Kamoru Ademola Adedokun

Plant-derived natural products are essential and prominent contributors to drug discovery, especially as anticancer agents. Medicinal plants used in alternative therapy are often obscured by poor definitions of the underlying mechanisms behind their bioactivity. In this study, we investigated the cytotoxic and mechanistic effects of an enriched bioactive fraction derived from Mondia whitei. Bioactivity-guided fractionation was performed using C18 solid-phase extraction. The cytotoxic effects were evaluated using the MTT assay, while cellular morphology and mechanistic pathways were examined through microscopy, acridine orange staining, cathepsin-based assay, and immunoblotting of apoptosis- and autophagy-related proteins. Chemical profiling of the fraction was conducted using GC–MS analysis. The enriched fraction exhibited enhanced cytotoxicity at low microgram concentrations. Morphological assessment revealed prominent cytoplasmic vacuolation, while acridine orange staining indicated the accumulation of acidic vesicles. Cathepsin-based assays and immunoblot analysis of LC3-I/II confirmed lysosomal involvement and autophagy perturbation, whereas increased p62 levels suggested disruption of the autophagy–lysosome perturbation. In parallel, activation of intrinsic apoptosis was evidenced by the increased expression of caspase-9 and caspase-3. GC–MS profiling tentatively identified lupeol and cis-vaccenic acid as the major constituents of the fraction. The results from these studies demonstrate that the enriched fraction of Mondia whitei induced vacuolation-associated cytotoxicity through autophagy–lysosome perturbation and caspase-dependent apoptosis, providing mechanistic insight into its anticancer potential.

Exosomes, the nanoscale extracellular vesicles released by most cell types, are increasingly recognized as potent regulators of immune communication. This review provides a mechanistic and integrative perspective on the immunological functions of exosomes, highlighting their roles in both immune stimulation and suppression across physiological and pathological contexts. We begin by dissecting the molecular architecture of exosomes—focusing on immunologically active components such as ESCRT proteins, tetraspanins, RabGTPases, and lipid mediators—and explore how these elements contribute to exosome biogenesis and immune function. The review further examines exosomal cargo enriched in pattern recognition receptor (PRR) ligands, including damage-associated molecular patterns (DAMPs), pathogen-associated molecular patterns (PAMPs), and microRNAs, and discusses how these molecules activate toll-like receptors and other PRRs to orchestrate innate immune responses through endosomal and cytosolic signaling cascades. Special emphasis is given to MHC-mediated antigen presentation via exosomes, distinguishing classical and non-canonical pathways and their interplay with downstream immune signaling mechanisms. We present a dichotomous view of exosomes as both immunostimulatory and immunosuppressive agents, detailing their roles in T-cell cross-priming, dendritic cell maturation, tumor progression, and metastasis. Moreover, we review pathogen-driven hijacking of exosomal pathways and their implications for immune evasion. Finally, we discuss the therapeutic promise of exosomes in cancer immunotherapy and vaccine design, advocating for their strategic integration into next-generation immunomodulatory approaches.

Background: HIV/AIDS remains a global health crisis marked by profound regional disparities. Sub‐Saharan Africa (SSA) bears the greatest burden but has achieved partial progress in reducing its impact. Within the region, however, heterogeneous patterns of progress and setbacks persist, underscoring ongoing challenges in epidemic control and suggesting potential misalignment in the focus of current interventions. Methods: We analysed HIV/AIDS disability‐adjusted life years (DALYs) from 2016 to 2021, disaggregated at subregional and local levels across continents using Global Burden of Disease (GBD) estimates. This high‐resolution analytical approach enabled the identification of nuanced temporal trends and geographic hotspots requiring urgent intervention, with particular emphasis on SSA. Findings: Southern SSA recorded a 20.8% decline in DALY rates, from 18 280 to 14 470 per 100 000 population, while eastern, western and central SSA each achieved reductions exceeding 27%. Despite these gains, some areas maintained alarmingly high burdens, including Lesotho (26 516), eastern Cape, South Africa (25 004), Eswatini (22 944) and Homa Bay, Kenya (21 747). Outside Africa, the Caribbean achieved a 29% decline, whereas North America and Europe registered more modest improvements. In Asia, several Indian states recorded up to 27% reductions, contrasted by increases in parts of Pakistan, Mongolia, China and Yemen. Interpretation: Marked regional contrasts highlight the need to reframe HIV/AIDS control strategies at the subregional level. Despite setbacks linked to the COVID‐19 pandemic, targeted, data‐driven interventions in persistent high‐burden areas remain essential to sustain progress and accelerate the global HIV/AIDS response. Yet, just as encouraging transitions are beginning to take hold across several parts of SSA, the continent is now confronted—suddenly and unprepared—for a renewed challenge: a decline in HIV/AIDS funding.

