Research Articles (Physiology)

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Effectiveness of self-management programmes for athletes with patellofemoral pain syndrome : a systematic review
Masoudi, A.; Chemane, N.; Magida, Nontembiso; Useh, U.; Bello, B. (South African Sports Medicine Association, 2025)
BACKGROUND : Patellofemoral pain syndrome (PFPS) is a common condition that can severely hinder an athlete's ability to perform and compete at their full potential and overall well-being. The emergence of self-management programmes presents a potential treatment avenue for athletes with PFPS. Self-management programmes aim to empower patients through education, symptom monitoring, tailored exercises, and gradual activity progression while respecting pain thresholds. Despite their potential benefits, limited data evaluates the effectiveness of self-management programmes specifically tailored for athletes with PFPS. OBJECTIVES : To assess the effectiveness of self-management programmes in improving pain and functional ability among athletes with PFPS. METHODS : A systematic search was conducted across PubMed/MEDLINE, Cochrane Library, CINAHL, and PsycINFO databases. Randomised and non-randomised controlled trials comparing self-management interventions to other treatments or control groups for improving pain and functional ability among athletes with patellofemoral pain syndrome were included. Studies including athletes with PFPS (defined as pain persisting for >12 weeks) were eligible. Four reviewers independently extracted data and assessed quality using the Physiotherapy Evidence Database (PEDro) scale. RESULTS : Three trials involving 139 participants met the eligibility criteria. Identified self-management programmes comprised exercises, mindfulness training, and educational programmes tailored to athletes. Two of the eligible studies identified found that exercise consisting of the combination of mindfulness and/or dry needling reported an enhanced recovery rate in the studied population with regards to PFPS. The other study reported no added benefit whether exercise or education was used as a modality for the self-management of PFPS. CONCLUSION : While some studies showed promising results for self-management programmes involving exercises and mindfulness in managing patellofemoral pain syndrome among athletes, the overall evidence could be more extensive and consistent. High-quality controlled trials with consistent methodology and athletic populations are needed to identify the most effective self-management approaches for patellofemoral pain syndrome in athletes.
Antiproliferative effects of cannabinoids and cisplatin in cervical cancer cells
Mathibela, Sanele Priscilla; Lebelo, Maphuthi Tebogo; Steenkamp, Vanessa (Wiley, 2026-04-29)
INTRODUCTION: Cervical cancer remains a leading cause of cancer-related mortality among women globally, particularly in low-and middle-income countries. Cisplatin, a standard chemotherapeutic agent, is limited by severe toxicities and chemoresistance. This study aimed to assess the effects of cisplatin in combination with phytocannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on cell proliferation, morphology, cell cycle progression, cell death, and DNA damage. METHODS: Synergistic interactions between THC, CBD, and cisplatin were assessed in HeLa, SiHa, and MCF-12A cells using the checkerboard assay and SRB assay. Cell morphology, cell cycle progression, apoptosis induction, autophagic activity, and DNA repair gene expression were evaluated using various techniques. RESULTS: The THC–CBD–cisplatin combination exhibited the strongest apoptotic response in cancer cells (HeLa 53%, SiHa 58%),while minimally affecting MCF-12A cells (32%). Cannabinoid co-treatment amplified the antiproliferative and pro-apoptotic effects of cisplatin in HeLa and SiHa cells. The triple combination induced a G2/M arrest in HeLa cells and sub- G1 accumulation inSiHa cells. Autophagic activity, indicated by LC3B puncta formation, increased in HeLa and SiHa cells following THC and CBD exposure. DNA repair genes XRCC1 and RAD51 were downregulated by the cannabinoid–cisplatin combination. CONCLUSION: These findings demonstrate that combining THC and CBD with cisplatin results in enhanced and mechanistically diverse anticancer effects, with a higher degree of selectivity for cervical cancer cells compared to non-cancerous MCF-12A cells by inducing apoptosis and autophagy while inhibiting DNA repair capacity. This study highlights the potential of cannabinoid-based combination therapies as a promising approach for cervical cancer treatment.
