Search Results (198)

Disruption of the gut-microbiome-brain axis contributes to the development of chronic inflammation, impaired intestinal barrier integrity, and progressive tissue damage, ultimately reducing quality of life and increasing risk of comorbidities, including neurodegenerative diseases. Current therapies are often limited by adverse effects and insufficient long-term efficacy, highlighting the need for more comprehensive therapeutic approaches. Berberine (BRB), a plant-derived isoquinoline alkaloid, has attracted growing attention due to its pleiotropic immunomodulatory, neuroprotective, and gut-homeostasis-modulating properties, which involve reshaping the gut microbiota and underscore its therapeutic relevance within the gut–microbiome–brain axis. The aim of this review is to synthesize current scientific evidence regarding the anti-inflammatory mechanisms of BRB in inflammatory bowel disease (IBD). We compare its activity with first-line therapies and discuss its impact on microbial composition, including the bidirectional regulation of specific bacterial taxa relevant to intestinal and systemic disorders that originate in the gut. Furthermore, we emphasize that gut bacteria convert BRB into bioactive metabolites, contributing to its enhanced intraluminal activity despite its low systemic bioavailability. By integrating molecular and microbiological evidence, this review fills a critical knowledge gap regarding the comprehensive therapeutic potential of BRB as a promising candidate for future IBD interventions. The novelty of this work lies in unifying fragmented findings into a framework that explains how BRB acts simultaneously at the levels of host immunity, microbial ecology, and neuroimmune communication—thus offering a new conceptual model for its role within the gut–microbiome–brain axis. Full article

The aquaporin (AQP) gene family plays a critical role in water balance and osmotic regulation, yet its function and regulatory mechanisms in plateau reptiles remain poorly understood. In this study, we systematically identified 10 AQP genes in the Qinghai toad-headed agama (Phrynocephalus vlangalii) based on whole-genome data, and conducted a comprehensive analysis of their physicochemical properties, phylogenetic relationships, conserved domains, gene structures, and expression patterns. The results showed that the AQP genes of P. vlangalii are predicted to localize to the plasma membrane and exhibit significant tissue-specific expression, with the highest levels detected in the kidney and liver. Under low-temperature stress, multiple AQP genes displayed dynamic expression patterns during the stress and recovery phases. Specifically, AQP0, AQP2, and AQP5 were persistently downregulated in the liver, kidney, and brain, whereas AQP3, AQP7, and AQP9 were initially upregulated during early cold exposure but significantly downregulated during recovery, suggesting their coordinated roles in energy metabolism and water conservation. This study provides evidence supporting the involvement of the AQP gene family in the adaptation of P. vlangalii to the cold and arid plateau environment, providing new insights into the regulatory mechanisms of water metabolism in reptiles. Full article

Mesenchymal stem cells are multipotent stromal cells with immunomodulatory, anti-inflammatory, and trophic properties that support tissue repair and regeneration. Increasing evidence suggests that their therapeutic effects are primarily mediated by paracrine signaling, especially through extracellular vesicles, which can cross the blood–brain barrier and act as cell-free therapeutic agents. Preclinical and clinical studies in stroke, multiple sclerosis, spinal cord injury, and neurodegenerative diseases report encouraging outcomes but also reveal major challenges, including limited engraftment, donor-related heterogeneity, incomplete understanding of mechanisms, and potential oncogenic risks. Recent advances in biotechnology—such as mesenchymal stem cell-derived extracellular vesicles, genetic engineering using CRISPR/Cas9 or viral vectors, 3D culture systems, and bioengineered delivery platforms—offer new opportunities to overcome these limitations. Early clinical trials demonstrate promising safety and functional improvements, yet results remain inconsistent, highlighting the need for standardized protocols and large-scale controlled studies. This review outlines current knowledge, key challenges, and emerging strategies aimed at optimizing mesenchymal stem cell-based approaches for regenerative neurology. Full article

