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Glioblastoma multiforme (GBM) is the most fatal brain tumor with a poor prognosis with current treatments, mainly because of intrinsic resistance processes. GBM is also referred to as grade 4 astrocytoma, that makes up about 15.4 % of brain cancers globally as well as 60–75 % of astrocytoma. The most prevalent therapeutic choices for GBM comprise surgery in combination with radiotherapy and chemotherapy, providing patients with an average survival of 6–14 months. Nanocarriers provide various benefits such as enhanced drug solubility, biocompatibility, targeted activity, as well as minimized side effects. In addition, GBM treatment comes with several challenges such as the presence of the blood–brain barrier (BBB), blood–brain tumor barrier (BBTB), overexpressed efflux pumps, infiltration, invasion, drug resistance, as well as immune escape due to tumor microenvironment (TME) and cancer stem cells (CSC). Recent research has focused on nanocarriers due to their ability to self-assemble, improve bioavailability, provide controlled release, and penetrate the BBB. These nano-based components could potentially enhance drug accumulation in brain tumor tissues and reduce systemic toxicity, making them a compelling solution for GBM therapy. This review captures the complexities associated with multi-functional nano drug delivery systems (NDDS) in crossing the blood–brain barrier (BBB) and targeting cancer cells. In addition, it presents a succinct overview of various types of targeted multi-functional nano drug delivery system (NDDS) which has exhibited promising value for improving drug delivery to the brain.

Rotavirus (RV) is a common double-stranded RNA virus that causes diarrheal disease in young children. The prevalent species, Rotavirus A (RVA), is responsible for over 90% of human RV infections. With significant morbidity and mortality, this pathogen poses a serious global health challenge, particularly in underdeveloped countries. This study presents an immunoinformatics approach for designing an mRNA vaccine based on a multi-peptide construct to elicit robust immune responses against RVA. The VP4 was analyzed from 40 sequences using phylogenetic analysis. Prediction of cytotoxic (CTL) and helper T cell (HTL) epitopes was performed and validated. The 17 high-conservancy CTL/HTL epitopes were selected for vaccine construction. The mRNA vaccine based on multi-peptide was engineered with human beta-defensin 3 (hBD3) adjuvant and linkers to enhance immunogenicity. The designed mRNA vaccine product exhibited favorable physicochemical properties and was predicted to be a probable antigen, non-allergenic, and non-toxic. 2D and 3D structure validation demonstrated the quality of the model. Molecular docking with Toll-like receptor 2/3 (TLR2/3) indicated favorable interaction, and peptide docking with MHC-I/II alleles showed strong binding affinities and have significant Residue-Residue interactions. Simulation of immune responses revealed potent B-cell and T-cell activities, macrophage responses, and significant cytokine synthesis. Molecular dynamics simulation (MDS) confirmed the structural stability of the TLR3-vaccine complex, and MHC-peptide in 200ns and STQFTDFVSLNSLRF peptide have shown good interaction with MHC molecule. In addition, the MM/GBSA analysis yielded a binding free energy of − 89.77 kcal/mol, indicating a strong and stable interaction between the vaccine construct and the target receptor. Codon optimization and mRNA secondary structure prediction were carried out for efficient translation. Additionally, population coverage analysis indicated the vaccine’s effectiveness worldwide with 100% value. Overall, this study showcases a promising immunoinformatics approach for designing an mRNA vaccine based on a multi-peptide construct targeting RVA. The findings support the potential of this vaccine design to elicit robust and widespread immune responses against RVA infection, paving the way for future vaccine development strategies and this study needs experimental validation.

Pyroptosis, a caspase-dependent form of inflammatory programmed cell death, is driven by inflammasome activation and gasdermin-mediated membrane pore formation. Its immunogenic nature has attracted increasing attention in oncology, particularly for overcoming therapeutic challenges such as chemoresistance, radiotherapy failure, and immune checkpoint blockade non-responsiveness. By promoting the release of pro-inflammatory cytokines and damage-associated molecular patterns (DAMPs), pyroptosis can enhance antitumor immunity and reshape the tumor microenvironment (TME). However, sustained or dysregulated pyroptosis can lead to chronic inflammation, radiotherapy-induced tissue injury, and tumorigenesis, making it a double-edged sword. Emerging evidence shows that pyroptosis exhibits cancer-type-specific roles, depending on the molecular context and the extent of activation. Therefore, understanding the molecular regulators, tumor-specific signaling, and temporal dynamics of pyroptosis is essential for its therapeutic modulation. This review comprehensively outlines the dual roles of pyroptosis in cancer progression and treatment, discusses its molecular mechanisms, and highlights recent strategies to harness or suppress pyroptosis for therapeutic gain. Targeting pyroptosis offers a promising, yet complex, avenue for immune-enhancing cancer therapies. Graphical abstract

