Research Articles (Medical Bioscience)

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Protective efficacy of a plant-produced beta variant rsars-cov-2 vlp vaccine in golden syrian hamsters
(Elsevier Ltd, 2024) Lemmer, Yolandy; Chapman, Ros; Shaw, Megan L.
In the quest for heightened protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, we engineered a prototype vaccine utilizing the plant expression system of Nicotiana benthamiana, to produce a recombinant SARS-CoV-2 virus-like particle (VLP) vaccine presenting the S-protein from the Beta (B.1.351) variant of concern (VOC). This innovative vaccine, formulated with either a squalene oil-in-water emulsion or a synthetic CpG oligodeoxynucleotide adjuvant, demonstrated efficacy in a golden Syrian Hamster challenge model. The Beta VLP vaccine induced a robust humoral immune response, with serum exhibiting neutralization not only against SARS-CoV-2 Beta but also cross-neutralizing Delta and Omicron pseudoviruses. Protective efficacy was demonstrated, evidenced by reduced viral RNA copies and mitigated weight loss and lung damage compared to controls. This compelling data instills confidence in the creation of a versatile platform for the local manufacturing of potential pan-sarbecovirus vaccines, against evolving viral threats.
Therapeutic potential of natural products in schistosomiasis-associated liver fibrosis
(Frontiers Media SA, 2024) Liu, Cuiling; Fisher, David; Pronyuk, Khrystyna
Schistosomiasis is a parasitic disease that endangers human health and social development. The granulomatous reaction of Schistosoma eggs in the liver is the main cause of hepatosplenomegaly and fibrotic lesions. Anti liver fibrosis therapy is crucial for patients with chronic schistosomiasis. Although Praziquantel is the only clinical drug used, it is limited in insecticide treatment and has a long-term large-scale use, which is forcing the search for cost-effective alternatives. Previous research has demonstrated that plant metabolites and extracts have effective therapeutic effects on liver fibrosis associated with schistosomiasis. This paper summarizes the mechanisms of action of metabolites and some plant extracts in alleviating schistosomiasis-associated liver fibrosis. The analysis was conducted using databases such as PubMed, google scholar, and China national knowledge infrastructure (CNKI) databases. Some plant metabolites and extracts ameliorate liver fibrosis by targeting multiple signaling pathways, including reducing inflammatory infiltration, oxidative stress, inhibiting alternate macrophage activation, suppressing hepatic stellate cell activation, and reducing worm egg load. Natural products improve liver fibrosis associated with schistosomiasis, but further research is needed to elucidate the effectiveness of natural products in treating liver fibrosis caused by schistosomiasis, as there is no reported data from clinical trials in the literature.
In silico identification of compounds from Piper sarmentosum Roxb leaf fractionated extract inhibit interleukin-6 to prevent rheumatoid arthritis
(Frontiers, 2024) Van De Tran; Tran Nhat Phong Dao; Sunday Amos Onikanni
Objective: Medicinal herbs with a phytonutrient background has been applied globally as major alternatives to ameliorate the continuous increase in rheumatoid arthritis cases worldwide. We herein aimed to critically examine the bioactive components of the medicinal herb Piper sarmentosum Roxb leaf fractionated extract for its potential to inhibit the influx of interleukin-6 (IL-6) in rheumatoid arthritis. Methods: The Schrödinger platform was employed as the main computational acumen for the screening of bioactive compounds identified and reference compounds subjected to molecular simulation (MDS) for analyzing the stability of docked complexes to assess fluctuations and conformational changes during protein–ligand interactions. Results: The values of the simulatory properties and principal component analysis (PCA) revealed the good stability of these phytochemicals in the active pocket of interleukin-6 (IL-6). Discussion: Our findings reveal new strategies in which these phytochemicals are potential inhibitory agents that can be modified and further evaluated to develop more effective agents for the management of rheumatoid arthritis, thereby providing a better understanding and useful model for the reproduction and/ or discovery of new drugs for the management of rheumatoid arthritis and its complications.
