Research Articles (Medical Bioscience)

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Therapeutic efficacy of Agathosma betulina (P.J.Bergius) Pillans and Lessertia frutescens (L.) Goldblatt & J.C.Manning in promoting wound healing
(Elsevier B.V., 2026) Matthys, Chenické; Fisher, Randall; Fisher, Farzana
In developing regions such as Africa, chronic wounds represent a major healthcare challenge. Effective wound management has proven to be particularly difficult for immunocompromised patients in resource-limited areas. Although over 250 South African plant species have been identified for dermatological use, many plants, including Agathosma betulina and Lessertia frutescens, lack comprehensive scientific validation for their wound-healing potential. This study investigated the wound-healing ability, antioxidant capacity and immunomodulatory effects of A. betulina and L. frutescens extracts using an in vitro skin cell-culture model. Cell viability and migration were assessed using the MTT and scratch wound assays, respectively. Antioxidant capacity and intracellular reactive oxygen species (ROS) levels were analysed, while genetic expression of key angiogenic and inflammatory markers were quantified using qRT-PCR. Compared to L. frutescens, A. betulina demonstrated greater antioxidant capacity, significantly reducing intracellular ROS (p < 0.05), and showed higher radical scavenging activity across all biochemical assays. Both A. betulina and L. frutescens enhanced tissue repair, achieving 54% and 56% gap closure, respectively. This regenerative effect corresponds with the up-regulation of VEGF, HIF-1α, iNOS and COX-2, suggesting activation of pro-angiogenesis and inflammatory responses. Collectively, the results suggest that these extracts contribute to wound-healing by modulating distinct, complementary mechanistic pathways, primarily through oxidative stress reduction and stimulation of cell migration and angiogenesis. The findings provide important baseline data supporting the traditional use of these species in South African ethnomedicine.
Antioxidant, antidiabetic and cytoprotective activities of synthetic chloro-curcumin derivatives in C2C12 Myotubes
(Wiley-VCH Verlag, 2026) Adeleye, Adesola Oluwaseun; Oguntibeju, Oluwafemi Omoniyi; Titinchi, Salam; Opuwari, Chinyerum Sylvia
Curcumin possesses broad antioxidant and antidiabetic properties but is limited by poor stability and bioavailability. Structural modification through halogenation and heteroaromatic substitution has been explored to overcome some of these limitations. This study evaluated the antioxidant, antidiabetic and cytoprotective activities of three synthetic chloro-curcumin derivatives (compounds 1–3) in C2C12 myotubes. Antioxidant capacity was assessed using ferric reducing antioxidant power (FRAP) and diphenyl-1-picrylhydrazyl (DPPH) assays. Antidiabetic activities were evaluated by inhibition of α-amylase, α-glucosidase and porcine pancreatic lipase. Cytotoxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide (MTT) and crystal violet assays. Differentiated C2C12 myotubes were exposed to hyperglycaemic conditions (25 mM d-glucose, 48 h) before treatment with compounds 1–3 (6 h) to assess their cytoprotective potential and effects on cellular glucose utilization and uptake. All synthetic chloro-curcumin derivatives demonstrated antioxidant activity, with compound 1 exhibiting the greatest FRAP (absorbance 0.28 ± 0.02 at 700 nm, 10 µg/mL), significantly higher than ascorbic acid (0.22 ± 0.03) at the same concentration (p < 0.0001). Hyperglycaemia significantly reduced C2C12 myotube viability to 66.12% ± 1.47%, whereas treatment with the derivatives restored viability, with compound 3 increasing viability to 92.90% ± 6.77% at 0.25 µg/mL (p < 0.0001). All compounds significantly enhanced glucose utilization and uptake, with compound 3 producing the greatest increases to 130.70% ± 1.02% and 152.25% ± 4.25%, respectively, relative to the untreated control (p < 0.0001). The derivatives also exhibited moderate α-amylase and α-glucosidase inhibitory activities, with α-amylase inhibition generally comparable to acarbose, while pancreatic lipase inhibition remained comparatively weak relative to orlistat. Structural reengineering of curcumin produced derivatives that exhibit antioxidant, cytoprotective and glucose-modulating activities in a skeletal muscle cell model, highlighting their potential against oxidative stress-related metabolic disorders, particularly type 2 diabetes mellitus.
