Research Articles (School of Pharmacy)

Permanent URI for this collection

https://hdl.handle.net/10566/304

Browse

Now showing 1 - 20 of 182

Targeting myeloid cells with platelet-derived extracellular vesicles to overcome resistance of immune checkpoint blockade therapy
(Elsevier Ltd, 2025) Dube, Admire; Yao, Chenlu; Ma, Qingle
Immune checkpoint blockade (ICB) therapy is designed to boost antitumor immune responses, yet it may unintentionally alter the chemokine profile, which can attract suppressive myeloid cells to the tumor, leading to acquired immune resistance. To address this, we developed a platform that targets myeloid cells post-ICB therapy using platelet-derived extracellular vesicles (PEVs). Unlike free drug administration, this system selectively targets anti-PD-L1-treated tumors through the CXCL-CXCR2 axis, effectively redirecting myeloid cells and overcoming ICB resistance. Consequently, mice exhibited robust responses to subsequent ICB therapy cycles, resulting in significantly enhanced tumor clearance and prolonged survival. The PEVs’ targeting capability was also effective in tumors treated with chemotherapy and radiotherapy, suggesting a wide range of potential applications. In summary, PEVs offer a versatile platform for targeted immunomodulation to counteract acquired immune resistance during ICB therapy.
Assessing the potential for red seaweed Asparagopsis taxiformis aquaculture in Seychelles
(Western Indian Ocean Marine Science Association, 2025) Lerata, Mookho; Beukes, Denzil; de Vos, Bas
Asparagopsis taxiformis macroalgae can potentially reduce methane emissions when fed to rumi-nants, thus reducing the emission of greenhouse gasses into the atmosphere. Literature indicates water temperatures above 24 °C limit A. taxiformes growth rates during culture, however, it grows wild in Seychelles where water temperatures range from 25 to 31.5 °C. The feasibility of culti-vating the local strain of A. taxiformis in Seychelles was investigated, focusing on growth rates at higher temperatures and bromoform content, the compound responsible for methane reduction. Two tetrasporophyte growth trials were conducted in photobioreactors at 24 °C, 26 °C, 29 °C and 32 °C. In the first trial, unacclimated specimens showed poor growth, with no significant differences between temperatures. In the second trial, daily growth rates of acclimated specimens were 3.98 % across all temperatures, including 32 °C, where temperature did not significantly affect growth. Bromoform concentrations were lower than expected, likely due to storage con-ditions prior to sample processing. The local strain of A. taxiformis in Seychelles may therefore be adapted to higher temperatures, with potential for aquaculture. Further research to optimize cultivation techniques and ensure adequate bromoform content is required.
Formulation and clinical translation of inhalable nanomedicines for the treatment and prevention of pulmonary infectious diseases
(Springer, 2025) Ahmed, Rami; Aucamp, Marique; Dube, Admire
Pulmonary infections caused by bacteria, viruses and fungi are a significant global health issue. Inhalation therapies are gaining interest as an effective approach to directly target infected lung sites and nanoparticle-based pulmonary delivery systems are increasingly investigated for this purpose. In this review, we provide an overview of common pulmonary infectious diseases and review recent work on the application of inhalable nanoparticle-based formulations for pulmonary infectious diseases, the formulation strategies, and the current research for delivering inhalable nanomedicines. We also evaluate the current clinical development status, market landscape, and discuss challenges that impede clinical translation and propose solutions to overcome these obstacles, highlighting promising opportunities for future advancements in the field. Despite advancements made and products reaching the market, notable gap persists in translational research, with challenges in achieving the target product profile, availability of appropriate in vivo disease models, scale-up, and market related questions, likely hindering research translation to the clinic.