Current status of malaria control and elimination in Africa: epidemiology, diagnosis, treatment, progress and challenges
(Springer Science and Business Media B.V., 2024) David, Fisher; Jiahuan, Li; Haragakiza, Jean Docile
The African continent carries the greatest malaria burden in the world. Falciparum malaria especially has long been the leading cause of death in Africa. Climate, economic factors, geographical location, human intervention and unstable security are factors influencing malaria transmission. Due to repeated infections and early interventions, the proportion of clinically atypical malaria or asymptomatic plasmodium carriers has increased significantly, which easily lead to misdiagnosis and missed diagnosis. African countries have made certain progress in malaria control and elimination, including rapid diagnosis of malaria, promotion of mosquito nets and insecticides, intermittent prophylactic treatment in high-risk groups, artemisinin based combination therapies, and the development of vaccines. Between 2000 and 2022, there has been a 40% decrease in malaria incidence and a 60% reduction in mortality rate in the WHO African Region. However, many challenges are emerging in the fight against malaria in Africa, such as climate change, poverty, substandard health services and coverage, increased outdoor transmission and the emergence of new vectors, and the growing threat of resistance to antimalarial drugs and insecticides. Joint prevention and treatment, identifying molecular determinants of resistance, new drug development, expanding seasonal malaria chemo-prevention intervention population, and promoting the vaccination of RTS, S/AS01 and R21/Matrix-M may help to solve the dilemma. China’s experience in eliminating malaria is conducive to Africa’s malaria prevention and control, and China-Africa cooperation needs to be constantly deepened and advanced. Our review aims to help the global public develop a comprehensive understanding of malaria in Africa, thereby contributing to malaria control and elimination.
The pathophysiology of rhabdomyolysis in ungulates and rats: towards the development of a rodent model of capture myopathy
(Springer, 2023) Kohn, Tertius A; Lubbe, Crystal; Meyer, Leith C. R
Capture myopathy (CM), which is associated with the capture and translocation of wildlife, is a life-threatening condition that causes noteworthy morbidity and mortality in captured animals. Such wildlife deaths have a significant impact on nature conservation efforts and the socio-economic wellbeing of communities reliant on ecotourism. Several strategies are used to minimise the adverse consequences associated with wildlife capture, especially in ungulates, but no successful preventative or curative measures have yet been developed. The primary cause of death in wild animals diagnosed with CM stems from kidney or multiple organ failure as secondary complications to capture-induced rhabdomyolysis. Ergo, the development of accurate and robust model frameworks is vital to improve our understanding of CM. Still, since CM-related complications are borne from biological and behavioural factors that may be unique to wildlife, e.g. skeletal muscle architecture or flighty nature, certain differences between the physiology and stress responses of wildlife and rodents need consideration in such endeavours. Therefore, the purpose of this review is to summarise some of the major etiological and pathological mechanisms of the condition as it is observed in wildlife and what is currently known of CM-like syndromes, i.e. rhabdomyolysis, in laboratory rats. Additionally, we will highlight some key aspects for consideration in the development and application of potential future rodent models.
Microplastic sources, formation, toxicity and remediation: A review
(Springer, 2023) Osman, Ahmed I.; Hosny, Mohamed; Akinyede, Kolajo Adedamola
Microplastic pollution is becoming a major issue for human health due to the recent discovery of microplastics in most ecosystems. Here, we review the sources, formation, occurrence, toxicity and remediation methods of microplastics. We distinguish ocean-based and land-based sources of microplastics. Microplastics have been found in biological samples such as faeces, sputum, saliva, blood and placenta. Cancer, intestinal, pulmonary, cardiovascular, infectious and inflammatory diseases are induced or mediated by microplastics. Microplastic exposure during pregnancy and maternal period is also discussed. Remediation methods include coagulation, membrane bioreactors, sand filtration, adsorption, photocatalytic degradation, electrocoagulation and magnetic separation. Control strategies comprise reducing plastic usage, behavioural change, and using biodegradable plastics. Global plastic production has risen dramatically over the past 70 years to reach 359 million tonnes. China is the world's top producer, contributing 17.5% to global production, while Turkey generates the most plastic waste in the Mediterranean region, at 144 tonnes per day. Microplastics comprise 75% of marine waste, with land-based sources responsible for 80–90% of pollution, while ocean-based sources account for only 10–20%. Microplastics induce toxic effects on humans and animals, such as cytotoxicity, immune response, oxidative stress, barrier attributes, and genotoxicity, even at minimal dosages of 10 μg/mL.
