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Является ли изменение миелинодегенеративное изменение, связанное с возрастом, первоначальным фактором риска нейродегенеративных заболеваний?

Myelination, непрерывное покрытие нейронных аксонов, является пожизненным процессом в нервной системе, который необходим для точного, темпорального пространственного проведения потенциалов действий между нейронами. Myelin также оказывает межклеточную метаболическую поддержку аксонам. Даже незначительные нарушения целостности миелина могут ухудшить нейронные характеристики и повысить подверженность неврологическим заболеваниям. На самом деле, дегенерация миелина — это хорошо известное нейропологическое заболевание, связанное с нормальным старением и несколькими нейродегенеративными заболеваниям

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… This potassium is then either expelled into the extracellular space or transferred through gap junction-coupled astrocytes into capillaries (Brasko et al., 2017; Saab and Nave, 2017; Stadelmann et al., 2019). …

Доклад по делу: Существенное сокращение повреждений и структурные нейронные изменения после лечения ибогина при множественном склерозе.

Множественный склероз (MS) — изнуряющее нейродегенеративное заболевание, характеризующееся демиэлированием и нейронной потерей. Традиционная терапия часто не может остановить прогрессирование заболеваний или обратный неврологический дефицит. Ибогаин, психоактивный алкалоид, был предложен в качестве потенциального нейрогенеративного агента в силу его многогранного фармакологического профиля. Мы представляем два тематических исследования пациентов MS, которые прошли новое лечение ибогином, высветив значительные нейроимации и клинические улучшения. Пациент А продемонстрировал существенное сокраще

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… For Patient A (PA), a dramatic reduction in lesion volume and decreased ADC values may suggest possible remyelination and reduced extracellular space due to diminished inflammation or edema ( 20 ). …

High mobility group box 1 induces bone pain associated with bone invasion in a mouse model of advanced head and neck cancer.

Advanced head and neck cancer (HNC) can invade facial bone and cause bone pain, thus posing a significant challenge to the quality of life of patients presenting with advanced HNC. The present study was designed to investigate HNC bone pain (HNC‑BP) in an intratibial mouse xenograft model that utilized an HNC cell line (SAS cells). These mice develop HNC‑BP that is associated with an expression of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in dorsal root ganglia (DRG) sensory neurons. Our experiments demonstrated that the inhibition of high mobility gr

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… Our present findings demonstrated that HNC SAS cells express HMGB1 in the cytoplasm and subsequently release HMGB1 to the extracellular space. In addition, our in vivo data revealed that HNC cells actively effuse HMGB1 to the extracellular space in bone marrow. …

Plasma Heat Shock Protein 90 Alpha: A Valuable Predictor of Early Chemotherapy Effectiveness in Advanced Non-Small-Cell Lung Cancer.

BACKGROUND Heat shock protein-90 alpha (HSP90a) is more abundant in non-small-cell lung cancer (NSCLC) patients than in control individuals. However, whether it can reflect chemotherapy efficacy remains unknown. This study aimed to investigate the association of HSP90a with chemotherapy in advanced NSCLC. MATERIAL AND METHODS We retrospectively evaluated data from patients admitted to the Department of Respiratory Medicine, Shaoxing People's Hospital, from September 2016 to September 2018 with stage IIIB or IV NSCLC and administered 4 cycles of third-generation platinum-based combination chemo

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… Hsp90α levels in normal human plasma are very low; however, in the tumor state, HSP90α can be specifically secreted by tumor cells to the extracellular space, entering the blood circulation [ 11 , 12 ]. … In cancer, HSP90α is continuously secreted to the extracellular space and acts in the following aspects: (1) extracellular HSP90α functions as a molecular chaperone to keep mutant signaling proteins active; and (2) extracellular HSP90α affects the proto-oncogenes Her-2 and metalloproteinase 2 on the …

Коллаген типа I, скрытый в повреждениях белой материи, препятствует восстановлению и функциональному восстановлению.

Повреждения белой материи вызваны церебральным кровопотоком, связанным с инсультом и демиелинизирующими заболеваниями, такими, как множественный склероз. Ремилинизация происходит спонтанно после травмы белой материи, но прогрессирующий множественный склероз и инсульт белой материи обычно характеризуются провалом ремиэлации. Однако механизмы, лежащие в основе слабого воспоминания о повреждениях, вызванных обезвоживанием и инсультом, остаются неясными. В текущем исследовании мы продемонстрировали, что коллагенные волокна, накопившиеся в демиелионированных повреждениях нескольких склерозных пацие

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… Cerebral infarction causes cerebral oedema after vasoconstriction, leading to the excess accumulation of fluid in the intracellular or extracellular spaces of the brain [ 4 , 35 ]. Collagen fibres were present in intracellular and extracellular spaces after the induction of oedema (Fig. 3N ). … Therefore, these results suggest that collagen fibres were secreted by microglia/macrophages in the oedematous extracellular spaces. Col1a1 colocalises with Iba1-positive microglia/macrophages in ET1-induced lesions. …

Subventricular Zone Microstructure in Pediatric-Onset Multiple Sclerosis.

