surgical-protocols-for-deep-cervical-lymphovenous-anastomosis-rat

Surgical Protocols for Deep Cervical Lymphovenous Anastomosis in a Rat Model: Lymph Node and Lymphatic Vessel Anastomoses

Deep cervical lymphovenous anastomosis (dcLVA) has become a promising treatment strategy for Alzheimer&#39;s disease (AD), offering significant ...

The Second Affiliated Hospital of Harbin Medical University

Glioblastoma are highly aggressive brain tumors with poor prognosis. While various dysregulation of signaling pathways in gliomas have been described, the identification of biomarkers and therapy targets remains an important task for novel diagnostic and therapeutic approaches. Here we described that the Suppressor of fused (also known as Sufu) is significantly down-regulated in high-grade gliomas, correlating with a poor prognosis. We demonstrated that ectopic expression of Sufu inhibited cell proliferation, invasion and vasculogenic mimicry. In addition, overexpression of Sufu reduced Gli reporter gene transcription activity and prevented Gli1 nuclear accumulation, whereas knockdown of Sufu reversed these effects. Furthermore, overexpressed Sufu sensitized glioblastoma to Temozolomide and Cyclopamine. Thus, Sufu is potential tumor suppressor and therapeutic target in glioblastoma.

Suppressor of fused (Sufu) represses Gli1 transcription and nuclear accumulation, inhibits glioma cell proliferation, invasion and vasculogenic mimicry, improving glioma chemo-sensitivity and prognosis.

Neuroimaging studies have demonstrated both structural and functional abnormalities in widespread brain regions in patients with subcortical vascular mild cognitive impairment (svMCI). However, whether and how these changes alter functional brain network organization remains largely unknown.

Disrupted topological organization of resting-state functional brain network in subcortical vascular mild cognitive impairment.

Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Radiotherapy plus concomitant and adjuvant TMZ chemotherapy is the current standard of care for patients with GBM. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are key modulators of tumor invasion and metastasis due to their ECM degradation capacity. The aim of the present study was to identify the most informative MMP member in terms of prognostic and predictive ability for patients with primary GBM.

Comparative Analysis of Matrix Metalloproteinase Family Members Reveals That MMP9 Predicts Survival and Response to Temozolomide in Patients with Primary Glioblastoma.

To examine the temporal relationship of cortical autophagic flux with delayed neuronal cell death after hypoxia-ischemia (HI) in neonatal piglets. HI was produced with 45-min hypoxia and 7-min airway occlusion in 3-5-day-old piglets. Markers of autophagic, lysosomal and cell death signaling were studied via immunohistochemistry, immunoblotting, and histochemistry in piglet brains. In vitro, autophagy was impaired in cultured mouse cortical neurons treated with chloroquine with or without rapamycin for 1 d in the presence of Z-VAD-fmk, cyclosporine A, or vehicle control, and cell viability was assessed with the MTT assay. In vivo, neuronal cell death of sensorimotor cortex was delayed by 1-2 days after HI, whereas LC3-II, Beclin-1, PI3KC3, ATG12-ATG-5, and p-ULK1 increased by 1.5-6 h. Autophagosomes accumulated in cortical neurons by 1 d owing to enhanced autophagy and later to decreased autophagosome clearance, as indicated by LC3, Beclin-1, and p62 accumulation. Autophagy flux impairment was attributable to lysosomal dysfunction, as indicated by low lysosomal-associated membrane protein 2, cathepsin B, and cathepsin D levels at 1 d. Ubiquitin levels increased at 1 d. Autophagosome and p62 accumulated predominantly in neurons at 1 d, with p62 puncta occurring in affected cells. Beclin-1 colocalized with markers of caspase-dependent and caspase-independent apoptosis and necrosis in neurons. In vitro, mouse neonatal cortical neurons treated with rapamycin and chloroquine showed increased autophagosomes, but not autolysosomes, and increased cell death that was attenuated by cyclosporine A. Neonatal HI initially increases autophagy but later impairs autophagosome clearance, coinciding with delayed cortical neuronal death.

Impaired autophagosome clearance contributes to neuronal death in a piglet model of neonatal hypoxic-ischemic encephalopathy.

