therapeutic, adapalene in contra genetically identified microorganism. Improvement in rat behavior was reported for the first time and NEG8 abated the dermal contents/protein expression of IGF-1, TGF-β/collagen, Wnt/β-catenin, JAK2/STAT-3, NE, 5-HT, and the inflammatory markers; p(Ser536) NF-κBp65, TLR-2, and IL-6. Moreover, the level of dopamine, protective anti-inflammatory cytokine, IL-10 and PPAR-γ protein were enhanced, also the skin histological structures were improved. Thus, NEG8 could be a future potential topical clinical alternate to synthetic agents, with dual merit mechanism as bacteriostatic antibiotic action and non-antibiotic microbial pathway inhibitor.

scholarly journals Caenorhabditis elegans as an in vivo Model to Assess Amphetamine Tolerance

2021 ◽  
pp. 1-9
Author(s):  
Dayana Torres Valladares ◽  
Sirisha Kudumala ◽  
Murad Hossain ◽  
Lucia Carvelli
Keyword(s):  
Caenorhabditis Elegans ◽  
Molecular Mechanisms ◽  
Drugs Of Abuse ◽  
Genetic Model ◽  
In Vivo Model ◽  
C Elegans ◽  
Hyperactivity Disorder ◽  
In Vitro Data

Amphetamine is a potent psychostimulant also used to treat attention deficit/hyperactivity disorder and narcolepsy. In vivo and in vitro data have demonstrated that amphetamine increases the amount of extra synaptic dopamine by both inhibiting reuptake and promoting efflux of dopamine through the dopamine transporter. Previous studies have shown that chronic use of amphetamine causes tolerance to the drug. Thus, since the molecular mechanisms underlying tolerance to amphetamine are still unknown, an animal model to identify the neurochemical mechanisms associated with drug tolerance is greatly needed. Here we took advantage of a unique behavior caused by amphetamine in <i>Caenorhabditis elegans</i> to investigate whether this simple, but powerful, genetic model develops tolerance following repeated exposure to amphetamine. We found that at least 3 treatments with 0.5 mM amphetamine were necessary to see a reduction in the amphetamine-induced behavior and, thus, to promote tolerance. Moreover, we found that, after intervals of 60/90 minutes between treatments, animals were more likely to exhibit tolerance than animals that underwent 10-minute intervals between treatments. Taken together, our results show that <i>C. elegans</i> is a suitable system to study tolerance to drugs of abuse such as amphetamines.

scholarly journals Genetic Mouse Models as In Vivo Tools for Cholangiocarcinoma Research

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1868 ◽  
Author(s):  
Oihane Erice ◽  
Adrian Vallejo ◽  
Mariano Ponz-Sarvise ◽  
Michael Saborowski ◽  
Arndt Vogel ◽  
...  
Keyword(s):  
Mouse Models ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Current Knowledge ◽  
Genetic Alterations ◽  
In Vivo Model ◽  
In Vivo Models ◽  
Dismal Prognosis ◽  
Genetic Mouse Models

Cholangiocarcinoma (CCA) is a genetically and histologically complex disease with a highly dismal prognosis. A deeper understanding of the underlying cellular and molecular mechanisms of human CCA will increase our current knowledge of the disease and expedite the eventual development of novel therapeutic strategies for this fatal cancer. This endeavor is effectively supported by genetic mouse models, which serve as sophisticated tools to systematically investigate CCA pathobiology and treatment response. These in vivo models feature many of the genetic alterations found in humans, recapitulate multiple hallmarks of cholangiocarcinogenesis (encompassing cell transformation, preneoplastic lesions, established tumors and metastatic disease) and provide an ideal experimental setting to study the interplay between tumor cells and the surrounding stroma. This review is intended to serve as a compendium of CCA mouse models, including traditional transgenic models but also genetically flexible approaches based on either the direct introduction of DNA into liver cells or transplantation of pre-malignant cells, and is meant as a resource for CCA researchers to aid in the selection of the most appropriate in vivo model system.