Cytotoxicity potency of cannabinoids is by serum supplementation : implications for In Vitro cancer studies
Mathibela, Sanele Priscilla; Lebelo, Maphuti Tebogo; Steenkamp, Vanessa (Wiley, 2026-03-11)
BACKGROUND: Fetal calf serum (FCS) is a key supplement in cell culture, providing nutrients, and growth factors that support cancer cell proliferation. Studies suggest that compound cytotoxicity profiles in vitro vary depending on FCS concentration in culture medium. The study aimed to examine how extracellular conditions influence the in vitro response of cancer cells to phytocannabinoids, with particular emphasis on serum supplementation. METHODS AND RESULTS: Cells were exposed to CBD and THC in media containing 0.5% or 10% FCS for 24–72 h. Cell viability was assessed using the sulforhodamine B assay and live-cell imaging. Significantly enhanced cytotoxic effects of CBD and THC were noted under low-serum conditions (0.5% FCS) compared to standard conditions (10% FCS), particularly after 72 h incubation. THC demonstrated greater cytotoxicity than CBD in SiHa cells, while both compounds showed similar effects in HeLa cells. CONCLUSION: The study demonstrates that serum concentration critically modulates the cytotoxic potency of cannabinoids. Reduced FCS enhances cannabinoid efficacy by limiting protein binding, emphasizing the need to optimize serum conditions for accurate in vitro cytotoxicity assessments
Educational interventions for REDs in athletes : a scoping review
Chantler, Jessica; MacMillan, Candice; Sewry, Nicola Ann (Elsevier, 2026-05)
BACKGROUND AND OBJECTIVES : Athletes, coaches, and support staff generally lack adequate knowledge of Relative Energy Deficiency in Sport (REDs) and its causes, and one way to address this is through the use of educational interventions (EI). This scoping review aimed to summarise existing literature and identify research gaps concerning EI's for REDs and its physiological effects on athletes. METHODS : This review followed PRISMA-ScR guidelines. Articles were sourced using keywords such as “REDs”, “female athlete triad”, “low energy availability” and “educational interventions”. Two independent screeners conducted the screening in Covidence for title, abstract, and full-text screening. Data were extracted from the included articles using a standardised template. RESULTS : The search yielded 3856 articles, of which 33 met the eligibility criteria. Most studies were conducted in the United States of America (52%), with remaining studies in Europe and Asia. Most participants were female (61%), aged 18–25 years. Common educational topics included dietary importance (n = 30) and energy availability (n = 19), with lectures (n = 19), peer-led discussions (n = 13), and healthcare counselling (n = 12) as primary delivery methods. The EIs varied from once-off to 4-year interventions, most commonly between 2–4 months (n = 21; 64%). The most prevalent delivery timing was weekly (n = 19; 58%). CONCLUSIONS : Research on EIs in athletes concerning REDs and energy availability has grown, but many regions, including Africa, remain understudied. Most studies have investigated EI in female athletes, indicating a gap in understanding EIs for male athletes. Future research should assess the effectiveness of these interventions and explore areas of improvement in content and delivery. RESUME CONTEXTE ET OBJECTIFS : Les athlètes, entraîneurs et membres des équipes manquent généralement de bonnes connaissances sur le déficit énergétique relatif dans le sport (REDs) et ses causes. Une des façons d’y remédier est le recours à des interventions éducatives (IE). Cette revue de la littérature a pour objectif de résumer les travaux existants et d’identifier les lacunes de recherche concernant les IE sensibiliser aux risques de REDs et à ses effets physiopathologiques chez les athlètes. METHODES : Cette revue a suivi les recommandations PRISMA-ScR. Les articles ont été recherchés à l’aide de mots-clés tels que « REDs », « female athlete triad », « low energy availability » et « educational interventions ». Deux évaluateurs indépendants ont effectué le tri dans Covidence (titres, résumés et textes complets). Les données des articles inclus ont été extraites à l’aide d’un modèle standardisé. RESULTATS : La recherche a identifié 3856 articles, dont 33 répondaient aux critères d’inclusion. La majorité des études ont été réalisées aux États-Unis (52 %), les autres en Europe et en Asie. La plupart des participants étaient des femmes (61 %), âgées de 18 à 25 ans. Les sujets les plus fréquents abordés lors des interventions éducatives concernaient l’importance de l’alimentation (n = 30) et la disponibilité énergétique (n = 19). Les principales modalités de transmission étaient les cours magistraux (n = 19), les discussions dirigées par des pairs (n = 13) et le conseil en soins de santé (n = 12). Les IE variaient d’une intervention ponctuelle, unique, à des interventions réparties sur une durée de 4 ans, la période d’intervention la plus courante étant de 2 à 4 mois (n = 21 ; 64 %). Le rythme le plus fréquent des formations était hebdomadaire (n = 19 ; 58 %). CONCLUSIONS : Les recherches sur les IE pour la sensibilisation aux risques de REDs et de faible disponibilité énergétique chez les athlètes se sont développées, mais de nombreuses régions, notamment l’Afrique, restent peu abordées. La majorité des études se sont intéressées aux athlètes féminines, révélant un manque de connaissances concernant les IE destinées aux athlètes masculins. Les recherches futures devraient évaluer l’efficacité de ces interventions, explorer les pistes d’amélioration des contenus et des modalités de diffusion.
