Search Results (685)

The adrenal glands are central to the stress response in cetaceans, yet their morphological and molecular changes under chronic stress remain poorly described. We investigated adrenal histology and protein composition in stranded common dolphins (Delphinus delphis) to assess whether post-mortem material can provide insights into stress physiology. Adrenal glands from 58 dolphins recovered along the Irish coast during a period of reported nutritional stress in the species were analyzed for adrenal mass, cortex-to-medulla (C:M) ratios, and cortical cell density. Additionally, two archival formalin-fixed, paraffin-embedded (FFPE) tissues were included in a pilot trial to assess the feasibility of protein extraction and mass spectrometry analysis. While adrenal mass did not differ significantly between stress types, chronically stressed dolphins exhibited significantly higher C:M ratios and cortical mass, consistent with cortical hypertrophy. Protein extraction from FFPE tissues was feasible, with the in-gel digestion method yielding more proteins (136) than the filter-aided sample preparation method (22). These findings demonstrate that histological and proteomic approaches can detect stress-related signatures in dolphins and highlight the potential of archival tissues for retrospective biomarker discovery. Full article

Quantitative magnetic resonance imaging (qMRI) denotes MRI methods that estimate physical tissue parameters in units, rather than relative signal. Typical readouts include T1/T2 relaxation (ms; or R1/R2 in s⁻¹), proton density (%), diffusion metrics (e.g., ADC in mm²/s, FA), magnetic susceptibility (χ, ppm), perfusion (e.g., CBF in mL/100 g/min; rCBV; K^trans), and regional brain volumes (cm³; cortical thickness). This review synthesizes brain qMRI across T1/T2 relaxometry, myelin/MT (MWF, MTR/MTsat/qMT), diffusion (DWI/DTI/DKI/IVIM), susceptibility imaging (SWI/QSM), perfusion (DSC/DCE/ASL), and volumetry using a unified framework: physics and signal model, acquisition and key parameters, outputs and units, validation/repeatability, clinical applications, limitations, and future directions. Our scope is the adult brain in neurodegenerative, neuro-inflammatory, neuro-oncologic, and cerebrovascular disease. Representative utilities include tracking demyelination and repair (T1, MWF/MTsat), grading and therapy monitoring in gliomas (rCBV, K^trans), penumbra and tissue-at-risk assessment (DWI/DKI/ASL), iron-related pathology (QSM), and early dementia diagnosis with normative volumetry. Persistent barriers to routine adoption are protocol standardization, vendor-neutral post-processing/QA, phantom-based and multicenter repeatability, and clinically validated cut-offs. We highlight consensus efforts and AI-assisted pipelines, and outline opportunities for multiparametric integration of complementary qMRI biomarkers. As methodological convergence and clinical validation mature, qMRI is poised to complement conventional MRI as a cornerstone of precision neuroimaging. Full article

Cerebral ischemia/reperfusion (I/R) injury remains a significant contributor to adult neurological morbidity, primarily due to exacerbated neuroinflammation and cell apoptosis. These processes amplify brain damage through the release of various pro-inflammatory cytokines and pro-apoptotic mediators. Although long non-coding RNAs (lncRNAs) are increasingly recognized for their involvement in regulating diverse biological pathways, their precise role in cerebral I/R injury has not been fully elucidated. In the current study, transcriptomic profiling was conducted using a rat model of focal cerebral I/R, leading to the identification of lncRNA-1810026B05Rik—also referred to as CHASERR—as a novel lncRNA responsive to ischemic conditions. The elevated expression of this lncRNA was observed in mouse brain tissues subjected to middle cerebral artery occlusion followed by reperfusion (MCAO/R), as well as in primary cortical neurons derived from rats exposed to oxygen-glucose deprivation and subsequent reoxygenation (OGD/R). The results suggested that lncRNA-1810026B05RiK mediates the activation of the nuclear factor-kappaB (NF-κB) signaling pathway by physically binding to NF-kappa-B inhibitor alpha (IκBα) and promoting its phosphorylation, thus leading to neuroinflammation and neuronal apoptosis during cerebral ischemia/reperfusion. In addition, lncRNA-1810026B05Rik knockdown acts as an NF-κB inhibitor in the OGD/R and MCAO/R pathological processes, suggesting that lncRNA-1810026B05Rik downregulation exerts a protective effect on cerebral I/R injury. In summary, the lncRNA-1810026B05Rik has been identified as a critical regulator of neuronal apoptosis and inflammation through the activation of the NF-κB signaling cascade. This discovery uncovers a previously unrecognized role of 1810026B05Rik in the molecular mechanisms underlying ischemic stroke, offering valuable insights into disease pathology. Moreover, its involvement highlights its potential as a novel therapeutic target, paving the way for innovative treatment strategies for stroke patients. Full article