OBJECTIVE: The aim of this study was to explore the microstructural dynamics of the subventricular zone (SVZ) with aging and their associations with clinical disability and brain structural damage in pediatric-onset multiple sclerosis (MS) patients. METHODS: One-hundred and forty-one pediatric-onset MS patients (67 pediatric and 74 adults with pediatric-onset) and 233 healthy controls (HC) underwent neurological and 3.0 T MRI assessment. Fractional anisotropy (FA) and mean diffusivity (MD) were extracted from the SVZ and the thalamus (as control region). RESULTS: In HC, SVZ FA was higher unt

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… The increase in MD, on the other hand, can be associated with the dynamic changes in brain tissue composition, including a progressive increase in extracellular space and water content. 34 , 35 Compared to HC, FA values in the SVZ were significantly higher in patients with pediatric MS, whereas … On the other hand, in line with the hypothesis of an increased SVZ MD due to increased extracellular space in response to damage, we observed associations between this metric and higher T2 WM LV, lower NBV, normalized thalamic and caudate volumes in adults with pediatric‐onset MS. …

The Role of Extracellular Vesicles (EVs) in the Epigenetic Regulation of Bone Metabolism and Osteoporosis.

Extracellular vesicles (EVs) are complex phospholipidic structures actively released by cells. EVs are recognized as powerful means of intercellular communication since they contain many signaling molecules (including lipids, proteins, and nucleic acids). In parallel, changes in epigenetic processes can lead to changes in gene function and finally lead to disease onset and progression. Recent breakthroughs have revealed the complex roles of non-coding RNAs (microRNAs (miRNAs) and long non-coding RNAs (lncRNAs)) in epigenetic regulation. Moreover, a substantial body of evidence demonstrates tha

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… space and the subsequent exposition of collagen fibrils, degraded by metalloproteases and cathepsin K [ 15 , 16 ]. … An MVB can fuse with plasma membrane releasing its content in extracellular space. ( B ) Plasma membrane can undergo a complex remodeling by sophisticated molecular machinery, generating a bud from which a microvesicle is formed. ( C ) When a cell experiences a severe injury triggering irreversible damage …

Hyaluronan, fluid pressure, and stromal resistance in pancreas cancer.

Pancreatic ductal adenocarcinomas (PDAs) are notoriously aggressive and resistant to treatment. They distinguish themselves further by their robust fibroinflammatory, or desmoplastic, stromal reaction and degree of hypovascularity. Recent findings have revealed multiple mechanisms of stromal complicity in disease pathogenesis and resistance. In this review, we focus on altered physicomechanics as one mechanism of what we term as 'stromal resistance' in PDA. Extremely high interstitial fluid pressures and a dense extracellular matrix combine to limit the delivery and distribution of therapeutic

Никотинамид Аденин динуклеотид дополняет Cuprizone испытуемые многочисленные поведенческие изменения в C57BL/6J Mice.

ЦЕЛЬ: Изучение вопроса о том, может ли добавка никотинамида аденина динуклеотида (NAD+) улучшить поведенческие изменения в модели мыши, опьяненной мышью. МЕТОДЫ: Six- Неделю назад мыши C57BL/6J были разделены на three группы: two еда 0.2% cuprizone chow (cuprizone и cuprizone + NAD+ группы), а другая группа получила нормальную грызуновую (контрольную группу) 4 недель. Мыши в чашезоне + NAD+ группа получили 250 мг/кг/сут NAD+ interperitononyly один раз в день, в то время как другие мыши получали засос одновременно. Были проведены поведенческие тесты на пространственное воспоминание (Моррисский

Functional magnetic resonance imaging in oncology: state of the art.

In the investigation of tumors with conventional magnetic resonance imaging, both quantitative characteristics, such as size, edema, necrosis, and presence of metastases, and qualitative characteristics, such as contrast enhancement degree, are taken into consideration. However, changes in cell metabolism and tissue physiology which precede morphological changes cannot be detected by the conventional technique. The development of new magnetic resonance imaging techniques has enabled the functional assessment of the structures in order to obtain information on the different physiological proces

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… Figure 1 Demonstration of water molecules motion in the intra and extracellular spaces and within the extracellular space providing information on the degree of cellularity of the tissues. …

Множественный склероз: то, что мы узнали и можем узнать из электронной микроскопии.