The effects of methylprednisolone on non-inflamed and inflamed In vitro brain endothelial cells
(Taylor and Francis Ltd., 2026) Siebrits, Michaela Nicole; Fisher, David; Willemse, Chontrelle; Makhathini, Khayelihle Brian
The blood-brain barrier (BBB) is primarily regulated by highly selective endothelial cells. Inflammation of the brain capillaries can compromise the BBB’s functioning. Methylprednisolone (M-Pred), a synthetic glucocorticoid, is clinically prescribed to treat systemic inflammation; however, little is known about its effect on both non-inflamed and inflamed brain capillaries. This study evaluated the effectiveness of M-Pred in ameliorating the lipopolysaccharide (LPS)-induced inflammatory response using the in vitro BBB model (bEnd.3). Cultured brain endothelial cells (BECs) were exposed to LPS (500, 1000, 2000 ng/ml) and co-treated with selected concentrations of M-Pred (10, 20, 40 µM). Cell proliferation, quantification of pro-inflammatory cytokines TNF-α and IL-1β (ELISA), and monolayer permeability (Transendothelial Electrical Resistance) were investigated. LPS decreased live cell number, increased dead cell number, and increased cell monolayer permeability; LPS increased pro-inflammatory cytokine secretion. These data confirmed the experimental functionality of the in vitro inflammatory BBB model. In the absence of inflammation, M-Pred decreased bEnd.3 cell monolayer permeability and pro-inflammatory cytokine secretion. M-Pred failed to alleviate LPS-induced inflammation across all tested concentrations. Chronic M-Pred treatment in the absence of inflammation proved detrimental to bEnd.3 cells’ physiology.
Andrographis paniculata, metformin attenuate hyperglycaemia-induced neuroendocrine toxicity via antioxidant and cholinergic modulation
(Taylor and Francis Ltd., 2026) Azu, Onyemaechi Okpara; Onanuga, Ismail Olasile; Muniru, Elijah Taiwo
Hyperglycemia is associated with neuroendocrine disruption, oxidative stress, and reproductive dysfunction, often accompanied by cholinergic imbalance and structural tissue damage. This study investigated the comparative effects of Andrographis paniculata (AP), metformin, and their combination on biochemical, hormonal, and histological alterations induced by hyperglycemia in the Wistar rats. Hyperglycemia significantly disrupted hormone profiles, increased oxidative stress and cholinesterase activities and caused degenerative changes in brain and testicles. AP and metformin each restored several parameters, but the combination therapy produced the most substantial improvements. Notably, the combination group exhibited the highest antioxidant levels, lowest cholinesterase activity, restored testosterone, and well-preserved histoarchitecture. Induced neuroendocrine and oxidative alterations. However, the metformin and AP combination therapy demonstrated superior efficacy, suggesting a synergistic interaction in mitigating neuroendocrine toxicity and oxidative stress.Metformin exerted beneficial effects on hyperglycemia-induced neuroendocrine and oxidative alterations. However, the metformin and AP combination therapy demonstrated superior efficacy, suggesting a synergistic interaction in mitigating neuroendocrine toxicity and oxidative stress.
Development of a prediction model for acute kidney injury in critically ill patients with advanced colorectal cancer based on white blood cell-related indicators
(Frontiers Media SA, 2026) Fisher, David; Li, Lingjie; Guo, YuanJin
Background – Currently, most prediction models for acute kidney injury (AKI) in patients with colorectal cancer (CRC) are only applicable to postoperative situations, or rely on complex machine learning algorithms. There is currently no simple and feasible AKI prediction model for severely ill patients with advanced CRC. Objective – This study endeavors to devise and validate a novel clinical risk prediction model utilizing white blood cell (WBC)-related indicators to forecast AKI in critically ill patients with advanced CRC. Methods – A retrospective cohort study design was employed. The training cohort was derived from the eICU Collaborative Research Database, and the external validation cohort came from the Intensive Care Unit (ICU) of Wuhan Union Hospital. To screen for independent predictors of AKI and develop a new risk score model using multivariable logistic regression analysis. The assessment of model performance was conducted using receiver operating characteristic (ROC) curve analysis and compared with other scoring systems. The associations between different risk groups and survival outcomes as well as WBC counts were visualized using a heatmap. Kaplan-Meier survival analysis was used to compare in-hospital survival rates between the two groups. ROC curve analysis and decision curve analysis (DCA) served to evaluate the model’s predictive ability for in-hospital mortality. Subgroup analysis was applied to assess the consistency of this model across different critically ill cohorts with advanced CRC.
