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Item Plant-associated symbiotic burkholderia species lack hallmark strategies required in mammalian pathogenesis.(Public Library of Science, 2014-01-08) Angus, Annette A.; Agapakis, Christina M.; Fong, Stephanie; Yerrapragada, Shailaja; De Los Santos, Paulina Estradade ; Yang, Paul; Song, Nannie; Kano, Stephanie; Caballero-Mellado, Jesus; De Faria, Sergio M.; Dakora, Felix D.; Weinstock, George; Hirsch, Ann M.Burkholderia is a diverse and dynamic genus, containing pathogenic species as well as species that form complex interactions with plants. Pathogenic strains, such as B. pseudomallei and B. mallei, can cause serious disease in mammals, while other Burkholderia strains are opportunistic pathogens, infecting humans or animals with a compromised immune system. Although some of the opportunistic Burkholderia pathogens are known to promote plant growth and even fix nitrogen, the risk of infection to infants, the elderly, and people who are immunocompromised has not only resulted in a restriction on their use, but has also limited the application of non-pathogenic, symbiotic species, several of which nodulate legume roots or have positive effects on plant growth. However, recent phylogenetic analyses have demonstrated that Burkholderia species separate into distinct lineages, suggesting the possibility for safe use of certain symbiotic species in agricultural contexts. A number of environmental strains that promote plant growth or degrade xenobiotics are also included in the symbiotic lineage. Many of these species have the potential to enhance agriculture in areas where fertilizers are not readily available and may serve in the future as inocula for crops growing in soils impacted by climate change. Here we address the pathogenic potential of several of the symbiotic Burkholderia strains using bioinformatics and functional tests. A series of infection experiments using Caenorhabditis elegans and HeLa cells, as well as genomic characterization of pathogenic loci, show that the risk of opportunistic infection by symbiotic strains such as B. tuberum is extremely low.Item DnaK protein interaction of phage marked Bradyrhizobium of soybean.(BMC, 2013-12-19) Jaiswal, Sanjay Kumar; Vaishampayan, Akhouri; Singh, Vinay Kumar; Vaishampayan, Akhouri; Dhar, Banshi; Dakora, Felix DapareThe ability to rapidly adapt to changes in their environment is essential for the survival of microorganisms. DnaK is the prokaryotic analogue of eukaryotic Hsp70. These proteins protect the cell against heat injury or other forms of stress. In the present research, 78 rhizobial isolates were collected from different geographical regions of India and tested for their sensitivity. Forty-two out of 78 were shown to be susceptible to eight isolated phages. Only six Rhizobium strains out of 42 (MPSR033, MPSR041, MPSR052, MPSR084, MPSR220 and UPSR095) showed susceptibility to a single phage strain separately. All of these six rhizobial strains were slow growing and had the capability of Ex-planta nitrogenase activities. The PCR amplification of the dnaK region of the selected strain showed a single band~ 600 bp in length. The restriction endonuclease analysis of dnaK regions produced six restriction patterns. Sequence BLASTn analysis of DnaK showed linkage with Actinobacterium sp. and Bradyrhizobium sp. Multiple sequence alignment of all six Rhizobium dnaK regions exhibited a 99 % similarity betweenMPSR041 andMPSR220 and formed a close cluster with UPSR095 and MPSR033. The Prosite database showed that the functional domain of the DnaK protein presented three signatures, PS00297 IDLGTTNS (HSP70_1), PS00329 VYDLGGGTFDISIL (HSP70_2) and PS01036 VVLVGGMSRMPKVQE (HSP70_3), which belong to the HSP70 protein family. An in-silico interaction study revealed that DnaK protein is involved in interactions with blr, gap, grpE, pgk, hrcA and recA heat-shock proteins.Item Quantification of trace elements in raw cow’s milk by inductively coupled plasma mass spectrometry (ICP-MS).