Human metapneumovirus (hMPV), a prominent respiratory pathogen with a history of global circulation spanning over seven decades, has re-emerged as a critical public health concern. Since late 2024, there has been a significant global surge in hMPV cases, first reported in China and subsequently spreading to countries such as the USA, India, and Pakistan. Although the World Health Organization (WHO) and Chinese authorities have downplayed the severity of this increase, attributing it to expected seasonal trends, the growing prevalence of hMPV raises alarm due to its potential to cause severe respiratory illness. Particularly at risk are vulnerable populations, including children, the elderly, and immunocompromised individuals. Recent epidemiological data indicate a 17% increase in pediatric hMPV-related hospital admissions in the first quarter of 2025 compared to the same period in 2023 in both the USA and China, with similar trends observed among elderly and immunocompromised patients. These findings highlight the urgent need for enhanced surveillance and public health preparedness. This study explores the immunopathogenesis of hMPV, which is marked by its immune evasion strategies, including inhibition of interferon signaling pathways and suppression of key antiviral cytokines. These mechanisms enable persistent viral replication and contribute to severe respiratory pathologies. Moreover, dysregulated cytokine production, particularly the overexpression of pro-inflammatory cytokines, exacerbates immune responses and leads to tissue damage, further worsening clinical outcomes in vulnerable populations. This review delves into the complex immune dynamics of hMPV infection, highlighting impaired dendritic cell activation and suboptimal T-cell responses, which hinder long-lasting immunity, especially in immunocompromised individuals. The virus's high mutation rate (6.95 to 7.12 × 10⁻⁴ substitutions/site/year), along with its immune evasion mechanisms and significant cytopathic effects, further enhances its pathogenicity. The global spread of hMPV underscores its resilience and adaptability, making it a growing threat to public health. As hMPV-related immunology becomes increasingly relevant amid this new outbreak, this review emphasizes the need for robust genomic surveillance, targeted antiviral therapies, and vaccine development. Drawing on lessons from COVID-19 and Ebola, the importance of early detection systems, antiviral research, and targeted immunization strategies is paramount to mitigating the impact of this emerging viral threat. With insights from the current study, future immunological approaches should prioritize the development of novel vaccine candidates, enhancement of monoclonal antibody therapies, and improvement of host-directed immunomodulatory treatments. By integrating these strategies, global health systems can effectively respond to future hMPV outbreaks and safeguard vulnerable populations.

Despite the tremendous clinical successes recorded in the landscape of cancer therapy, tumor heterogeneity remains a formidable challenge to successful cancer treatment. In recent years, the emergence of high-throughput technologies has advanced our understanding of the variables influencing tumor heterogeneity beyond intrinsic tumor characteristics. Emerging knowledge shows that drivers of tumor heterogeneity are not only intrinsic to cancer cells but can also emanate from their microenvironment, which significantly favors tumor progression and impairs therapeutic response. Although much has been explored to understand the fundamentals of the influence of innate tumor factors on cancer diversity, the roles of the tumor microenvironment (TME) are often undervalued. It is therefore imperative that a clear understanding of the interactions between the TME and other tumor intrinsic factors underlying the plastic molecular behaviors of cancers be identified to develop patient-specific treatment strategies. This review highlights the roles of the TME as an emerging factor in tumor heterogeneity. More particularly, we discuss the role of the TME in the context of tumor heterogeneity and explore the cutting-edge diagnostic and therapeutic approaches that could be used to resolve this recurring clinical conundrum. We conclude by speculating on exciting research questions that can advance our understanding of tumor heterogeneity with the goal of developing customized therapeutic solutions.