Protective effects of moringa oleifera aqueous leaf extract on Tm3 Leydig cells against hydrogen peroxide-induced oxidative stress
(Wiley-VCH Verlag, 2026) Mohlala, Kutullo; Offor, Ugochukwu; Opuwari, Chinyerum Sylvia
Introduction: Moringa oleifera (M. oleifera) is a medicinal plant rich in dietary antioxidants that may protect reproductive cells from oxidative stress-induced damage and male fertility problems. This study investigated M. oleifera aqueous leaf extracts (ALE) effects on TM3 Leydig cells exposed to hydrogen peroxide (H2O2). Methods: M. oleifera ALE and ascorbic acid (10−1000 µg/mL) were assessed for antioxidant activity. TM3 Leydig cells were exposed to various concentrations of M. oleifera ALE (0−1000 µg/mL) or α-tocopherol (50 µM) for 24 h, alongside 200 µM H2O2, with or without hCG (4 ng/mL). Cell viability, testosterone production, mitochondrial membrane potential (MMP), total protein and oxidative stress parameters (reactive oxygen species [ROS], superoxide dismutase [SOD], reduced glutathione [GSH], total antioxidant capacity [TAC] and lipid peroxidation [MDA]) were assessed. Results: Ascorbic acid demonstrated superior DPPH radical scavenging and FRAP activity compared to M. oleifera ALE at most concentrations (p < 0.0001). H2O2 (200 µM) exposure significantly reduced cell viability, MMP, SOD, GSH and TAC levels, while increasing ROS and MDA levels (p < 0.05). Treatment with M. oleifera ALE or α-tocopherol significantly increased cell viability, total protein, SOD activity and GSH levels while reducing ROS and MDA compared to H2O2 control (p < 0.05). However, testosterone levels remained unchanged (p > 0.05). Conclusions: M. oleifera ALE effectively protects the TM3 Leydig cells from H2O2-induced oxidative stress by restoring the redox balance, though unchanged testosterone levels suggest limitations in using TM3 Leydig cells for assessing testosterone synthesis.
Beyond viral control: tenofovir's hidden impact on blood–brain barrier endothelial cells
(John Wiley and Sons Inc, 2026) Behardien, Saarah; Makhathini, Khayelihle Brian; Willemse, Chontrelle; Fisher, David
The blood–brain barrier (BBB) is a dynamic endothelial interface that protects the brain from harmful agents while regulating molecular exchange. Human immunodeficiency virus (HIV) compromises BBB integrity, promoting neurological damage. Antiretroviral (ARV) therapies suppress HIV replication, preventing immune system deterioration and progression to AIDS. Although Tenofovir-based ARV regimens are vital for HIV treatment and prevention, their impact on cerebrovascular function remains unclear. Aim: This study examined Tenofovir's effects on murine brain endothelial cells using an in vitro BBB model. Methods: Brain endothelial cells (bEnd.5) were treated with Tenofovir Disoproxil Fumarate (TDF; 9.8–98 ng/mL) or Tenofovir Alafenamide (TAF; 1–10 ng/mL) for 24–96 h. Cell proliferation, cell cycle progression (via flow cytometry) and monolayer permeability (via Transendothelial Electrical Resistance) were evaluated. Results: Both TDF and TAF treatments suppressed cell division by S-phase disruption of the cell cycle and increased monolayer permeability. Conclusion: These findings suggest that prolonged TDF or TAF exposure compromises BBB integrity by inhibiting endothelial cell division and altering barrier function, which could have implications for HIV-ARV-induced neurodegeneration in individuals receiving long-term Tenofovir-based therapy.
