Viruses exploit host genetic machinery to establish chronic infections and contribute to chronic neurodegenerative and immune disorders. By manipulating DNA methylation, histone modifications, and non-coding RNA networks, viruses such as Epstein-Barr virus (EBV), Herpes Simplex virus (HSV), Zika virus (ZIKV), and Human immunodeficiency virus (HIV) induce epigenetic changes that silence or delay the host antiviral defenses and reprogram host gene expression. For instance, EBV recruits DNA methyltransferases (DNMTs) to hypermethylate genes such as SOCS1 while ZIKV disrupts neuronal DNA methylation via heterochromatinization. Concurrently, HIV-1 encoded Tat protein disrupts H3K27 acetylation in astrocytes that potently triggers glutamate excitotoxicity. Viruses also subvert the chromatin architecture to modulate 3D interactions and reader protein recruitment, thus rewiring transcriptional programs. Such epigenetic alterations correlate with neuropathologies wherein global hypomethylation and histone acetylation contribute to Alzheimer's or Parkinson's disease. Although several mechanisms are known, the field of viral control in neuroepigenetics is underexplored. Emerging therapies that target viral-host epigenetic crosstalk through DNMT or HDAC inhibitors are promising. This review highlights how neurotropic viruses co-opt epigenetic pathways to drive neurodegeneration. We also explore biomarker-driven strategies for personalized interventions in neurodegenerative disorders thus emphasizing potential epigenetic editing tools to restore neuronal homeostasis.

Polymeric nanospheres with narrow size distribution and composition are attractive building blocks for advanced nanomedicine applications, particularly in targeted drug delivery. This work report a continuous and controllable strategy for the synthesis of polymeric nanospheres (PNSs) based on the integration of ultrasound-assisted emulsification with a flow reactor system. Ultrasound irradiation enables the formation of a stable and homogeneous nanoemulsion, while the flow reactor ensures precise control over polymerization conditions. Systematic optimization of key parameters, including temperature, residence time, and monomer concentration, yields narrowly dispersed PNSs with tunable physicochemical properties. The resulting nanospheres were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), confirming their uniform size distribution and well-defined morphology. Furthermore, the PNSs were successfully functionalized with FITC-conjugated monoclonal antibodies targeting plasma membrane-bound Hsp70, generating anti-mHsp70-FITC-mAbs@PNSs. This functionalization tested on mHsp70-positive glioma C6 cells demonstrates the suitability of the platform for bioconjugation and targeted delivery applications. Overall, this study highlights a process intensified approach on ultrasound-assisted continuous flow reactor based synthesis as a scalable and versatile approach for producing functional PNSs for biomedical and drug delivery applications.

Background: High-grade gliomas pose formidable challenges in neuro-oncology, with a median overall survival (OS) of 12-18 months. Laser interstitial thermal therapy (LITT) offers a minimally invasive cytoreductive option for deep-seated or recurrent tumors, achieving ablation rates of 85-98%. In parallel, artificial intelligence and machine learning are increasingly being applied to neuro-oncology to improve diagnosis, treatment planning, and outcome prediction, although these applications remain largely investigational. Methods: A literature search was conducted using the PubMed, MEDLINE, Embase, and ClinicalTrials.gov databases. The search terms included "laser interstitial thermotherapy," "glioblastoma," and "high-grade glioma", "machine learning", "artificial intelligence". A total of 196 articles were identified. Inclusion criteria comprised primary studies, meta-analyses, and systematic reviews involving human data, with LITT used as a primary or secondary treatment modality. Sixty-nine studies were included in this review, while case reports and animal studies were excluded. Results: LITT represents a precision therapy for inoperable gliomas, achieving ablation rates of 85-98%. For primary glioblastoma, median overall survival (mOS) ranges from 11-16 months, and median progression-free survival (mPFS) from 4-9.5 months. In recurrent glioblastoma, LITT demonstrates a median overall survival ranging from 8.5 to 14.1 months and a median progression-free survival of 3-3.5 months with lower complication rates (5.7% vs. 13.8%) and shorter hospital stays (2.2 vs. 7 days). Overall complication rates range from 20-35%, predominantly due to cerebral edema, which is generally responsive to steroid therapy. Its value may be expanded by machine learning tools that integrate clinical, molecular, and imaging features to support patient selection and predict outcomes, though these remain at the proof-of-concept stage. In addition, LITT may serve as a platform for combination therapies, including immunotherapy, chemotherapy, targeted agents, and radiotherapy. Conclusions: Based on current evidence, LITT demonstrates outcomes that appear favorable in selected patient populations with high-grade gliomas and may be considered as a treatment option for primary tumors with challenging localization, near-spherical geometry, and volumes of approximately 30 cm3. It has a particularly important role in recurrent glioblastomas with similar characteristics, offering efficacy comparable to resection but with an improved safety profile in retrospective comparisons. LITT is evolving from a technically focused ablation method into a data-driven therapeutic platform. Integration with artificial intelligence may improve precision, safety, and personalization, helping define the role of LITT within modern neuro-oncology as higher-quality clinical evidence continues to accumulate.