(Elsevier Ltd., 2008-03-16) Ataro, A.; McCrindle, R.I.; Botha, B.M.; McCrindle, C.M.E.; Ndibewu, P.P.The levels of trace elements are an important component of safety and quality of milk. While certain elements such as chromium are essential at low levels, an excess can result in deleterious effects on human health. International quality control standards for milk are published by the Codex Alimentarious Commission and levels of heavy metals in milk intended for human consumption are routinely monitored. This paper describes a new method for demonstrating the levels of V, Cr, Mn, Sr, Cd and Pb in raw cow’s milk, using an ICP-MS. Samples (n = 24) of raw cow’s milk were collected from dairy farms close to mines in Gauteng and Northwest Provinces of South Africa. In order to destroy organic matrix, each freeze-dried milk sample was mineralised by using a microwave assisted digestion procedure. Concentrations of trace elements in digested milk samples were measured by ICP-MS. A whole milk powder reference material (NIST SRM 8435) was used to evaluate the accuracy of the proposed method. It was found that the levels of V, Cr, Mn, Sr, Cd and Pb obtained using the new method showed concordance with certified values.Item Science and technology backyard model: Implications for sustainable agriculture in Africa.(Higher Education Press, 2020-08-25) Jiao, Xiaoqiang; Feyisa, Derara Sori; Kanomanyanga, Jasper; Muttendango, Ngula David; Mudare, Shingirai; Ndiaye, Amadou; Kabeto, Bilisuma; Dakora, Felix DapareSustainable food production to feed the growing population in Africa remains a major challenge. Africa has 64% of the global arable land but produces less than 10% of its food locally due to its inherently low soil nutrient concentrations. Poor soil fertility and a lack of fertilizer use are the major constraints to increasing crop yields in Africa. On average only about 8.8 kg NPK fertilizer is applied per hectare by African smallholder farmers. There is therefore considerable potential for increasing food production through sustainable intensification of the cropping systems. The low crop yields in Africa are also partly due to limited farmer access to modern agronomic techniques, including improved crop varieties, a lack of financial resources, and the absence of mechanisms for dissemination of information to smallholders. This study analyzed the Science and Technology Backyards (STBs) model and investigated its use for them transformation of agriculture in Africa. Some key lessons for sustainable crop intensification in Africa can be found from analysis of the STB model which is well established in China. These include (1) scientist-farmer engagement to develop adaptive and innovative technology for sustainable crop production, (2) dissemination of technology by empowering smallholders, especially leading farmers, and (3) the development of an open platform for multiple resource involvement rather than relying on a single mechanism. This review evaluates the benefits of the STB model used in China for adoption to increase agricultural productivity in Africa, with a perspective on sustainable crop intensification on the continent.Item Antimicrobial and anti-biofilm activities of bio-inspired nanomaterials for wound healing applications(Elsevier, 2023-09) Arshad, Rabia; Razlansari, Mahtab; Hosseinikhah, Seyedeh Maryam; Pandey, Aprajita Tiwari; Ajalli, Narges; Manicum, Amanda-Lee Ezra; Thorat, Nanasaheb; Rahdar, Abbas; Zhu, Yangzhi; Tabish, Tanveer AChronic wounds are ubiquitously inhabited by bacteria, and they remain a challenge as they cause significant discomfort and because their treatment consumes huge clinical resources. To reduce the burden that chronic wounds place upon both patients and health services, a wide variety of approaches have been devised and investigated. Bioinspired nanomaterials have shown great success in wound healing when compared to existing approaches, showing better ability to mimic natural extracellular matrix (ECM) components and thus to promote cell adhesion, proliferation, and differentiation. Wound dressings that are based on bioinspired nanomaterials can be engineered to promote anti-inflammatory mechanisms and to inhibit the formation of microbial biofilms. We consider the extensive potential of bioinspired nanomaterials in wound healing, revealing a scope beyond that covered previously.Item In vitro toxicity and internalization of gold nanoparticles (AuNPs) in human epithelial colorectal adenocarcinoma (Caco-2) cells and the human skin keratinocyte (HaCaT) cells.