Chitosan–hyaluronic acid engineered polycaprolactone nanoparticles enhance curcumin antiplasmodial activity and preserve blood–brain barrier integrity
(Taylor&Francis, 2026) Mwajombe, James; Maphasa, Retsepile E; Willemse, Chontrelle
Cerebral malaria (CM) is a severe neurological complication of Plasmodium falciparum infection associated with endothelial activation, neuroinflammation, and disruption of the blood–brain barrier (BBB). While curcumin (Cur) possesses antiplasmodial and anti-inflammatory properties, its therapeutic potential is limited by poor aqueous solubility, rapid metabolism, and insufficient brain bioavailability. In this study, we hypothesized that polysaccharide-driven surface engineering could regulate nanoparticles (NPs) interfacial properties to improve BBB compatibility and antiplasmodial efficacy. Cur-loaded polycaprolactone (PCL) NPs were fabricated through a single-emulsion solvent evaporation technique and sequentially coated with chitosan (CS) and hyaluronic acid (HA) to establish defined structure-property relationships. The resulting nanoformulations were characterized for particle size, surface charge, polysaccharide deposition, encapsulation efficiency (EE), and release kinetics. In-vitro biological performance was evaluated through hemocompatibility, brain endothelial cell viability, BBB integrity through transendothelial electrical resistance measurements, and in-vitro antiplasmodial activity against P. falciparum FCR3. Dual polysaccharide coating produced stable NPs with controlled size, enhanced surface charge, sustained Cur release, and significantly improved endothelial compatibility compared with free Cur and non-hyaluronic-acid formulations. Notably, HA coating strengthened BBB integrity and enhanced antiplasmodial potency. These findings demonstrate that CS– HA surface functionalization governs critical structure-property relationships, highlighting the potential of polysaccharide-engineered nanocarriers for adjunctive CM drug delivery.
Biomonitoring toxic element exposure in Sudanese artisanal gold miners using µ-PIXE and LIBS hair analysis technique
(Elsevier B.V., 2026) Eisa, Mohamed; Mars, Johan André; Cloete, Karen
Artisanal mining has become a lucrative sector due to rising global demand and prices for rare and rare-earth elements. In Sudan, this informal industry supports rural livelihoods but lacks effective regulation and occupational safety. The absence of protective equipment exposes miners to mercury vapor, dust, and other toxic substances, posing serious health and environmental risks. This study applies Particle-Induced X-ray Emission (PIXE) and Laser-Induced Breakdown Spectroscopy (LIBS) to analyse toxic and essential trace elements in miners’ hair, used as a non-invasive biological indicator of chronic exposure. Elements detected include S, Cl, K, Ca, Ti, Mn, Fe, Cu, Zn, Br, Sr, and Pb. Multivariate analysis through Principal Component Analysis (PCA) and binarization reveals elemental correlations and exposure patterns. The integrated PIXE–LIBS approach offers a robust framework for biomonitoring, occupational safety improvement, and sustainable artisanal mining practices in Sudan.
Computed tomography investigation of the cribriform plate and associated structures in Kwazulu-Natal population: dimensional, morphometric and sex-related variations
(Springer Nature, 2026) Hlatshwayo, Nondumiso Ngiphiwe; Olojede, Samuel Oluwaseun; Rennie, Carmen Olivia; Azu, Onyemaechi Okpara; Lawal, Sodiq Kolawole; Naidu, Edwin Coleridge Stephen
Background: The cribriform plate is a crucial small bony structure in the anterior cranial fossa that plays a key role in surgical procedures and forensic identification. Despite its importance in olfaction, there is limited research on its morphological, morphometrical variations and sexual dimorphism in African populations, prompting a study to investigate these aspects in a selected KwaZulu-Natal population. Methods: Fifty-five (55) CT scans of the cribriform plate were assessed from the axial and coronal views. Morphology of the cribriform plate was recorded based on the Kawahara method, morphometry and related structures of the cribriform plate were investigated to identify any sexual dimorphism. Result: Type IV plates were most common in males, while Types I and II dominated among females. Males generally had larger measurements, though females showed longer and deeper right-sided plates. The anterior ethmoidal artery (AEA) was typically located below the skull base in both sexes. The teardrop type of crista galli was most common type in both sexes. Keros Type II was most prevalent in both sexes. On both sides of both sexes, the AEA was commonly located below the skull base. Ethnic differences showed Black individuals had longer right-sided plates, while White females had greater width and depth. Conclusions: This study found no statistically significant differences in the morphology and morphometry of the cribriform plate within the KwaZulu-Natal population. However, the observed variations may have clinical implications for surgical planning, particularly in procedures involving the anterior skull base.