Development of an African paediatric oncology pharmacy curriculum: a SIOP Africa 2024 pharmacy workshop output
(SAGE Publications Ltd, 2025) Wiafe, Ebenezer; Zimbwe, Kauke Bakari; Mageto, Susan Nyabate
Background: The practice of paediatric oncology pharmacy (POP) has been in existence in Africa for several decades. However, most POP practitioners lack formal education and training. Training and credentialing of pharmacists requires the availability of an appropriate curriculum developed to meet local needs. Hence, the African POP technical working group (TWG) of the International Society of Paediatric Oncology (SIOP) embarked on a process to develop a curriculum in POP. Method: The curriculum development followed a modified Delphi approach: the formalisation of the POP TWG, the initial development of the curriculum, community and stakeholder engagement via a modified Delphi scoring, and the finalisation of the curriculum at the pharmacy workshop of the SIOP Africa Congress in South Africa. Results: A POP TWG of 23 members with diverse experiences was formed. The initial curriculum, focusing on 36 theoretical and 5 clinical components, was developed. The modified Delphi process restructured the 36 theoretical contents to 27, the 5 clinical contents to 9, and introduced 6 research modules. The theoretical and clinical components were assigned 86 and 240 credit hours respectively, with a research component culminating in a published manuscript. Twenty-eight individuals from 13 countries attended the workshop, resulting in unanimous approval of the curriculum. Conclusions: The SIOP Africa Pharmacy TWG has developed a POP curriculum specific to Africa. The implementation of the curriculum through African universities and specialist colleges is imperative to reduce the education and training gaps in POP.
The preparation of abacavir-loaded liposomes for improved drug solubility and dissolution rate
(Springer, 2025) Okafor, Nnamdi Ikemefuna; Nnaji, Nnaemeka Joshua.N.
This study was aimed at developing abacavir (ABC)-loaded liposomes to facilitate improved drug solubility and dissolution rate in an effort to provide a potential dose reduction of ABC with pediatric patients in mind. By utilizing the design of an experimental approach, various liposome formulation parameters were investigated. Drug-loaded liposomes were characterized in terms of particle size, zeta potential, polydispersity index, encapsulation efficiency, as well as other physicochemical characteristics such as thermal behavior, particle morphology, ABC equilibrium solubility, and finally ABC dissolution rate. The optimal formulation parameters were found to be a lecithin: cholesterol ratio of 1:1, a thin-film hydration time of 60 min, a vortex time of 2 min, a sonication time of 10 min, and 10 mLof water as hydration fluid in which 75 mg ABC was dissolved. The drug-loaded liposomes exhibited significant encapsulation efficiency, with the highest encapsulation efficiency of 98%, a particle size within a range of 523 nm, and a strong zeta potential of –53 mV. The liposomes further revealed an increased and enhanced aqueous solubility for the drug entrapped within the formulations, while showing the release of the drug from formulation. The results proved that ABC can be successfully loaded into a simple and cost-effective liposome formulation, providing a significantly enhanced ABC solubility and dissolution rate, which could ultimately have a positive effect on the bioavailability of ABC, especially because ABC is a BCS I drug, thus offering the potential to formulate a reduced dosage form aimed at pediatric patients.
The global, regional, and national burden attributable to low bone mineral density, 1990–2020: an analysis of a modifiable risk factor from the Global Burden of Disease Study 2021
(Elsevier Ltd, 2025) Okonji, Osaretin; Hsieh, Evelyn; Bryazka, Dana
Fractures related to osteoporosis and low bone mineral density lead to substantial morbidity, mortality, and cost to individuals and health systems. Here we present the most up-to-date global, regional, and national estimates of the contribution of low bone mineral density to the burden of fractures from falls and additional categories of injuries from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. The burden of low bone mineral density was estimated from 1990 to 2020 in terms of years lived with disability (YLDs), disability-adjusted life years (DALYs), and deaths, for individuals aged 40 years and older, using data from population-based studies from 48 countries or territories (169 unique sources). Mean standardised femoral neck bone mineral density values were estimated by GBD location, age, and sex by meta-regression. Based on a separate meta-analysis of population-based studies from nine countries (12 unique sources), we also estimated the pooled relative risk of fractures per unit decrease in bone mineral density (g/cm²). The population-attributable fraction for low bone mineral density was calculated by comparing the observed distributions of standardised femoral neck bone mineral density to an age-specific and sex-specific counterfactual distribution, defined as the 99th percentile of five rounds of the National Health and Nutrition Examination Survey in the USA, by 5-year age group and sex. Hospital and emergency department data were used to derive the incidence of fractures for six categories of injury (road injuries, other transport injuries, falls, non-venomous animal contact, exposure to mechanical forces, and physical interpersonal violence) using ICD codes. Deaths due to fractures were estimated as the proportion of in hospital deaths due to the specified injury causes for which a fracture (nature of injury code) was more severe than the cause of injury code. YLDs and DALYs attributable to low bone mineral density by cause of injury were also determined according to previous GBD methods.