(Elsevier, 2022-09-29) Magogotya, M.; Vetten, M.; Roux-Van der Merwe, M.P.; Badenhorst, J.; Gulumian, M.Ingestion and transdermal delivery are two common routes of nanoparticle (NP) exposure. In this study, the intracellular uptake, cytotoxicity and genotoxicity of 14 nm and 20 nm citrate-stabilized gold nanoparticles (AuNPs), 14 nm polyethylene glycol (PEG)-liganded carboxyl AuNPs, 14 nm PEG-liganded hydroxyl AuNPs and 14 nm PEG-liganded amine AuNPs were assessed on human epithelial colorectal adenocarcinoma (Caco-2) cells and the human skin keratinocyte (HaCaT) cells. The uptake of AuNPs in the cells was confirmed through darkfield microscopy and hyperspectral imaging followed by spectral angle mapping (SAM). A high level of citrate AuNPs was found in both cell lines whilst uptake of PEGylated AuNPs was low, irrespective of their functional groups. Cytotoxicity assessed by cell impedance was only observed for the 14 nm citrate-stabilized AuNPs. Enhanced cell proliferation was also observed in 14 nm PEG-liganded hydroxyl and 14 nm PEGliganded amine AuNP-treated Caco-2 and HaCaT cells. For the assessment of genotoxicity, the in vitro micronucleus assay was used. Dose-dependent genotoxicity was observed in both Caco-2 and HaCaT cells, with all the AuNPs inducing genotoxicity. In conclusion, the entry of NPs into the cells as well as toxicity was dependent on their physicochemical properties such as surface coating and different chemical functional groups.Item Antifungal properties of nanosilver clay composites against fungal pathogens of agaricus bisporus.(Wiley, 2023-08) Ramakutoane, Tebogo Levy; Roux-van der Merwe, Magaretha Petronella; Badenhorst, Jacqueline; Pillai, Sreejarani Kesavan; Ray, Suprakas SinhaThis study aimed to determine the possible control of selected pathogenic and competitive fungi of A. bisporus by threenanosilver clay composites and establish the effective concentrations of the composites for inhibiting pathogens. Nanosilver(AgNPs) clay (zeolite, montmorillonite, and palygorskite) composites were synthesized by a microwave-assisted surfacefunctionalization technique, and various techniques characterized the products. Zeolite and montmorillonite composites showed uniformly distributed spherical AgNPs with an average size of 3.33 nm and 2.85 nm, respectively, whereas palygorskite presented agglomerated and unevenly distributed AgNPs. The influence of the various composites on 9 fungi, including strains of T. aggressivum f. aggressivum, L. fungicola, C. dendroides, and Mycogone sp., was determined in vitro at different concentrations. At 10 mg/mL, AgNP-zeolite and AgNP-montmorillonite inhibited 8 out of 9 pathogens, while AgNP-palygorskite only inhibited 1 pathogen. The nanosilver clay composites tested against A. bisporus revealed no adverse effects on mycelial growth at any concentrations tested. This study confirms that AgNP-zeolite and AgNP-montmorillonite composites have effective antifungal properties and can be used as alternative fungicides against mushroom pathogens without affecting A. bisporus growth. However, further investigation is required to unravel the mechanism of selective antifungal activity observed in this study.Item Crystal structure of fac-(acetylacetonato-κ2O,O′) tricarbonyl(tri-m-tolyl phosphane-κP)rhenium(I), C29H28O5PRe(De Gruyter, 2017-10-23) Manicum, Amanda-Lee; Alexander, Orbett; Schutte-Smith, Marietjie; Visser, Hendrik G.C29H28O5PRe, monoclinic, P21/n (no. 14), a = 10.548(5) Å,b = 22.996(5) Å, c = 11.022(5) Å, β = 98.011(5)°, V =2647.4(18) Å3, Z = 4, Rgt(F) = 0.0306, wRref(F2) = 0.0911,T = 100 K.Item Review of the traditional uses, phytochemistry, and pharmacological activities of rhoicissus species (Vitaceae)(MDPI, 