Glioblastoma is the most common primary tumor of the central nervous system, characterized by an infiltrative growth pattern, which results in the most unfavorable prognosis. The average survival time of patients after diagnosis of this tumor is typically several months, with complete recovery from glioma being very rare. In recent years, significant involvement of exosomes in the development of cancer, including malignant brain tumors, has been discovered. Exosomes are extracellular vesicles that carry signaling molecules and participate in communication between cells. They influence cell survival, proliferation, migration, and increased neoangiogenesis, all of which significantly contribute to tumor recurrence. Molecules carried by exosomes are considered potential diagnostic markers, enabling early diagnosis of cancer and prompt implementation of appropriate treatment. Of particular diagnostic importance are microRNA molecules, which promote increased cell proliferation and inhibition of apoptosis. Equally important exosomal transmitters include proteins such as PSMD2 and EGFR, which enhance tumor invasiveness and resistance to chemotherapeutic agents. Recent studies suggest the possibility of using exosomes as carriers for new anticancer drugs, potentially improving the therapeutic treatment of cancers resistant to standard treatment methods. This review aimed to provide a comprehensive analysis of recent research on glioblastoma, the role of exosomes in its progression, the potential of exosomes as diagnostic biomarkers, and their use as therapeutic targets for patients who have not responded to conventional treatments.

Incomplete immune reconstitution is characterized by chronic immune activation and systemic inflammation, which are not fully reversed by antiretroviral therapy. Dihydroartemisinin (DHA) has demonstrated anti-inflammatory and immunosuppressive properties, which may benefit individuals with incomplete immune reconstitution. This study aimed to investigate the biological mechanisms underlying incomplete immune reconstitution and evaluate the therapeutic potential of DHA in modulating immune activation in immunological non-responders (INRs). This study aimed to investigate the biological mechanisms underlying incomplete immune reconstitution and evaluate the therapeutic potential of DHA in modulating immune activation in immunological non-responders (INRs).

RNA sequencing data (GSE106792) was retrieved from the Gene Expression Omnibus database. R software and Bioconductor packages were used to identify differentially expressed genes (DEGs) among INRs, immune responders (IRs), and healthy controls (HCs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, along with protein-protein interaction (PPI) network construction, were performed. Potential DHA-binding proteins were predicted using the STITCH server and molecular docking studies. Validation experiments were conducted on peripheral blood mononuclear cells from 18 INRs. Cells were treated with varying concentrations of DHA, and CD4+ and CD8+ T cell activation markers (CD38 and HLA-DR) were measured via flow cytometry.

Enrichment and PPI network analysis identified 119, 56, and 189 DEGs in the INR vs. HC, INR vs. IR, and IR vs. HC comparisons, respectively. Enrichment and PPI analyses showed that DEGs were mainly involved in immune response pathways. DHA was predicted to interact with multiple target proteins, indicating anti-inflammatory effects. In vitro, DHA significantly reduced the frequency of CD38− HLA-DR+ CD4+ T cells and CD38+ HLA-DR+ CD8+ T cells at 1,000 µM and 500 µM compared to the control.

This study provides insights into the biological mechanisms underlying incomplete immune reconstitution and supports DHA’s potential as a therapeutic agent. DHA effectively inhibits T cell activation in INRs, presenting a novel and promising treatment strategy.

Therapy-related B-lymphoblastic leukemia (B-ALL) following treatment for multiple myeloma is a rare occurrence. Despite its rarity and the lack of recognition by the World Health Organization as a distinct disease entity, previous publications indicate its possible emergence following myeloma treatment.

The patient is a 65-year-old gentleman with a history of IgG kappa multiple myeloma, status post multiple lines of therapy. The patient presented with a fever, and a complete blood count showed cytopenia. Bone marrow morphologic evaluation revealed numerous blasts. Immunophenotypic analysis demonstrated that these blasts were B lymphoblasts, despite MYC and unusual surface kappa light chain expression. A diagnosis of B-ALL with surface kappa light chain expression post-myeloma treatment was made. Ancillary studies indicated that the B-ALL and the previous myeloma were clonally unrelated. Next-generation gene sequencing revealed pathogenic mutations in KDM6A and KRAS.