Williams–Beuren Syndrome (WBS) is a rare neurodevelopmental disease caused by a microdeletion on chromosome 7 (7q11.23) and associated with behavioral disorders such as hypersociability, impaired visuospatial memory, anxiety, and motor disorders. The precise underlying neurobiological bases remain unknown. The CD mouse is a genetic model that reproduces the deletion found in WBS patients on the equivalent mouse locus. Taking into account that monoaminergic systems are known to modulate behaviors that are altered in WBS, we hypothesized that CD mice could present quantitative and qualitative changes in brain noradrenaline, dopamine, and serotonin systems compared to wild-type (WT) littermates. We sampled 10 brain regions in female mice for quantifying monoamines and related compounds by high-performance liquid chromatography coupled to electrochemical detection. We found a decrease in dopamine in the nucleus accumbens and serotonin and its metabolites in the hypothalamus. Using correlative approaches of tissue content across the brain, we found that the relationships between neurotransmitters or their metabolic ratios (metabolite/neurotransmitter) changed in CD compared to WT. Notably, compared to WT, the ratios in CD mice showed striatal correlations for the serotonin/dopamine systems interaction, and cortical, thalamic, and hypothalamic correlations for the noradrenaline/dopamine systems interaction. The data suggest specific alterations of monoaminergic systems across the brain that could sustain the abnormal behavioral responses displayed by CD mice. Full article

Background: Reconstruction of distal forearm and hand soft tissue defects remains a complex surgical challenge due to the functional and aesthetic significance of the region. Several flap options have been established such as the posterior interosseous artery flap (PIA) or temporalis fascia flap (TFF), yet the anterolateral thigh flap (ALT) has gained increasing attention for its versatility and favorable risk profile. Methods: We retrospectively analyzed 12 patients (7 males, 5 females; mean age 51.8 years) who underwent free microvascular ALT reconstruction for distal forearm and hand defects between May 2020 and May 2025. Etiologies included infection, chemical burns, explosion injuries, and traffic accidents. The mean defect size was 75.4 cm², and the average operative time was 217 min. Secondary flap thinning was performed in eight cases. In one patient without available recipient veins, a pedicle vein was anastomosed using a coupler device anchored into a cortical window of the distal radius to establish venous outflow via the bone marrow. Results: All flaps demonstrated complete survival with successful integration. Minor complications included transient venous congestion in one case and superficial wound dehiscence in four cases. Functional outcomes were favorable, with postoperative hand function rated as very good in 10 of 12 patients at follow-up. The bone-anchored venous anastomosis provided effective venous drainage in the salvage case. Conclusions: The free microvascular ALT is a reliable and highly adaptable method for distal forearm and hand reconstruction. It provides excellent soft tissue coverage, allows for secondary contouring, and achieves both functional and aesthetic goals. Furthermore, intraosseous venous anastomosis using a coupler device might represent a novel adjunct that may expand reconstructive options in cases with absent or unusable recipient veins. Full article

Optimizing in vitro culture conditions for cryopreserved–thawed human ovarian cortical fragments (OCFs) represents a critical step in fertility preservation strategies. OCFs predominantly contain primordial follicles (PMFs), whose survival and integrity are essential for ex vivo folliculogenesis. This study aimed to evaluate the impact of different culture media supplementations on PMF survival and tissue morphology by comparing alpha-Minimum Essential Medium (αMEM) supplemented with Human Serum Albumin (HSA), Human Serum (HS), or Serum Substitute Supplement (SSS). Twenty-nine OCFs were cultured for three days, and follicular density and were morphology assessed. Generalized linear mixed model analysis showed that PMF density was significantly higher in OCFs cultured in medium supplemented with SSS (213 PMFs/mm³) compared to those cultured with HSA (107 PMFs/mm³) or HS (93 PMFs/mm³). Furthermore, SSS supplementation was associated with a significant increase in the number of PMFs showing healthy morphologies. These findings indicate that SSS supplementation to αMEM enhances the survival and preserves better morphologies of the human PMFs in short-term culture, highlighting its potential as a suitable culture supplement for ovarian tissue preservation. Full article