2021-03-25) Dube, Nondumiso P; Siwe-Noundou, Xavier; Krause, Rui W. M.; Kemboi, Douglas; Tembu, Vuyelwa Jacqueline; Manicum, Amanda-LeeSpecies within the genus Rhoicissus (Vitaceae) are commonly used in South African traditional medicine. The current review discusses the occurrence, distribution, traditional uses, phytochemistry, and pharmacological properties of Rhoicissus species covering the period 1981–2020. The data reported were systematically collected, read, and analysed from scientific electronic databases including Scopus, Scifinder, Pubmed, and Google Scholar. Reported evidence indicates that species in this genus are used for the treatment of gastrointestinal complaints, sexually transmitted infections (STIs), and infertility, as well as to tone the uterus during pregnancy and to facilitate delivery. Pharmacological studies have further shown that members of the Rhoicissus genus display antidiabetic, uterotonic, ascaricidal, hepatoprotective, antioxidant, antimicrobial, anticancer, and anti-inflammatory properties. They are linked to the presence of bioactive compounds isolated from the genus. Hence, Rhoicissus species can potentially be an alternative therapeutic strategy to treat diseases and develop safer and more potent drugs to combat diseases. Plant species of this genus have valuable medicinal benefits due to their significant pharmacological potential. However, scientific investigation and information of the therapeutic potential of Rhoicissus remain limited as most of the species in the genus have not been fully exploited. Therefore, there is a need for furtherinvestigations to exploit the therapeutic potential of the genus Rhoicissus. Future studies should evaluate the phytochemical, pharmacological, and toxicological activities, as well as the mode of action, of Rhoicissus crude extracts and secondary compounds isolated from the species.Item Transition metal-decorated B12N12−X (X = Au, Cu, Ni, Os, Pt, and Zn) nanoclusters as biosensors for carboplatin.(ACS Publications, 2023-01-09) Benjamin, Innocent; Louis, Hitler; Okon, Gideon A.; Qader, Suhailah W.; Afahanam, Lucy E.; Fidelis, Chidera F.; Eno, Ededet A.; Ejiofor, Emmanuel E.; Manicum, Amanda-Lee E.Theoretical studies on the adsorption, sensibility, and reactivity of a boron nitride nanocage decorated with Au, Cu, Ni, Os, Pt, and Zn metals as a biosensor material were carried out for the adsorption of carboplatin by applying the density functional theory computation at the B3LYP-GD3BJ/def2svp level of theory. All the optimized structures, as well as the calculations as regards the studied objective including electronic properties, geometry optimization parameters, adsorption energy studies, natural bond orbital analysis, topology studies, sensor mechanistic parameters, and thermodynamic properties (ΔG and ΔH), were investigated herein. As a result, the noticeable change in the energy gap of the studied surfaces when interacting with carboplatin accounted for the surfaces’ reactivity, stability, conductivity, work function, and overall adsorption ability, implying that the studied decorated surfaces are good sensor materials for sensing carboplatin. Furthermore, the negative adsorption energies obtained for interacting surfaces decorated with Cu, Ni, Os, and Zn suggest that the surface has a superior ability to sense carboplatin as chemisorption was seen. Substantially, the geometric short adsorption bond length after adsorption, thermodynamically spontaneous reactions, and acceptable sensor mechanism results demonstrate that the investigated surfaces have strong sensing characteristics for sensing carboplatin.Item Heteroatom (B, N, P, and S)-doped Cyclodextrin as a Hydroxyurea (HU) drug Nanocarrier: A computational approach(ACS Publications, 2022-12-20) Afahanam, Lucy E.; Louis, Hitler; Benjamin, Innocent; Gber, Terkumbur E.; Ikot, Immaculata J.; Manicum, Amanda-Lee E.Theoretical examination of hydroxyurea adsorption capabilities toward the cyclodextrin surface for proper drug delivery systems was carried out utilizing DFT simulations. The study aims to assess the efficacy of