Dual GSK3β/SIRT1 modulators for Alzheimer’s: mechanisms, drug discovery and future perspectives
(Frontiers Media SA, 2025) Kareem, Afeez I; Kapp, Erika; Joubert, Jacques
Alzheimer’s disease (AD) remains without effective disease-modifying therapies, in part due to the limited efficacy of single-target approaches. Dual modulation of glycogen synthase kinase-3β (GSK3β), a key driver of tau hyperphosphorylation and amyloid-β (Aβ) production, and sirtuin-1 (SIRT1), a neuroprotective NAD+-dependent deacetylase, has emerged as a promising therapeutic strategy. This review explores the mechanistic rationale for concurrently inhibiting GSK3β and activating SIRT1 to disrupt AD’s pathological cascade while enhancing endogenous neuroprotective pathways. Natural compounds such as resveratrol, berberine, pterostilbene, and quercetin exhibit this dual activity and provide scaffolds for rational drug design. However, challenges related to target selectivity, blood-brain barrier penetration, and clinical translation persist. Advances in multi-target drug discovery, including pharmacophore hybridization, structure-based modelling, cheminformatics, nanoformulation and delivery strategies offer new avenues to overcome these hurdles. A dual GSK3β/SIRT1-targeting strategy exemplifies a systems-level approach to restoring neurophysiological balance and holds potential to achieve more effective, disease-modifying outcomes in AD.
Exploring the clinical workflow in pharmacogenomics clinics: an observational study
(Multidisciplinary Digital Publishing Institute (MDPI), 2025) Keuler, Nicole; McCartney, Jane; Coetzee, Renier
Background: Pharmacogenomics (PGx) is the future of healthcare and implementation is being driven by increasing evidence. Understanding the workflow in a PGx clinic provides insight into the development and implementation of PGx services. It considers the patient’s perspective, the role of the interprofessional team and the pivotal input of the pharmacist. Objectives: The purpose of this study was to describe the clinical workflow followed in selected PGx clinics. Methods: Four different sites that offer PGx clinical services (United States of America) were included. Qualitative data were collected through semi-structured interviews and observations providing valuable insights into the workflow followed in both community-based and hospital-based PGx clinics. Results: Although each setting differed, the processes were similar with setting-specific workflows and barriers. This study highlights the role of the pharmacist and the interprofessional team, the resources used for interpretation of PGx test results and the importance of patient and healthcare education. Conclusions: Understanding the workflow and the role of the interprofessional team in PGx is essential to ensure successful implementation and sustainable precision medicine practices in resource-limited settings.
Nanomedicine solutions for alzheimer’s disease: a critical review of therapeutic nanoparticle strategies
(American Chemical Society, 2025) Tutubala, Teboho; Egunlusi, Ayodeji; Joubert, Jacques; Fisher, David; Dube, Admire
Alzheimer’s disease (AD) is a debilitating disorder marked by progressive memory and cognitive function loss. Current treatments, including acetylcholinesterase and N-methyl-d-aspartate receptor inhibitors, offer symptomatic relief but lack disease-modifying effects. The recent approval of aducanumab, an antibody clearing amyloid beta plaques, brings hope, though its therapeutic benefits are controversial. AD’s etiology is multifactorial, involving over 40 genetic variants, and remains poorly defined. Nanotechnology offers a promising avenue for optimized drug candidates, addressing challenges such as solubility, stability, and blood–brain barrier permeation. This review explores nanoformulations targeting key AD aspects, including amyloid beta, Tau protein, oxidative stress, and neuroinflammation. Notably, multifunctional nanocarriers present a comprehensive approach, demonstrating the potential for effective AD therapy. Despite extensive research, only a small fraction of these studies progress to clinical trials. Continuous nanomedicine research is poised to play a vital role in future AD management, providing innovative solutions to this devastating disease.
