The potential of a site-specific delivery of thiamine hydrochloride as a novel insect repellent exerting long-term protection on human skin: In-vitro, ex-vivo study and clinical assessment

The F1sub-complex of ATP synthase is a biological nanomotor that converts the free energy of ATP hydrolysis into mechanical work with an astonishing efficiency of up to 100% (Kinosita et al., 2000). To probe the principal mechanics of the machine, I re-engineered the active site ofE.coliF1ATPase with a structure-based protein design approach: by incorporation of a site-specific, photoswitchable crosslinker, whose end-to-end distance can be modulated by illumination with light of two different wavelengths, a dynamic constraint was imposed on the inter-atomic distances of the α and β subunits. Crosslinking reduced the ATP hydrolysis activity of four designs tested in vitro and in one case created a synthetic ATPase whose activity can be reversibly modulated by subsequent illumination with near UV and blue light. The work is a first step into the direction of the long-term goal to design nanoscaled machines based on biological parts that can be precisely controlled by light.

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Strategies to Protect Hematopoietic Stem Cells from Culture-Induced Stress Conditions

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200225091339 ◽

2020 ◽

Vol 15 ◽

Author(s):

Fatima Aerts-Kaya

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

Ex Vivo ◽

Stress Conditions ◽

Stress Factors ◽

Hematopoietic Stem ◽

Induced Stress

: In contrast to their almost unlimited potential for expansion in vivo and despite years of dedicated research and optimization of expansion protocols, the expansion of Hematopoietic Stem Cells (HSCs) in vitro remains remarkably limited. Increased understanding of the mechanisms that are involved in maintenance, expansion and differentiation of HSCs will enable the development of better protocols for expansion of HSCs. This will allow procurement of HSCs with long-term engraftment potential and a better understanding of the effects of the external influences in and on the hematopoietic niche that may affect HSC function. During collection and culture of HSCs, the cells are exposed to suboptimal conditions that may induce different levels of stress and ultimately affect their self-renewal, differentiation and long-term engraftment potential. Some of these stress factors include normoxia, oxidative stress, extra-physiologic oxygen shock/stress (EPHOSS), endoplasmic reticulum (ER) stress, replicative stress, and stress related to DNA damage. Coping with these stress factors may help reduce the negative effects of cell culture on HSC potential, provide a better understanding of the true impact of certain treatments in the absence of confounding stress factors. This may facilitate the development of better ex vivo expansion protocols of HSCs with long-term engraftment potential without induction of stem cell exhaustion by cellular senescence or loss of cell viability. This review summarizes some of available strategies that may be used to protect HSCs from culture-induced stress conditions.

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Aryl Maleimides as Apoptosis Inducers on L5178-Y Murine Leukemia Cells (in silico, in vitro and ex vivo Study)

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520615666160504094417 ◽

2016 ◽

Vol 16 (12) ◽

pp. 1615-1621 ◽

Cited By ~ 3

Author(s):

Erik Andrade-Jorge ◽

Marycarmen Godínez-Victoria ◽

Luvia Enid Sánchez-Torres ◽

Luis Humberto Fabila-Castillo ◽

José G. Trujillo-Ferrara

Keyword(s):

In Silico ◽

Ex Vivo ◽

Leukemia Cells ◽

Ex Vivo Study ◽

Murine Leukemia

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Experimental Design And Characterization Of Nanoemulsion Based Topical Herbal Gel Developed For Site-Specific Activity Of Glycyrrhiza Glabra Extract: In Vitro And Ex- Vivo Studies

Bioscience Biotechnology Research Communications ◽

10.21786/bbrc/12.2/25 ◽

2019 ◽

Vol 12 (2) ◽

pp. 408-418 ◽

Cited By ~ 1

Author(s):

Anil Tatiya ◽

Snehal Bhavsar ◽

Hitendra Mahajan ◽

Sanjay Surana

Keyword(s):

Experimental Design ◽

Specific Activity ◽

Ex Vivo ◽

Glycyrrhiza Glabra ◽

Site Specific

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64Cu-ATSM/64Cu-Cl2 and their relationship to hypoxia in glioblastoma: a preclinical study

EJNMMI Research ◽

10.1186/s13550-019-0586-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Elodie A. Pérès ◽

Jérôme Toutain ◽

Louis-Paul Paty ◽

Didier Divoux ◽

Méziane Ibazizène ◽

...

Keyword(s):