Dihydromyricetin a potential candidate for the treatment of cholestatic liver injury via inhibition of the NLRP3 inflammasome
(Elsevier B.V., 2026-05-28) Fisher, David; Zhang, Hao; Dang, Yiping; Guo, Yuanjin; Hien, Nguyen Thi Thu
Objective Cholestatic liver injury is a hepatic disorder caused by abnormal bile acid metabolism and biliary obstruction, with limited clinical treatment options. Activation of the NLRP3 inflammasome is recognized as a key pathogenic mechanism. This study aims to investigate whether DHM, a natural flavonoid, alleviates cholestatic liver injury by modulating the NLRP3 inflammasome and to elucidate its underlying mechanism. Methods The protective effects of DHM were evaluated both in vivo (using an ANIT-induced mouse cholestasis model) and in vitro (using an LPS plus nigericin-induced ANA-1 macrophage model). Assessments included liver function, histopathology, inflammatory cytokine levels, and the expression of key molecules in the NLRP3 inflammasome pathway (NLRP3, ASC, Caspase-1, GSDMD, IL-1β, IL-18). Cell viability was measured by CCK-8 assay, while molecular expression was analyzed via Western blot, qPCR, ELISA, and immunofluorescence. The specific role of NLRP3 was confirmed using siRNA knockdown. Results DHM demonstrated good safety profiles in both experimental settings. In the ANIT-induced cholestatic model, DHM significantly improved liver function markers (ALT, AST, ALP, TBIL), reduced histopathological damage, and suppressed the expression and activation of key components in the NLRP3 inflammasome pathway. In vitro studies further confirmed that DHM exerts its anti-inflammatory effects by inhibiting ROS burst, preventing NLRP3 inflammasome assembly, and blocking the subsequent pyroptosis process. NLRP3 knockdown experiments indicated that the anti-inflammatory effect of DHM is highly dependent on the presence of NLRP3. Conclusion DHM alleviates cholestatic liver injury by inhibiting the activation of the NLRP3 inflammasome in macrophages, a mechanism involving multi-level anti-inflammatory and antioxidant pathways. This study provides a theoretical foundation for DHM as a potential therapeutic agent against cholestatic liver injury and identifies the NLRP3 inflammasome as its critical molecular target.
Exploring medicinal plants used by South African bush doctor communities for wound healing purposes: a follow-up investigation
(Elsevier, 2026) Ndlovu, Banele; Fisher, Farzana
Traditional medicine is an essential component of healthcare in South Africa, where medicinal plants serve as a primary therapeutic source. Despite the region's rich biodiversity and long history of use, the indigenous knowledge of a small group of traditional “bush doctors” in the Western Cape (WC), including their methods for treating wounds, is poorly documented and at risk of being lost. As a follow-up to previous research, this study aimed to identify, document and analyse the medicinal plants used by practising bush doctors for wound care. The data was analysed to assess plant diversity, dominant families and frequency of use, providing a foundation for preserving indigenous knowledge and supporting future pharmacological validation. Given the small size of this practitioner population, a snowball sampling approach was used to recruit 20 bush doctors in the WC from this established cohort of 32 healers, using a modified protocol. The investigation documented 35 medicinal plant species representing 21 botanical families. The Asphodelaceae family was the most represented, confirming its importance in the regional pharmacopoeia. Species with the highest frequency of citation (FC), reflecting strong clinical relevance, included Aloe ferox (FC=16) and Eucomis autumnalis (FC=13). In contrast, species such as Galenia africana and Xerophyta retinervis had low FC values among participants and remain unexplored in the literature. These findings add great insight into ethnomedicinal knowledge preserved by bush doctors for wound treatment and help safeguard an important record of this endangered cultural heritage. Moreover, this study provides a framework for evaluating the pharmacological potential of both popularly cited and less common plant species used by bush doctors. This targeted approach can accelerate the development of new, evidence-based wound therapies.
The effects of cynaroside on lipid metabolism and lipid-related diseases: a mechanistic overview
(Frontiers Media SA, 2025) Cen, Chenyi; Fisher, David; Li, Jiahuan
Cynaroside is a natural flavonoid compound, which is widely found in plants. It has the effects of lowering fat, anti-diabetes, anti-inflammatory, antioxidant, anticancer, antibacterial and liver protection. Recent studies have shown that cynaroside regulates fat metabolism through multiple mechanisms, including modulating lipase activity, enhancing gut health and suppressing inflammatory responses. These processes involve the NF-κB, NLRP3 and JAK/STAT inflammatory pathways, and other signaling pathways. By controlling complications associated with abnormal fat metabolism, cynaroside has been demonstrated therapeutic effects on obesity, fatty liver disease, type 2 diabetes and other conditions. Therefore, it shows great potential as an alternative treatment for lipid metabolism-related diseases. However, although the extraction method of cynaroside has been mature, the study of its monomer is still in the initial stage, and there is no complete human efficacy and safety evaluation report. This paper introduces the molecular structure, source and pharmacological action of cynaroside, and systematically reviews the mechanism of regulating lipid metabolism of cynaroside, so as to expand the application value of cynaroside. In addition, it also puts forward the challenges, solutions and future research directions in the clinical application of cynaroside.