Introduction Vaccination is considered as one of the most promising strategies to overcome the COVID-19 pandemic. However, it could be associated with rare but serious complications. In the present study, we aimed to review the clinical course and etiology of post COVID-19 vaccination meningitis. Methods After a systematic search in PubMed, Scopus, and Web of Sciences online databases as well as Google Scholar, documents were screened and qualified. Then data extraction was performed and the most frequent underlying agent of meningitis was found based on the reported cases . Results Overall, 35 cases of post COVID-19 vaccination meningitis from 33 articles were included in the review. Among them, 12 cases had proven viral diagnosis and 23 of them were reported to be vaccine-induced. The most frequent viral pathogen among the cases was VZV. The most prevalent symptom was headache, and the most common time of appearance symptoms was one week after vaccination. Conclusion Overall, our study suggested meningitis as a critical but not devastating complication of COVID-19 vaccination. Almost all patients responded well to common agents used to manage viral or vaccine-induced meningitis. It is recommended to monitor patients with a history of chickenpox after COVID-19 vaccination regarding the development of meningitis.

Breast cancer (BCA) remains the most prevalent cancer globally and the leading cause of cancer-related mortality among women, with rising incidence rates driven by genetic, lifestyle, and environmental factors. Early detection through precise screening is essential to improve prognosis and survival; yet, challenges persist, especially in resource-limited areas. Recent advances in Artificial Intelligence (AI), particularly machine learning and deep learning algorithms, have illustrated significant potential to enhance breast cancer screening, diagnosis, and treatment personalization. This review highlights the multifaceted role of AI in BCA management, encompassing its applications in image-based screening modalities, genomic and immunologic profiling, and drug discovery. AI-driven approaches offer diagnostic accuracy, cost-effectiveness, time-saving, and individualized treatment regimens. Despite promising developments, further research is crucial to overcome current challenges and regulatory hurdles in clinical settings. This article highlights the positive aspects of AI technologies in advancing BCA care and the importance of continued interdisciplinary research to optimize their implementations in breast cancer workflows.

Shigella infection is a major global cause of diarrhea, particularly among children in low- and middle-income countries. While most cases are self-limited, certain strains such as Shigella flexneri can lead to severe systemic complications, including encephalopathy. Among the rarest and most fatal forms is Ekiri syndrome, primarily reported in East Asian literature, characterized by fulminant neurotoxicity, high fever, seizures, and rapid progression to coma or death. In this study, we report the case of a previously healthy 14-year-old girl who presented with vomiting, diarrhea, and low-grade fever, initially treated conservatively. Her condition worsened with progressive lethargy and a generalized seizure, leading to ICU admission. Brain imaging showed diffuse cerebral edema, and her temperature intermittently spiked to 44–45 °C. Laboratory findings revealed marked leukopenia, and stool culture confirmed Shigella flexneri . Despite supportive management including anticonvulsants, empiric antibiotics, and antivirals for suspected CNS infection, her neurologic status continued to deteriorate. As per family request, she was referred to a tertiary center, where her condition rapidly worsened. She developed multi-organ failure with acute kidney injury requiring dialysis, elevated liver enzymes, cardiac dysfunction, and pneumothorax. Despite intensive care, she succumbed to complications after nearly ten days of hospitalization. This case illustrates a fulminant presentation of Shigella-associated encephalopathy consistent with Ekiri syndrome. Clinicians should maintain a high index of suspicion in pediatric patients with gastrointestinal and early neurological symptoms. Early recognition and aggressive supportive care are essential to improving outcomes in this rare but devastating condition.

Infertility is a significant global health issue affecting millions of couples, with noncoding RNAs (ncRNAs) emerging as pivotal regulators in reproductive biology. This review explores the roles of various ncRNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), PIWI-interacting RNAs (piRNAs), and circular RNAs (circRNAs) in male and female infertility. These ncRNAs modulate critical processes such as spermatogenesis, oogenesis, follicular development, and embryo implantation through mechanisms like post-transcriptional regulation, chromatin remodeling, and transposon silencing. Dysregulation of ncRNAs is linked to reproductive disorders such as azoospermia, polycystic ovarian syndrome (PCOS), and endometriosis, highlighting their potential as diagnostic biomarkers. For instance, seminal plasma miRNAs and follicular fluid-derived ncRNAs offer non-invasive tools for assessing fertility status. Additionally, ncRNAs hold therapeutic promise, with synthetic mimics and inhibitors being explored to restore fertility. However, challenges such as variability in ncRNA expression, lack of standardized protocols, and the need for extensive clinical validation hinder their translation into clinical practice. This review synthesizes current knowledge on ncRNA mechanisms in infertility, underscores their biomarker potential, and discusses innovative therapeutic strategies, while addressing the obstacles to their clinical application. Graphical Abstract