The blood–brain barrier (BBB) represents a major challenge in effective drug delivery systems intended for treating neurological disorders. It restricts the transport of therapeutic agents to the brain. Chitosan-based nanoparticles (CNPs) can be used for brain drug delivery because of their biocompatibility, biodegradability, and ability to enhance drug permeability across the BBB. This review article discusses the design and application of CNPs for brain-targeted drug delivery, exploring their mechanisms of action, including adsorptive-mediated and receptor-mediated endocytosis. Surface modifications with ligands such as chlorotoxin are discussed for improving specificity and therapeutic results. Findings show that CNPs allow controlled drug release, enhance stability, and reduce side effects, which make them effective for treating multiple neurological conditions, including Alzheimer’s disease, Parkinson’s disease, brain tumors, and ischemic stroke. CNPs can encapsulate multiple therapeutic agents, such as anti-inflammatory drugs, cytotoxic agents, and genetic materials, and maintain stability under different physiological conditions. Intranasal delivery routes are mainly discussed in this paper for their ability to bypass systemic circulation and achieve direct brain targeting. This review also addresses challenges such as cytotoxicity and the need for optimizing nanoparticle size, charge, and surface properties to improve the therapy results. While CNPs are suitable for brain drug delivery, there is a research gap, which is the lack of systematic studies evaluating their long-term effects on brain tissue and health. Most studies focus on acute therapeutic outcomes and in vitro or short-term in vivo analysis, which do not address some questions about the chronic exposure risks, biodistribution, and clearance pathways of CNPs. This review also explores the use of chitosan-based nanoparticles to deliver drugs to the brain for the treatment of multiple neurological disorders. Full article

Cardiovascular disease (CVD) encompasses ischemic conditions of the heart, brain, and bodily tissues, primarily resulting from hyperlipidemia, atherosclerosis (AS), hypertension, and other related factors. CVD accounts for over 40% of global non-communicable disease mortality, making it the leading cause of death and a significant medical burden worldwide. AS, the principal pathological basis for most cardiovascular diseases, is characterized as a chronic, sterile inflammatory condition triggered by lipid overload and various other factors. In recent years, natural bioactive compounds have gained prominence in the treatment of human diseases. Among these, curcumin (Cur) has garnered considerable attention due to its anti-inflammatory, lipid-lowering, antihypertensive, and endothelial protective properties. This review examines traditional pharmacological approaches for treating AS, with particular emphasis on the critical mechanisms through which Cur exerts its therapeutic effects. Additionally, it introduces novel nanoformulations designed to address the inherent limitations of Cur, providing valuable insights for researchers investigating its application in AS therapy. Full article

Background/Objectives: Traumatic brain injury (TBI) disrupts both the intestinal epithelium and blood–brain barrier (BBB), contributing to oxidative stress, neuroinflammation, and behavioral impairments. Vitis vinifera leaf (VVL) extract possesses antioxidant and anti-inflammatory properties, but its protective effects on the brain–gut axis following TBI remain unclear. This study aimed to evaluate whether VVL supplementation preserves barrier integrity and improves neurobehavioral outcomes after TBI. Methods: A murine model of TBI was used, with animals receiving daily oral supplementation of the VVL extract. Neurobehavioral performance was assessed through behavioral testing, while histopathological examinations, biochemical assays, and gene expression profiling were performed to evaluate neuronal and intestinal integrity, antioxidant defense, and inflammatory responses. Results: VVL supplementation significantly alleviated anxiety- and depression-like behaviors and preserved the structural integrity of neuronal and intestinal tissues. Antioxidant defense mechanisms were strengthened, as shown by increased catalase and superoxide dismutase activities, together with upregulation of Nrf2 and HO-1 expression. Tight junction proteins, including ZO-1 and occludin, were upregulated in both brain and gut tissues, reflecting improved barrier integrity. Furthermore, VVL markedly reduced pro-inflammatory cytokine expression. Conclusions: VVL extract confers dual protection of the gut and brain barriers after TBI by enhancing endogenous antioxidant defenses, maintaining tight junction integrity, and suppressing inflammation. These findings suggest that VVL may represent a natural therapeutic strategy to mitigate oxidative stress, neuroinflammation, and behavioral dysfunctions associated with TBI. Full article

Glioblastoma (GB) is one of the most aggressive and treatment-resistant cancers affecting the central nervous system (CNS), predominantly in adults. Despite significant advancements in this field, GB treatment still relies primarily on conventional approaches, including surgical resection, radiotherapy, and chemotherapy, which, due to its complex pathological characteristics, resistance mechanisms, and restrictive nature of the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB), remain of limited efficacy. In this context, the development of innovative therapeutic strategies able to overcome these barriers, induce cancer cell death, and improve patient prognosis is crucial. Recently, nanoparticle platforms and focused ultrasounds seem to be promising approaches for cancer treatment. Nanoparticles enable targeting and controlled release, whilst focused ultrasounds enhance tissue permeation, increasing drug accumulation in a specific organ. However, nanoparticles can suffer from synthesis complexity, long-term biocompatibility and accumulation in the body with consequent toxicity, whereas focused ultrasounds require specialized equipment and can potentially cause thermal damage, hemorrhage, or cavitation injury. Cyclodextrins (CYDs) possess good properties and represent a versatile and safer alternative able to improve drug stability, solubility, and bioavailability, and depending on the type, dose, and administration route, can reduce local and systemic toxicity. Thus, CYDs emerge as promising novel excipients in GB treatment. Despite these advantages, CYD complexes suffer from receptor specificity, reducing their potential in precision medicine. By combining CYD complexes with polymeric or lipidic platforms, the advantages of CYD safety and drug solubilization together with their specific targeting can be obtained, thus enhancing selectivity and maximizing efficacy while minimizing recurrence and systemic toxicity. This review provides a comprehensive overview of GB pathology, conventional treatments, and emerging CYD-based strategies aimed at enhancing drug delivery and therapeutic efficacy. Full article