Raman spectroscopy-based metabolic fingerprinting of seminal plasma reveals distinct profiles among fertile men
(Elsevier Inc., 2026) Gilany, Kambiz; Jafarzadeh, Naser; Hosseini, Elham; Bi Bi Fatemeh Nobakht, M.Gh.; Henkel, Ralf; Amirjannati, Negin; Tayanloo-Beik, Akram
Traditional semen analysis provides valuable insights into male fertility but fails to capture the full biochemical complexity underlying sperm function. This study explored metabolic variability among fertile men using Raman spectroscopy to analyze the seminal plasma metabolome. In a cross-sectional design, semen samples were collected from 29 clinically fertile men (n = 29) and analyzed according to WHO guidelines. Metabolites were extracted using methanol/water (3:1), and Raman spectroscopy was applied to generate metabolic fingerprints of the seminal plasma. Multivariate statistical analyses, including Principal Component Analysis (PCA) and Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA), revealed two distinct metabolic subgroups among fertile men. Significant differences were identified in key biochemical features such as phenylalanine, alcohols, alkanes, aldehydes, and amides. The OPLS-DA model demonstrated excellent classification performance (R2X = 0.942, R2Y = 0.992, Q2 = 0.987), indicating robust subgroup separation and high predictive validity. These findings suggest that even within normozoospermic individuals, seminal plasma exhibits substantial metabolic heterogeneity. Raman-based metabolomic fingerprinting thus represents a promising complementary diagnostic tool to conventional semen analysis, offering deeper insight into male reproductive physiology and providing a foundation for future biomarker discovery in fertility research.
Progressive hypoxia exacerbates breast cancer metastasis by paracrine modulation of the blood-brain barrier endothelium
(Springer, 2026) Brinders, Kyle Alan; Fisher, David; Willemse, Chontrelle; Makhathini, Khayelihle Brian
Cancer remains a major global concern, with metastasis responsible for most cancer-related deaths. Disseminated cancer cells become circulating tumour cells (CTCs) that travel until arresting at preferential vascular sites such as the blood-brain barrier (BBB), where they cross into the central nervous system (CNS). Given that the BBB robustly maintains CNS homeostasis, the mechanism whereby CTCs metastatically enter the brain is largely unknown. The triple-negative breast cancer (TNBC) (MDA-MB-231 cell line) cells were cultured under normoxic (21% O2), physioxic (5% O2), and hypoxic (1.5-2% O2) conditions to generate conditioned media (CM). Diluted CM was used to treat brain endothelial cells (BECs: bEnd.5 cell line). Endothelial suppression of cell division was assessed using the trypan blue exclusion assay. Morphological changes and an abnormality index were evaluated using hematoxylin and eosin (H&E) staining. Transendothelial electrical resistance (TEER) measured the BEC monolayer integrity following CM exposure. Comparatively, all oxygen-derived CM suppressed BEC suppression of cellular division; however, hypoxic-derived CM was most severe, reducing cell division by 67.7% at 96 h. H&E staining similarly showed that hypoxic-derived CM induced an abnormality rate of 980 abnormalities per 1 000 cells. TEER measurements demonstrated that the hypoxic-derived CM overwhelmed BEC homeostatic mechanisms, significantly increasing monolayer permeability. A clear pattern of progressive dysfunction correlated with decreasing oxygen tension in MDA-MB-231 cell cultures. While the normoxic and physioxic CM had comparable effects, hypoxic-derived CM elicited exacerbated responses, with substantial impairment detectable as soon as 24 h. These findings suggest hypoxic tumour secretomes overwhelm the endothelial regulatory mechanisms, leading to BEC dysfunction and, ultimately, BBB compromise.