INTRODUCTION:Despite a combined approach to manage malignant brain tumors (including glioblastoma), which includes surgical removal of the tumor followed by cycles of radiotherapy and chemotherapy, patient survival remains extremely low. Advances in nanotechnology in recent decades offer hope for the use of nanoscale agents for the successful diagnosis and treatment of brain tumors. AREAS COVERED:This review analyzes the results of preclinical and clinical studies of nanoparticles of various physico-chemical compositions (e.g. SPIONs, AuNPs, QDs, etc) in the diagnosis and therapy (theranostics) of brain tumors. Particular attention is paid to the challenges of targeted drug delivery, antitumor activity, and future development strategies in this field. EXPERT OPINION:Nanoscale agents of diverse physicochemical compositions have demonstrated transformative potential in the diagnosis and treatment of brain tumors, bridging the gap between bench research and clinical application. By enabling precise imaging, targeted delivery, and real-time therapeutic monitoring, nanotechnology offers a multifaceted platform for advancing personalized neuro-oncology. Further interdisciplinary research, standardization of preclinical protocols, and carefully designed clinical trials will be vital in translating these advances into tangible clinical benefits. Nanoparticle-based theranostics are poised to redefine the therapeutic landscape of brain tumors moving from broad cytotoxicity toward targeted, adaptive, and patient-centered treatment paradigms.

ObjectiveGlioma invasion into surrounding brain tissue drives disease progression but is challenging to evaluate with conventional MRI. This study aimed to determine whether radiomic features extracted from the peritumoral zone capture biologically relevant invasion-associated imaging phenotypes, using membrane-bound Hsp70 (mHsp70) as a molecular correlate.MethodsA retrospective study was performed using preoperative MRI data from 80 patients with glioma, including adult glioblastoma (GBM), adult lower-grade glioma (LGG), and pediatric GBM/ATRT cases. Voxel-wise radiomic features were extracted from the peritumoral region and used to train a stochastic gradient descent (SGD) classifier to distinguish GBM-associated invasion-enriched imaging phenotypes from LGG-associated comparison phenotypes. Patient-level cohort separation was used throughout model development to prevent data leakage. Feature importance was assessed using SHAP analysis. In a biologically validated subgroup of 23 patients, membrane-bound Hsp70 (mHSP70) expression was quantified in peritumoral tissue samples using confocal microscopy. Patient-level radiomic invasion metrics were correlated with mHsp70 fluorescence intensity.ResultsThe SVM classifier demonstrated good discriminative performance, achieving an AUC of 0.875 (95% CI: 0.736–0.896) in the independent test cohort. SHAP analysis identified higher-order texture features, including GLCM-, GLRLM-, and LoG-derived radiomic descriptors, as major contributors to model predictions. Reproducibility analysis demonstrated good-to-excellent agreement for all 20 SHAP-selected features, with mean ICC values ranging from 0.859 to 0.986. In the biological validation subgroup, the radiomics-derived Invasion Burden Index (IBI) showed a significant positive correlation with mHsp70 expression (Spearman ρ = 0.67, p = 0.0004, 95% CI: 0.232–0.805, n = 23). Leave-one-out sensitivity analysis demonstrated stable correlations, indicating that the observed association was not driven by individual cases. Regions exhibiting elevated invasion-associated radiomic signatures frequently extended beyond the conventional MRI-defined tumor margin and showed spatial correspondence with areas of subsequent tumor progression on follow-up imaging.ConclusionsVoxel-wise radiomic analysis of the peritumoral zone identifies invasion-associated imaging phenotypes that correlate with membrane Hsp70 expression, a biological marker associated with aggressive tumor behavior. These findings support the potential utility of radiomic invasion mapping as a non-invasive tool for characterizing infiltrative glioma biology and generating hypotheses regarding patterns of tumor progression. Further prospective studies with spatially matched biological validation are needed.