doped cyclodextrin (doped with boron, nitrogen, phosphorus, and sulfur atoms) in increasing its stability and efficiency in intermolecular interactions, hence facilitating optimal drug delivery. The adsorption energies were found to follow a decreasing order of B@ACD-HU>N@ACD-HU>P@ ACD-HU>S@ACD-HU with energies of −0.046, −0.0326, −0.015, and 0.944 kcal/mol, respectively. The S@ACD-HU complex, unlike previous systems, had a physical adsorption energy. The N@ACD-HU and B@ACD-HU complexes had the shortest bond lengths of 1.42 Å (N122-C15) and 1.54 Å (B126- C15), respectively. The HOMO and LUMO values were also high in identical systems, −6.367 and −2.918 eV (B@ACD-HU) and −6.278 and −1.736 eV (N@ACD-HU), respectively, confirming no chemical interaction. The N@ACD-HU has the largest energy gap of 4.54 eV. For the QTAIM analysis and plots, the maximum electron density and ellipticity index were detected in B@ACD HU, 0.600 au (H70-N129) and 0.8685 au (H70-N129), respectively, but N@ACD-HU exhibited a high Laplacian energy of 0.7524 a.u (H133-N122). The fragments’ TDOS, OPDOS, and PDOS exhibited a strong bond interaction of greater than 1, and they had different Fermi levels, with the highest value of −8.16 eV in the N@ACD-HU complex. Finally, the NCI analysis revealed that the complexes were noncovalent. According to the literature, the van der Waals form of interactions is used in the intermolecular forces of cyclodextrin cavities. The B@ACD-HU and N@ACD-HU systems were more greenish in color with no spatial interaction. These two systems have outperformed other complexes in intermolecular interactions, resulting in more efficient drug delivery. They had the highest negative adsorption energies, the shortest bond length, the highest HOMO/LUMO energies, the highest energy gap, the highest stabilization energy, the strongest bonding effect, the highest electron density, the highest ellipticity index, and a strong van der Waals interaction that binds the drug and the surface together.Item Coinoculation impact on plant growth promotion: A review and meta‑analysis on coinoculation of rhizobia and plant growth‑promoting bacilli in grain legumes.(Springer, 2022-07-28) Kaschuk, Glaciela; Aule, André Carlos; Vieira, Crislaine Emidio; Dakora, Felix Dapore; Jaiswal, Sanjay K.; Da Cruz, Sonia PurinCoinoculation of symbiotic N2- fixing rhizobia and plant growth-promoting Bacillus on legume seeds can increase crop productivity. We collected highly resolved data on coinoculation of rhizobia and bacilli on 11 grain legume crops: chickpea, common bean, cowpea, faba bean, groundnut, lentil, mung bean, pea, pigeon pea, soybean, and urad bean to verify the magnitude of additive effects of coinoculation in relation to single inoculation of rhizobia on plant growth and yield of grain legumes. Coinoculation of rhizobia and bacilli on legume seeds and/or soil during sowing significantly increased nodulation, nitrogenase activity, plant N and P contents, and shoot and root biomass, as well as the grain yield of most grain legumes studied. There were however a few instances where coinoculation decreased plant growth parameters. Therefore, coinoculation of rhizobia and Bacillus has the potential to increase the growth and productivity of grain legumes and can be recommended as an environmental-friendly agricultural practice for increased crop yields.Item Steric and electronic influence of Re(I) tricarbonyl complexes with various coordinated β-diketones(Elsevier, 2022-05-09) Manicum, Amanda-Lee Eza; Schutte-Smith, Marietjie; Malan, Frederick P.; Visser, Hendrik GideonRe(I) tricarbonyl complexes, with coordinated β-diketones, are the center of attention as they form part of a library of promising cancer therapeutic and diagnostic agents. In this study, we present three new Re(I) crystal structures. {fac [Re(Benzac)(CO)3(PCy3)] (4), fac-[Re(Tfaa)(CO)3(PCy3)] (5), and fac-[Re(Hfaa)(CO)3(PCy3)] (6); benzoylacetone = Benzac; trifluoroacetylacetone = Tfaa and hexafluoroacetylacetone = Hfaa; PCy3 = tricyclohexylphosphine}. The three reported complexes were synthesized with ease and