Diseases caused by phytoparasitic nematodes are still a heavy constraint on modern farming, causing losses in crop yields as well as increased production costs due to pest management. Root-lesion nematodes (RLNs) are soil-dwelling migratory endoparasites that infect the roots of several crop species. RLNs feed and reproduce in the cortical cells of affected plant roots typically characterized by development of necrotic spots. Injuries to plant tissues result in weakened plants that become more prone to attack from opportunistic pathogens. In alfalfa (Medicago sativa L.), resistance to Pratylenchus penetrans has been linked to increased transcription of key enzymes in the biosynthesis of phenylpropanoids, important molecules for countering oxidative stress. However, the mechanisms of resistance are still unknown. The present work analyzed indicators of oxidative stress in extracts from transgenic roots of susceptible (cv. Baker) and resistant (cv. MNGRN-16) alfalfa. On extracts of susceptible alfalfa transgenic roots, levels of lipid peroxidation were more than three times higher after seven and fourteen days of growth, while activity of guaiacol peroxidase (GPX) was approximately four times higher after fourteen and twenty-one days of growth, in comparison to the resistant cultivar. This suggests that resistance response may be dependent on plant redox state. Future work will focus on metabolomic characterization of these varieties in contact with RLNs. Full article

Background/Objectives: The role of the molecular chaperone heat shock protein 90 (Hsp90) in pain and analgesia has been recognized; however, no study to date has investigated its role in facial allodynia during headache. In the current study, we examined the role of Hsp90 and its possible connection to the endocannabinoid system utilizing a rodent model of cortical spreading depression (CSD). Methods: CSD, a physiological phenomenon associated with headache disorders, was induced by cortical injection of KCl in female Sprague Dawley rats. To selectively inhibit Hsp90, 17-AAG was applied on the dura mater 24 h before CSD induction. Periorbital allodynia was assessed by von Frey filaments, while tissue samples were subjected to LC-MS, qPCR, Western immunoblotting, and the GTPγS coupling assay. Results: Increased expression of Hsp90 was selectively observed in the periaqueductal gray (PAG) harvested 90 min after cortical KCl injection, suggesting increased cellular stress from CSD induction. Application of 17-AAG (0.5 nmol) on dura mater 24 h before CSD induction significantly prevented facial allodynia as measured by von Frey filaments. This effect was blocked by injection of the CB₁R antagonist rimonabant (1 mg/kg, ip). The pretreatment with 17-AAG significantly increased the level of anandamide (AEA) in PAG 90 min after cortical insult, as measured by LC-MS. This effect was accompanied by reduced expression of FAAH and increased expression of NAPE-PLD in the same nuclei. Conclusions: These results suggest that Hsp90 inhibition positively modulates the endocannabinoid system, causing pain relief through descending pain modulation in PAG post-CSD. Full article

Background/Objectives: Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by motor neuron loss, muscle weakness, and respiratory dysfunction, often culminating in ventilatory failure. Evidence suggests that High-Definition Transcranial Direct Current Stimulation (HD-tDCS) may modulate motor cortical excitability and potentially influence motor and respiratory function in ALS. This study aims to evaluate the effects of home-based HD-tDCS applied over the primary diaphragmatic motor cortex on respiratory parameters and disease progression in individuals with ALS. Methods: This is a multicenter, randomized, controlled clinical trial. Eligible participants (aged 18–80, both sexes, diagnosed with ALS) will be randomized into an active HD-tDCS group (gTDCS) or a sham group (gSham). The intervention consists of 30 min daily HD-tDCS sessions (3 mA) applied for two weeks (5 days/week), using a 4 × 1 ring configuration targeting the diaphragmatic motor cortex. Sham stimulation includes an identical setup but only delivers ramp currents (30 s) with a minimal ongoing current (0.1 mA). Results: Pre-, intra-, and post-intervention evaluations will include measures of cortical excitability, cerebral and tissue perfusion, surface electromyography, respiratory and pulmonary function, fatigue, sleep quality, pain, motor performance, dyspnea, quality of life, and adverse effects. All procedures will be conducted at participants’ homes with appropriate safety monitoring. Conclusions: This study will investigate the effects of HD-tDCS on respiratory and motor function in ALS and explore the feasibility of a home-based neuromodulation intervention. The outcomes may provide insight into non-pharmacological strategies for respiratory management in ALS. Full article