Polymeric nanospheres with narrow size distribution and composition are attractive building blocks for advanced nanomedicine applications, particularly in targeted drug delivery. This work report a continuous and controllable strategy for the synthesis of polymeric nanospheres (PNSs) based on the integration of ultrasound-assisted emulsification with a flow reactor system. Ultrasound irradiation enables the formation of a stable and homogeneous nanoemulsion, while the flow reactor ensures precise control over polymerization conditions. Systematic optimization of key parameters, including temperature, residence time, and monomer concentration, yields narrowly dispersed PNSs with tunable physicochemical properties. The resulting nanospheres were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), confirming their uniform size distribution and well-defined morphology. Furthermore, the PNSs were successfully functionalized with FITC-conjugated monoclonal antibodies targeting plasma membrane-bound Hsp70, generating anti-mHsp70-FITC-mAbs@PNSs. This functionalization tested on mHsp70-positive glioma C6 cells demonstrates the suitability of the platform for bioconjugation and targeted delivery applications. Overall, this study highlights a process intensified approach on ultrasound-assisted continuous flow reactor based synthesis as a scalable and versatile approach for producing functional PNSs for biomedical and drug delivery applications.

Heat shock proteins (HSPs), particularly HSP70 and HSP90, are highly conserved molecular chaperones that protect cells from a wide range of stressors and maintain proteome homeostasis. In cancer, tumor cells frequently overexpress and actively release HSPs into the extracellular space and circulation in response to metabolic alterations, hypoxia, oxidative stress, and therapeutic interventions. Consequently, circulating HSP levels are often elevated in patients with malignancies compared with healthy individuals. This review summarizes current evidence on the diagnostic, prognostic, and predictive value of circulating HSPs in both solid and hematological cancers. Clinical studies indicate that circulating HSP concentrations are associated with tumor type, disease stage, lymph node involvement, metastatic burden, treatment response, and risk of recurrence. Importantly, membrane-associated and extracellular vesicle-associated forms of HSP70 appear to exhibit greater tumor specificity than freely circulating proteins, highlighting the importance of selecting appropriate analytical approaches for biomarker assessment. Beyond their utility as biomarkers, extracellular HSPs actively participate in tumor biology and anti-tumor immunity. Depending on the cellular and immunological context, they can either support tumor progression or stimulate immune responses through activation of natural killer cells, antigen-presenting cells, and cross-presentation of tumor-derived antigens. These immunomodulatory properties have provided the foundation for the development of HSP-based vaccines and adoptive immunotherapeutic strategies, several of which have demonstrated encouraging results in clinical trials. We further discuss the relationship between extracellular chaperone biology and responses to major anticancer treatments, including radiotherapy, chemotherapy, HSP90-targeted therapies, and immune checkpoint blockade. In conclusion, the available evidence supports circulating extracellular HSPs as promising non-invasive biomarkers and potential pharmacodynamic indicators that may improve patient stratification, treatment monitoring, and prediction of therapeutic efficacy in clinical oncology.

Multimodal treatment for Alzheimer's disease (AD) is a pivotal option because of its complex pathogenesis. The major challenge of pharmacotherapies is effective drug delivery to the diseased brain and reduction of associated toxicity. Here, we propose a dual-target nanomedicine (PDA@R@M/K) for the management of AD by coating engineered microglial cell membrane (M/K) onto polydopamine (PDA) cores encapsulated with rivastigmine. M/ K conferred nanoparticles (NPs) with reduced circulation clearance, pathological blood-brain barrier recognition, and enhanced brain inflammation chemotaxis. PDA cores not only acted as potent ROS scavengers to alleviate neuroinflammation but also piggybacked rivastigmine and implemented responsive release. After applying PDA@R@M/K in preclinical transgenic mouse models, amyloid plaque deposition, neurologic changes, and cognitive decline were largely rescued. These results provide the possibility of directly using NPs as therapeutics rather than merely as nanocarriers, and demonstrate the feasibility of engineered microglia membrane-coated NPs to improve the pharmacokinetics and efficacy of anti-AD drugs.