Infra-slow EEG neurofeedback for insomnia : a single-case experimental study in primary care
Edvardsson, Arne; Smith, Michael G.; Rolstad, Sindre Engelbrekt; Steingrimsson, Steinn; Enriquez-Geppert, Stefanie; Balt, Karlien; Landahl, Jonas; Weineland, Sandra (Frontiers Media, 2026-07-16)
BACKGROUND : Insomnia is a prevalent and burdensome condition in primary care, associated with impaired functioning, increased health risks, and suffering. Infra-slow neurofeedback (ISF-NF) has been proposed as an intervention for stress-related sleep dysregulation, yet empirical evidence from primary care remains scarce. OBJECTIVE : To examine the feasibility, acceptability, and preliminary effects of ISF-NF for insomnia in primary care using a single-case experimental design. METHODS : A single-case experimental design with repeated measures was applied. Ten patients with insomnia and related comorbidities (e.g., stress-related exhaustion, migraine, anxiety) were enrolled. Nine completed the intervention, and eight had sufficient data for analysis following a 2-week baseline and 12 weekly ISF-NF sessions with individualized adjustment of the temporal integration (frequency) parameter. Subjective sleep quality was assessed daily using the Brief Self-Reported Sleep Quality Assessment (BSRSQA). Standardized questionnaires including the Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) were collected at baseline, post-intervention, and 3-month follow-up. Treatment effects were evaluated using visual analysis and non-parametric Tau-U statistics. Wearable sleep data (Fitbit Inspire 3) were analyzed descriptively to contextualize subjective outcomes. RESULTS : Visual single-case analyses revealed heterogeneous but interpretable trajectories, with several participants showing improved perceived sleep quality. Five of eight participants demonstrated statistically significant Tau-U effects (p < 0.05). Group-level analyses showed reductions in sleep problems (PSQI) and depressive symptoms (PHQ-9) from pre to post-intervention, with partial return toward baseline at three-month follow-up. Wearable sleep metrics indicated variability and limited convergence with total sleep time but suggested improvements in sleep consolidation and timing in some cases. Feasibility and acceptability were supported by high treatment adherence, therapeutic alliance, and few reported adverse effects. CONCLUSION : These findings suggest that ISF-NF may be a feasible and well-tolerated intervention in a primary care context, with preliminary indications of benefit in a subset of individuals. Effects were heterogeneous and should be interpreted cautiously. Individualized parameter adjustment and visual single-case analysis may provide a useful framework for capturing treatment dynamics in adaptive interventions. Wearable sleep data may offer contextual information but should be interpreted alongside subjective outcomes. Controlled studies are needed to evaluate efficacy and underlying mechanisms.
Epidemiology of ranger injuries among members of the Game Rangers Association of Africa : service-related risk and the call for targeted prevention strategies
Viljoen, Carel Thomas; Van Mechelen, Willem; Sykes, Leanne M.; Clark, James Robert; De Bruin, Louise; Mushonga, Tafadzwa; Janse van Rensburg, Dina Christina (Elsevier, 2026-09)
OBJECTIVES : To determine the epidemiology of ranger injuries, risk factors for injury, and health support needs among members of the Game Rangers Association of Africa (GRAA). METHODS : We employed a retrospective cross-sectional design to collect data online using a questionnaire developed specifically for this study. We used convenience sampling to include 120 rangers aged 18 years or older who were actively working in Africa. RESULTS : Our findings showed a career injury prevalence of 52 % and period prevalence (past 12 months) of 33 %. The lower limb was the most frequently injured anatomical region (38 %), followed by the upper limb (31 %) and trunk (19 %), specifically affecting the hand (19 %), ankle (14 %), and foot (13 %). The most common injury types included skin lacerations (29 %), followed by muscle injuries (23 %), and fractures (10 %). Working for more than 15 years as a ranger is associated with an increased risk for career injury (OR=2.63) compared to working for 10 years or less. Injuries resulted in a median of 7 days (IQR=0–20 days) lost from work, with most injuries requiring either emergency medical care (31 %) or consultation with a medical doctor (26 %). Rangers need better equipment, cardiovascular fitness training programs, safety training, and mental health support. CONCLUSION : One in every two rangers associated with the GRAA sustains an injury across their careers, with a third of rangers reporting being injured in the past 12 months. Working more than 15 years as a ranger was associated with an increased risk for career injury. Our findings should be used in conjunction with sound clinical reasoning to aid in the development of future injury prevention strategies for rangers working in Africa.
A multi-model ensemble for robust and consistent scoring of reflective essays
Baphumelele, Masikisiki; Marivate, Vukosi; Hlophe, Yvette Nkondo; Adam, Sumaiya (Institute of Electrical and Electronics Engineers, 2026-06-17)
Automated essay scoring has the potential to improve assessment efficiency, yet its adoption in medical education remains limited due to concerns regarding scoring reliability, robustness to linguistic variation, and the interpretability of automated feedback. This challenge is particularly evident in reflective writing assessment, where transparency and pedagogical relevance are essential. This study introduces LLAMPT (Linguistically-Aware Majority Prediction Transformer), an ensemble framework that combines multiple instruction-tuned large language models to generate assessment scores and explanatory rationales. The framework is trained and evaluated on a domain-specific dataset of 13,125 reflective essays written by medical students in South Africa, addressing an underrepresented context in AES research. Experimental results demonstrate strong agreement with expert human markers (Quadratic Weighted Kappa = 0.963). Robustness analysis using progressively paraphrased essays showed sustained scoring consistency across all transformation levels (QWK > 0.94), with mean score deviations below 0.125 rubric points and practical equivalence confirmed through TOST analysis. Interpretability was examined through attribution-based analyses and a mixed-methods evaluation involving clinical educators. While educators generally viewed generated justifications as coherent and contextually relevant, qualitative feedback highlighted limitations related to explanation faithfulness, stylistic nuance, and the continued need for human oversight. These findings demonstrate the potential of large language model ensembles for reflective writing assessment while highlighting important considerations for their responsible integration into medical education workflows.
