In vivo follow up of the cytotoxic effect of ricin toxin vectorized by multivalent hybrid antibody on target cells

Spleen cells sensitized against trinitrophenyl (TNP)-modified stimulator cells displayed a cytotoxic effect against syngeneic TNP-modified but not dinitrophenyl (DNP)-modified target cells. The same finding was observed in the opposite direction; that is, effector cells sensitized against DNP-modified stimulator cells did not cross kill TNP-modified targets. The specificity of the anti-TNP effector cells was confirmed in a cold target competition assay. Presensitization in vivo with hapten-modified cells followed by rechallenge and testing in vitro did not alter the specificity of the response between the haptens. These data indicate that the receptor(s) on the cytotoxic T cell can distinguish between two closely related haptenic molecules.

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Leishmanicidal activity of Artemisinin against cutaneous Leishmaniasis, in Vitro

Journal of Biotechnology Research Center ◽

10.24126/jobrc.2019.13.1.563 ◽

2019 ◽

Vol 13 (1) ◽

pp. 16-22

Author(s):

Guffran M. Hassan ◽

Hayder Z. Ali

Keyword(s):

Cutaneous Leishmaniasis ◽

Cytotoxic Effect ◽

Leishmania Tropica ◽

Herbal Drug ◽

Undesirable Side Effect ◽

Leishmanicidal Activity ◽

Herbal Compound

Background: Cutaneous leishmaniasis (CL) is a neglected disease in tropical countries, including Iraq. Several studies have sought to examine chemotherapies for leishmaniasis treatment but most of them are of toxic and/or undesirable side effect, therefore, the need for investigating new fewer toxic therapies is essential. Aim of study: In this study, the cytotoxic effect of Artemisinin (ART), a novel herbal compound, was screened against the two forms, promastigotes and amastigotes, of the Iraqi isolate of Leishmania tropica, the causative agent of Baghdad boil. Material and methods: Different concentrations (1000, 500, 250, 125, 62.5, 31.25, 15.6 and 7.8) µM of Artemisinin were screened to investigate the leishmanicidal activity of the herbal compound against the two forms of the parasite along three times of follow up (24, 48, 72) hour using MTT cytotoxicity assay. Results: The results showed that growth rate and cell viability were significantly decreased at all studied concentrations. The IC50 was measured after 72 hours of follow up and was 2.625 µM and 2.636 µM for promastigotes and amastigotes, respectively. Conclusion: These findings approved the leishmanicidal efficacy of Artemisinin against the of L. tropica and can be further studied to screen its effectiveness in vivo for exploring a safer herbal drug for treatment of cutaneous leishmaniasis.

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Non-Viral Vectors for Gene Delivery

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681208666180110154233 ◽

2018 ◽

Vol 9 (1) ◽

pp. 4-11 ◽

Cited By ~ 5

Author(s):

Aparna Bansal ◽

Himanshu

Keyword(s):

Gene Therapy ◽

Viral Vectors ◽

Transfection Efficiency ◽

Gene Transfection ◽

Expression System ◽

Target Cells ◽

Specific Expression ◽

Naked Dna

Introduction: Gene therapy has emerged out as a promising therapeutic pave for the treatment of genetic and acquired diseases. Gene transfection into target cells using naked DNA is a simple and safe approach which has been further improved by combining vectors or gene carriers. Both viral and non-viral approaches have achieved a milestone to establish this technique, but non-viral approaches have attained a significant attention because of their favourable properties like less immunotoxicity and biosafety, easy to produce with versatile surface modifications, etc. Literature is rich in evidences which revealed that undoubtedly, non–viral vectors have acquired a unique place in gene therapy but still there are number of challenges which are to be overcome to increase their effectiveness and prove them ideal gene vectors. Conclusion: To date, tissue specific expression, long lasting gene expression system, enhanced gene transfection efficiency has been achieved with improvement in delivery methods using non-viral vectors. This review mainly summarizes the various physical and chemical methods for gene transfer in vitro and in vivo.

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Bromamine T (BAT) Exerts Stronger Anti-Cancer Properties than Taurine (Tau)

Cancers ◽

10.3390/cancers13020182 ◽

2021 ◽

Vol 13 (2) ◽

pp. 182

Author(s):

Stella Baliou ◽

Maria Goulielmaki ◽

Petros Ioannou ◽

Christina Cheimonidi ◽

Ioannis P. Trougakos ◽

...

Keyword(s):

Cytotoxic Effect ◽

Human Colon ◽

Mitogen Activated Protein Kinase ◽

Mitochondrial Apoptosis ◽

Therapeutic Modalities ◽

Cancer Pathogenesis ◽

Extracellular Signal ◽

Anti Cancer ◽

Mitogen Activated Protein

Background: Taurine (Tau) ameliorates cancer pathogenesis. Researchers have focused on the functional properties of bromamine T (BAT), a stable active bromine molecule. Both N-bromotaurine (TauNHBr) and BAT exert potent anti-inflammatory properties, but the landscape remains obscure concerning the anti-cancer effect of BAT. Methods: We used Crystal Violet, colony formation, flow cytometry and Western blot experiments to evaluate the effect of BAT and Tau on the apoptosis and autophagy of cancer cells. Xenograft experiments were used to determine the in vivo cytotoxicity of either agent. Results: We demonstrated that both BAT and Tau inhibited the growth of human colon, breast, cervical and skin cancer cell lines. Among them, BAT exerted the greatest cytotoxic effect on both RKO and MDA-MB-468 cells. In particular, BAT increased the phosphorylation of c-Jun N-terminal kinases (JNK½), p38 mitogen-activated protein kinase (MAPK), and extracellular-signal-regulated kinases (ERK½), thereby inducing mitochondrial apoptosis and autophagy in RKO cells. In contrast, Tau exerted its cytotoxic effect by upregulating JNK½ forms, thus triggering mitochondrial apoptosis in RKO cells. Accordingly, colon cancer growth was impaired in vivo. Conclusions: BAT and Tau exerted their anti-tumor properties through the induction of (i) mitochondrial apoptosis, (ii) the MAPK family, and iii) autophagy, providing novel anti-cancer therapeutic modalities.