Adverse effects of nicotine on human sperm nuclear proteins
(Korean Society for Sexual Medicine and Andrology, 2025) Firouzabadi, Amir Masoud; Henkel, Ralf; Niaki, Maryam Tofighi; Fesahat, Farzaneh
The effects of smoking on human health have long been documented. However, only a few studies have highlighted the direct effects of nicotine on sperm function. Nicotine, as a chemical compound found in tobacco, has been shown to modulate different aspects of spermatogenesis and sperm functions. Nicotine can lead to a reduction in the number of sperm, their motility and functionality. It can change the molecular expressions involved in sperm function, including genes encoding sperm nuclear proteins. The most important nuclear proteins that play a critical role in sperm function are known as H2B histone family, member W, testis-specific (H2BFWT), transition protein 1 (TNP1), transition protein 2 (TNP2), protamine-1 (PRM1), and protamine-2 (PRM2). These proteins are involved in sperm chromatin condensation, which in turn affects fertilization and embryonic development. Any alteration in the expression of these genes due to nicotine exposure/usage may lead to adverse implications in couples’ fertility and the health of future generations. Since research in this area is still relatively new, it underscores the importance of understanding the potential side effects of environmental factors such as nicotine on reproductive health.
Optimizing boar epididymal sperm preservation: comparative analysis of slicing float-up vs. flushing and bts vs. andromed® extenders on sperm motility and morphometry traits
(Science Publications, 2026) Thema, Angelinah; Van der Horst, Gerhard; Maree, Liana
Epididymal sperm collection represents a valuable strategy for preserving genetics from deceased or castrated boars of superior breeding value. The two primary collection methods slicing float-up (high sperm yield) and flushing (low blood contamination risk) differ in sperm recovery efficiency, while semen extenders provide cryoprotective nutrients that protect against cold shock during preservation. This study compared the effects of slicing float-up versus flushing collection methods and Beltsville Thawing Solution (BTS) versus Andromed® extenders on motility and morphometric characteristics of boar epididymal sperm. Epididymides were collected from 40 testes obtained at a local slaughterhouse and processed within 30 minutes post-slaughter at 5°C. Sperm retrieved from the cauda epididymis were diluted with BTS or Andromed® and analyzed using computer-assisted sperm analysis (CASA) for motility assessment and morphometric evaluation. The flushing-Andromed® combination produced the lowest total (29.7%), progressive (4.9%), and rapid (1.24%) motility values. Conversely, slicing float-up with BTS yielded the highest total (85.0%), progressive (57.7%), and rapid (31.8%) motility. Andromed® treatment induced decreased sperm head diameter and acrosomal morphology alterations, consistent with premature acrosome reaction, thereby reducing sperm head dimensions. Sperm head morphometric parameters remained within acceptable reference ranges across all treatment groups (length: 8.2-8.9 µm; perimeter: 18.2-19.9 µm; width: 4.1-4.6 µm; area: 34.8-38.6 µm2). These findings recommend slicing float-up with BTS extender as the optimal protocol for boar epididymal sperm collection and short-term preservation, with implications for swine genetic resource conservation.
A core outcome set for future male infertility research: development of an international consensus
(Elsevier Inc, 2025) Rimmer, Michael P; Howie, Ruth A; Anderson, Richard A; Barratt, Christopher L.R; Barnhart, Kurt T; Beebeejaun, Yusuf; Bertolla, Ricardo Pimenta; Bortoletto, Pietro; Brannigan, Robert E; Cantineau, Astrid E.P; Caroppo, Ettore; Collura, Barbara L; Coward, Kevin; Duncan, William Colin; Eisenberg, Michael L; Gellatly, Steven A; Geyter, Christian De; Goulis, Dimitrios G; Henkel, Ralf R; Ho, Vu N.A; Hussein, Alayman F; Huyser, Carin; Kadijk, Jozef H; Kamath, Mohan S; Khashaba, Shadi; Khattak, Hajra; Kobori, Yoshitomo; Kopeika, Julia; Kucuk, Tansu; Luján, Saturnino; Matsaseng, Thabo Christopher; Mathur, Raj S; McEleny, Kevin; Mitchell, Rod T; Mol, Ben W; Murage, Alfred M; Ng, Ernest H.Y; Pacey, Allan; Perheentupa, Antti H; Du Plessis, Stefan; Rives, Nathalie; Sarris, Ippokratis; Schlegel, Peter N; Shabbir, Majid; Śmiechowski, Maciej; Subramanian, Venkatesh; Sunkara, Sesh K; Tarlarzis, Basil C; Tüttelmann, Frank; Vail, Andy; van Wely, Madelon; Vazquez-Levin, Mónica H; Lan N. Vuong; Wang, Alex Y; Wang, Rui; Duffy, James M.N; Farquhar, Cindy M; Niederberger, Craig
Objective: To develop a core outcome set for male infertility trials. Design: A two-round Delphi survey and consensus development workshop were undertaken with healthcare professionals, researchers and clinicians globally. Subjects: 334 participants from 39 countries participated in the Delphi Survey, while 44 participants from 21 countries participated in the consensus development workshop. Exposure: NA Main Outcome Measures: The core outcome set for male infertility trials has been developed by the inclusion of specific male-factor outcomes in addition to the general infertility core outcome set which focuses on female-factor outcomes. Results: The outcomes identified include assessment of semen using the World Health Organisation recommendations for semen analysis; viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancies); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Although not a requirement as part of the core outcome set, other outcomes were identified as potentially useful in certain study settings. Conclusion: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes, which are inconsistently reported at present. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set for male infertility trials.