Cerebral small vessel diseases play a crucial role in both vascular and non-vascular dementias. The location of white matter hyperintensities (WMHs), a neuroimaging marker of cerebral small vessel disease, has been found to vary between different types of dementias, and those in the basal ganglia (BG) have been particularly associated with vascular cognitive impairment (VCI). However, anatomical variation of WMHs across BG nuclei and its effect on brain network dysconnectivity has not been clearly elucidated. The study sample consisted of 40 patients with amnestic mild cognitive impairment (aMCI), 40 with subcortical vascular MCI (SVMCI), and 40 healthy control subjects. We examined the volume of WMH using T2-weighted magnetic resonance imaging. We also assessed the disturbances in BG-cortical communication by measuring resting-state functional connectivity (rsFC) from the functional magnetic resonance imaging signal. WMHs were more pronounced in the SVMCI group particularly in the caudate regions. In SVMCI patients, while higher WMHs in the dorsal caudate correlated with weaker FC with executive control regions and worse immediate recall performance, WMHs in the ventral caudate were associated with weaker FC with anterior default mode regions and worse delayed recall performance. In contrast, in aMCI patients, BG WMHs were not correlated with their changes in functional connectivity changes, which showed weaker connectivity with almost all BG structures, rather than restricting to specific BG subdivisions as observed in the SVMCI group. Our findings demonstrate that heterogeneously distributed BG WMHs are associated with changes in functional network interactions and verbal episodic memory performance only in SVMCI patients, which establishes a link between cerebrovascular-related structural abnormality, functional integrity of BG circuits, and episodic memory impairments in SVMCI, and may reflect a differential role of the cerebrovascular pathology in disrupting network-level communications and cognition between Alzheimer's and subcortical vascular dementia.

White Matter Hyperintensities Relate to Basal Ganglia Functional Connectivity and Memory Performance in aMCI and SVMCI.

Increasing evidence indicates that glioma topographic location is linked to the cellular origin, molecular alterations and genetic profile. This research aims to (a) reveal the underlying mechanisms of tumor location predilection in glioblastoma multiforme (GBM) and lower-grade glioma (LGG) and (b) leverage glioma location features to predict prognosis. MRI images from 396 GBM and 190 LGG (115 astrocytoma and 75 oligodendroglioma) patients were standardized to construct frequency maps and analyzed by voxel-based lesion-symptom mapping. We then investigated the spatial correlation between glioma distribution with gene expression in healthy brains. We also evaluated transcriptomic differences in tumor tissue from predilection and nonpredilection sites. Furthermore, we quantitively characterized tumor anatomical localization and explored whether it was significantly related to overall survival. Finally, we employed a support vector machine to build a survival prediction model for GBM patients. GBMs exhibited a distinct location predilection from LGGs. GBMs were nearer to the subventricular zone and more likely to be localized to regions enriched with synaptic signaling, whereas astrocytoma and oligodendroglioma tended to occur in areas associated with the immune response. Synapse, neurotransmitters and calcium ion channel-related genes were all activated in GBM tissues coming from predilection regions. Furthermore, we characterized tumor location features in terms of a series of tumor-to-predilection distance metrics, which were able to predict GBM 1-year survival status with an accuracy of 0.71. These findings provide new perspectives on our understanding of tumor anatomic localization. The spatial features of glioma are of great value in individual therapy and prognosis prediction.

New insights into glioma frequency maps: From genetic and transcriptomic correlate to survival prediction.

Subcortical vascular mild cognitive impairment (svMCI) is associated with structural and functional changes in the cerebral cortex affecting major brain networks. While recent studies have shown that the intrinsic cerebral connectivity networks can be mapped onto the cerebellum, and the cortex and cerebellum are interconnected  the cortico-basal ganglia-cerebellar circuit, structural and functional disruptions in cerebellum in svMCI are rarely studied. In this study, we conducted voxel-based morphometry analysis to investigate gray matter atrophy pattern across cerebellar regions in 40 svMCI patients, and explored alterations in functional connectivity between the basal ganglia and cerebellum. The results showed that the amount of cerebellar atrophy within the default mode, salience, and frontoparietal networks correlated with their counterpart in the cerebral cortex. Moreover, key regions of the cerebellum, including the lobule VI, VIIb, VIII, and Crus I, which are reported to have a role in cognitive function, showed both anatomical atrophy and decreased functional connectivity with the striatum. These atrophy and connectivity patterns in the cerebellum also correlated with memory performances. These findings demonstrate that there are coupled changes in cerebral and cerebellar circuits, reflecting that degeneration patterns in svMCI are not limited to the cerebral cortex but similarly extend to the cerebellum as well, and suggest the cortico-basal ganglia-cerebellar circuit may play an important role in the pathology of svMCI.