The 11th IUPS Workshop for Physiology Education : towards a new global horizon in the teaching of Physiology, Löwenstein, Germany, September 14-16, 2025
Silverthorn, Dee U.; Carroll, Robert G.; Marcondes, Fernanda Klein; Schubert, Rudolf; Irfannuddin, Muhammad; Nyakudya, Trevor Tapiwa; Schroder, Katrin; Tansey, Etain A. (American Physiological Society, 2026-06)
The International Union of Physiological Sciences (IUPS), founded in 1889, represents the physiological societies of more than 60 countries around the globe. The IUPS Congress meets every 4 years, and since 1983, there has been a satellite-teaching workshop, organized by the IUPS Education Committee, associated with each Congress. The goal of these workshops is to bring together physiology educators from around the world to discuss the latest developments in evidence-based educational practices and to share their own innovations and challenges when teaching physiology in various settings.
Mapping mental health problems in elite female athletes—a scoping review. Emphasising limited research in Africa and South America
Naidoo, Dhavina; Chantler, Jessica; Gouttebarge, Vincent; Janse van Rensburg, Dina Christina; MacMillan, Candice (Elsevier, 2026)
BACKGROUND : Mental health symptoms and disorders are growing concerns among elite athletes facing unique psychological stressors from high-performance competition. While prevalence has been studied in male athletes and regions like Europe and Australia, significant gaps exist regarding elite female athletes from underrepresented regions, including Africa. OBJECTIVES : To conduct a scoping review on the literature of mental health symptoms and disorders in elite female athletes globally, identify geographic research gaps, and summarise key contributing factors and methodologies. DESIGN : Scoping review. METHODS : While focusing on mental health symptoms and disorders among elite female athletes, studies including both female and male participants were considered to provide a comprehensive overview. A search was conducted in PubMed, PsycINFO, CINAHL, and Scopus databases. Two reviewers independently screened studies, extracted data, and charted results on study characteristics, descriptive study-level prevalence estimates, associated factors, and methodologies. RESULTS : Fifty-nine studies were included. Only seven investigated elite female athletes, 22 reported sex-disaggregated prevalence estimates, and 30 presented aggregated results. Most studies (88.1%) were cross-sectional. Only three studies investigated disorders, and the remaining 56 investigated symptoms such as depression, anxiety, and disordered eating. Risk associations included injury, illness, career dissatisfaction, financial stress, and gender. Research originated mainly from Europe (n = 27), with only one study from Africa and three from South America. CONCLUSIONS : Mental health symptoms are prevalent among elite female athletes, yet evidence is skewed toward high-income regions and often lacks female-specific data. More geographically inclusive, longitudinal, and sex-disaggregated research is needed, particularly in Africa and South America, to ensure the development of equitable interventions and policies.
Mechanistic links between obesity and breast cancer progression : cellular crosstalk, metabolic reprogramming and microenvironmental drivers
Basson, Charlise; Pepper, Michael Sean; Joubert, Anna Margaretha; Ambele, Melvin Anyasi (Wiley, 2026-07)
Obesity is increasingly recognised as an important factor contributing to cancer progression, particularly in breast cancer. However, the cellular and molecular mechanisms underlying obesity-driven breast cancer remain unclear. Several theories have been proposed to explain the complex interactions between adipose tissue and cancer, incorporating both local and distant crosstalk. This review describes existing theories on the cellular and molecular mechanisms linking obesity and breast cancer progression with a focus on inflammation, oxidative stress, metabolic reprogramming, the tumour microenvironment and crosstalk between adipose tissue and tumours. The nature of these interactions appears to be influenced by the specific characteristics of adipose tissue, including its type and anatomical location, which play distinct roles in modulating breast cancer risk and outcomes. Understanding the cellular and molecular mechanisms that underlie obesity-driven breast cancer progression may pave the way for the development of targeted therapies. SUMMARY Obesity is a major modifiable risk factor for breast cancer incidence, progression and metastasis. Despite the reported association between obesity and poor breast cancer outcomes, the exact underlying biological mechanisms remain incompletely defined. Theories on the cellular and molecular mechanisms underlying the cancer–obesity relationship include direct adipose–tumour interactions, inflammation, oxidative stress and metabolic reprogramming. Understanding how obesity-associated factors influence breast cancer is essential for improving current therapies and identifying new therapeutic targets in patients with obesity.