Vitamin D3 loaded polycaprolactone nanoparticles enhance the expression of the antimicrobial peptide cathelicidin in macrophages
(Taylor and Francis Ltd., 2025) Dlozi, Prince; Ahmed, Rami; Khoza, Star; Dube, Admire
Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis, remains a global health burden. Current antibiotic treatments are limited by adverse effects, poor adherence, and drug resistance, necessitating new therapeutic approaches. Recent studies highlight the role of vitamin D3 (VD3) in enhancing host immune responses against the mycobacterium via cathelicidin (an antimicrobial peptide) and autophagy activation. In this study, VD3-loaded poly-ƹ-caprolactone (PCL) nanoparticles (NPs) were synthesized to enhance cathelicidin expression in macrophages. NPs containing cholecalciferol, calcifediol, and calcitriol were synthesized using an emulsification solvent-evaporation technique. Average sizes of synthesized NPs ranged from 304.7 to 458.7 nm, with polydispersity index (PDI) and zeta potential (ZP) ranging from 0.103 to 0.257 and −17.3 to −7.47 mV, respectively. Encapsulation efficiencies were 9.68%, 10.99%, and 19.28% for cholecalciferol, calcifediol, and calcitriol, respectively. VD3-encapsulated NPs stimulated a dose-dependent increase in cathelicidin expression in THP-1 macrophages. Encapsulated calcifediol and calcitriol (100 ng/ml) induced the expression of 243.46 ng/ml ± 4.55 ng/ml and 396.67 ng/ml ± 25.24 ng/ml of cathelicidin, respectively, which was significantly higher than that induced by the free drugs. These findings suggest that NP encapsulation may offer a more efficient approach to using vitamin D3 for inducing cathelicidin expression as a host-directed treatment for TB.
Exploring the potential of deep brain stimulation in managing cluster headache: a systematic review
(BioMed Central Ltd, 2025) Bisetegn, Lydia Daniel; Uwishema, Olivier; Shariff, Sanobar
Background: The debilitating nature of cluster headache (CH) is typified by intense, repeated cephalgia that are often referred to as “suicide headaches” owing to their severity. Individuals may not respond appropriately to therapeutic interventions despite various alternatives being readily available. This warrants an investigation into further management options. One of the promising solutions for CH has been identified as deep brain stimulation (DBS), which specifically targets the posterior hypothalamus. Aim: This systematic review aims to summarize the current literature on the safety and efficacy of DBS in the management of CH. Method and materials: A comprehensive literature search identified 15 relevant studies comprising clinical trials, case reports, and observational studies from Embase, Web of Science, PubMed/MEDLINE, Scopus, and the Cochrane Library using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 standards. Results: The systematic review elucidated that DBS, with a focus on the posterior hypothalamus, facilitated significant reductions in the frequency, severity, and duration of cephalgic ‘attacks’ associated with CH observed. While individual responses varied, DBS was generally well-tolerated, with transient and reversible adverse effects involving focal neurological deficits (i.e., diplopia) being the most common. Importantly, long-term benefits were observed in vast populations, improving their overall quality of life. Furthermore, DBS demonstrated effects beyond localized hypothalamic stimulation, with evidence suggesting modulation of the pain processing network. Additionally, DBS was found to alleviate nocturnal CH attacks without disrupting circadian rhythms. These findings suggest that DBS holds promise as a therapeutic option for CH, particularly in individuals refractory to other treatments. Conclusion: Existing research suggests that DBS, particularly when targeting the posterior hypothalamus, can significantly reduce CH ‘attack’ frequency, severity, and duration. Further research should focus on patient selection criteria and a deeper understanding of the mechanisms underpinning DBS to optimize its effectiveness in managing such a disabling cephalgia.
Strengthening signal detection in pharmacovigilance by using international nonproprietary name (INN) stems
(Springer Nature Link, 2025) Malan, Sarel; Balocco, Raffaella; Aronson, Jeffrey
‘Stems’, which mark pharmacological relationships between substances, form the backbone of the International Nonproprietary Name (INN) system, developed by the WHO in the 1950s. In this paper, we propose using the INN stems to enhance pharmacovigilance signal detection. After analysis of historical cases and current pharmacovigilance practices, we discuss how stem-based classification could facilitate understanding of the adverse-effects profile of each stem, to be used as a benchmark for early identification of adverse drug reactions that deviate from expected class effects, in other words signals associated with newly marketed medicines or different uses of well-known medicines. We propose a potential framework for integrating stem-based analysis into existing pharmacovigilance databases, supplemented by artificial intelligence approaches, such as machine learning. While acknowledging limitations, such as stem variability and reporting bias, we suggest that this approach offers potential advantages for regulatory authorities and healthcare professionals in post-marketing surveillance. Implementation of stem-based post-marketing surveillance could enhance signal-detection efficiency and contribute to improved patient safety through earlier identification of unexpected adverse effects and adverse reactions.
