Theses and Dissertations
http://nur.nu.edu.kz:80/handle/123456789/514
2024-03-28T22:30:32ZOral administration of chitosan/DNA nanoparticles containing DNA coding for FVIII and FC IgG fragment or IL-10 for the modulation of immune responses to FVIII in hemophilia mice
http://nur.nu.edu.kz:80/handle/123456789/3523
Oral administration of chitosan/DNA nanoparticles containing DNA coding for FVIII and FC IgG fragment or IL-10 for the modulation of immune responses to FVIII in hemophilia mice
Yerkesh, Zhadyra
Hemophilia A is an X-linked bleeding disorder, which occurs due to deficiency of
clotting protein FVIII. Current treatment involves regular lifelong infusion of
recombinant or plasma-derived FVIII protein, which is suboptimal, invasive and very
expensive. One of the biggest challenges of the current therapy is the recognition of
FVIII by immune system as a foreign substance, leading to the development of
neutralizing antibodies, which makes further administration of FVIII ineffective.
Therefore, an alternative cost effective and safe treatment to Hemophilia A is highly
desirable. We propose chitosan-mediated oral non-viral gene therapy as a safe and costeffective
strategy for immune modulation in severe hemophilia A cases. Having a
strong affinity for DNA and forming nanoparticles, chitosan-DNA complexes protect
plasmid DNA fi-om degradation by the low pH envu-onment of the stomach and from
nucleases in the GI tract; further, safe re-administration of nanoparticles is possible. We
also propose to include in the plasmid DNA coding for the Fc fragment of IgG heavy
chain region, which contains Tregitope sequences, T cell epitopes that specifically
activate regulatory T cells or anti-inflammatory cytokine IL-10 that may modulate the
immune response against FVIII protein. Therefore, it is hypothesized that orally
administered chitosan/DNA nanoparticles will lead to clinically relevant amount of
FVIII in the host without an immune response, providing long term, cost-effective and
safe treatment for hemophilia A.
For this study we aimed to: I) optimize nanoparticles in terms of effective gene
expression in vitro; 2) treat hemophilic mice orally with chitosan nanoparticles
containing DNA coding for FVIII and for immunomodulatory elements (Fc fragment of
IgG and IL-10) to induce tolerance to FVIII. We found that the key factors contributing
to the effectiveness of gene expression in chitosan/DNA nanoparticles are the type of
chitosan, the charge ratio (N/P) and the DNA concentration. In vivo, the optimized
nanoparticles containing FVIII+Fc DNA significantly decreased antibody formation
specific to F V I I I in prophylactic group of mice, and in 4/6 mice receiving nanoparticles
containing FVIII+IL-10. It is tempting to hypothesize that this strategy might also be
extended to modulate immune responses to other antigens.
2016-01-01T00:00:00ZMigration characteristics of cancer cells grown in embryonic microenvironment and under antiviral agents
http://nur.nu.edu.kz:80/handle/123456789/3521
Migration characteristics of cancer cells grown in embryonic microenvironment and under antiviral agents
Karapina, Orynbassar
This study describes a method for investigating reprogramming of cancer cells using chicken embryo extract and dimishing cancer cell progressing with acyclovir and it was used as innovative approach to address whether aggressive cancer cells with high potential to proliferate and migrate to distant organs could respond to the treatments, which could control cell fate determination
2016-01-01T00:00:00ZDevelopment of flow cytometry and microscopy techniques to monitor freshwater phytoplankton communities in Kazakhstani lakes
http://nur.nu.edu.kz:80/handle/123456789/3520
Development of flow cytometry and microscopy techniques to monitor freshwater phytoplankton communities in Kazakhstani lakes
Dashkova, Veronika
In this project, we tested an approach based on separating fluorescent viability and metabolic dyes between different excitation lasers in order to reach minimal spectral overlap with the autofluorescent signal using flow and imaging cytometry
2016-01-01T00:00:00ZCo-expression of FVIII with human IGG FC Fragment or mouse IL-10 in encapsulated G8 myoblast cells as a potential treatment of hemophilia A
http://nur.nu.edu.kz:80/handle/123456789/3519
Co-expression of FVIII with human IGG FC Fragment or mouse IL-10 in encapsulated G8 myoblast cells as a potential treatment of hemophilia A
Kanketayeva, Zhansaya
In this master thesis study we have shown that recombination G8 myoblasts, encapsulated in alginate-PLL microcapsules can successfully secrete detectable levels of both Fc and IL-10 out of the capsules and sustain good viability, showing the potential of co-delivering FVIII by encapsulated cells.
2016-01-01T00:00:00ZRole of astrocyte aging in the pathogenesis of Alzheimer`s disease
http://nur.nu.edu.kz:80/handle/123456789/3518
Role of astrocyte aging in the pathogenesis of Alzheimer`s disease
Imangali, Nurgul
In this study we presented in vitro model for replicative senescence of primary human astrocytes isolated from fetal brains
2016-01-01T00:00:00ZMorphometric characteristics of cancer cells grown in embryonic microenvironment and under antiviral treatment
http://nur.nu.edu.kz:80/handle/123456789/3517
Morphometric characteristics of cancer cells grown in embryonic microenvironment and under antiviral treatment
Shaimerdenova, Madina
We describe here that both embryonic microenvironment treatment and antiviral treatment have the potential to serve as effective factors in changing morphometric characteristics of two highly aggressive cancer cell lines, with proven capability to decrease viability of cancer cells, reduce amount of colonies formed after treatment, alter intracellular features of cell such as nucleus and cytoskeleton and diminish aldehyde dehydrogenase activity after treatment
2016-01-01T00:00:00Z