The evaluation of an HIV-PrEP drug on the vascular health outcomes in a diet-induced prediabetes condition rat model
Maswanganyi, Khanyisa; Sedibe, Amogelang; Khathi, Andile; Gamede, Mlindeli (Nature Research, 2026-05)
The prevalence of both prediabetes and cardiovascular diseases (CVD) is a public health concern in high-risk individuals using HIV pre-exposure prophylaxis (HIV-PrEP) treatment. The combined effect of prediabetes and HIV-PrEP use on endothelial function remains underexplored. Hence, the aim of this study was to investigate the effects of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) on endothelial function, oxidative stress, inflammation and lipid markers. Prediabetes was induced using a high-fat high-carbohydrate diet over a 20-week period. Prediabetes diagnosis was confirmed using fasting blood glucose and an oral glucose tolerance test. FTC/TDF was orally administered to the rats for a further 12 weeks. Biochemical analysis was performed using colorimetric assays. The prediabetic animals had higher fasting blood glucose (FBG), vascular endothelial growth factor A (VEGF-A), endothelin-1(ET-1), nitric oxide (NO), NO/ET-1 ratio, hydrogen peroxide (H2O2), interleukin-6, tumour necrosis factor α (TNF-α), triglycerides(TG), low-density lipoprotein cholesterol (LDL-C), endothelial nitric oxide synthase (eNOS), total antioxidant capacity (TAOC) and lower high-density lipoprotein cholesterol (HDL-C) when compared to the non-prediabetic control. However, the FTC/TDF treatment increased VEGF-A, HDL-C, LDL-C and it reduced TGs, NO, NO/ET-1 ratio, H2O2, eNOS, TAOC, interleukin-6, TNF-α and had minimal effect on FBG and ET-1 levels in prediabetic animals .In the non-prediabetic state, FTC/TDF treatment increased VEGF-A, ET-1, NO, NO/ET-1 ratio, H2O2 and interleukin-6 while decreasing eNOS, TAOC, TNF-α and HDL-C and it had a minimal effect on FBG, LDL-C and TGs. FTC/TDF treatment could increase the risk of cardiovascular complications via oxidative stress and endothelial dysfunction. Further studies are needed to fully understand the molecular mechanisms underlying these observed effects.
The effects of neonatal zingerone administration and adolescent alcohol exposure on bone health markers and morphometry in male Sprague–Dawley rats
De Vos, Brunhildé; Asiedu, Bernice; Joubert, Anna Margaretha; Kasonga, Abe E.; Nyakudya, Trevor Tapiwa (Wiley, 2026-04-29)
OBJECTIVE: Neonatal interventions influence long-term developmental outcomes, with excessive alcohol consumption impairing metabolism and bone health. Zingerone, a natural antioxidant, may possess health benefits against alcohol-induced oxidative damage and inflammation, promoting bone health. This study investigates the effects of zingerone on markers of bone turnover and morphometry in neonatal rats subjected to alcohol exposure during critical developmental stages. METHODS: Ten-day-old male Sprague–Dawley rats (N = 35) were randomized and treated with water (C), zingerone (Z) (40 mg/kg), alcohol (A) (1 g/kg) or zingerone–alcohol combination (ZA) for 9 days. During adolescence, rats received either water or a secondary A insult (20% v/v) for 54 days. At termination, ELISA kits were used to measure biomarkers of bone formation (bone-specific alkaline phosphatase, osteocalcin, and procollagen Type I N-terminal propeptide). Bone morphology and morphometry was assessed using microcomputed tomography. RESULTS: Neonatal zingerone (Z + A; ZA + A) and double alcohol exposure (A + A) significantly increased plasma BALP and P1NP levels (p < 0.05). Tibial length remained unchanged across groups (p > 0.05). Neonatal zingerone with adolescent alcohol (Z + A) significantly reduced tibial mass, bone mass-to-length ratios, and trabecular architecture near the growth plate (p < 0.05). Neonatal and adolescent administration of alcohol (A + A) significantly increased midshaft cortical thickness (p < 0.05). CONCLUSION: Adolescent alcohol treatment impaired bone function and morphology, neonatal zingerone alone offering limited protection. Coadministration of zingerone with alcohol neonatally produced variable and context-dependent changes with no clear evidence of sustained protection against the effects of alcohol exposure. These findings underscore the importance of optimizing timing, dosage, and combination therapies for bone health. Further studies are warranted to clarify whether zingerone has clinically meaningful bone-protective effects.