Background/Objectives: The Sox transcription factor family is critical for gonadal development and sex differentiation in animals, yet its roles in chelonians, particularly in the Chinese soft-shelled turtle (Pelodiscus sinensis), have rarely been investigated. Methods: This study cloned and analyzed the cDNA sequences of Sox3 and Sox30 genes from P. sinensis, examining their amino acid sequences and structural properties. Real-time quantitative PCR (RT-qPCR) was used to assess the expression of these two genes in different adult tissues and at various stages of embryonic gonadal development. Additionally, the effects of exogenous hormones (17β-estradiol, E₂ and 17α-Methyltestosterone, MT) on the expression of Sox3 and Sox30 were also investigated. Results: The results indicated that Sox3 showed significantly elevated expression in female gonads, kidney, brain, liver, lung, spleen, and muscle relative to male counterparts, displaying a female-biased expression pattern. In contrast, Sox30 showed a male-biased pattern, with higher expression in male gonads, spleen, muscle, brain, and liver than in females, showing expression. Both genes were expressed at low levels. Exogenous hormone treatments revealed that MT significantly downregulated Sox3 expression in female embryos, whereas E₂ significantly enhanced Sox3 expression in male embryos. Furthermore, MT treatment significantly upregulated Sox30 expression in female embryos, and E₂ treatment also significantly increased Sox30 expression in male embryos. Conclusions: These findings suggest that Sox3 and Sox30 play crucial roles in the gonadal development of P. sinensis, with Sox3 potentially involved in ovarian development and Sox30 in testicular maturation. Both genes are regulated by exogenous hormones, highlighting their importance in sex differentiation and gonadal development. This study provides valuable theoretical insights for further exploration of the molecular mechanisms of sex regulation in reptiles. Full article

Exosomes, naturally derived extracellular vesicles, have emerged as powerful bio-nanocarriers in precision medicine. Their endogenous origin, biocompatibility, and ability to encapsulate and deliver diverse therapeutic payloads position them as transformative tools in drug delivery, gene therapy, and regenerative medicine. This review presents a comprehensive analysis of exosome-based therapeutics across multiple biomedical domains, including cancer, neurological and infectious diseases, immune modulation, and tissue repair. Exosomes derived from stem cells, immune cells, or engineered lines can be loaded with small molecules, RNA, or CRISPR-Cas systems, offering highly specific and low-immunogenic alternatives to viral vectors or synthetic nanoparticles. We explore endogenous and exogenous loading strategies, surface functionalization techniques for targeted delivery, and innovations that allow exosomes to traverse physiological barriers such as the blood–brain barrier. Furthermore, exosomes demonstrate immunomodulatory and regenerative properties in autoimmune and degenerative conditions, with promising roles in skin rejuvenation and cosmeceuticals. Despite their potential, challenges remain in large-scale production, cargo loading efficiency, and regulatory translation. Recent clinical trials and industry efforts underscore the accelerating momentum in this field. Exosomes represent a promising platform in precision medicine, though further standardization and validation are required before widespread clinical use. This review offers critical insights into current technologies, therapeutic mechanisms, and future directions to unlock the full translational potential of exosomes in clinical practice. Full article

Ganoderma lucidum (Lingzhi), a traditional medicinal mushroom, is renowned for its immunomodulatory, anti-inflammatory, and antioxidant properties, primarily attributed to its bioactive components such as polysaccharides and triterpenoids. This review focuses on the mechanisms by which Ganoderma lucidum modulates immune responses, particularly in the context of gut–liver–brain axis disorders. Polysaccharides enhance immune function by activating macrophages, natural killer cells, and T cells, thereby promoting phagocytosis and cytokine production. Triterpenoids contribute through anti-inflammatory and antioxidant activities, inhibiting inflammatory mediators and protecting tissues from damage. Ganoderma lucidum also influences immune regulation via key signaling pathways, including NF-κB and MAPK, and supports immune tolerance, potentially reducing the risk of autoimmune diseases. Additionally, it modulates gut microbiota, which further impacts systemic immunity. Importantly, polysaccharides and triterpenoids demonstrate promising clinical application prospects in metabolic diseases, inflammatory conditions, neurodegenerative disorders, and cancer immunotherapy, attributed to their multi-target immunomodulatory activities and prebiotic properties. Despite promising applications in treating metabolic, inflammatory, and neurodegenerative diseases, further research is needed to fully elucidate the molecular mechanisms and potential of Ganoderma lucidum in precision medicine. This comprehensive analysis underscores the value of Ganoderma lucidum as a multifaceted immunomodulatory agent. Full article