Advances in cancer therapy have markedly improved survival rates; however, long-term neurological sequelae represent a significant clinical challenge. Cancer treatment-related cognitive impairment (CRCI), commonly referred to as “chemobrain”, affects a substantial proportion of cancer survivors and encompasses a broad spectrum of neuropsychiatric and cognitive symptoms, including anxiety, depression, fatigue, balance disturbances, and deficits in attention, memory, processing speed, and executive function. Increasing evidence suggests that these manifestations reflect accelerated biological aging of the brain, rather than merely transient toxic effects. This review synthesizes current clinical, molecular, and neuroimaging evidence supporting the concept of accelerated brain aging associated with multimodal cancer therapy. We summarize key molecular and cellular mechanisms including oxidative stress, neuroinflammation, blood–brain barrier dysfunction, mitochondrial impairment, cellular senescence with a senescence-associated secretory phenotype, and epigenetic remodeling that overlap with physiological brain aging hallmarks. Particular attention is given to circulating molecular biomarkers of accelerated aging, such as inflammatory mediators, senescence markers, endothelial and neuronal injury indicators, and epigenetic age acceleration, and their potential translational relevance. We discuss clinical and neuropsychological data alongside structural and functional magnetic resonance imaging findings demonstrating cortical thinning, altered gyrification, white matter microstructural changes, disrupted functional connectivity, and increased brain age estimates following cancer therapy. Framing CRCI within an accelerated brain aging paradigm may improve risk stratification, guide biomarker development, and inform personalized survivorship care.

Background Epichaperomes are stable, stress-induced supramolecular assemblies formed through extensive integration of molecular chaperones, co-chaperones, signaling proteins, and client proteins. Although increasing evidence indicates that epichaperomes act as organizational hubs that coordinate proteostasis and signaling networks in cancer, neurodegenerative disorders, and chronic inflammatory diseases, their potential physical roles in cellular organization remain largely unexplored. Results Here, the Epichaperome Matrix Theory, a systems-level theoretical framework that conceptualizes the epichaperome as a dynamic, nonequilibrium biomolecular matrix possessing emergent transport-regulatory properties is proposed. In this model, epichaperome assemblies generate heterogeneous electrostatic landscapes through the collective distribution of charged amino acid residues, phosphorylation-dependent charge accumulation, ATP-driven conformational dynamics, and high-order network connectivity. By integrating principles from Poisson-Boltzmann electrostatics, Nernst-Planck transport theory, active matter physics, percolation theory, graph theory, biomolecular condensate thermodynamics, and porous hydrogel transport models, a mathematical description in which epichaperomes function as adaptive organizational scaffolds capable of influencing molecular flux, signaling efficiency, and spatial coordination within cells is developed. This framework is further extended through the Transcellular Epichaperome Continuum Hypothesis, proposing that intracellular epichaperomes may be functionally coupled to plasma membrane-associated and extracellular epichaperome assemblies, forming a multiscale organizational network spanning individual cells, tissues, and organ systems. In this extended model, membrane-bound epichaperomes act as coupling interfaces between intracellular and extracellular compartments, while secreted chaperones, extracellular vesicles, and extracellular protein assemblies contribute to intercellular connectivity. Mathematical analysis predicts the emergence of percolating transport networks, electrostatic coupling domains, synchronized conformational dynamics, and stress-responsive communication pathways when epichaperome connectivity exceeds critical thresholds. Conclusions The proposed framework suggests that epichaperomes may represent more than stress-associated protein interaction networks and could function as dynamic organizational matrices integrating molecular organization, signaling, and adaptive responses across multiple biological scales. Although the theory remains speculative and currently lacks direct experimental validation, it generates testable predictions regarding membrane-associated epichaperomes, extracellular epichaperome assemblies, electrostatic organization, and intercellular transport behaviors. By providing a unified theoretical foundation linking stress biology, chaperone networks, systems biology, and biophysics, this work expands the conceptual landscape of epichaperome research and identifies new directions for investigating the role of higher-order chaperome organization in health and disease.