Assessing the cytotoxic effects of Group IX metal N-heterocyclic carbene complexes of iridium and rhodium on B16-F10 melanoma and non-cancerous RAW 264.7 cells
Van Vuuren, Estefan; Nadasen, Carolyn Courtney; Malan, F.P. (Frederick); Hlophe, Yvette Nkondo; Serem, June Cheptoo; Landman, Marile (Elsevier, 2026-09-15)
The development of highly effective and selective anticancer agents remains a central challenge in oncological research. Herein, we report a systematic evaluation of the anticancer activity of a series of rhodium- and iridium-based NHC (N-heterocyclic carbene) complexes (complexes 1, 3, 5–7), including the novel complex 3, as well as two imidazole-containing complexes (2 and 4). Their cytotoxic profiles were investigated against B16-F10 melanoma cells and benchmarked against non-cancerous RAW 264.7 macrophage cells to assess cancer selectivity. Cytotoxicity of complexes 1–7 was quantified using the crystal violet assay following exposure to 0.01 mM and 0.1 mM concentrations over 24, 48, and 72 h. Half-maximal inhibitory concentrations (IC50) were determined to establish comparative selectivity and potency indices. Mechanistic insight was further obtained through morphological assessment of treated cells at IC50 values using polarised light optical differential interference contrast (PlasDIC) microscopy. At 0.1 mM, all complexes induced a pronounced reduction in B16-F10 cell viability, with complexes 2 and 3 emerging as the most potent, achieving >90% inhibition after 72 h. Notably, early time-point IC50 values (24 h) revealed marked cytotoxicity in melanoma cells (complex 2: 0.04 mM; complex 3: 0.05 mM), while eliciting minimal effects in RAW 264.7 macrophages, indicating selective anti-cancer activity. Morphological analysis of B16-F10 cells demonstrated features consistent with both apoptosis (membrane blebbing, apoptotic bodies, nuclear fragmentation) and necrosis (cell swelling, debris). Cell cycle analysis demonstrated a general increase in the S phase in B16-F10 cells, indicative of replication stress or cell cycle arrest, whereas no significant changes were observed in RAW 264.7 cells. Collectively, complexes 2, 3, and 5, display a compelling combination of potency and selectivity towards B16-F10 melanoma cells, with reduced cytotoxicity towards non-cancerous RAW 264.7 cells. These results support the continued development of NHC-based metal complexes as promising selective anticancer agents and warrant further mechanistic and in vivo investigation. HIGHLIGHTS • Range of Rh and Ir metal complexes tested against B16F10 melanoma cells and non-cancerous RAW 264.7 macrophage cells with moderate activity (0.04–0.09 mM IC50) and high selectivity. • Morphological analysis of B16-F10 cells revealed both apoptotic (membrane blebbing, apoptotic bodies, nuclear fragmentation) and necrotic (cell swelling, debris) features. • Cell cycle analysis showed a general increase in S phase in B16-F10 cells and showed no significant changes in RAW 264.7 cells.
Pathogenic variants reveal candidate genes for prostate cancer germline testing formen of African ancestry
Gheybi, Kazzem; Soh , Pamela X.Y.; Jiang, Jue; Mbeki, Tumisang M.N.; Louw, Melanie; Burns, Daniel; Mundra, Piyushkumar; Kiriy, Daria; Hasan, Md. Mehedi; Jaratlerdsiri, Weerachai; Lebelo, Maphuti Tebogo; Campbell, Raymond A.; Radzuma, Mulalo B.; Nenzhelele, Mukudeni; Obida, Muvhulawa; Obida, Martin; Ombuki, Winstar M.; Oyaro, Micah O.; Patrick, Sean Mark; Loda , Massimo; Wedge, David C.; Bristow, Robert G.; Brewer, Daniel S.; Cooper, Colin S.; Cancel-Tassin, Geraldine; Cussenot, Olivier; Cocoran, Niall M.; Stricker, Phillip D.; Schlomm, Thorsten; Prins, Gail S.; Karina Dalsgaard; Sørensen, Karina Dalsgaard; Maria S. (Riana); Bornman, Maria S. (Riana); Eeles , Rosalind A.; Cooper, Colin S.; G. Steven S.; Bova, G. Steven S.; Bristow, Robert G.; Brook, Mark N.; Brors, Benedict; Burns, Daniel; Adam; Butler, Adam; Favero, Francesco; Gerhauser, Clarissa; Gihawi, Abraham; Girma, Etsehiwot G.; Vincent J.; Gnanapragasam, Vincent J.; Hamid, Anis; He, Housheng Hansen; Hovens, Chris M.; Imada, Eddie Luidy; Jakobsdottir; Jakobsdottir, G. Maria; Jiang, Jue; Jung, Chol-Hee; Khani, Francesca; Kiriy, Daria; Zsofia; Kote-Jarai, Zsofia; Leeman, Gregory; Loda, Massimo; Lutsik, Pavlo; Marchionni; Marchionni, Luigi; Papenfuss, Anthony T.; Pellegrina, Diogo; Pope, Bernard; Queiroz, Lucio R.; Queiroz, Lucio R.; Tobias; Rausch, Tobias; Robinson, Brain; Sahli; Sahli, Atef; Sørensen, Karina Dalsgaard; Wedge, David C.; Weischenfeldt , Joachim; Xu; Xu, Yaobo; Zanettini, Claudio (Nature Research, 2025)
Prostate cancer (PCa) germline testing, while gaining momentum, is ancestry restrictive and African exclusive. Through whole genome sequencing for 217 African ancestral cases (186 southern African, 31 Pan representative), we identify 172 potentially pathogenic variants in 78 DNA damage repair or PCa related genes. Prevalence for reported (13/217, 5.99%) and cumulative predicted (24/217, 11.06%) variants of significance (11 genes) falls below that reported for non-Africans. Conversely, BRCA1, HOXB13, CDK12, MLH1, MSH2, and BRIP1 remain unimpacted. Through pathogenic ranking based on variant frequency and functionality, clinical presentation and tumour-matched biallelic inactivation, top-ranked candidates include PREX2, POLE, FAT1, BRCA2, POLQ, LRP1B and ATM. Besides notable impact of DNA polymerases, including POLG, Fanconi anaemia genes include FANCD2, FANCA, FANCG, ERCC4, FANCE and FANCI, while DNA mismatch repair genes MSH3 and PMS1 outranked known namesakes MSH6 and PMS2. This study provides insights into the spectrum of African-relevant potentially pathogenic PCa variants, highlighting much-needed gene candidates for ancestry-inclusive germline testing.