scholarly journals Chloramphenicol Resurrected: A Journey from Antibiotic Resistance in Eye Infections to Biofilm and Ocular Microbiota

2019 ◽  
Vol 7 (9) ◽  
pp. 278 ◽  
Author(s):  
Lorenzo
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
In Vivo Studies ◽  
Antibiofilm Activity ◽  
Eye Infections ◽  
Treatment And Prevention ◽  
Old Drugs

The advent of multidrug resistance among pathogenic bacteria is devastating the worth of antibiotics and changing the way of their administration, as well as the approach to use new or old drugs. The crisis of antimicrobial resistance is also due to the unavailability of newer drugs, attributable to exigent regulatory requirements and reduced financial inducements. The emerging resistance to antibiotics worldwide has led to renewed interest in old drugs that have fallen into disuse because of toxic side effects. Thus, comprehensive efforts are needed to minimize the pace of resistance by studying emergent microorganisms and optimize the use of old antimicrobial agents able to maintain their profile of susceptibility. Chloramphenicol is experiencing its renaissance because it is widely used in the treatment and prevention of superficial eye infections due to its broad spectrum of activity and other useful antimicrobial peculiarities, such as the antibiofilm properties. Concerns have been raised in the past for the risk of aplastic anemia when chloramphenicol is given intravenously. Chloramphenicol seems suitable to be used as topical eye formulation for the limited rate of resistance compared to fluoroquinolones, for its scarce induction of bacterial resistance and antibiofilm activity, and for the hypothetical low impact on ocular microbiota disturbance. Further in-vitro and in vivo studies on pharmacodynamics properties of ocular formulation of chloramphenicol, as well as its real impact against biofilm and the ocular microbiota, need to be better addressed in the near future.

scholarly journals Chloroquine enhances temozolomide cytotoxicity in malignant gliomas by blocking autophagy

2014 ◽  
Vol 37 (6) ◽  
pp. E12 ◽  
Author(s):  
Encouse B. Golden ◽  
Hee-Yeon Cho ◽  
Ardeshir Jahanian ◽  
Florence M. Hofman ◽  
Stan G. Louie ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
In Vivo Model ◽  
Autophagosome Formation ◽  
Individual Drug ◽  
In Vivo Experiments ◽  
Associated Proteins

Object In a recent clinical trial, patients with newly diagnosed glioblastoma multiforme benefited from chloroquine (CQ) in combination with conventional therapy (resection, temozolomide [TMZ], and radiation therapy). In the present study, the authors report the mechanism by which CQ enhances the therapeutic efficacy of TMZ to aid future studies aimed at improving this therapeutic regimen. Methods Using in vitro and in vivo experiments, the authors determined the mechanism by which CQ enhances TMZ cytotoxicity. They focused on the inhibition-of-autophagy mechanism of CQ by knockdown of the autophagy-associated proteins or treatment with autophagy inhibitors. This mechanism was tested using an in vivo model with subcutaneously implanted U87MG tumors from mice treated with CQ in combination with TMZ. Results Knockdown of the autophagy-associated proteins (GRP78 and Beclin) or treatment with the autophagy inhibitor, 3-methyl adenine (3-MA), blocked autophagosome formation and reduced CQ cytotoxicity, suggesting that autophagosome accumulation precedes CQ-induced cell death. In contrast, blocking autophagosome formation with knockdown of GRP78 or treatment with 3-MA enhanced TMZ cytotoxicity, suggesting that the autophagy pathway protects from TMZ-induced cytotoxicity. CQ in combination with TMZ significantly increased the amounts of LC3B-II (a marker for autophagosome levels), CHOP/GADD-153, and cleaved PARP (a marker for apoptosis) over those with untreated or individual drug-treated glioma cells. These molecular mechanisms seemed to take place in vivo as well. Subcutaneously implanted U87MG tumors from mice treated with CQ in combination with TMZ displayed higher levels of CHOP/GADD-153 than did untreated or individual drug-treated tumors. Conclusions Taken together, these results demonstrate that CQ blocks autophagy and triggers endoplasmic reticulum stress, thereby increasing the chemosensitivity of glioma cells to TMZ.