ObjectiveRecurrent intracranial meningiomas are a significant therapeutic challenge due to their invasive growth and high recurrence risk after surgery and radiotherapy. This study investigates the feasibility of a novel integrated approach combining 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery (FGS) with intraoperative photodynamic therapy (PDT) for recurrent atypical and anaplastic meningiomas.MethodsIn a single-center, prospective cohort study, 23 patients with recurrent atypical and anaplastic meningiomas received the experimental treatment protocol (FGS+PDT). A retrospective control group (n=35) underwent conventional microsurgery. The intervention included preoperative 5-ALA administration, FGS with visual (Fluorescence Intensity Score, FIS) and quantitative biospectroscopy (Fluorescence Index, FI) guidance, tumor resection, and subsequent PDT (635 nm laser) applied to the resection cavity and tumor matrix. Biospectroscopy guided PDT endpoint (photobleaching and decreasing of FI). Primary outcomes included feasibility, safety, and extent of resection (Simpson Grade), short follow-up period. Histopathological and immunofluorescence analyses of paired pre-/post-PDT biopsies assessed biological effects.ResultsThe FGS+PDT protocol was successfully completed in all patients with an excellent safety profile; no adverse events were attributed to 5-ALA or PDT. All tumors exhibited visible 5-ALA fluorescence. Gross-total resection (Simpson I-II) was achieved in 95.6% (22/23) of the study group versus 77.1% (27/35) in controls (p<0.05). Biospectroscopy revealed significant PpIX accumulation even in visually low-fluorescence tumors. Over a median follow-up of 16 months, no recurrences were observed in the experimental group. Histopathological analysis demonstrated profound PDT-induced effects, including total ablation of progesterone receptor expression in the tumor matrix and a significant increase in caspase-3-mediated apoptosis in the peritumoral zone (36.3 ± 9.6 vs. 14.8 ± 2.2 cells/mm², p<0.0001). Confocal microscopy confirmed subcellular damage, including mitochondrial dysfunction, nuclear degradation, and Hsp70 overexpression.ConclusionThe integrated FGS and PDT protocol is feasible, safe, and demonstrates compelling preliminary efficacy for recurrent atypical and anaplastic meningiomas. It enhances resection and induces profound cytotoxic and apoptotic effects in the residual tumor bed and peritumoral zone. These results need to be further validated in larger, randomized controlled trials.

Heat shock proteins belong to a highly conserved family of chaperone proteins, and in addition to their participation in the regulation of cellular proteostasis (folding of polypeptides and proteins, disaggregation of incorrectly folded peptides, and participation in autophagy processes), also play a significant immunomodulatory role in both innate and adaptive immunity. Changes in the HSP level, both downwards (e.g., in neurodegenerative diseases) and upwards (e.g., autoimmune, oncological diseases), underlie the pathogenesis of many somatic and oncological pathologies. In this review, we consider the main physiological mechanisms of HSP level regulation and also analyze pharmacological, genetically engineered methods of modulating the chaperone level, citing the advantages and disadvantages of a particular method of influence. In conclusion, modulation of the HSP level, according to numerous preclinical studies, can have a significant impact on the course of various pathological conditions, which, in turn, can be used to develop new therapeutic approaches, when the effect on the level of chaperones can be used as monotherapy or as an adjuvant method of action.

Characteristics of adult patients with high-grade gliomas.

Motility of Hsp70-positive cells in a GBM tumor sample detected using laser scanning confocal microscopy during observation for 1 h.

Motility of Hsp70-positive cells emerging from a piece of tumor during cultivation for three days.

Grade content and co-localization of biomarkers (Hsp70, Nestin, SOX2) on histological preparations of human GBM.

Analysis of the mass-spectrometry data from isolated lipid rafts.