SARS-CoV-2 main protease dysregulates hepatic insulin signaling and glucose uptake : implications for post-COVID-19 diabetogenesis
Nhau, Praise Tatenda; Gamede, Mlindeli; Khathi, Andile; Sibiya, Ntethelelo (MDPI, 2025-08-04)
BACKGROUND : There is growing evidence suggesting that SARS-CoV-2 may contribute to metabolic dysfunction. SARS-CoV-2 infection is associated with systemic inflammation, oxidative stress, and metabolic dysregulation, all of which may impair liver function and promote glucose intolerance. This study investigated the role of SARS-CoV-2, specifically its Main Protease (Mpro), in accelerating insulin resistance and metabolic dysfunction in HepG2 cells in vitro. METHODS : HepG2 cells were treated with varying concentrations of Mpro (2.5, 5, 10, 20, 40, 80, and 160 nmol/mL) for 24 h to assess cytotoxicity and glucose uptake. Based on initial findings, subsequent assays focused on higher concentrations (40, 80, and 160 nmol/mL). The effects of Mpro on cell viability, protein kinase B (AKT) expression, matrix metallopeptidase-1 (MMP1), dipeptidyl peptidase 4 (DPP4), interleukin-6 (IL-6) expression, and lipid peroxidation were investigated. RESULTS : Our findings reveal that the SARS-CoV-2 Mpro treatment led to a concentration-dependent reduction in glucose uptake in HepG2 cells. Additionally, the Mpro treatment was associated with reduced insulin-stimulated AKT activation, particularly at higher concentrations. Inflammatory markers such as IL-6 were elevated in the extracellular medium, while DPP4 expression was decreased. However, extracellular soluble DPP4 (sDPP4) levels did not show a significant change. Despite these changes, cell viability remained relatively unaffected, suggesting that the HepG2 cells were able to maintain overall metabolic functions under Mpro exposure. CONCLUSIONS : This study demonstrated the concentration-dependent impairment of hepatic glucose metabolism, insulin signaling, and inflammatory pathways in HepG2 cells acutely exposed to the SARS-CoV-2 Mpro. These findings warrant further investigation to explore the long-term metabolic effects of SARS-CoV-2 and its proteases in the liver and to develop potential therapeutic approaches for post-viral metabolic complications.
Identification of physical attributes and injury risk in South African female cricketers
Postma, Tania; Rugbeer, Nivash; Pienaar, Licinda; MacMillan, Candice (Sage, 2026)
There is a global need, including in South Africa, to understand cricket-related injuries among female players better. Hence, this study investigated the relationships between anthropometric characteristics, physical fitness, kinetic factors, and in-season injury occurrence. An observational longitudinal cohort design was employed, involving 31 adult elite female cricketers from four South African franchises. Pre-season assessments included a baseline questionnaire and a standardised testing protocol. These measures were subsequently correlated with injury incidence, which was monitored weekly throughout the competitive season from October 2024 to March 2025. The in-season injury incidence was 41.90%. Multivariable modified Poisson linear regression analysis suggested that injuries were associated with higher medicine ball power throw test values, whereas shorter broad jump distances and slower 20 m sprint time are independently associated with lower injury risk. These findings suggest a performance–injury trade-off, where higher physical outputs may increase mechanical loading and injury susceptibility in the absence of appropriate load management, recovery strategies, and neuromuscular control. Accordingly, these variables should be used for athlete monitoring and profiling rather than for selection or deselection purposes. While this study has limitations, the findings contribute to the development of pre-season screening approaches that consider the balance between performance and injury risk. Further research is required to confirm these relationships and inform evidence-based injury prevention strategies.
Chrysin exhibits bone-protective effects through osteoclastogenesis inhibition : in vitro and in vivo evaluation in RAW 264.7 murine macrophages and Sprague-Dawley rats
Mason, Caitlin; Nyakudya, Trevor Tapiwa; Kasonga, Abe E. (Wiley, 2026-02)
Bone is a metabolically active tissue that is constantly being reformed and resorbed by osteoblasts and osteoclasts. Abnormal increases in osteoclast activity can lead to bone deterioration. This study investigated the potential beneficial effects of chrysin on osteoclast formation in RAW 264.7 murine macrophages and bone health in Sprague–Dawley rats. Tartrate-resistant acid phosphatase (TRAP) staining was conducted to determine the effect of chrysin on osteoclast differentiation. Quantitative polymerase-chain reaction, western blotting, and immunofluorescence were conducted to determine the molecular mechanism of chrysin in osteoclasts. Sprague–Dawley rats were fed a diet of 50 mg/kg chrysin from postnatal Day 7 until 22. On Day 130, the rats were euthanized, and their tibiae were extracted and assessed by micro-computed tomography (microCT). Chrysin reduced the number of TRAP-positive osteoclasts formed by inhibiting nuclear factor κB (NFκB) nuclear translocation. Crucial genes involved in the activation of osteoclasts were further down-regulated. Chrysin significantly increased the area, volume, and segmented bone density of the midpoint of the tibiae. The findings suggest that chrysin inhibits osteoclastogenesis via the inhibition of the NFκB signaling pathway. Chrysin further induced moderate improvements in bone health parameters. These findings suggest chrysin may exert bone-protective effects by inhibiting osteoclasts.