This case highlights the potential for therapy-related B-ALL following myeloma treatment, a phenomenon deserving further investigation. The expression of surface light chain in blasts can present a diagnostic pitfall.

Cardiovascular diseases (CVDs) remain the leading cause of global morbidity and mortality, highlighting the urgent need for innovative diagnostic and prognostic approaches to address their complex pathophysiology. Recent advances in molecular cardiology have unveiled immune-derived microRNAs (miRNAs), or immuno-miRs, as pivotal regulators in the interplay between immune responses and cardiovascular pathology. Secreted by immune cells such as T lymphocytes, macrophages, and neutrophils, these small non-coding RNAs modulate critical signaling pathways by regulating gene expression. Immuno-miRs influence essential processes, including inflammation, endothelial dysfunction, and fibrotic remodeling—core mechanisms underlying conditions such as atherosclerosis, myocardial infarction, and heart failure. Moreover, their presence in systemic circulation within extracellular vesicles underscores their role in intercellular communication, impacting both immune and non-immune cardiovascular cells, such as cardiomyocytes and endothelial cells. This dual functionality renders immuno-miRs promising candidates as diagnostic biomarkers for early disease detection and as prognostic tools for assessing disease progression and therapeutic efficacy. Furthermore, emerging miRNA-based interventions—such as miRNA mimics and inhibitors—show considerable promise in modulating immune dysregulation in CVDs, although clinical translation remains a significant challenge. In this review, we comprehensively examine the regulatory roles of immuno-miRs in both innate and adaptive immune responses and explore recent advancements in miRNA-based therapies. By consolidating current knowledge and identifying existing gaps, we provide a comprehensive overview of the transformative potential of immuno-miRs in CVD management. Integrating these molecules into personalized medicine may pave the way for more effective, targeted, and minimally invasive strategies to combat one of the world’s most pressing health challenges.

Ischemic colitis has been previously associated with the use of certain medications; however, no cases have been reported in connection with zolmitriptan. This study aimed to describe a case of ischemic colitis associated with zolmitriptan use. A 56-year-old female patient taking zolmitriptan presented to the hospital with complaints of abdominal pain, bloody diarrhea, and emesis. Colonoscopy and abdominal imaging with computed tomography revealed findings consistent with ischemic colitis. After recognizing the association between ischemic colitis and zolmitriptan use, the medication was discontinued, and the patient recovered with supportive therapy. This is the first reported case of ischemic colitis associated with zolmitriptan.

Tumors are complex systems characterized by variations across genetic, transcriptomic, phenotypic, and microenvironmental levels. This study introduced a novel framework for quantifying cancer cell heterogeneity using single-cell RNA sequencing data. The framework comprised several scores aimed at uncovering the complexities of key cancer traits, such as metastasis, tumor progression, and recurrence.

This study leveraged publicly available single-cell transcriptomic data from three human breast cancer subtypes: estrogen receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative. We employed a quantitative approach, analyzing copy number alterations (CNAs), entropy, transcriptomic heterogeneity, and diverse protein-protein interaction networks (PPINs) to explore critical concepts in cancer biology.

We found that entropy and PPIN activity related to the cell cycle could distinguish cell clusters with elevated mitotic activity, particularly in aggressive breast cancer subtypes. Additionally, CNA distributions varied across cancer subtypes. We also identified positive correlations between the CNA score, entropy, and the activities of PPINs associated with the cell cycle, as well as those linked to basal and mesenchymal cell lines.

This study addresses a gap in the current understanding of breast cancer heterogeneity by presenting a novel quantitative approach that offers deeper insights into tumor biology, surpassing traditional marker-based methods.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by distinct histological subtypes and a poor prognosis. Among these, the micropapillary pattern, typically observed focally, has been associated with worse outcomes in various cancers. This study aimed to evaluate the prognostic significance of the micropapillary pattern in PDAC, focusing on its percentage within the tumor and its impact on overall survival.

A retrospective analysis was conducted on 71 patients with surgically resected PDAC. Micropapillary patterns were categorized based on their percentage within the tumor (≥20%) and compared to non-micropapillary cases. Demographic, clinical, and histological data, including tumor nodule metastasis stage, tumor grade, peripancreatic fat tissue invasion, and resection margin status, were analyzed. Survival data were assessed using Kaplan-Meier and Cox proportional hazards models. A p-value < 0.05 was considered statistically significant.