scholarly journals In Vitro and In Vivo Activity of Single and Dual Antimicrobial Agents Against KPC-producing Klebsiella pneumoniae

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S379-S379
Author(s):  
Farzad Moussavi ◽  
Sarath Nath ◽  
Daniel Abraham ◽  
David Landman ◽  
John Quale
Keyword(s):  
Antimicrobial Agents ◽  
Galleria Mellonella ◽  
Survival Rates ◽  
Polymyxin B ◽  
The Other ◽  
In Vivo Model ◽  
Serious Infections ◽  
Time Kill

Abstract Background Options for treatment of infections due to KPC-producing K. pneumoniae are limited, and combination therapy is often recommended. In this report, the in vitro and in vivo activity of potential therapeutic agents and combinations was assessed against four KPC-producing K. pneumoniae isolates. Methods Using clinically-relevant concentrations, time-kill experiments and the Galleria mellonella model of infection were used to examine the activity of polymyxin B, ceftazidime-avibactam, meropenem, rifampin, and amikacin alone and in combination. Four isolates of KPC-producing K. pneumoniae were studied, including two isolates that were resistant to polymyxin B and had ceftazidime-avibactam MICs of 8 µg/mL. The other two K. pneumoniae isolates were susceptible to polymyxin B and had lower MICs of ceftazidime-avibactam. Results Two isolates that were resistant to polymyxin B and with ceftazidime-avibactam MICs of 8 µg/mL were also resistant to amikacin and meropenem. When ceftazidime-avibactam was combined with either amikacin or meropenem, synergy was observed in vitro, and these combinations were associated with improved survival with the in vivo model. The other two K. pneumoniae isolates were susceptible to polymyxin B and had lower MICs of ceftazidime-avibactam. At concentrations four times the MIC, ceftazidime-avibactam had bactericidal activity in vitro; at one fourth the MIC, synergy was observed when combined with meropenem. Improved survival rates were observed with therapy with ceftazidime-avibactam, particularly when combined with a second agent for one isolate. In the in vivo model, polymyxin B with or without rifampin or meropenem, was ineffective against polymyxin B resistant strains. Conclusion Pending clinical studies, combining ceftazidime-avibactam with another agent (e.g., a carbapenem) should be encouraged when treating serious infections due to these pathogens, especially for isolates with ceftazidime-avibactam MICs near the susceptibility breakpoint. Disclosures All authors: No reported disclosures.

scholarly journals Drosophila Accessory Gland: A Complementary In Vivo Model to Bring New Insight to Prostate Cancer

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2387
Author(s):  
Amandine Rambur ◽  
Marine Vialat ◽  
Claude Beaudoin ◽  
Corinne Lours-Calet ◽  
Jean-Marc Lobaccaro ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Improve Patient Care ◽  
Accessory Gland ◽  
In Vivo Model ◽  
Cancer Models ◽  
Aging Men ◽  
Functional Equivalent ◽  
High Level

Prostate cancer is the most common cancer in aging men. Despite recent progress, there are still few effective treatments to cure its aggressive and metastatic stages. A better understanding of the molecular mechanisms driving disease initiation and progression appears essential to support the development of more efficient therapies and improve patient care. To do so, multiple research models, such as cell culture and mouse models, have been developed over the years and have improved our comprehension of the biology of the disease. Recently, a new model has been added with the use of the Drosophila accessory gland. With a high level of conservation of major signaling pathways implicated in human disease, this functional equivalent of the prostate represents a powerful, inexpensive, and rapid in vivo model to study epithelial carcinogenesis. The purpose of this review is to quickly overview the existing prostate cancer models, including their strengths and limitations. In particular, we discuss how the Drosophila accessory gland can be integrated as a convenient complementary model by bringing new understanding in the mechanisms driving prostate epithelial tumorigenesis, from initiation to metastatic formation.

scholarly journals Galleria mellonella: The Versatile Host for Drug Discovery, In Vivo Toxicity Testing and Characterising Host-Pathogen Interactions