Optimizing boar epididymal sperm preservation: comparative analysis of slicing float-up vs. flushing and bts vs. andromed® extenders on sperm motility and morphometry traits
(Science Publications, 2026) van der Horst, Gerhard; Maree, Liana; Thema, Angelinah
Epididymal sperm collection represents a valuable strategy for preserving genetics from deceased or castrated boars of superior breeding value. The two primary collection methods slicing float-up (high sperm yield) and flushing (low blood contamination risk) differ in sperm recovery efficiency, while semen extenders provide cryoprotective nutrients that protect against cold shock during preservation. This study compared the effects of slicing float-up versus flushing collection methods and Beltsville Thawing Solution (BTS) versus Andromed® extenders on motility and morphometric characteristics of boar epididymal sperm. Epididymides were collected from 40 testes obtained at a local slaughterhouse and processed within 30 minutes post-slaughter at 5°C. Sperm retrieved from the cauda epididymis were diluted with BTS or Andromed® and analyzed using computer-assisted sperm analysis (CASA) for motility assessment and morphometric evaluation. The flushing-Andromed® combination produced the lowest total (29.7%), progressive (4.9%), and rapid (1.24%) motility values. Conversely, slicing float-up with BTS yielded the highest total (85.0%), progressive (57.7%), and rapid (31.8%) motility. Andromed® treatment induced decreased sperm head diameter and acrosomal morphology alterations, consistent with premature acrosome reaction, thereby reducing sperm head dimensions. Sperm head morphometric parameters remained within acceptable reference ranges across all treatment groups (length: 8.2-8.9 µm; perimeter: 18.2-19.9 µm; width: 4.1-4.6 µm; area: 34.8-38.6 µm2). These findings recommend slicing float-up with BTS extender as the optimal protocol for boar epididymal sperm collection and short-term preservation, with implications for swine genetic resource conservation.
The impact of diabetes mellitus-related oxidative stress on male fertility: a review
(John Wiley and Sons Inc, 2025) Dena, Simon Mwaringa; Adeleye, Adesola Oluwaseun; Mohlala, Kutullo; Langa, Bridget Cebisile; Opuwari, Chinyerum Sylvia
Diabetes mellitus (DM) significantly impairs male reproductive health, largely through hyperglycemia-induced oxidative stress (OS). Elevated glucose activates detrimental metabolic pathways, notably the polyol pathway, which depletes antioxidant defenses and generates reactive oxygen species (ROS). This oxidative burden damages spermatozoa, leading to reduced motility, abnormal morphology, DNA fragmentation, and disrupted membrane integrity. OS also compromises the hypothalamic–pituitary–gonadal axis, lowering testosterone synthesis and impairing spermatogenesis. The formation of advanced glycation end products (AGEs) and chronic inflammation further exacerbate Leydig and Sertoli cell dysfunction, microvascular injury, and testicular apoptosis. Clinical evidence consistently links DM to deteriorated semen parameters, hormonal imbalances, and reduced natural conception rates, with poorer outcomes in assisted reproductive technologies. Obesity and metabolic syndrome, common comorbidities in DM, amplify oxidative stress and further impair fertility potential. While seminal plasma contains enzymatic and non-enzymatic antioxidants, these defenses are often insufficient in diabetic men. Targeted interventions, including antioxidant therapy, lifestyle modifications, glycemic control, and management of comorbidities, offer promise in mitigating oxidative damage. This review synthesizes current evidence on the molecular, endocrine, and clinical consequences of DM-related oxidative stress on male fertility, underscoring the need for integrated management strategies to preserve reproductive function in diabetic men.

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