Brain gliomas are highly infiltrative and heterogenous tumors, whose early and accurate detection as well as therapeutic management are challenging. Artificial intelligence (AI) has the potential to redefine the landscape in neuro-oncology and can enhance glioma detection, imaging segmentation, and non-invasive molecular characterization better than conventional diagnostic modalities through deep learning-driven radiomics and radiogenomics. AI algorithms have been shown to predict genotypic and phenotypic glioma traits with remarkable accuracy and facilitate patient-tailored therapeutic decision-making. Such algorithms can be incorporated into surgical planning to optimize resection extent while preserving eloquent cortical structures through preoperative imaging fusion and intraoperative augmented reality-assisted navigation. Beyond resection, AI may assist in radiotherapy dose distribution optimization, thus ensuring maximal tumor control while minimizing surrounding tissue collateral damage. AI-guided molecular profiling and treatment response prediction models can facilitate individualized chemotherapy regimen tailoring, especially for glioblastomas with MGMT promoter methylation. Applications in immunotherapy are emerging, and research is focusing on AI to identify tumor microenvironment signatures predictive of immune checkpoint inhibition responsiveness. AI-integrated prognostic models incorporating radiomic, histopathologic, and clinical variables can additionally improve survival stratification and recurrence risk prediction remarkably, to refine follow-up strategies in high-risk patients. However, data heterogeneity, algorithmic transparency concerns, and regulatory challenges hamstring AI implementation in neuro-oncology despite its transformative potential. It is therefore imperative for clinical translation to develop interpretable AI frameworks, integrate multimodal datasets, and robustly validate externally. Future research should prioritize the creation of generalizable AI models, combine larger and more diverse datasets, and integrate multimodal imaging and molecular data to overcome these obstacles and revolutionize AI-assisted patient-specific glioma management. Full article

Intracortical microelectrode arrays (MEAs) are tools for recording and stimulating neural activity, with potential applications in prosthetic control and treatment of neurological disorders. However, when chronically implanted, the long-term functionality of MEAs is hindered by the foreign body response (FBR), characterized by gliosis, neuronal loss, and the formation of a glial scar encapsulating layer. This response begins immediately after implantation and is exacerbated by factors such as brain micromotion and the mechanical mismatch between stiff electrodes and soft brain tissue, leading to signal degradation. Despite progress in mitigating these issues, the underlying mechanisms of the brain’s response to MEA implantation remain unclear, particularly regarding how cells sense and respond to the associated mechanical forces. Mechanosensitive ion channels, such as the Piezo family, are key mediators of cellular responses to mechanical stimuli. In this study, silicon-based NeuroNexus MEAs consisting of four shanks were implanted in the rat somatosensory cortex for sixteen weeks. Weekly neural recordings were conducted to assess signal quality over time, revealing a decline in active electrode yield and signal amplitude. Immunohistochemical analysis showed an increase in GFAP intensity and decreased neuronal density near the implant site. Furthermore, Piezo1—but not Piezo2—was strongly expressed in GFAP-positive astrocytes within 25 µm of the implant. Piezo2 expression appeared relatively uniform within each brain slice, both in and around the MEA implantation site across cortical layers. Our study builds on previous work by demonstrating a potential role of Piezo1 in the chronic FBR induced by MEA implantation over a 16-week period. Our findings highlight Piezo1 as the primary mechanosensitive channel driving chronic FBR, suggesting it may be a target for improving MEA design and long-term functionality. Full article