good yield, involving the "2 + 1" mixed ligand approach. The complexes were characterized using analytical tools: IR, NMR, UV/Vis, single-crystal X-ray diffraction. The Tolman cone angles (θ) were calculated as 141.93°, 148.77°, and 149°; and compared to the Equivalent cone angles obtained from DFT calculations. These were 131.25°, 134.34°, and 134.28° for (4), (5), and (6), respectively. The DFT analysis observed that the Re-P bond distances decrease as the number of electron-withdrawing groups (CF3) on the β-diketonato ligands increase. In general, the theoretical and experimental Re-P and Re-OOO bond distances compared well among the complexes, with the most significant deviation occurring for 4 (relative differences of 0.055 A˚ (Re-P) and 0.015 A˚ (average Re-O)). Hirshfeld surface analysis was used to obtain the fingerprint plots, and the Hirshfeld surfaces were mapped with dnorm for 4, 5, and 6.Item Anti-hypertensive properties of 2-[N-(4-methylbenzenesulfonyl)-1- phenylformamido]-n-(4-nitrophenyl)-3-phenylpropenamide: Experimental and theoretical studies(Elservier, 2022-12-30) Ugwu, David I.; Asogwa, Frederick C.; Olisaeloka, Sunday G.; Ezungwu, James A.; Ogbuke, Sunday C.; Benjamin, Innocent; Louis, Hitler; Gber, Terkumbur E.; Ugwu, Mirabel C.; Eze, Florence U.; Manicum, Amanda-Lee E.Experimental and theoretical investigation of the anti-hypertensive activity of novel 2-[N-(4-methyl-benzenesulfonyl)-1-phenylformamido]-N-(4-nitrophenyl)-3-phenylpropenamide (MBPNPP) was carried out. The experimental approach followed the dietary induction of spontaneously hypertensive adult male Wistar rats (SHRs) using 66% w/v D-fructose and the angiotensin I-converting enzyme (ACE) inhibitory activity assay while the theoretical study was achieved using DFT calculations and molecular docking against hypertension responsive proteins. The Becke-3-Paramater-Lee-Yang-Parr (B3LYP) functional/6–311G++(d,p) basis set was adopted. The molecular electronic properties such as the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) and other chemical reactivity parameters were evaluated to bring to light, the reactivity and stabilization mechanisms of MBPNPP. The highest daily oral dose of MBPNPP (10 mg/kg) significantly prevented increase in systolic blood pressure (SBP) comparable to positive and normal control groups receiving captopril (10 mg/kg/day) and distilled water (5 ml/kg) ad libitum respectively from 167.23 (negative control) to 124.50 and 120.17 (positive control). Molecular simulation was also carried out with target proteins; 2ydm, 2 × 8Y, and 3ZQZ, and the theoretical data expresses a much plausible therapeutic significance towards the control of hypertension. The frontier orbital energy gap of 3.066 eV was an indicator that the charge transfer interaction occurred within the molecule and indicates high chemical reactivity. Relative to the reference drug, Spironolactone, the compound under study showed a significant binding affinity of -9.0 kcal/mol, -8.3 kcal/mol, and -7.9 kcal/mol with the target proteins and better protein-ligand hydrogen bond interactions. The data gathered from the experimental and theoretical analysis including the docking scores showed excellent anti-hypertensive activity by MBPNPP.Item Crystal structure of fac-(acetylacetonato-κ2O,O′) tricarbonyl(tri(p-tolyl)phosphine-κP)rhenium(I), C29H28O5PRe.(De Gruyter, 2017-08-15) Manicum, Amanda-Lee; Schutte-Smith, Marietjie; Visser, Hendrik G.Item Crystal structure of tetraethylammonium factricarbonyl(hexafluoroacetylacetonato-κ 2O,O′)- (nitrato-κO)rhenium(I), C16H21O8N2F6Re(De Gruyter, 2016-01-18) Manicum, Amanda-Lee; Schutte-Smith, Marietjie; Visser, Hendrik G.; Pretorius, Carla; Roodt, AndreasC16H21O8N2F6Re, triclinic, P1¯, a = 9.161(5) Å, b = 10.283(5) Å, c = 12.974(5) Å, α = 87.739(5)°, β = 78.339(5)°, γ = 75.047(5)°,V = 1156.3(10) Å3, Z = 2, Rgt(F) = 0.037, wRref(F2) = 0.1012,T = 100(2) K.Item Phytochemistry, pharmacology, and nutraceutical profile of carissa species: An updated review.(MDPI, 2021-11-15) Dhatwalia, Jyoti; Kumari, Amita; Verma, Rachna; Upadhyay, Navneet; Guleria, Ishita; Lal, Sohan; Thakur, Shabnam; Gudeta, Kasahun; Kumar, Vikas; Chao, Jane C.