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1545
Author(s):  
Magdalena Piatek ◽  
Gerard Sheehan ◽  
Kevin Kavanagh
Keyword(s):  
Antimicrobial Agents ◽  
Galleria Mellonella ◽  
Toxicity Testing ◽  
In Vivo Model ◽  
Ethical Considerations ◽  
Food Preservatives ◽  
In Vivo Toxicity ◽  
Greater Wax Moth ◽  
Development Processes

Larvae of the greater wax moth, Galleria mellonella, are a convenient in vivo model for assessing the activity and toxicity of antimicrobial agents and for studying the immune response to pathogens and provide results similar to those from mammals. G. mellonella larvae are now widely used in academia and industry and their use can assist in the identification and evaluation of novel antimicrobial agents. Galleria larvae are inexpensive to purchase and house, easy to inoculate, generate results within 24–48 h and their use is not restricted by legal or ethical considerations. This review will highlight how Galleria larvae can be used to assess the efficacy of novel antimicrobial therapies (photodynamic therapy, phage therapy, metal-based drugs, triazole-amino acid hybrids) and for determining the in vivo toxicity of compounds (e.g., food preservatives, ionic liquids) and/or solvents (polysorbate 80). In addition, the disease development processes are associated with a variety of pathogens (e.g., Staphylococcus aureus, Listeria monocytogenes, Aspergillus fumigatus, Madurella mycotomatis) in mammals are also present in Galleria larvae thus providing a simple in vivo model for characterising disease progression. The use of Galleria larvae offers many advantages and can lead to an acceleration in the development of novel antimicrobials and may be a prerequisite to mammalian testing.

scholarly journals Adult Mouse Retina Explants: From ex vivo to in vivo Model of Central Nervous System Injuries

2020 ◽  
Vol 13 ◽  
Author(s):  
Julia Schaeffer ◽  
Céline Delpech ◽  
Floriane Albert ◽  
Stephane Belin ◽  
Homaira Nawabi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Mechanisms ◽  
Axon Regeneration ◽  
Ex Vivo ◽  
Mouse Retina ◽  
In Vivo Model ◽  
Cns Regeneration ◽  
Single Axon

In mammals, adult neurons fail to regenerate following any insult to adult central nervous system (CNS), which leads to a permanent and irreversible loss of motor and cognitive functions. For a long time, much effort has been deployed to uncover mechanisms of axon regeneration in the CNS. Even if some cases of functional recovery have been reported, there is still a discrepancy regarding the functionality of a neuronal circuit upon lesion. Today, there is a need not only to identify new molecules implicated in adult CNS axon regeneration, but also to decipher the fine molecular mechanisms associated with regeneration failure. Here, we propose to use cultures of adult retina explants to study all molecular and cellular mechanisms that occur during CNS regeneration. We show that adult retinal explant cultures have the advantages to (i) recapitulate all the features observed in vivo, including axon regeneration induced by intrinsic factors, and (ii) be an ex vivo set-up with high accessibility and many downstream applications. Thanks to several examples, we demonstrate that adult explants can be used to address many questions, such as axon guidance, growth cone formation and cytoskeleton dynamics. Using laser guided ablation of a single axon, axonal injury can be performed at a single axon level, which allows to record early and late molecular events that occur after the lesion. Our model is the ideal tool to study all molecular and cellular events that occur during CNS regeneration at a single-axon level, which is currently not doable in vivo. It is extremely valuable to address unanswered questions of neuroprotection and neuroregeneration in the context of CNS lesion and neurodegenerative diseases.

Conditioning in the rat: an in vivo model to investigate the molecular mechanisms and clinical implications of brain-immune communication

2001 ◽  
Vol 184 (1) ◽  
pp. 226-235 ◽  
Author(s):  
Michael S. Exton ◽  
Juliane Herklotz ◽  
Jurgen Westermann ◽  
Manfred Schedlowski
Keyword(s):  
Molecular Mechanisms ◽  
In Vivo Model ◽  
Clinical Implications
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