Background: The Tibetan Plateau, which is known for its high elevation and low oxygen levels, presents a challenging environment for its inhabitants. To adapt to these hypoxic conditions, species of Schizothoracine, a subfamily of Cyprinidae, have developed unique physiological mechanisms and functions. Transforming growth factor-β (TGF-β) is a multifunctional cytokine involved in the regulation of cell growth, differentiation, apoptosis, and the cellular immune response. However, its specific role in adaptation to hypoxia remains poorly understood. Methods: In this study, we aimed to characterize the TGF-β1 gene in Gymnocypris dobula (Gd) and Schizothorax prenanti (Sp) and to test whether TGF-β1 contributes to hypoxia adaptation in plateau Schizothoracine fish. The predicted protein for Gd-TGF-β1 contains several primary domains, including cwf21 (cdc5 protein 21), GYF (Glycine-Tyrosine-Phenylalanine), FN1 (Fibronectin 1), a conservative domain, and a signal peptide. Results: The results of tissue distribution revealed that the mRNA level of TGF-β1 in brain, heart, muscle, skin, gills, and spleen—which are key tissues involved in oxygen sensing, transport, and physiological adaptation to hypoxic environments—was significantly lower in G. dobula than that in S. prenanti. Western blotting analysis revealed that the expression of activated TGF-β1 in G. dobula was significantly higher than that in S. prenanti. To investigate whether TGF-β1 in G. dobula possesses hypoxic adaptive features, Gd-TGF-β1 and Sp-TGF-β1 were cloned into an expression vector and transfected into 293-T cells, which are widely used due to their ease of culture, high transfectability, and well-characterized properties. We found that the survival rate of cells transfected with Gd-TGF-β1 was significantly higher than that of cells transfected with Sp-TGF-β1 after hypoxia treatment. Conclusions: These findings suggest that G. dobula may promote hypoxic adaptation through the activation and increased expression of TGF-β1. Changes in TGF-β1 expression may play a role in the adaptation of G. dobula to hypoxic conditions. Full article

Background: The pathophysiology of Alzheimer’s disease (AD) is strongly linked to damage to the cholinergic systems of the central nervous system (CNS), mainly due to the formation of β-amyloid peptide plaques, which trigger intense inflammatory responses and are currently the main cause of the symptoms of the disease. Among the therapeutic strategies under investigation, classes of natural products with immunomodulatory properties, action on the CNS, and potent antioxidant activity, which contribute to neuroprotection, stand out. Methods: We aimed to evaluate the flavonoid quercetin using in silico, in vitro, and in vivo methods for the treatment of AD. Initially, the compounds were selected, and molecular dynamics simulations were performed. The in vitro assays included tests of antioxidant activity (DPPH), enzymatic inhibition of acetylcholinesterase (AChE), and prediction of oral toxicity. The in vivo studies investigated the effects on scopolamine-induced learning deficits and conducted histopathological analysis of the brain. Results: Quercetin showed structural stability in the complex with (AChE), with no significant alterations in the Root Mean Square Deviation (RMSD), SASA and radius of gyration (Rg) parameters. Through the same method it was possible to predict stability between the quercetin and inducible nitric oxide synthase (iNOS) complex, a possible mechanism for quercetin immunomodulation in the CNS. In the AChE inhibition test, the IC₅₀ obtained for quercetin was 59.15 μg mL⁻¹, while in the antioxidant test with DPPH, the concentration of 33.1 µM exhibited 50% of the scavenging of reactive oxygen species. This corroborates the perspective of quercetin having neuroprotective activity. This activity was also corroborated in vivo, in a zebrafish model, in which quercetin reduced the cognitive deficit induced by scopolamine. Histopathological analysis revealed its ability to prevent atrophy, caused by scopolamine, in the nervous tissue of animals, reinforcing the potential of quercetin as a neuroprotective agent. Conclusions: The results of the tests carried out with quercetin suggest that this molecule has antioxidant, AChE inhibitory, and neuroprotective activities, making it a good candidate for use in future clinical trials to ensure its efficacy and safety. Full article