The reporting of injury epidemiology and risk factors in women's rugby : a scoping review
Bellingan, Lenel; Sewry, Nicola Ann; MacMillan, Candice; Viljoen, Carel (Elsevier, 2026-03)
OBJECTIVES : To map the methodology in currently available scientific literature on injury epidemiology and injury risk factors in women’s rugby union. DESIGN : A scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. METHODS : Studies reporting injury epidemiology or injury risk factors in women’s rugby union were included through a search across nine databases. Studies were screened based on the eligibility criteria, and data were extracted and analysed from the studies that were included. RESULTS : Out of 3259 records produced, 55 studies met the inclusion criteria. There was an increase in publications over the last decade, but a lack of studies across Africa and South America. Most studies (n = 17; 31 %) used unique injury definitions, and collected injury data using clinical assessment (n = 26; 47 %). Twenty-five different injury incidence measures were reported, and 33 (60 %) studies reported injury prevalence. Thirty-one (56%) studies investigated risk factors associated with injury in women’s rugby. Sixteen (52 %) studies pooled the data for males and females or rugby fifteens, sevens, and tens. CONCLUSIONS : Current research on women’s rugby injuries highlights several gaps, including limited research across certain countries, pooled data reporting, and univariate risk factor analysis without injured-uninjured player comparisons. Despite existing consensus statements for injury in female sports, studies used varied reporting of injury incidence and prevalence, with most studies using their own study definitions and reporting methods. Future research should follow published guidelines and focus specifically on women’s rugby.
Stretch-shortening cycle force–time and power–time waveform analysis indicates limitations of the contralateral limb benchmark in athletes with ACL injury
Al-Saket, Shadan; McClean, Zachary; Boon-van Mossel, Nathan; Botha, Tanita; Bayne, Helen; De Franca, Cassidy; Pasanen, Kati; Jordan, Matthew (Wiley, 2026)
Please read abstract in the article.
Flavonol-mediated modulation of angiogenesis-related microRNAs in breast cancer : a narrative synthesis of current evidence and knowledge gaps
Ramali, Dakalo Portia; Maphoso, Tania Mmapule; Mulaudzi, Thanyani Victor; Ambele, Melvin Anyasi; Maharaj, Vinesh J.; Mabeta, Peaceful Lucy; Damane, Botle Precious (Taylor and Francis, 2026-05-08)
Angiogenesis is essential for breast cancer progression and metastasis; however, the clinical impact of vascular endothelial growth factor (VEGF)-targeted therapies remains limited due to adaptive resistance and activation of compensatory angiogenic pathways. Angiogenesis-regulating microRNAs (angiomiRs) act as upstream modulators of both VEGF-dependent and VEGF-independent signaling networks contributing to vascular plasticity, immune evasion, and therapeutic escape. Dietary flavonols such as kaempferol, myricetin, and quercetin have demonstrated anti-angiogenic activity in preclinical models, yet their mechanistic interaction with angiomiR-mediated regulation in breast cancer remains poorly characterized. This narrative review critically evaluates evidence identified through structured searches of Google Scholar, PubMed, Scopus, and Web of Science (2010–2026). We synthesize mechanistic and translational findings linking flavonols to microRNA-associated regulation of hypoxia signaling, endothelial activation, extracellular vesicle communication, and vascular normalization. Available evidence indicates that flavonols may influence angiogenic pathways both directly, by inhibiting key signaling cascades, and indirectly, through modulation of non-coding RNA networks. Despite these insights, experimental validation of specific flavonol-angiomiR interactions in breast cancer remains limited. AngiomiR modulation by flavonols, therefore, represents a mechanistically grounded but predominantly preclinical concept that warrants further translational investigation to clarify its therapeutic relevance and potential applications within precision oncology in breast cancer. PLAIN LANGUAGE SUMMARY : Blood vessels are essential for supplying breast cancer tumors with nutrients and oxygen. Tumors often rely on a molecule called vascular endothelial growth factor (VEGF) to form new blood vessels. For this reason, treatments that block VEGF have been developed to slow tumor growth. However, these treatments can lose effectiveness over time because cancer cells can find alternative ways to keep their blood supply. Blood vessel formation is controlled by signals within cells. MicroRNAs (miRNAs) are very small molecules that help turn genes on or off, influencing how blood vessels develop and how tumors respond to treatment. Flavonols are naturally occurring compounds found in certain fruits and vegetables. Some studies suggest that flavonols can affect blood vessel growth, possibly by influencing miRNAs involved in this process. Although early findings are promising, most evidence comes from laboratory and preclinical studies. Further research is needed to determine whether targeting these pathways could lead to safe and effective treatment strategies for patients with breast cancer.

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