-J.; Sharma, Somesh; Kumar, Ashwani; Manicum, Amanda-Lee Ezra; Lorenzo, José M.; Amarowicz, RyszardCarissa, a genus of the Apocynaceae family, consists of evergreen species, such as shrubs as well as small trees that are native to Asia, Africa, and Oceania’s subtropical and tropical regions. Most of the Carissa species are traditionally used to treat various diseases, such as chest pain, headaches, gonorrhoea, rheumatism, syphilis, oedema, rabies, stomach pain, hepatitis, cardiac diseases, and asthma. The pharmacological studies on Carissa species revealed its antioxidant, antimicrobial, anticancer, cardioprotective, antipyretic, analgesic, wound healing, anticonvulsant, antiarthritic, adaptogenic, anti-inflammatory, and antidiabetic activities, thus validating its use in indigenous medicine systems. The review article summarised the comprehensive literature available, including morphology, indigenous uses, bioactive composition, nutraceutical, and pharmacological activities of Carissa species. A total of 155 research papers were cited in this review article. The Carissa fruits are rich in dietary fibre, lipids, proteins, carbohydrates, vitamin C, and macro- and micro-elements. A total of 121 compounds (35 polyphenols (flavonoids and phenolic acids), 30 lignans, 41 terpenoids, 7 steroids, 2 coumarins, and 6 cardiac glycosides) have been extracted from C. spinarum, C. carandas, and C. macrocarpa. Among all chemical constituents, lupeol, carissol, naringin, carisssone, scopoletin, carissaeduloside A, D, J, carandinol, sarhamnoloside, carissanol, olivil, carinol, 3β-hydroxyolean11-en-28,13β-oilde, ursolic acid, and carissone are the key bioactive constituents responsible for pharmacological activities of genus Carissa. The gathered ethnopharmacological information in the review will help to understand the therapeutic relevance of Carissa as well as paving a way for further exploration in the discovery of novel plant-based drugs.Item Nano-immunotherapeutic strategies for targeted RNA delivery: Emphasizing the role of monocyte/macrophages as nanovehicles to treat glioblastoma multiforme.(Elsevier, 2022-03-25) Manicum, Amanda-Lee Ezra; Sargazi, Saman; Razzaq, Sobia; Kumar, Govindarajan Venkat; Rahdar, Abbas; Er, Simge; Ain, Qurrat Ul; Bilal, Muhammad; Aboudzadeh, M. AliGlioblastoma multiforme (GBM) is considered the most aggressive and heterogeneous type of brain malignancy. The substantial invasion of the central nervous system parenchyma is a typical hallmark of all grades of glioma. To improve tumor localization and prevent unanticipated toxicity, anti-tumor drug delivery mechanisms must be upgraded in parallel with pharmacotherapeutics. Monocytes can easily pass the blood-brain barrier, and thus, drugs with difficulty entering the brain can be loaded into monocytes, resulting in the treatment of brain cancers. RNA as a natural and biocompatible polymer has many advantages for biomedical applications, and RNA-based therapies can provide regulated biological functions by highly selective and controlling means. In this context, macrophages are excellent carriers for distributing RNA-based treatments. However, developing an efficient macrophage-targeted RNA delivery has remained challenging. Several approaches have been introduced in the last decade to efficiently deliver RNA-based therapy via macrophages to treat GBM and inflammatory conditions. This review summarizes the most suitable nano-carrier systems to deliver RNA into immunocytes; also, different methods of synthesizing RNA-loaded nanoparticles and their application, with an emphasis on targeting GBM, are discussed. Furthermore, it focuses specifically on the stability of such nanoformulations and the effect of targeting moieties and adjuvants in determining the worth of the aroused immune response. Finally, the critical aspects of delivering RNA-lipid hybrid nanoparticles (LNPs) via oral, systemic, and local routes are highlighted. We hope that these findings will pave the way for more effective treatment of solid