The plasma membrane (PM) of eukaryotic cells plays a key role in the response to stress, acting as the first line of defense against environmental changes and protecting cells against intracellular perturbations. In this work, we explore how membrane-bound chaperones and membrane lipid domains work together to shape plasma membrane properties—a partnership we refer to as the “epichaperome–plasma membrane lipid axis.” This axis influences membrane fluidity, curvature, and domain organization, which in turn shapes the spatial and temporal modulation of signaling platforms and pathways essential for maintaining cellular integrity and homeostasis. Changes in PM fluidity can modulate the activity of ion channels, such as transient receptor potential (TRP) channels. These changes also affect processes such as endocytosis and mechanical signal transduction. The PM proteome undergoes rapid changes in response to membrane perturbations. Among these changes, the expression of heat shock proteins (HSPs) and their accumulation at the PM are essential mediators in regulating the physical state and functional properties of the membrane. Because of the pivotal role in stress adaptation, HSPs influence a wide range of cellular processes, which we grouped into three main categories: (i) mechanistic insights, differentiating in vitro (liposome, reconstituted membrane systems) and in vivo evidence for HSP-PM recruitment; (ii) functional outputs, spanning how ion channels are affected, changes in membrane fluidity, transcytosis, and the process of endocytosis and exosome release; and (iii) pathological effects, focusing on how rewired lipid–chaperone crosstalk in cancer drives resistance to drugs through altered membrane composition and signaling. Finally, we highlight Membrane Lipid Therapy (MLT) strategies, such as nanocarriers targeting specific PM compartments or small molecules that inhibit HSP recruitment, as promising approaches to modulate the functional stability of epichaperome assembly and membrane functionality, with profound implications for tumorigenesis.

The epichaperome, a dynamic and integrated network of chaperone proteins, extends its roles beyond basic protein folding to protein stabilization and intracellular signal transduction to orchestrating a multitude of cellular processes critical for tumor survival. In this review, we explore the multifaceted roles of the epichaperome, delving into its diverse cellular locations, factors that modulate its formation and function, its liquid–liquid phase separation, and the key signaling and crosstalk pathways it regulates, including cellular metabolism and intracellular signal transduction. We further highlight techniques for isolating and identifying epichaperome networks, pitfalls, and opportunities. Further, we review the profound implications of the epichaperome for cancer treatment and therapy design, underscoring the need for strategic engineering that hinges on a comprehensive insight into the comprehensive structure and workings of the epichaperome across the heterogeneous cell subpopulations in the tumor milieu. By presenting a holistic view of the epichaperome’s functions and mechanisms, we aim to underscore its potential as a key target for novel anti-cancer strategies, revealing that the epichaperome is not merely a piece of protein folding machinery but a mastermind that facilitates the malignant phenotype.

Chemotherapy-related cognitive impairment termed «chemobrain» is a prevalent complication in breast cancer survivors that requires early detection for the development of novel therapeutic approaches. Magnetic resonance voxel morphometry (MR morphometry), due to its high sensitivity, might be employed for the evaluation of the early changes in the volumes of brain structures in order to explore the «chemobrain» condition. Methods: The open, prospective, single-center study enrolled 86 breast cancer survivors (43.3 ± 4.4 years) and age-matched 28 healthy female volunteers (44.0 ± 5.68). Conventional MR sequences (T1- and T2-weighted, TIRM, DWI, MPRAGE) were obtained in three mutually perpendicular planes to exclude an organ pathology of the brain. Additionally, the MPRAGE sequence was performed for subsequent MR morphometry of the volume of brain structures using the open VolBrain program. The evaluation was performed at two follow-up visits 6 months and 3 years after the completion of BC treatment. Results: According to the MR morphometry, breast cancer survivors presented with significantly decreased volumes of brain structures (including total brain volume, cerebellum volume, subcortical gray matter, etc.) as compared to healthy volunteers. Evaluation over the follow-up period of 3 years did not show the restoration of brain volume structures. Conclusions: The data obtained employing MR morphometry revealed significant reductions (that were not detected on the conventional MR sequences) in both gray and white matter in breast cancer survivors following chemotherapy. This comprehensive analysis indicated the utility of MR morphometry in detecting subtle yet statistically significant neuroanatomical changes associated with cognitive and motor impairments in patients, which can in turn provide valuable insights into the extent of structural brain alterations, helping to identify specific regions that are most affected by treatment.