The search for markers applicable for efficient differential diagnosis and personalized therapy is a priority task of experimental neuro-oncology. Modern molecular methods allow us to analyze human biopsy material; however, further actions with this extracted tumor tissue are limited. Relevant and sophisticated CNS tumor models are required for precise therapy development. Although it is possible to use human biomaterial to create 2D and 3D cultures and implant them into xenograft animals, the data generated from such models is limited. Due to changes in the classification of the CNS tumors in 2021, a representative model should have not only morphological similarity to human tumors but also key genetic aberrations for studying the mechanisms of carcinogenesis and personalized therapy (such as PDGFRa, Olig1/2, Sox2, and Mki67) for different glioma models such as astrocytoma, oligodendroglioma, and glioblastoma. On the basis of a unique scientific facility “The Collection of experimental tumors of the nervous system and neural tumor cell lines” (Avtsyn Research Institute of Human Morphology of “Petrovsky National Research Center of Surgery”), there is a biobank of chemically induced transplantable tumors of laboratory animals. Their properties, mechanisms, and progression closely correlate with malignant CNS neoplasms in humans. These are potentially useful for identifying novel signaling pathways associated with oncogenesis in the nervous system and personalizing therapeutic approaches. In our work, we characterized a tissue-transplantable brain tumor strain of rat glioma101.8 using MRI, IHC, scRNA-seq, and qPCR-RT methods. According to this study, the cellular composition of the tissue-transplantable rat glioma 101.8 strain was determined, as well as the major genetic signature characteristics of each cell population of this tissue-transplantable strain and its microenvironment. Full article

Three-dimensional (3D) bioprinting has emerged as a versatile platform in regenerative medicine, capable of replicating the structural and functional intricacies of the central and peripheral nervous systems (CNS and PNS). Beyond structural repair, it enables the construction of engineered tissues that closely recapitulate neural microenvironments. This review provides a comprehensive and critical synthesis of current bioprinting strategies for neural tissue engineering, with particular emphasis on comparing natural, synthetic, and hybrid polymer-based bioinks from mechanistic and translational perspectives. Distinctively, it highlights gradient-based modulation of Schwann cell behavior and axonal pathfinding using mechanically and chemically patterned constructs. Special attention is given to printing modalities such as extrusion, inkjet, and electrohydrodynamic jet printing, examining their respective capacities for controlling spatial organization and microenvironmental cues. Representative applications include brain development models, neurodegenerative disease platforms, and glioblastoma scaffolds with integrated functional properties. Furthermore, this review identifies key translational barriers—including host tissue integration and bioink standardization—and explores emerging directions such as artificial intelligence-guided biofabrication and organ-on-chip integration, to enhance the fidelity and therapeutic potential of neural bioprinted constructs. Full article

Background: The epidermal growth factor receptor (EGFR) is an important factor in the behavior of diffuse glioma, serving as a potential biomarker for tumor aggressiveness and a therapeutic target. Diffusion tensor imaging (DTI) provides insights into the microstructural integrity of brain tissues, allowing for detailed visualization of tumor-induced changes in white matter tracts. This imaging technique can complement molecular pathology by correlating imaging findings with molecular markers and genetic profiles, potentially enhancing the understanding of tumor behavior and aiding in the formulation of targeted therapeutic strategies. The present study aimed to investigate the molecular properties of diffuse glioma based on DTI sequences. Methods: A total of 27 patients with diffuse glioma (in accordance with the WHO 2021 classification) were investigated using preoperative DTI sequences. The study was conducted using the tractography software DSI Studio (Hou versions 2025.04.16). Following the preprocessing of the raw data, volumes of the arcuate fasciculus (AF), frontal aslant tract (FAT), inferior fronto-occipital fasciculus (IFOF), superior longitudinal fasciculus (SLF), and uncinate fasciculus (UF) were reconstructed, and fractional anisotropy (FA) was derived. Molecular pathological examination was conducted to assess the presence of EGFR amplifications. Results: The mean age of patients was 56 ± 13 years, with 33% females. EGFR amplification was observed in 8/27 (29.6%) of cases. Following correction for multiple comparisons, FA in the left AF (p = 0.025) and in the left FAT (p = 0.020) was found to be significantly lowered in EGFR amplified glioma. In the right language network, however, no statistically significant changes were observed. Conclusions: EGFR amplification may be associated with lower white matter integrity of left hemispheric language tracts, possibly impairing neurological function and impacting surgical outcomes. The underlying molecular and cellular mechanisms driving this association require further investigation. Full article