Objectives: Recent molecular studies show that breast cancer (BC) is a heterogeneous disease, and several molecular changes may accumulate over time to influence treatment response. As a result, employing reliable molecular biomarkers to monitor these modifications may help deliver personalised treatment. However, this may be unrealistic in the resource-limited parts of the world. Thus, this study aimed to investigate the expression pattern of hormone receptors and p53 tumour suppressor using immunohistochemistry (IHC) in BC compared to the traditional tumour grade. Methods: In total, 205 cases were investigated, and the Modified Bloom-Richardson score system was adopted in grading the tumours. The tissue sections of the cases were stained with specific primary antibodies at dilutions of 1:60 for oestrogen receptors (ER) and progesterone receptors (PR), 1:350 for the human epidermal growth factor (HER-2/neu) and 1:50 for p53. Results: Invasive ductal carcinoma of no-specific type (n = 190, 92.7%) was predominant and grade II tumour (n = 146, 71.2%) was the most frequent. Hormone receptors ER (n = 127) and PR (n = 145) had 62.0% and 70.7% positive cases, respectively; 34.1% (n = 70) were positive for HER-2/ neu, while 76.1% (n = 156) were positive for p53. Significant associations between Nottingham grade and expression patterns of ER (P <0.01), PR (P <0.001), HER-2/neu (P <0.001) and p53 (P = 0.001) were observed. Conclusion: Nottingham grade had a high degree of concordance with the patterns of expression of hormone receptors, HER- 2/neu and p53, suggesting that it may play an important role in connection with the predictive and prognostic biomarkers for BC.

Background: In low-and middle-income countries, high burden of cervical cancer is associated with human papillomavirus (HPV) due to poor screening and diagnostic methods at early stage. Reports showed that there are discrepancies in data correlating HPV-infection with development of cervical cancer while the functional roles of P53 oncogenic mutation are controversial. Furthermore, the molecular pathogenesis of multiple HPV-genotypes remains an open question. Thus, advancing investigations on HPV-associated cervical abnormalities would add to early diagnostic precision. Methods: Two hundred (n=200) cervical samples were collected from apparently healthy, active adult women following an ethical approval. Laboratory analyses were conducted through cytological assessment and histochemistry screening using the Papanicolaou smear. PCR methods were used to characterize HPV-DNA genotypes and P53 gene mutations. Positive cervical dysplasia cases were matched with HPV-DNA, and the HPV-genotypes were used to evaluate the prevalence of various HPV-subtypes and the risk of cervical cancer. Results: Twenty-six (n=26) cervical dysplasia and fifty-one (n=51) HPV+ were identified comprising single and multiple genotypes. While nine cases (n=9) showed p53 gene mutation with concurrent multiple high-risk HPV (hrHPV) genotypes, none of the single hrHPV genotypes had p53 mutation. More so, individuals with coexisting p53 mutation and multiple hrHPV-genotypes already manifesting cervical dysplasia were 22.2% of the group, while 77.8% had normal cervical architecture, the fate of whom was unknown during investigation. There was a higher cervical dysplasia among those with HPV oncogenes; there were connections between the HPV positivity with some genotypes (hrHPV16,18,31 and 33, respectively) and p53 mutation. Conclusion: P53 gene mutation was independent of HPV-associated cervical abnormalities in single hrHPV-genotype, though other mechanistic drivers attributed to p53 dysfunction by E6 and E7 remain plausible. On the other hand, infection with multiple hrHPVs showed a concomitant predominance with the P53 mutation, implying a potential interplay and an increased risk of cervical cancer.