Effects of temperature and storage time on the motility, viability, DNA integrity and apoptosis of processed human spermatozoa
(Wiley, 2019) Iranpour, Farhad Golshan; Nateghian, Zohre; Henkel, Ralf
The aim of this study was to evaluate motility, viability, DNA integrity and apoptosis of spermatozoa when washed semen samples were kept for up to 12 days at 4–6°C and 25°C. In this experimental study, 26 normozoospermic semen samples were washed twice in Modified Ham's F10 and resuspended in IVF fertilisation medium. Half of the specimens were stored at 4–6°C, and the other half was kept at 25°C for 12 days. The proportions of viable, motile, spermatozoa with double-stranded DNA and apoptotic spermatozoa were examined during storage time. Apoptosis was measured using annexin V-PI staining followed by flow cytometry. Results showed that sperm motility and viability decreased during 12 days of sample storage (p < .001). There was no significant difference between the two temperatures in terms of motility and viability for up to 2 days (p < .05).
Critical evaluation of two models of flow cytometers for the assessment of sperm DNA fragmentation: an appeal for performance verification
(Medknow Publications, 2019) Sharma, Rakesh; Gupta, Sajal; Henkel, Ralf
Lack of standardized, reproducible protocols and reference values is among the challenges faced when using new or upgraded versions of instruments in reproductive laboratories and flow cytometry. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay combined with flow cytometry routinely used for diagnostic measurement of sperm DNA fragmentation (SDF) is a unique example. Any change in the setting of the standard instrument, including upgrades of hardware or software, can lead to different results and may affect clinicians’ decision for treatment. Therefore, we compared TUNEL results of SDF obtained from a standard (C6) flow cytometer with a newer version of the same instrument (C6 Plus) and examined the cutoff, sensitivity, and specificity without calibration (adjustment) and after adjustment. Identical sperm preparation and matched acquisition settings were used to examine the performance of two flow cytometers. The strength of agreement of the results between the two observers was also assessed. After adjustment of the settings, overall concordance became high and the two cytometers showed 100% positive and negative predictive value with 100% area under the curve. The overall correlation coefficient observed between C6 and C6 Plus was highly significant (P < 0.0001; r = 0.992; 95% confidence interval [CI]: 0.982–0.997). After adjustment, the two cytometers showed very high precision of 98% and accuracy of >99%. The interobserver agreement on C6 flow cytometer for the two observers was 0.801 ± 0.062 and 0.746 ± 0.044 for C6 Plus. We demonstrated a strong agreement between the samples tested on the two flow cytometers after calibration and established the robustness of both instruments.
Autoimmune progesterone dermatitis: Case report with history of urticaria, petechiae and palpable pinpoint purpura triggered by medical abortion
(South African Medical Association, 2016) Mbonile, Lumuli
Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised endogenous progesterone levels that occur during the luteal phase of the menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations develop cyclically during the luteal phase of the menstrual cycle when progesterone levels are elevated. APD symptoms usually start 3 - 10 days before menstruation and resolve 1 - 2 days after menstruation ceases. A 30-year-old woman presented with urticaria, petechiae and palpable pinpoint purpura lesions of the legs, forearms, neck and buttocks 1 week prior to her menses starting and 2 months after a medical abortion. She was diagnosed with allergic contact dermatitis and topical steroids were prescribed. Her skin conditions did not improve and were associated with her menstrual cycle. We performed an intradermal test using progesterone, which was positive. She was treated with oral contraceptive pills and the symptoms were resolved. This is a typical case of APD triggered by increased sensitivity to endogenous progesterone induced a few months after medical abortion.
