Identification of novel therapeutic agents targeting Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication
- Authors: Okpara, Michael Obinna
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432181 , vital:72849
- Description: Access restricted. Expected release date 2025. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Authors: Okpara, Michael Obinna
- Date: 2023-10-13
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432181 , vital:72849
- Description: Access restricted. Expected release date 2025. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
Dual and targeted photodynamic therapy ablation of bacterial and cancer cells using phthalocyanines and porphyrins in the presence of carbon-based nanomaterials
- Authors: Openda, Yolande Ikala
- Date: 2022-10-14
- Subjects: Phthalocyanines , Porphyrins , Active oxygen , Biofilms , Breast Cancer Treatment , Nanostructured materials , Combination therapy , Photochemotherapy
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365945 , vital:65804 , DOI https://doi.org/10.21504/10962//365946
- Description: Phthalocyanines (Pcs) and porphyrins bearing substituents that possess antibacterial/anticancer properties are used as photosensitizers (PS) for the first time in the work. For targeting specificity and improved photoactivity, the PSs were afterward functionalized with carbon nanomaterials such as graphene quantum dots (GQDs) and detonation nanodiamonds (DNDs) via covalent conjugation (amide or ester bonds) or by non-covalent conjugation (π-π stacking and electrostatic interactions). Furthermore, the PSs-DNDs nanoconjugates were conjugated to either chitosan-capped silver nanoparticles (CSAg) via amide bonds or to the bare silver nanoparticles (Ag NPs) using the silver- nitrogen affinity. The as-synthesized nanoconjugates were also fully characterized by spectroscopic and microscopic methods together with thermal analysis. The potential photocytotoxicity of the complexes alone and their nanoconjugates against S. aureus and/or E. coli planktonic and biofilm cultures has been evaluated in vitro. Compared to the non- quaternized PSs, the cationic analogs exhibited a higher photodynamic inactivation against the planktonic cells with log10 reduction values above 9 in the viable count using a concentration of ca. 1.25 μM following 30 min exposure to light (Light dose: 943 J/cm2 for Pcs and 250 mW/cm2 for porphyrins). Whereas, at a concentration of ca. 100 μM the cationic PSs showed complete eradication of biofilms upon 30 min exposure to light. As a result of conjugation to carbon-based nanomaterials and silver nanoparticles, the compounds proved to be more effective as they exhibited stronger antibacterial and anti-biofilm activities on the multi-drug resistant bacteria strains due to synergetic effect, compared to PSs alone. This suggests that the newly prepared nanohybrids (PS concentration ca. 100 μM) could be used as potential antimicrobial agents in the treatment of biofilm-related infections. The target nanoconjugates showed all the advantages of two different groups existing on a single entity. In light of the potential advantages of combined chemotherapy and photodynamic antimicrobial chemotherapy (PACT), this work reports for the first time the use of PACT-ciprofloxacin (CIP) dual therapy using selected indium quaternized PSs which showed higher photoactivity with complete eradication of both Gram-positive and Gram-negative bacteria biofilms at concentrations of 8 μM of PS versus 2 μg/mL of the antibiotic following 15 min irradiation time (light dose: 471 J/cm2 for Pcs and fluence: 250 mW/cm2 for porphyrins) on S. aureus. Whereas the total killing of E. coli was obtained when combining 8 or 16 μM of PS combined with 4 μg/mL of CIP. The combined treatment resulted in the complete eradication of the matured biofilms with the highest log10 reduction values of 7.05 and 7.20 on S. aureus and E. coli, respectively. Used as a model, positively charged dimethylamino-chalcone Pcs also exhibited interesting photodynamic therapy (PDT) activity against MCF-7 cancer cells giving IC50 values of 17.9 and 7.4 μM, respectively following 15 min irradiation. Additionally, the TD-B3LYP/LanL2DZ calculations were run on the dimethylaminophenyl- porphyrins to compare the singlet excitation energies of quaternized and non-quaternized porphyrins in vacuo. the study shows excellent agreement between time-dependent density- functional theory (TD-DFT) exciting energies and the experimental S1>S0 excitation energies. The small deviation observed between the calculated and experimental spectra arises from the solvent effect. The excitation energies observed in these UV-Vis spectra mostly originated from electron promotion between the highest occupied molecular orbital (HOMO) for the less intense band and the HOMO-1 for the most intense band of the ground states to the lower unoccupied molecular orbital (LUMO) of the excited states. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Authors: Openda, Yolande Ikala
- Date: 2022-10-14
- Subjects: Phthalocyanines , Porphyrins , Active oxygen , Biofilms , Breast Cancer Treatment , Nanostructured materials , Combination therapy , Photochemotherapy
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365945 , vital:65804 , DOI https://doi.org/10.21504/10962//365946