The cohort included 28 female and 43 male patients, with a mean age of 63.25 years. Of the 71 cases, 23.9% (n = 17) exhibited a micropapillary pattern. The median overall survival for the micropapillary group was eight months, compared to 18 months for the non-micropapillary group (p = 0.017). Multivariate analysis revealed that the micropapillary group had an increased risk of mortality (hazard ratio = 1.892, p = 0.042), independent of tumor nodule metastasis stage.

Our findings indicate that the micropapillary pattern, even when present in as little as 20% of the tumor, serves as an independent prognostic factor for decreased survival in PDAC. Incorporating the percentage of the micropapillary pattern into pathology reports could provide valuable insights into the tumor’s biological behavior, potentially enhancing patient management strategies.

Despite significant advances in Parkinson’s disease (PD) treatment, it remains incurable, with limited therapeutic options. Currently, repurposing already tested, safe drugs has emerged as an effective therapeutic strategy against various neurodegenerative diseases, including PD. Using a drug-repurposing approach, the current study investigated the neuroregenerative potential of polysialic acid mimicking compounds, 5-nonyloxytryptamine oxalate (5-NOT) and Epirubicin (Epi), an anti-cancer drug, in 1-methyl-4-phenylpyridinium (MPP+)-treated human neuroblastoma SH-SY5Y cells as a PD model.

The excitotoxic model was established by exposing SH-SY5Y cells to 500 µM of MPP+ and subsequently treating them with the test compounds. The effect of MPP+-induced toxicity on cellular and nuclear morphology, as well as on the expression of neuroplasticity and cell survival proteins, were studied by immunostaining, gelatin zymogram, and Western blot assays.

Treatment with 5-NOT and Epi significantly promoted the survival of MPP+-challenged SH-SY5Y cells and prevented changes in their cellular and nuclear morphology by regulating the expression of microtubule-associated protein (MAP-2) and polysialylated-neural cell adhesion molecule (PSA-NCAM) and NCAM synaptic plasticity proteins. Further, 5-NOT and Epi treatment also protected SH-SY5Y cells by restoring levels of nitric oxide, matrix metalloproteinase, and stress response proteins. Interstingly, 5-NOT attenuated MPP+-induced toxicity in SH-SY5Y cells by regulating the intrinsic protein kinase AKT/BAD apoptotic pathway and the P-38 MAP kinase synaptic plasticity pathway.

These preliminary findings suggest that 5-NOT, as a potential polysialic acid glycomimetic, may serve as a promising drug candidate for targeting neurodegeneration of dopaminergic neurons, a hallmark feature of PD.

Gastrointestinal complications are common in patients after ischemic stroke. Gastric motility is regulated by gastric pace-making activity (also called gastric myoelectrical activity (GMA)) and autonomic function. The aim of this study was to evaluate GMA, assessed by noninvasive electrogastrography (EGG), and autonomic function, measured via spectral analysis of heart rate variability derived from the electrocardiogram in patients with ischemic stroke.

EGG and electrocardiogram were simultaneously recorded in both fasting and postprandial states in 14 patients with ischemic stroke and 11 healthy controls. Multi-channel surface EGG was used to measure GMA, and autonomic function was evaluated by heart rate variability spectral analysis.

Compared to healthy subjects, patients with ischemic stroke, especially those with a modified Rankin scale ≥ 4, had impaired GMA in both fasting and postprandial states. This included a lower percentage of normal gastric slow waves (the basic rhythmic waves of GMA) and a higher percentage of tachygastria, bradygastria, or arrhythmia. Patients with ischemic stroke also showed a decrease in the dominant frequency and power of the gastric slow waves. Autonomic functions were altered in ischemic stroke patients with a modified Rankin scale ≥ 4, as reflected by increased sympathetic activity and reduced parasympathetic activity.

Gastric pace-making activity is impaired in patients with severe ischemic stroke, as evidenced by a reduced percentage of normal gastric slow waves and a lower frequency of gastric slow waves, likely due to impaired autonomic functions.