Structural atrophy and functional dysconnectivity patterns in the cerebellum relate to cerebral networks in svMCI.

Cortical and subcortical microstructural modifications are critical to understanding the pathogenic changes in frontotemporal lobar degeneration (FTLD) subtypes. In this study, we investigated cortical and subcortical microstructure underlying cognitive and language impairments across behavioral variant of frontotemporal dementia (bvFTD), semantic variant of primary progressive aphasia (svPPA), and nonfluent variant of primary progressive aphasia (nfvPPA) subtypes.

Association of cortical and subcortical microstructure with disease severity: impact on cognitive decline and language impairments in frontotemporal lobar degeneration.

Isocitrate dehydrogenase-wildtype (IDHwt) glioblastoma (GBM) is one of the most aggressive primary brain tumors. The recurrence of GBM is almost inevitable. As an adjuvant option to surgery, intraoperative radiotherapy (IORT) is gaining increasing attention in the treatment of glioma. This study is aimed to evaluate the therapeutic efficacy of IORT on recurrent IDHwt GBM.

Intraoperative radiotherapy in recurrent IDH-wildtype glioblastoma with gross total resection: A single-center retrospective study.

Gliomas are primary brain tumors and are among the most malignant types. Adult-type diffuse gliomas can be classified based on their histological and molecular signatures as IDH-wildtype glioblastoma, IDH-mutant astrocytoma, and IDH-mutant and 1p/19q-codeleted oligodendroglioma. Recent studies have shown that each subtype of glioma has its own specific distribution pattern. However, the mechanisms underlying the specific distributions of glioma subtypes are not entirely clear despite partial explanations such as cell origin. To investigate the impact of multi-scale brain attributes on glioma distribution, we constructed cumulative frequency maps for diffuse glioma subtypes based on T1w structural images and evaluated the spatial correlation between tumor frequency and diverse brain attributes, including postmortem gene expression, functional connectivity metrics, cerebral perfusion, glucose metabolism, and neurotransmitter signaling. Regression models were constructed to evaluate the contribution of these factors to the anatomic distribution of different glioma subtypes. Our findings revealed that the three different subtypes of gliomas had distinct distribution patterns, showing spatial preferences toward different brain environmental attributes. Glioblastomas were especially likely to occur in regions enriched with synapse-related pathways and diverse neurotransmitter receptors. Astrocytomas and oligodendrogliomas preferentially occurred in areas enriched with genes associated with neutrophil-mediated immune responses. The functional network characteristics and neurotransmitter distribution also contributed to oligodendroglioma distribution. Our results suggest that different brain transcriptomic, neurotransmitter, and connectomic attributes are the factors that determine the specific distributions of glioma subtypes. These findings highlight the importance of bridging diverse scales of biological organization when studying neurological dysfunction.

Multi-scale brain attributes contribute to the distribution of diffuse glioma subtypes.

The integration of hippocampal oscillations during non-rapid eye movement (NREM) sleep is crucial for memory consolidation. However, how cardinal sleep oscillations bind across various subfields of the human hippocampus to promote information transfer and synaptic plasticity remains unclear. Using human intracranial recordings from 25 epilepsy patients, we find that hippocampal subfields, including DG/CA3, CA1, and SUB, all exhibit significant delta and spindle power during NREM sleep. The DG/CA3 displays strong coupling between delta and ripple oscillations with all the other hippocampal subfields. In contrast, the regions of CA1 and SUB exhibit more precise coordination, characterized by event-level triple coupling between delta, spindle, and ripple oscillations. Furthermore, we demonstrate that the synaptic plasticity within the hippocampal circuit, as indexed by delta-wave slope, is linearly modulated by spindle power. In contrast, ripples act as a binary switch that triggers a sudden increase in delta-wave slope. Overall, these results suggest that different subfields of the hippocampus regulate one another through diverse layers of sleep oscillation synchronization, collectively facilitating information processing and synaptic plasticity during NREM sleep.

Coordinated NREM sleep oscillations among hippocampal subfields modulate synaptic plasticity in humans.