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Let-7f miRNA regulates SDF-1α- and hypoxia-promoted migration of mesenchymal stem cells and attenuates mammary tumor growth upon exosomal release

Cell Death and Disease ◽

10.1038/s41419-021-03789-3 ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Virginia Egea ◽

Kai Kessenbrock ◽

Devon Lawson ◽

Alexander Bartelt ◽

Christian Weber ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Tumor Growth ◽

Molecular Mechanisms ◽

Hypoxia Inducible Factor ◽

Human Mesenchymal Stem Cells ◽

Target Cells ◽

Autophagic Flux ◽

Stromal Cell Derived Factor

AbstractBone marrow-derived human mesenchymal stem cells (hMSCs) are recruited to damaged or inflamed tissues where they contribute to tissue repair. This multi-step process involves chemokine-directed invasion of hMSCs and on-site release of factors that influence target cells or tumor tissues. However, the underlying molecular mechanisms are largely unclear. Previously, we described that microRNA let-7f controls hMSC differentiation. Here, we investigated the role of let-7f in chemotactic invasion and paracrine anti-tumor effects. Incubation with stromal cell-derived factor-1α (SDF-1α) or inflammatory cytokines upregulated let-7f expression in hMSCs. Transfection of hMSCs with let-7f mimics enhanced CXCR4-dependent invasion by augmentation of pericellular proteolysis and release of matrix metalloproteinase-9. Hypoxia-induced stabilization of the hypoxia-inducible factor 1 alpha in hMSCs promoted cell invasion via let-7f and activation of autophagy. Dependent on its endogenous level, let-7f facilitated hMSC motility and invasion through regulation of the autophagic flux in these cells. In addition, secreted let-7f encapsulated in exosomes was increased upon upregulation of endogenous let-7f by treatment of the cells with SDF-1α, hypoxia, or induction of autophagy. In recipient 4T1 tumor cells, hMSC-derived exosomal let-7f attenuated proliferation and invasion. Moreover, implantation of 3D spheroids composed of hMSCs and 4T1 cells into a breast cancer mouse model demonstrated that hMSCs overexpressing let-7f inhibited tumor growth in vivo. Our findings provide evidence that let-7f is pivotal in the regulation of hMSC invasion in response to inflammation and hypoxia, suggesting that exosomal let-7f exhibits paracrine anti-tumor effects.

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The Effect of Q-Switched Nd:YAG 1064 nm/532 nm Laser in the Treatment of Onychomycosis In Vivo

Dermatology Research and Practice ◽

10.1155/2013/379725 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 23

Author(s):

Kostas Kalokasidis ◽

Meltem Onder ◽

Myrto-Georgia Trakatelli ◽

Bertrand Richert ◽

Klaus Fritz

Keyword(s):

Clinical Study ◽

Treatment Time ◽

Prospective Clinical Study ◽

Self Evaluation ◽

Time Period ◽

Level Of Satisfaction ◽

Before And After ◽

532 Nm

In this prospective clinical study, the Q-Switched Nd:YAG 1064 nm/532 nm laser (Light Age, Inc., Somerset, NJ, USA) was used on 131 onychomycosis subjects (94 females, 37 males; ages 18 to 68 years). Mycotic cultures were taken and fungus types were detected. The laser protocol included two sessions with a one-month interval. Treatment duration was approximately 15 minutes per session and patients were observed over a 3-month time period. Laser fluencies of 14 J/cm2were applied at 9 billionths of a second pulse duration and at 5 Hz frequency. Follow-up was performed at 3 months with mycological cultures. Before and after digital photographs were taken. Adverse effects were recorded and all participants completed “self-evaluation questionnaires” rating their level of satisfaction. All subjects were well satisfied with the treatments, there were no noticeable side effects, and no significant differences were found treating men versus women. At the 3-month follow-up 95.42% of the patients were laboratory mycologically cured of fungal infection. This clinical study demonstrates that fungal nail infections can be effectively and safely treated with Q-Switched Nd:YAG 1064 nm/532 nm laser. It can also be combined with systemic oral antifungals providing more limited treatment time.

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Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots

Nanomaterials ◽

10.3390/nano11010180 ◽

2021 ◽

Vol 11 (1) ◽

pp. 180

Author(s):

Maud Weiss ◽

Jiahui Fan ◽

Mickaël Claudel ◽

Luc Lebeau ◽

Françoise Pons ◽

...

Keyword(s):

Carbon Dots ◽

Lung Inflammation ◽

Adverse Outcome ◽

Cellular Responses ◽

Target Cells ◽

Inflammasome Activation ◽

Adverse Outcome Pathway ◽

Acute Lung Inflammation

With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches. We first investigated the effect of a single administration of CDs on mouse airways. We showed that CDs induce an acute lung inflammation and identified airway macrophages as target cells of CDs. Then, we studied the cellular responses induced by CDs in an in vitro model of macrophages. We observed that CDs are internalized by these cells (molecular initial event) and induce a series of key events, including loss of lysosomal integrity and mitochondrial disruption (organelle responses), as well as oxidative stress, inflammasome activation, inflammatory cytokine upregulation and macrophage death (cellular responses). All these effects triggering lung inflammation as tissular response may lead to acute lung injury.

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