The value of a structured, systematic approach to benefit-risk assessment of medicines: a South African regulator case study
(Academic Press Inc., 2025) Khoza, Star; Danks, Lorraine; Semete-Makokotlela, Boitumelo
This study investigates the utility of the Universal Methodology for Benefit-Risk Assessment (UMBRA) framework within the South African Health Products Regulatory Authority (SAHPRA) to determine whether adopting a structured approach improves consistency, transparency, and quality in benefit-risk assessments of new chemical entities (NCEs). The UMBRA eight-step framework was applied retrospectively and prospectively to six NCEs to systematically document the decision context, identify benefits and risks, and interpret the benefit-risk balance. Comparisons were made between initial SAHPRA narrative assessments and structured UMBRA-based evaluations. Reviewer feedback was collected through a questionnaire and group discussions. The retrospective study revealed that UMBRA provided greater clarity and alignment with decisions by global reference authorities, improving transparency in the weighting of benefits and risks. The prospective study demonstrated UMBRA’s utility in highlighting local demographic and clinical considerations, enhancing regulatory reliance decisions. The UMBRA framework enhances the benefit-risk assessment process by providing a structured, transparent, and reproducible methodology. It facilitates comprehensive decision-making that aligns with global best practices, reducing reliance on subjective judgements. Implementing UMBRA at SAHPRA and other African regulatory authorities could promote harmonised regulatory practices, improve public trust, and enable transparent communication of decisions. The study recommends integrating UMBRA into routine assessments, training programs for
Ferrocene-bisphosphonates hybrid drug molecules: In vitro antibacterial and antifungal, in silico adme, drug-likeness, and molecular docking studies
(Elsevier, 2024) Egieyeh, Samuel; Anusionwu, Chioma; Fonkui, Thierry Youmbi
The design of hybrid molecules is a promising drug development strategy to prepare effective antimicrobial drugs that employ the concept of combination therapy. This strategy combines two therapeutic agents covalently to target different cellular pathways for synergistic effects. Ferrocene-bisphosphonate hybrid compounds, 1–8 were evaluated in vitro for their antibacterial and antifungal activities against selected fungal strains, gram-positive, and gram-negative bacteria. Hybrid compounds, 5, 6, and 8 exhibited significant antibacterial activity against all the bacterial strains than the control, fosfomycin with the lowest MIC value of ≤ 3 against Proteus mirabilis and Klebsiella aerogenes. The antifungal activity of hybrids, 2, 4, 5, and 6 against Penicillum Citrinum and Aspergillus ochraceus was high when compared to the control, nystatin. The lowest MIC values were 107 and 214 µM against Penicillum Citrinum and Aspergillus ochraceus for hybrid 5. The molecular docking studies revealed the inhibition of urease enzymes in Klebsiella aerogenes with a high binding energy of − 3.973 and − 4.645 Kcal/mol, respectively for hybrids 5 and 6. The in silico toxicity revealed the non-toxic effects of the hybrid compounds. The SwissADME parameters of the hybrid molecules further predicted good permeability, water solubility, and oral bioavailability, inability to cross the blood–brain barrier (BBB) and non-inhibition effects on some CYP isoenzymes, suggesting that their biotransformation will not be via the cytochrome isoenzymes. Most of the hybrids, 4–8 were predicted to be P-glycoprotein substrates. The hybrids obeyed Lipinski’s rules with one violation, the Ghose rule, and the Egan rule. These findings indicate that the efficacy of hybrid compounds as promising antimicrobials and future studies are needed.A
Synthesis, characterization, and biological evaluation of coumarin-nitric oxide donor hybrids as anti-tubercular agents
(Elsevier, 2024) Kareem, Afeez I.; Malan, Sarel F.; Kapp, Erika; Shamido, Sean; Joubert, Jacques
This study presents a series of coumarin nitric oxide donor hybrids that were synthesized, and characterized using FT-IR, H NMR, C NMR, and HR-MS techniques. Initial screening for anti-tubercular activity was conducted against Mycolicibacterium smegmatis MC2 155 (M.smeg) under both nutrient-rich and nutrient-poor conditions. Under nutrient-rich conditions, little inhibition was observed. However, four compounds (1e, 2o, 3f, and 5e) demonstrated notable antiproliferative activity under nutrient-poor conditions, with inhibition rates exceeding 95 % at a 50 μM concentration. Subsequent testing of these compounds on Mycobacterium tuberculosis (M.tb) under nutrient-rich conditions showed inhibition rates ranging from 11 % to 37 % at 50 μM. These results indicate that the coumarin nitric oxide donor hybrids are potentially effective in nutrient-limited environments, similar to the intracellular conditions faced by M.tb. In silico cytotoxicity predictions, compared with rifampicin, indicated potentially low toxicity for these compounds. Further optimization and studies are needed to enhance their efficacy under normal conditions, which could lead to the development of new therapeutic strategies against tuberculosis.