Contaminants of emerging concern (cecs) and male reproductive health: Challenging the future with a double-edged sword
(MDPI, 2023) Marcu, Daniel; Keyser, Shannen; Petrik, Leslie
Approximately 9% of couples are infertile, with half of these cases relating to male factors. While many cases of male infertility are associated with genetic and lifestyle factors, approximately 30% of cases are still idiopathic. Contaminants of emerging concern (CECs) denote substances identified in the environment for the first time or detected at low concentrations during water quality analysis. Since CEC production and use have increased in recent decades, CECs are now ubiquitous in surface and groundwater. CECs are increasingly observed in human tissues, and parallel reports indicate that semen quality is continuously declining, supporting the notion that CECs may play a role in infertility. This narrative review focuses on several CECs (including pesticides and pharmaceuticals) detected in the nearshore marine environment of False Bay, Cape Town, South Africa, and deliberates their potential effects on male fertility and the offspring of exposed parents, as well as the use of spermatozoa in toxicological studies.
Trends in semen parameters of infertile men in South Africa and Nigeria
(2023) Akang, Edidiong Nnamso; Opuwari, Chinyerum Sylvia; Enyioma‑Alozie, Swesme
There are conflicting reports on trends of semen parameters from different parts of the globe. However, in recent times there is dearth of information on the trend in Sub-Saharan countries. Therefore, in this study we aimed at determining the trends in semen parameters in Nigeria and South Africa between 2010 and 2019. A retrospective study of semen analyses of 17,292 men attending fertility hospitals in Nigeria and South Africa in 2010, 2015 and 2019. Patients who had undergone vasectomy and those who had a pH less than 5 or greater than 10 were excluded from this study. The following variables were assessed: ejaculate volume, sperm concentration, progressive motility, total progressively motile sperm count (TPMSC), total sperm count, and normal sperm morphology. Between 2010 and 2019, significant trends of decreasing values were observed in normal sperm morphology (− 50%), and the ejaculatory volume (− 7.4%), indicating a progressive deterioration of the values in both countries. In Nigeria, there were significant decreases in progressive motility (− 87%), TPMSC (− 78%), and sperm morphology (− 55%) between 2010 and 2019 (P < 0.001). Spearman`s rank correlation revealed significant negative associations between age and morphology (ρ = − 0.24, P < 0.001), progressive motility (ρ = − 0.31. P < 0.001), and TPMSC (ρ = − 0.32, P < 0.001). Patients in South Africa were younger than those from Nigeria, with also a significantly higher sperm morphology, sperm concentration, progressive motility, total sperm count and TPMSC. Our findings provide a quantitative evidence of an alarming decreasing trend in semen parameters in Nigeria and South Africa from 2010 to 2019. It also proves that astheno- and teratozoospermia are the leading causes of male infertility in these regions. In addition to this, it also shows empirically that semen parameters decrease with advancement in age. These findings are the first report of temporal trends in semen parameters in Sub-Saharan countries, necessitating a thorough investigation on the underlying factors promoting this worrisome decline.
Fiber type and metabolic characteristics of skeletal muscle in 16 breeds of domestic dogs
(Wiley, 2023) van Boom, Kathryn M.; Schoeman, Johan P.; Kohn, Tertius A.
The domestic dog (Canis lupus familiaris) species comprises hundreds of breeds, each differing in physical characteristics, behavior, strength, and running capability. Very little is known about the skeletal muscle composition and metabolism between the different breeds, which may explain disease susceptibility. Muscle samples from the triceps brachii (TB) and vastus lateralis (VL) were collected post mortem from 35 adult dogs, encompassing 16 breeds of varying ages and sex. Samples were analyzed for fiber type composition, fiber size, oxidative, and glycolytic metabolic capacity (citrate synthase [CS], 3-hydroxyacetyl-coA dehydrogenase [3HAD], creatine kinase [CK], and lactate dehydrogenase [LDH] enzyme activities).