Background/Objectives: Cinnamon leaves, an important source of the functional compound cinnamaldehyde (CA), have been shown to be effective in improving type II diabetes and Parkinson’s disease (PD) in rats following the incorporation of cinnamon leaf extract into a nanoemulsion. However, the effect of a cinnamon leaf extract nanoemulsion (CLEN) on improving Alzheimer’s disease (AD), the most prevalent type of dementia, remains unexplored. The objectives of this study were to determine functional compounds in cinnamon leaves by UPLC-MS/MS, followed by the preparation of a nanoemulsion and its byproducts to study their effects on AD and PD in rats. Methods: Oven-dried (60 °C for 2 h) cinnamon leaf powder and hydrosol, obtained by steam distillation of cinnamon leaf powder, were stored at 4 °C. After determination of basic composition (crude protein, crude fat, carbohydrate, moisture and ash) of cinnamon leaf powder, it was extracted with 80% ethanol with sonication at 60 °C for 2 h and analyzed for bioactive compounds by UPLC-MS/MS. Then, the CLEN was prepared by mixing cinnamon leaf extract rich in CA with lecithin, soybean oil, tween 80 and ethanol in an optimal ratio, followed by evaporation to form thin-film and redissolving in deionized water. For characterization, mean particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and surface morphology were determined. Animal experiments were done by dividing 90 male rats into 10 groups (n = 9), with groups 2–8 being subjected to mini-osmotic pump implantation surgery in brain to infuse Amyloid-beta 40 (Aβ40) solution in groups 2–8 for induction of AD, while groups 9 and 10 were pre-fed respectively with cinnamon powder in water (0.5 g/10 mL) and in hydrosol for 4 weeks, followed by induction of AD as shown above. Different treatments for a period of 4 weeks included groups 1–9, with group 1 (control) and group 2 feeding with sterilized water, while groups 3, 4 and 5 were fed respectively with high (90 mg/kg), medium (60 mg/kg) and low (30 mg/kg) doses of cinnamon leaf extracts, groups 6, 7 and 8 fed respectively with high (90 mg/kg), medium (60 mg/kg) and low (30 mg/kg) doses of nanoemulsions, groups 9 and 10 fed respectively with 10 mL/kg of cinnamon powder in water and hydrosol (0.5 g/10 mL). Morris water maze test was conducted to determine short-term memory, long-term memory and space probing of rats. After sacrificing of rats, brain and liver tissues were collected for determination of Aβ40, BACE1 and 8-oxodG in hippocampi, and AchE and malondialdehyde (MDA) in cortices, antioxidant enzymes (SOD, CAT, GSH-Px) and MDA in both cortices and livers, and dopamine in brain striata by using commercial kits. Results: The results showed that the highest level of CA (18,250.7 μg/g) was in the cinnamon leaf powder. The CLEN was prepared successfully, with an average particle size of 17.1 nm, a polydispersity index of 0.236, a zeta potential of −42.68 mV, and high stability over a 90-day storage period at 4 °C. The Morris water maze test revealed that the CLEN treatment was the most effective in improving short-term memory, long-term memory, and spatial probe test results in AD rats, followed by the cinnamon leaf extract (CLE), powder in hydrosol (PH), and powder in water (PW). Additionally, both CLEN and CLE treatments indicated a dose-dependent improvement in AD rats, while PH and PW were effective in preventing AD occurrence. Furthermore, AD occurrence accompanied by PD development was demonstrated in this study. With the exception of the induction group, declines in Aβ40, BACE1, and 8-oxodG in the hippocampi and AchE and MDA in the cortices of rats were observed for all the treatments, with the high-dose CLEN (90 mg/kg bw) exhibiting the highest efficiency. The antioxidant enzyme activity, including that of SOD, CAT, and GSH-Px, in the cortices of rats increased. In addition, dopamine content, a vital index of PD, was increased in the striata of rats, accompanied by elevations in SOD, CAT, and GSH-Px and decreased MDA in rat livers. Conclusions: These outcomes suggest that the CLEN possesses significant potential for formulation into a functional food or botanical drug for the prevention and treatment of AD and/or PD in the future. Full article