Population pharmacokinetics of amodiaquine and piperaquine in African pregnant women with uncomplicated plasmodium falciparum infections
(John Wiley & Sons, 2024) Ding, Junjie; Ravinetto, Raffaella; Hoglund, Richard
Artemisinin-based combination therapy (ACT) is the first-line recommended treatment for uncomplicated malaria. Pharmacokinetic (PK) properties in pregnant women are often based on small studies and need to be confirmed and validated in larger pregnant patient populations. This study aimed to evaluate the PK properties of amodiaquine and its active metabolite, desethylamodiaquine, and piperaquine in women in their second and third trimester of pregnancy with uncomplicated P. falciparum infections. Eligible pregnant women received either artesunate-amodiaquine (200/540 mg daily, n = 771) or dihydroartemisinin-piperaquine (40/960 mg daily, n = 755) for 3 days (NCT00852423). Population PK properties were evaluated using nonlinear mixed-effects modeling, and effect of gestational age and trimester was evaluated as covariates. 1071 amodiaquine and 1087 desethylamodiaquine plasma concentrations, and 976 piperaquine plasma concentrations, were included in the population PK analysis. Amodiaquine concentrations were described accurately with a one-compartment disposition model followed by a two-compartment disposition model of desethylamodiaquine. The relative bioavailability of amodiaquine increased with gestational age (1.25% per week). The predicted exposure to desethylamodiaquine was 2.8%–32.2% higher in pregnant women than that reported in non-pregnant women, while day 7 concentrations were comparable. Piperaquine concentrations were adequately described by a three-compartment disposition model. Neither gestational age nor trimester had significant impact on the PK of piperaquine. The predicted exposure and day 7 concentrations of piperaquine were similar to that reported in non-pregnant women. In conclusion, the exposure to desethylamodiaquine and piperaquine was similar to that in non-pregnant women. Dose adjustment is not warranted for women in their second and their trimester of pregnancy.
Inhalational delivery of β-glucan-chitosan-poly(lactic co-glycolic) acid nanoparticles enhance alveolar macrophage rifampin concentrations for the treatment of tuberculosis
(John Wiley and Sons Inc, 2024) Dube, Admire; Kutscher, Hilliard L.; Chaves, Lee
Despite multiple treatments for tuberculosis (TB), there are ≈10 million new cases and 1.5 million deaths annually, warranting the need for new therapeutics. Major clinical treatment issues include the length of treatment which is associated with patient non-compliance; and poor cellular drug penetration leading to the generation of drug-resistant strains. This study underscores the potential of β-glucan-chitosan (CS) poly(lactic co-glycolic) acid (PLGA) nanoparticles as a promising immunostimulatory adjunct for TB treatment. To facilitate drug delivery to alveolar macrophage, a CS-PLGA nanoparticle is developed containing rifampin in the core with β-glucan as a surface ligand, to stimulate the immune system. Mice are administered a single dose of nanoparticles or free rifampin by oropharyngeal aspiration. Pharmacokinetic investigations reveal sustained release properties of rifampin in vivo, extending over a week. Furthermore, comprehensive analysis indicates stimulation of the innate immune system, as evidenced by cytokine profiling, while concurrently revealing no detrimental effects on the alveolar epithelium, as indicated by histological examination and albumin lung leak assessment. These findings collectively establish a strong foundation for the development of a novel adjuvant immunotherapy approach for TB.
Towards integrated mental health services in low-income and middle-income countries: organisation of primary healthcare providers – a scoping review protocol
(BMJ Publishing Group, 2024) Ward, Kim; Marimwe, Chipiwa; Tanyaradzwa Dube, Lorraine; Parker, Mariam B.