A plant-produced SARS-CoV-2 spike protein elicits heterologous immunity in hamsters
(Frontiers Media, 2023) Margolin, Emmanuel; Schäfer, Georgia; Shaw, Megan L.
Molecular farming of vaccines has been heralded as a cheap, safe and scalable production platform. In reality, however, differences in the plant biosynthetic machinery, compared to mammalian cells, can complicate the production of viral glycoproteins. Remodelling the secretory pathway presents an opportunity to support key post-translational modifications, and to tailor aspects of glycosylation and glycosylation-directed folding. In this study, we applied an integrated host and glyco-engineering approach, NXS/T Generation™, to produce a SARS-CoV-2 prefusion spike trimer in Nicotiana benthamiana as a model antigen from an emerging virus. The size exclusion-purified protein exhibited a characteristic prefusion structure when viewed by transmission electron microscopy, and this was indistinguishable from the equivalent mammalian cell-produced antigen.
Unveiling the Inhibitory Potentials of Peptidomimetic Azanitriles and Pyridyl Esters towards SARS-CoV-2Main Protease: A MolecularModelling Investigation
(MDPI, 2023) Mushebenge, Aganze G; Ugbaja, Samuel C; Mtambo, Sphamandla E; Odugbemi, Adeshina I
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for COVID-19, which was declared a global pandemic in March 2020 by the World Health Organization (WHO). Since SARS-CoV-2 main protease plays an essential role in the virus’s life cycle, the design of small drug molecules with lower molecular weight has been a promising development targeting its inhibition. Herein, we evaluated the novel peptidomimetic azatripeptide and azatetrapeptide nitriles against SARS-CoV-2 main protease. We employed molecular dynamics (MD) simulations to elucidate the selected compounds’ binding free energy profiles against SARS-CoV-2 and further unveil the residues responsible for the drug-binding properties. Compound 8 exhibited the highest binding free energy of 􀀀49.37 0.15 kcal/mol, followed by compound 7 (􀀀39.83 0.19 kcal/mol), while compound 17 showed the lowest binding free energy (􀀀23.54 0.19 kcal/mol). In addition, the absorption, distribution, metabolism, and excretion (ADME) assessment was performed and revealed that only compound 17 met the drug-likeness parameters and exhibited high pharmacokinetics to inhibit CYP1A2, CYP2C19, and CYP2C9 with better absorption potential and blood-brain barrier permeability (BBB) index. The additional intermolecular evaluations suggested compound 8 as a promising drug candidate for inhibiting SARS-CoV-2 Mpro. The substitution of isopropane in compound 7 with an aromatic benzene ring in compound 8 significantly enhanced the drug’s ability to bind better at the active site of the SARS-CoV-2 Mpro.
Use of a rat ex-vivo testis culture method to assess toxicity of select known male reproductive toxicants
(Elsevier, 2016) Goldstein, Keith M.; Seyler, David E.; Baker, Thomas K.
Due to the complex physiology of the testes, in vitro models have been largely unsuccessful at modeling testicular toxicity in vivo. We conducted a pilot study to evaluate the utility of the Durand ex vivo rat seminiferous tubule culture model [1], [2], [3] that supports spermatogenesis through meiosis II, including the formation of round spermatids. We used this system to evaluate the toxicity of four known testicular toxicants: 1,3-dinitrobenzene (DNB), 2-methoxyacetic acid (MAA), bisphenol A (BPA), and lindane over 21 days of culture.
Muscle fiber type and metabolic profiles of four muscles from the African black ostrich
(Meat Science, 2023) Kohn, Tertius A; Magwaza, S'thandiwe N; Adamson, Luqmaan; Anley, Megan J.