Autophagy plays a critical role in the pathogenesis of glioblastoma (GBM) and is increasingly being explored as a therapeutic target to enhance the efficacy of chemotherapy across various malignancies. However, comprehensive systematic reviews focusing on autophagy in GBM remain limited. This study aimed to explore emerging trends and future directions in the field of autophagy and GBM through a bibliometric analysis. Relevant literature was retrieved from the Web of Science Core Collection (WoSCC) on September 10, 2024. Comprehensive analyses were conducted using CiteSpace, VOSviewer, and Scimago Graphica to identify key patterns and developments in the field. A total of 1621 publications spanning 20 years of scientific research were retrieved. China and the USA led in article production, with the International Journal of Molecular Sciences and Cancers being the most prolific journals. China Medical University ranked as the top institution for output. Authors Zhan Li and Joanna Jakubowicz-Gil demonstrated the highest productivity, while Roger Stupp had the highest co-citation count. Recent keywords with strong citation burst strength included "Beclin 1," "epithelial-mesenchymal transition," "chloroquine," "unfolded protein response," and "drug resistance." This bibliometric analysis provides an overview of the fundamental knowledge in the fields of autophagy and glioblastoma, highlighting key areas such as the role of autophagy in glioblastoma therapeutic resistance, the dual functions of autophagy in glioblastoma, and the potential of autophagy regulators when combined with conventional therapies. These topics, along with the underlying mechanisms, are expected to be the central focus of future research.

A bibliometric analysis of global research trends in autophagy and glioblastomas.

Benzo[a]pyrene (BaP) is a known environmental carcinogen linked to multiple tumors, but its role in glioblastoma (GBM) remains poorly understood. This study aimed to explore BaP's tumorigenic mechanisms in GBM through an integrated approach combining network toxicology, single-cell transcriptomics, Mendelian randomization, and bibliometric analysis.

Deciphering the carcinogenic role of benzo[a]pyrene in glioblastoma: Insights from network toxicology, single-cell transcriptomics, and Mendelian randomization.

Article	Year
Suppressor of fused (Sufu) represses Gli1 transcription and nuclear accumulation, inhibits glioma cell proliferation, invasion and vasculogenic mimicry, improving glioma chemo-sensitivity an... Oncotarget\| PubMed ID: 25373737	2014
Disrupted topological organization of resting-state functional brain network in subcortical vascular mild cognitive impairment. CNS neuroscience & therapeutics\| PubMed ID: 26257386	2015
Comparative Analysis of Matrix Metalloproteinase Family Members Reveals That MMP9 Predicts Survival and Response to Temozolomide in Patients with Primary Glioblastoma. PloS one\| PubMed ID: 27022952	2016
Impaired autophagosome clearance contributes to neuronal death in a piglet model of neonatal hypoxic-ischemic encephalopathy. Cell death & disease\| PubMed ID: 28703794	2017
White Matter Hyperintensities Relate to Basal Ganglia Functional Connectivity and Memory Performance in aMCI and SVMCI. Frontiers in neuroscience\| PubMed ID: 31798401	2019
New insights into glioma frequency maps: From genetic and transcriptomic correlate to survival prediction. International journal of cancer\| PubMed ID: 36305649	2023
Structural atrophy and functional dysconnectivity patterns in the cerebellum relate to cerebral networks in svMCI. Frontiers in neuroscience\| PubMed ID: 36711147	2022
Association of cortical and subcortical microstructure with disease severity: impact on cognitive decline and language impairments in frontotemporal lobar degeneration. Alzheimer's research & therapy\| PubMed ID: 36941645	2023
Intraoperative radiotherapy in recurrent IDH-wildtype glioblastoma with gross total resection: A single-center retrospective study. Clinical neurology and neurosurgery\| PubMed ID: 38199118	2024
Multi-scale brain attributes contribute to the distribution of diffuse glioma subtypes. International journal of cancer\| PubMed ID: 38949756	2024
Coordinated NREM sleep oscillations among hippocampal subfields modulate synaptic plasticity in humans. Communications biology\| PubMed ID: 39354050	2024
A bibliometric analysis of global research trends in autophagy and glioblastomas. Naunyn-Schmiedeberg's archives of pharmacology\| PubMed ID: 40960516	2025
Deciphering the carcinogenic role of benzo[a]pyrene in glioblastoma: Insights from network toxicology, single-cell transcriptomics, and Mendelian randomization. Ecotoxicology and environmental safety\| PubMed ID: 41038024	2025

Liye Yi

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