Introduction Mental health conditions constitute a significant percentage of the global burden of disease. A shortfall of mental health specialists and a lack of integration of services in primary care in low-income and middle-income countries (LMICs) contribute towards a mental health treatment gap in excess of 70%. Organising and equipping non-specialist healthcare workers is, therefore, an important strategy for improving access to mental health services in LMICs. This scoping review aims to map literature that addresses the organisation of and support provided to health teams in primary care settings within the context of integrated mental healthcare and as it relates to detection, treatment and referral of mental health conditions. The review will be guided by the ‘Innovative Care for Chronic Conditions’ framework. Methods and analysis This review protocol will employ the methodological framework first developed by Arksey and O’Malley and later advanced by others and will follow the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews guidelines. This process will entail identifying the research questions, locating relevant literature, choosing eligible reports and studies, extracting the data and summarising the results in English-language studies and reports from 2008 to 2023 will be sourced from PubMed, CINAHL, Cochrane Library, PsycARTICLES, Scopus, Web of Science, Academic Search Complete and the WHO website.
Exploring antimycobacterial potential: safety evaluation and active compound isolation from gymnopilus junonius
(Multidisciplinary Digital Publishing Institute (MDPI), 2025) Beukes, Denzil; Lerata, Mookho; Didloff, Jenske
Background/Objectives: Tuberculosis remains a major public health crisis, and it is imperative to search for new antimycobacterial drugs. Natural products, including medicinal macrofungi, have been used as sources for the discovery of pharmaceuticals; however, research on their antimycobacterial activity remains limited. This study aimed to isolate and identify the bioactive compound responsible for antimycobacterial activity, thereby expanding on the limited knowledge regarding the antimicrobial activity and bioactive compounds present in Gymnopilus junonius. Methods: Bioassay-guided fractionation using column chromatography and preparative thin-layer chromatography were employed to isolate the active compound. Antimycobacterial activity against Mycobacterium tuberculosis H37 was assessed using a resazurin microplate assay (REMA). The chemical structure was determined by 1H nuclear magnetic resonance (NMR) spectroscopy, heteronuclear single quantum coherence (HSQC) spectroscopy, heteronuclear multiple bond correlation (HMBC) spectroscopy, and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes in M. tuberculosis induced by the compound. Cytotoxicity was evaluated in African green monkey kidney cells (Vero), human liver cells (C3A), and zebrafish embryos/larvae. Results: Bioassay-guided fractionation led to the isolation of gymnopilene, which showed inhibitory activity against M. tuberculosis (MIC: 31.25 µg/mL). TEM analysis revealed that treatment with gymnopilene caused ultrastructural damage observed as the disruption and disintegration of the cell wall. While gymnopilene demonstrated cytotoxicity in Vero and C3A cells, no toxicity was observed in zebrafish embryos/larvae for the crude extract. Conclusions: This study highlights that macrofungi, such as G. junonius, could be a valuable resource of bioactive compounds.
Synthesis of immunomodulatory biomimetic lipid polymer hybrid nanoparticles and application of zebrafish larvae in immunomodulation screening
(Elsevier B.V., 2025) Irabin, Aime; Ahmed, Rami; Dube, Admire
Since the antibiotic golden era of the mid-20th century, there have been limited antibiotics approved, while antibiotic resistance continues to escalate disproportionately, outpacing the rate of novel antibiotic discovery. This imbalance poses a serious global health concern, with an estimated annual death toll of 10 million due to antibiotic resistance by 2050. There is a growing interest in immunotherapy as an alternative approach to conventional antibiotics due to its ability to target and stimulate immune system, leveraging its innate ability to self-eradicate pathogens. This study synthesized lipid polymer hybrid nanoparticles (LPHNPs) conjugated with two immunomodulatory agents, namely, curdlan and mycolic acid (MA), as a potential immunotherapy for bacterial infections. LPHNPs were synthesized using lecithin and polycaprolactone (PCL) at a 15 % lipid-to-polymer (w/w) ratio. Additionally, PCL-curdlan copolymer, comprising 15 % w/w curdlan, was successfully synthesized and used to conjugate the LPHNPs with various curdlan concentrations. Furthermore, The LPHNPs were conjugated with varying MA concentrations, with or without curdlan. In-vivo assessment of the immunomodulatory effect of the LPHNPs was conducted using a larval zebrafish model assessing behaviour and immunofluorescence, as indicators of immune stimulation. The data suggests that curdlan exhibits a more complex immunoregulatory role as demonstrated by the countered stimulated behavioural effect while inflammation remained heightened. This work also provides new insights that zebrafish larvae are a valuable screening tool in the development of nanoparticle immunotherapies.

Browse

Recent Submissions