- Description: Phthalocyanines (Pcs) and porphyrins bearing substituents that possess antibacterial/anticancer properties are used as photosensitizers (PS) for the first time in the work. For targeting specificity and improved photoactivity, the PSs were afterward functionalized with carbon nanomaterials such as graphene quantum dots (GQDs) and detonation nanodiamonds (DNDs) via covalent conjugation (amide or ester bonds) or by non-covalent conjugation (π-π stacking and electrostatic interactions). Furthermore, the PSs-DNDs nanoconjugates were conjugated to either chitosan-capped silver nanoparticles (CSAg) via amide bonds or to the bare silver nanoparticles (Ag NPs) using the silver- nitrogen affinity. The as-synthesized nanoconjugates were also fully characterized by spectroscopic and microscopic methods together with thermal analysis. The potential photocytotoxicity of the complexes alone and their nanoconjugates against S. aureus and/or E. coli planktonic and biofilm cultures has been evaluated in vitro. Compared to the non- quaternized PSs, the cationic analogs exhibited a higher photodynamic inactivation against the planktonic cells with log10 reduction values above 9 in the viable count using a concentration of ca. 1.25 μM following 30 min exposure to light (Light dose: 943 J/cm2 for Pcs and 250 mW/cm2 for porphyrins). Whereas, at a concentration of ca. 100 μM the cationic PSs showed complete eradication of biofilms upon 30 min exposure to light. As a result of conjugation to carbon-based nanomaterials and silver nanoparticles, the compounds proved to be more effective as they exhibited stronger antibacterial and anti-biofilm activities on the multi-drug resistant bacteria strains due to synergetic effect, compared to PSs alone. This suggests that the newly prepared nanohybrids (PS concentration ca. 100 μM) could be used as potential antimicrobial agents in the treatment of biofilm-related infections. The target nanoconjugates showed all the advantages of two different groups existing on a single entity. In light of the potential advantages of combined chemotherapy and photodynamic antimicrobial chemotherapy (PACT), this work reports for the first time the use of PACT-ciprofloxacin (CIP) dual therapy using selected indium quaternized PSs which showed higher photoactivity with complete eradication of both Gram-positive and Gram-negative bacteria biofilms at concentrations of 8 μM of PS versus 2 μg/mL of the antibiotic following 15 min irradiation time (light dose: 471 J/cm2 for Pcs and fluence: 250 mW/cm2 for porphyrins) on S. aureus. Whereas the total killing of E. coli was obtained when combining 8 or 16 μM of PS combined with 4 μg/mL of CIP. The combined treatment resulted in the complete eradication of the matured biofilms with the highest log10 reduction values of 7.05 and 7.20 on S. aureus and E. coli, respectively. Used as a model, positively charged dimethylamino-chalcone Pcs also exhibited interesting photodynamic therapy (PDT) activity against MCF-7 cancer cells giving IC50 values of 17.9 and 7.4 μM, respectively following 15 min irradiation. Additionally, the TD-B3LYP/LanL2DZ calculations were run on the dimethylaminophenyl- porphyrins to compare the singlet excitation energies of quaternized and non-quaternized porphyrins in vacuo. the study shows excellent agreement between time-dependent density- functional theory (TD-DFT) exciting energies and the experimental S1>S0 excitation energies. The small deviation observed between the calculated and experimental spectra arises from the solvent effect. The excitation energies observed in these UV-Vis spectra mostly originated from electron promotion between the highest occupied molecular orbital (HOMO) for the less intense band and the HOMO-1 for the most intense band of the ground states to the lower unoccupied molecular orbital (LUMO) of the excited states. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
Former farm workers of foreign descent in communal areas in post-fast track Zimbabwe : the case of Shamva District
- Authors: Chadambuka, Patience
- Date: 2021-10-29
- Subjects: Migrant agricultural laborers -- Zimbabwe -- Shamva District , Agricultural laborers, Foreign -- Zimbabwe -- Shamva District , Land reform -- Zimbabwe , Belonging (Social psychology) -- Zimbabwe -- Shamva District , Social integration-- Zimbabwe -- Shamva District , Fast Track Land Reform Programme (FTLRP)
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/178420 , vital:42938 , 10.21504/10962/178420
- Description: Land and ethnicity continue to condition contestations in relation to belonging amongst rural Zimbabweans. The colonial era defined Zimbabwe’s land politics in a highly racialised and ethnicised manner. Racially, the colonial era gave birth to white-owned fertile farm lands, while blacks (or Africans) were resettled in agriculturally-unproductive Reserves, later referred to as communal areas in the post-colonial era. Though they were initially created with a segregatory and oppressive intent bent on disenfranchising native Africans, the Reserves became a definitive landscape embedded in ethnic and ancestral belonging for the autochthonous Natives. The Reserves were created exclusively for autochthonous Africans, and the colonial administration ensured that foreign migrant Africans recruited mainly as covenanted labour from nearby colonies would not be accommodated and consequently belong in Reserves. Migrant Africans were instead domiciled in white commercial farms, mines and urban areas, and deprived of land rights accorded to the autochthones. In the case of white farms specifically, the labourers experienced a conditional belonging (to the farm). This overall exclusionary system was later inherited and maintained by the post-colonial Zimbabwean government, up until the year 2000. Zimbabwe’s highly documented Fast Track Land Reform Programme (FTLRP) from the year 2000 did away with the entrenched racial bifurcations of land, as white commercial farms became fast track farms. However, it did not undercut the existence of communal areas. The FTLRP had a profound effect on