Muscle fiber type, fiber cross-sectional area (CSA), enzyme activities (citrate synthase (CS), 3-hydroxyacetyl Co A dehydrogenase (3HAD), lactate dehydrogenase (LDH) and phosphofructokinase (PFK)) and glycogen content were analyzed in the M. iliotibialis cranialis (ITC), M. iliotibialis lateralis, M. gastrocnemius (G) and M. fibularis longus (FL) muscles from 24 ostriches. Type I and II fiber proportions were similar across the 4 muscles, but the ITC had overall the smallest fibers. CS activity was the highest in the ITC, but similar between the remainder of the muscles. 3HAD activities were very low in all muscles, ranging between 1.9 and 2.7 μmol/min/g protein, indicating poor β-oxidation. The ITC also had the lowest PFK activity. Glycogen content averaged ∼85 mmol/kg dry weight across the muscles with large intramuscular variations. The 4 ostrich muscles present with low fat oxidation capacity and low glycogen content, which could have significant implications on meat quality attributes.
Potential for increasing folate contents of traditional African fermented sorghum gruel (Motoho) using presumptive probiotic lactic acid bacteria
(Elsevier, 2023) Fayemi, Olanrewaju E.; Akanni, Gabriel B.; Oelofse, Andre
Folate deficiency is commonly observed in most developing countries. Lactic acid bacteria (LAB) fermentation of cereal-based foods could be an alternative to improving folate intake. This study evaluated the possibility of improving the folate contents of traditional African fermented sorghum gruel (motoho) using indigenous po- tential probiotic LAB. A total of 220 LAB strains isolated from maize gruel were screened for extracellular and intracellular folate production. Strains were further examined for in vitro probiotic characteristics and antimi- crobial activity. Sixteen (16) LAB strains exhibited high production of total folate which ranged between 44 and 180 μg/100 mL with the lowest and highest value in L. plantarum S8 and L. plantarum S49, respectively. Fermentation of sorghum gruel with folate producing probiotic LAB strains for in situ folate production in motoho was determined. The folate contents of sorghum motoho fermented with LAB ranged between 13 and 20 μg/100 mL while the control was below 2.5 μg/100 mL. Indigenous LAB strains from traditional African fermented gruel possess desirable in vitro probiotic properties and ability to produce folates, thus, could be used for natural in situ folate fortification. This study presents a strategy for future application of indigenous probiotic LAB cultures as natural means of fortifying cereal foods with folates.
The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data
(Nature Research, 2023) Hampton, Leonard L; Ruqaya, Murtadha; Martinez-Carrasco, Alejandro; Pillay, Nikita Simone
Open science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD
Call for special issue papers: Global public health — contributions of traditional, complementary, and integrative medicine in primary care
(Mary Ann Liebert, 2022) Hughes, Gail D.; Sommers, Elizabeth; Steel, Amie
The 2018 Declaration of Astana* issued by the World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF) represents a landmark step for all of primary health care, public health, and traditional complementary and integrative medicine. It brings together the priorities of the WHO’s 1978 Alma-Ata Declaration, the international importance of universal health coverage, and the ongoing efforts of the global community to reach UNICEF’s Sustainable Development Goals. It is the first global primary health care document to explicitly acknowledge the value and importance of traditional medicine systems in achieving successful primary health services; ‘success’ being underpinned by specific commitments and evaluated by key success measures**. The Declaration explicitly refers to the application of traditional knowledge and the appropriate inclusion of traditional medicines as factors that will drive the success of primary care. However, the Declaration also makes commitments and identifies other success drivers that, despite not being directly linked to traditional and integrative care, are equally relevant. These omissions represent potentially untapped and overlooked opportunities for meaningful engagement to improve primary care.
Face-to-face versus online-based lectures: A COVID-19 induced study on assessments
(Frontiers in Education, 2022) Fisher, D
The students were found to be resilient in adapting to things and learning, online presentations, and computer-based assessments. No gender-based difference or advantage to adjusting to newly introduced blended learning and concomitant changes in learning assessment strategies was found. The online-home-based assessments proved to incentivize prior learning and preparation for assessments by implementing strict time limits or assessments and randomizing the selections of questions and respective (MCQ) answer choices.

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