Epithelial-mesenchymal transition (EMT) is a physiological program during which polarised, immobile epithelial cells lose connection with their neighbours and are converted to migratory mesenchymal phenotype. Mechanistically, EMT occurs via a series of genetic and cellular events leading to the repression of epithelial-associated markers and upregulation of mesenchymal-associated markers. EMT is very crucial for many biological processes such as embryogenesis and ontogenesis during human development, and again it plays a significant role in wound healing during a programmed replacement of the damaged tissues. However, this process is often hijacked in pathological conditions such as tumour metastasis, which constitutes the most significant drawback in the fight against cancer, accounting for about 90% of cancer-associated mortality globally. Worse still, metastatic tumours are not only challenging to treat with the available conventional radiotherapy and surgical interventions but also resistant to several cytotoxic agents during treatment, owing to their anatomically diffuse localisation in the body system. As the quest to find an effective method of addressing metastasis in cancer intervention heightens, understanding the molecular interplay involving the signalling pathways, downstream effectors, and their interactions with the EMT would be an important requisite while the challenges of metastasis continue to punctuate. Unfortunately, the molecular underpinnings that govern this process remain to be completely illuminated. However, it is becoming increasingly clear that EMT, which initiates every episode of metastasis, significantly requires some master regulators called EMT transcription factors (EMT-TFs). Thus, this review critically examines the roles of TFs as drivers of molecular rewiring that lead to tumour initiation, progression, EMT, metastasis, and colonisation. In addition, it discusses the interaction of various signalling molecules and effector proteins with these factors. It also provides insight into promising therapeutic targets that may inhibit the metastatic process to overcome the limitation of “undruggable” cancer targets in therapeutic design and upturn the current spate of drug resistance. More so, it extends the discussion from the basic understanding of the EMT binary switch model, and ultimately unveiling the E/M cellular plasticity along a phenotypic spectrum via multiple trans-differentiations. It wraps up on how this knowledge update shapes the diagnostic and clinical approaches that may demand a potential shift in investigative paradigm using novel technologies such as single-cell analyses to improve overall patient survival.

Background and aim: As the rage of coronavirus disease 2019 (COVID-19) pandemic continues to spread globally much effort is being directed to contain it through various efforts - genomic studies, drug discoveries, clinical trials, vaccine development, and the innovation of diagnostic techniques. However, some pertinent areas involving accurate and sensitive diagnostics, immunoglobulin specificity, evolution of mutant strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the drug combination strategy to combat it still require more attention. Methods: This review critically examines the COVID-19 response and containment operations. It also addresses some standing challenges involving the areas of diagnostics, vaccine development and prospect, and treatment strategies in relation to antiviral drug treatment and immunotherapy. Designated set of keywords such as ‘SARS-CoV-2’; ‘coronavirus’; ‘severe acute respiratory syndrome coronavirus’; ‘repurposed’; ‘vaccination’; ‘containment’; ‘laboratory diagnostic’; ‘immunotherapy’; ‘antiviral’; ‘antiparasitic’; ‘antibiotic’; ‘antiprotozoal’; ‘antibody’; ‘anti-inflammatory’; ‘antitumour’; ‘corticosteroid’; ‘hypertensive drug’; ‘statin’; ‘supplement’; ‘biological’ along with ‘COVID-19’ were inserted on electronic databases to retrieve articles and clinical trial information relevant to the study objectives. The search databases include ClinicalTrials.gov, NIH.gov, PubMed, Scinapse, CINAHL, Medline, Google Scholar, Academic Search Premier, SAGE, EBSCO Host, and Scopus. Relevance for patients: The difficulties associated with SARS-CoV-2 rapid mutations are unceasingly evolving and re-evolving. These pose serious concerns and downplay the efficacy and effectiveness of the current pipeline antiviral drugs and vaccines. Entities encompassing immunotherapy, antiviral drug therapies, viral genomics, protein-protein interaction and improved diagnostics as well as drug combination strategy against the emerging genetic variability of SARS-CoV-2 were critically appraised. This study suggests that robust collaborations in the development of more sensitive, rapid and accurate diagnostics, development of immunoglobulin specific agents and improved anti-viral treatment focus against multiple mutant genes of SARS-COV-2 should be aggressively pursued for the overall benefits of the patients.