the lives of commercial farm workers, particularly those of foreign origin who had no other home or source of livelihood to fall back on after fast track displacements. Some though sought to move into communal areas, from which they had been excluded previously. Within this context, most scholarly studies of the post fast track period ignore the plight of former farm workers especially those that moved to, and into, communal areas. This ethnographic study, specifically of former farm workers of foreign origin in Shamva communal areas, therefore seeks to contribute to Zimbabwean studies in this regard. It documents and examines the perceptions, practices and lived experiences of former farm workers of foreign origin now residing in the Bushu communal areas of Shamva, and how they interface with Bushu autochthones in seeking to belong to Bushu. This is pursued by way of qualitative research methods (including lengthy stays in the study sites) as well as through the use of a theoretical framing focusing on lifeworlds, interfaces, belonging, othering and strangerhood. Key findings reveal that belonging by the former farm workers in Bushu entails a non-linear and convoluted process characterised by a series of contestations around for instance land shortages, limited livelihood strategies and cultural difference. This project of belonging does not entail assimilation on the part of the former farm workers, as they continue to uphold certain historical practices, leading to a form of co-existence between the autochthones and allochthones in Bushu. In this way, the former farm workers seem to develop a conditional belonging in (and to) Bushu, albeit different than the one experienced on white farms in the past. , Thesis (PhD) -- Faculty of Humanities, Sociology, 2021
- Full Text:
- Authors: Chadambuka, Patience
- Date: 2021-10-29
- Subjects: Migrant agricultural laborers -- Zimbabwe -- Shamva District , Agricultural laborers, Foreign -- Zimbabwe -- Shamva District , Land reform -- Zimbabwe , Belonging (Social psychology) -- Zimbabwe -- Shamva District , Social integration-- Zimbabwe -- Shamva District , Fast Track Land Reform Programme (FTLRP)
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/178420 , vital:42938 , 10.21504/10962/178420
- Description: Land and ethnicity continue to condition contestations in relation to belonging amongst rural Zimbabweans. The colonial era defined Zimbabwe’s land politics in a highly racialised and ethnicised manner. Racially, the colonial era gave birth to white-owned fertile farm lands, while blacks (or Africans) were resettled in agriculturally-unproductive Reserves, later referred to as communal areas in the post-colonial era. Though they were initially created with a segregatory and oppressive intent bent on disenfranchising native Africans, the Reserves became a definitive landscape embedded in ethnic and ancestral belonging for the autochthonous Natives. The Reserves were created exclusively for autochthonous Africans, and the colonial administration ensured that foreign migrant Africans recruited mainly as covenanted labour from nearby colonies would not be accommodated and consequently belong in Reserves. Migrant Africans were instead domiciled in white commercial farms, mines and urban areas, and deprived of land rights accorded to the autochthones. In the case of white farms specifically, the labourers experienced a conditional belonging (to the farm). This overall exclusionary system was later inherited and maintained by the post-colonial Zimbabwean government, up until the year 2000. Zimbabwe’s highly documented Fast Track Land Reform Programme (FTLRP) from the year 2000 did away with the entrenched racial bifurcations of land, as white commercial farms became fast track farms. However, it did not undercut the existence of communal areas. The FTLRP had a profound effect on the lives of commercial farm workers, particularly those of foreign origin who had no other home or source of livelihood to fall back on after fast track displacements. Some though sought to move into communal areas, from which they had been excluded previously. Within this context, most scholarly studies of the post fast track period ignore the plight of former farm workers especially those that moved to, and into, communal areas. This ethnographic study, specifically of former farm workers of foreign origin in Shamva communal areas, therefore seeks to contribute to Zimbabwean studies in this regard. It documents and examines the perceptions, practices and lived experiences of former farm workers of foreign origin now residing in the Bushu communal areas of Shamva, and how they interface with Bushu autochthones in seeking to belong to Bushu. This is pursued by way of qualitative research methods (including lengthy stays in the study sites) as well as through the use of a theoretical framing focusing on lifeworlds, interfaces, belonging, othering and strangerhood. Key findings reveal that belonging by the former farm workers in Bushu entails a non-linear and convoluted process characterised by a series of contestations around for instance land shortages, limited livelihood strategies and cultural difference. This project of belonging does not entail assimilation on the part of the former farm workers, as they continue to uphold certain historical practices, leading to a form of co-existence between the autochthones and allochthones in Bushu. In this way, the former farm workers seem to develop a conditional belonging in (and to) Bushu, albeit different than the one experienced on white farms in the past. , Thesis (PhD) -- Faculty of Humanities, Sociology, 2021
- Full Text:
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