tumors, such as GBM, in the future.Item Synthesis, characterisation, X-ray diffraction and biological evaluation of new thiourea derivatives against Mycobacterium tuberculosis and cervical cancer(2024-04-29) Makhakhanyi, Luleka; Malan, Frederick P.; Senzani, Sibusiso; Tukulula, Matshawandile; Davison, Candace; De la Mare, Jo-Anne; Nkambule, Comfort M.; Tembu, Vuyelwa J.; Manicum, Amanda-Lee E.In this study, thiourea derivatives were prepared to identify potentially effective compounds against tuberculosis and cervical cancer. The newly synthesized compounds, namely N-(cyclohexyl(methyl)carbomothioyl) benzamide (TU1), N-(cyclohexyl(methyl)carbamothioyl)-2-methylbenzamide (TU2), N-(dicyclohexylcarbamothioyl) benzamide (TU3), N-(dicyclohexylcarbamothioyl)-4-nitrobenzamide (TU4), N-(diphenylcarbamothioyl) benzamide (TU5), and N(diphenylcarbamothioyl)-4-nitrobenzamide (TU6), were obtained in high purity and yields. The compounds were successfully characterized by infrared spectroscopy (IR), ultraviolet-visible spectroscopy (UV-Vis), nuclear magnetic resonance (NMR), single crystal X-ray diffractometer (SCXRD), mass spectrometry (MS) and the melting points (mp). Crystal structure analyses of TU1, TU2 and TU6 were carried out which showed, that in the solid state, the molecules were linked together by intermolecular hydrogen bonds, specifically N–H⋯S and C–H⋯O interactions. In-vitro testing against M. tuberculosis (Mtb) revealed compounds TU1 and TU2 to be the most potent with MIC90 values of 28.2 and 11.2 μM, respectively. However, compounds TU4, TU5, and TU6, with MIC90 values of 80.3, 82.8 and 107.7 µM, respectively, exhibit mild antituberculosis activity, whereas TU3 with a MIC90 value of 752.7 µM is considered inactive against the Mtb strain. None of the compounds demon strated significant selectivity for bacterial cells versus human cells and thus further studies could be dedicated to creating derivatives of TU1 and TU2 that are more selective. In vitro biological screening against HeLa cells revealed two highly toxic compounds, TU2 and TU6, with respective IC50 values of 12.00 ± 1.21 μM (SI = 1.06) and 8.45 ± 1.21 μM (SI = 0.08); and two moderately toxic compounds, TU4 (IC50 = 27.75 ± 1.15 µM; SI = 0.35) and TU5 (IC50 = 23.66 ± 1.24 µM; SI = 0.29).Item Rubus ellipticus Sm. fruit extract mediated zinc oxide nanoparticles: A green approach for dye degradation and biomedical applications.(MDPI, 2022-03-31) Dhatwalia, Jyoti; Kumari, Amita; Chauhan, Ankush; Mansi, Kumari; Thakur, Shabnam; Saini, Reena V.; Guleria, Ishita; Lal, Sohan; Kumar, Ashwani; Batoo, Khalid Mujasam; Choi, Byung Hyune; Manicum, Amanda-Lee. E.; Kumar, RajeshRubus ellipticus fruits aqueous extract derived ZnO-nanoparticles (NPs) were synthesized through a green synthesis method. The structural, optical, and morphological properties of ZnO-NPs were investigated using XRD, FTIR, UV-vis spectrophotometer, XPS, FESEM, and TEM. The Rietveld refinement confirmed the phase purity of ZnO-NPs with hexagonal wurtzite crystalline structure and p-63-mc space group with an average crystallite size of 20 nm. XPS revealed the presence of an oxygen chemisorbed species on the surface of ZnO-NPs. In addition, the nanoparticles exhibited significant in vitro antioxidant activity due to the attachment of the hydroxyl group of the phenols on the surface of the nanoparticles. Among all microbial strains, nanoparticles’ maximum antibacterial and antifungal activity in terms of MIC was observed against Bacillus subtilis (31.2 µg/mL) and Rosellinianecatrix (15.62 µg/mL), respectively. The anticancer activity revealed 52.41% of A549 cells death (IC50: 158.1 ± 1.14 µg/mL) at 200 µg/mL concentration of nanoparticles, whereas photocatalytic activity showed about 17.5% degradation of the methylene blue within 60 min, with a final dye degradation efficiency of 72.7%. All these results suggest the medicinal potential of the synthesized ZnO-NPs and therefore can be recommended for use in wastewater treatment and medicinal purposes by pharmacological industries.
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