The widespread application of organoids in disease modeling and drug development is significantly constrained by challenges in automated quantitative analysis. In bright-field microscopy images, organoids exhibit complex characteristics, including irregular morphology, blurred boundaries, and substantial scale variations, largely stemming from their dynamic self-organization that mimics in vivo tissue development. Existing convolutional neural network-based methods are limited by fixed receptive fields and insufficient modeling of inter-channel relationships, making them inadequate for detecting such evolving biological structures. To address these challenges, we propose a novel detection head, termed Interactive Dual-Perception Head (IDP-Head), inspired by hierarchical perception mechanisms in the biological visual cortex. Integrated into the RTMDet framework, IDP-Head comprises two bio-inspired components: a Large-Kernel Global Perception Module (LGPM) to capture global morphological dependencies, analogous to the wide receptive fields of cortical neurons, and a Progressive Channel Synergy Module (PCSM) that models inter-channel semantic collaboration, echoing the integrative processing of multi-channel stimuli in neural systems. Additionally, we construct a new organoid detection dataset to mitigate the scarcity of annotated data. Extensive experiments on both our dataset and public benchmarks demonstrate that IDP-Head achieves a 5-percentage-point improvement in mean Average Precision (mAP) over the baseline model, offering a biologically inspired and effective solution for high-fidelity organoid detection. Full article

Selective proteasome inhibitors, used to model Parkinsonian-like pathology, are known to disrupt calcium homeostasis, but the role of calcium ions in dopaminergic neuron degeneration remains unclear. The present in vivo study examined the effects of a 7-day intraperitoneal administration of cinnarizine (10 or 30 mg/kg), a voltage-gated calcium channel blocker, in rats unilaterally injected into the substantia nigra compacta (SNc) with lactacystin (Lac; 1 µg/2 µL) or vehicle. Dopamine (DA) and its metabolites were quantified in striatal homogenates via high-performance liquid chromatography. The SN of rats treated with 10 mg/kg cinnarizine was used for Western blot analysis of tyrosine hydroxylase (TH), while tissue from animals receiving 30 mg/kg was processed for histological analysis of TH-immunoreactive (TH-ir) and cresyl violet (CV)-stained neurons. Significant reductions in striatal DA and its metabolites were observed one week after Lac injection, along with increased DA catabolism. Cinnarizine at both doses partially prevented DA loss and attenuated enhanced DA turnover. Moreover, 10 mg/kg cinnarizine partially preserved TH protein levels, while 30 mg/kg provided histological protection of TH-ir neurons in the SN. Cinnarizine was also tested in vitro in human SH-SY5Y neuroblastoma cells and primary mouse cortical neurons exposed to Lac or rotenone to further assess its neuroprotective potential. In SH-SY5Y cells, cinnarizine (1–10 µM) significantly increased cell viability and reduced lactate dehydrogenase release after toxin exposure. Cinnarizine failed to counteract lactacystin-induced toxicity in primary cortical neurons but markedly reduced rotenone-evoked cell death at similar concentrations. These findings indicate that cinnarizine exerts dose-dependent neuroprotective effects in vivo and selective protective actions in vitro, supporting the potential utility of voltage-gated calcium channel blockers in treating Parkinson’s disease. Full article

Objectives: The presence of gingival buccal recession is a frequent problem especially in the canine area. The cortical buccal bone may be absent in presence of health normal lingual/palatal bone and of other periodontal pockets. The present case report describes a minimally invasive approach in a 76-year-old patient with previously endodontically treated lower canine affected by root fracture and by a serious chronic buccal recession. Methods: The tooth was characterized by a deep vestibular bone defect, lack of buccal bone and acute periapical lesion. After extraction, Maryland bridge was positioned on the edentulous area. A two-piece convergent neck transmucosal implant was inserted with a flapless approach after 6 months. Maryland bridge was left in place for additional 3 months. After this time, digital impressions were taken, and a customized abutment was positioned. A provisional crown was designed according to Biologically Oriented Preparation Technique (BOPT) concept and maintained for 6 months. A zirconia definitive crown was digitally designed and cemented with a polycarboxylate-based cement. The Pink Esthetic Score (PES) was used as an index to assess peri-implant soft tissue stability over time (preoperatively, at 9 months, at 12 months and 72 months). Results: The patient was followed for 6 years under a conventional hygienic recall program. No complications occurred, and the PES improved from 4 preoperatively to 8 at 9 months, 10 at 12 months and 13 at 72 months. Conclusions: The use of Maryland bridge prevented occlusal trauma on healing tissues and appeared to support bone and soft tissue healing for transmucosal implant placement. A stable aesthetic rehabilitation was achieved up to 6 years. Full article