Ex Vivo ◽

In Vitro Study ◽

Tumor Location ◽

Preclinical Study ◽

Significant Rise ◽

Lower Oxygen ◽

Cu Complexes ◽

Ex Vivo Study

Abstract Background Diacetyl-bis(N4-methylthiosemicarbazone), labeled with 64Cu (64Cu-ATSM) has been suggested as a promising tracer for imaging hypoxia. However, various controversial studies highlighted potential pitfalls that may disable its use as a selective hypoxic marker. They also highlighted that the results may be tumor location dependent. Here, we first analyzed uptake of Cu-ATSM and its less lipophilic counterpart Cu-Cl2 in the tumor over time in an orthotopic glioblastoma model. An in vitro study was also conducted to investigate the hypoxia-dependent copper uptake in tumor cells. We then further performed a comprehensive ex vivo study to compare 64Cu uptake to hypoxic markers, specific cellular reactions, and also transporter expression. Methods μPET was performed 14 days (18F-FMISO), 15 days (64Cu-ATSM and 64Cu-Cl2), and 16 days (64Cu-ATSM and 64Cu-Cl2) after C6 cell inoculation. Thereafter, the brains were withdrawn for further autoradiography and immunohistochemistry. C6 cells were also grown in hypoxic workstation to analyze cellular uptake of Cu complexes in different oxygen levels. Results In vivo results showed that Cu-ASTM and Cu-Cl2 accumulated in hypoxic areas of the tumors. Cu-ATSM also stained, to a lesser extent, non-hypoxic regions, such as regions of astrogliosis, with high expression of copper transporters and in particular DMT-1 and CTR1, and also characterized by the expression of elevated astrogliosis. In vitro results show that 64Cu-ATSM showed an increase in the uptake only in severe hypoxia at 0.5 and 0.2% of oxygen while for 64Cu-Cl2, the cell retention was significantly increased at 5% and 1% of oxygen with no significant rise at lower oxygen percentages. Conclusion In the present study, we show that Cu-complexes undoubtedly accumulate in hypoxic areas of the tumors. This uptake may be the reflection of a direct dependency to a redox metabolism and also a reflection of hypoxic-induced overexpression of transporters. We also show that Cu-ATSM also stained non-hypoxic regions such as astrogliosis.

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Phase Variation of Campylobacter jejuni 81-176 Lipooligosaccharide Affects Ganglioside Mimicry and Invasiveness In Vitro

Infection and Immunity ◽

10.1128/iai.70.2.787-793.2002 ◽

2002 ◽

Vol 70 (2) ◽

pp. 787-793 ◽

Cited By ~ 154

Author(s):

Patricia Guerry ◽

Christine M. Szymanski ◽

Martina M. Prendergast ◽

Thomas E. Hickey ◽

Cheryl P. Ewing ◽

...

Keyword(s):

Campylobacter Jejuni ◽

Phase Variation ◽

Outer Core ◽

Gene Encoding ◽

Site Specific ◽

Reading Frame ◽

Specific Mutation ◽

Normal Human ◽

A Site

ABSTRACT The outer cores of the lipooligosaccharides (LOS) of many strains of Campylobacter jejuni mimic human gangliosides in structure. A population of cells of C. jejuni strain 81-176 produced a mixture of LOS cores which consisted primarily of structures mimicking GM2 and GM3 gangliosides, with minor amounts of structures mimicking GD1b and GD2. Genetic analyses of genes involved in the biosynthesis of the outer core of C. jejuni 81-176 revealed the presence of a homopolymeric tract of G residues within a gene encoding CgtA, an N-acetylgalactosaminyltransferase. Variation in the number of G residues within cgtA affected the length of the open reading frame, and these changes in cgtA corresponded to a change in LOS structure from GM2 to GM3 ganglioside mimicry. Site-specific mutation of cgtA in 81-176 resulted in a major LOS core structure that lacked GalNAc and resembled GM3 ganglioside. Compared to wild-type 81-176, the cgtA mutant showed a significant increase in invasion of INT407 cells. In comparison, a site-specific mutation of the neuC1 gene resulted in the loss of sialic acid in the LOS core and reduced resistance to normal human serum but had no affect on invasion of INT407 cells.

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Selective photodynamic inactivation of Helicobacter pylori by a cationic benzylidene cyclopentanone photosensitizer - an in vitro and ex vivo study

Journal of Photochemistry and Photobiology B Biology ◽

10.1016/j.jphotobiol.2021.112287 ◽

2021 ◽

Vol 223 ◽

pp. 112287

Author(s):

Ying Wang ◽

Xianghuan Guo ◽

Shaona Zhou ◽

Leili Wang ◽

Yanyan Fang ◽

...

Keyword(s):

Helicobacter Pylori ◽

Ex Vivo ◽

Photodynamic Inactivation ◽

Ex Vivo Study

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FORMULATION AND EVALUATION OF FAST DISSOLVING ORAL FILMS OF PROCHLORPERAZINE MALEATE

INDIAN DRUGS ◽

10.53879/id.52.12.10351 ◽

2015 ◽

Vol 52 (12) ◽

pp. 23-33

Author(s):

R. Kanekar ◽

◽

P. M. Dandagi ◽

A. P. Gadad

Keyword(s):

Ex Vivo ◽

Rapid Onset ◽

Drug Release Profile ◽

Onset Of Action ◽

In Vitro Drug Release ◽

Physico Chemical ◽

Film Forming ◽

Oral Films ◽

Ex Vivo Study

The objective of the present study was to prepare and evaluate fast-dissolving oral films of prochlorperazine maleate (PCM), in order to enhance the bioavailability of the drug and to provide rapid onset of action thereby improving patient compliance. The solubility of the drug was increased by preparing inclusion complex with 2-hydroxypropyl-β-cyclodextrin (2HPβCD) and then incorporating it into the fast dissolving films. The fast-dissolving films of PCM were prepared by solvent casting method using different film forming polymers such as HPMC E15 and HPMC E5, either as single polymer or combination of the two. The film formulations were evaluated for various physico-chemical parameters. All formulations released more than 85% of the drug within 15 minutes. Formulation F4 showed best in vitro drug release profile. From the ex vivo study it was found that 94.79% of drug permeated through the porcine oral mucosa from the optimized formulation F4 within 60 mins.

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