Множественный склероз (MS) — воспалительное нейродегенеративное заболевание, характеризующееся возникновением демиелинированных повреждений в центральной нервной системе. Повреждения MS могут подвергаться воспоминанию, временно смягчая симптомы, но по мере развития болезни воспроизводство становится менее эффективным. Помимо повреждений, нормальные появляющиеся ткани мозга имеют тонкие изменения, потенциально указывающие на более широкую диффузную патологию и/или повышенную подверженность воздействию повреждений. Патология MS варьируется между повреждениями серых и белых веществ и их нормальны

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… Additional analysis of these axons, extracellular space and neighbouring cells may provide ultrastructural clues on why for example remyelination fails or occurs. … Indeed, in EAE, calcium influx from the extracellular space leads to increased intra-axonal calcium that drives axonal degeneration [ 122 ]. …

Advanced Diagnostic Techniques

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Extracellular Vesicles in Bone Metastasis: Key Players in the Tumor Microenvironment and Promising Therapeutic Targets.

Extracellular vesicles (EVs) are lipid membranous vesicles that are released from every type of cell. It has become clear that EVs are involved in a variety of biological phenomena, including cancer progression, and play critical roles in intracellular communication through the horizontal transfer of cellular cargoes such as proteins, DNA fragments, RNAs including mRNA and non-coding RNAs (microRNA, piRNA, and long non-coding RNA) and lipids. The most common cause of death associated with cancer is metastasis. Recent investigations have revealed that EVs are deeply associated with metastasis.

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… Introduction The existence of membrane-enclosed structures found in the extracellular space has been known for more than 70 years; Chargaff and West first reported platelet-derived procoagulant particles after high-speed centrifugation of human plasma in 1946 [ 1 ]. … These MVBs fuse with the limiting plasma membrane to release exosomes into the extracellular space. Microvesicles originate by direct shedding or budding from the plasma membrane. Apoptotic bodies are released from the cell undergoing programmed cell death [ 13 ]. …

Наномедицина - мощная терапия CAR-T для множественной миеломы: к программируемой, долговременной и точной иммунотерапии.

Множественная миелома (ММ) по-прежнему является трудновыполнимой гематологией. Несмотря на то, что терапия против созревания клеток B (BCMA), ориентированная на химерик антигенный рецептор Т-клектор (CAR-T), существенно углубила клиническую реакцию у пациентов с рецидивом/переносом MM, ее более широкое клиническое применение по-прежнему сдерживается рецидивом после лечения, недостаточной устойчивостью реакции, длительными сроками производства и ограниченной доступностью. Растущие данные свидетельствуют о том, что рецидив после лечения CAR-T в MM происходит не из одного механизма, а из конверге

[Treatment of Bell's palsy: Report of 36 cases].

BACKGROUND: Immune checkpoint inhibitors, including antibodies against programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are being used with increasing frequency for the treatment of cancer. Immune-related adverse events (irAEs) including colitis, dermatitis, and pneumonitis are well described, but less frequent events are now emerging with larger numbers of patients treated. Herein we describe the incidence and spectrum of thrombocytopenia following immune checkpoint inhibitor therapy and two severe cases of idiopathic thrombocytopenic purpura (ITP). CASE PRESENTATIONS

Medication-Related Osteonecrosis of the Jaw: A Systematic Review and a Bioinformatic Analysis.

The objective was to evaluate the current evidence regarding the etiology of medication-related osteonecrosis of the jaw (MRONJ). This study systematically reviewed the literature by searching PubMed, Web of Science, and ProQuest databases for genes, proteins, and microRNAs associated with MRONJ from the earliest records through April 2023. Conference abstracts, letters, review articles, non-human studies, and non-English publications were excluded. Twelve studies meeting the inclusion criteria involving exposure of human oral mucosa, blood, serum, saliva, or adjacent bone or periodontium to a

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… DEGs were predominantly linked to the extracellular region and the extracellular space. Table 5 Gene ontology enrichment analysis performed in Cytoscape using the BiNGO extension. The full set of dysregulated genes/proteins was considered in the analysis. … DEGs were predominantly located in the extracellular space and region, as indicated in Table 6 . Table 6 Gene ontology enrichment analysis in Cytoscape using the BiNGO extension. A set of seventeen hub-dysregulated genes/proteins was considered in the analysis. …

Proteome analysis of urinary biomarkers in a cigarette smoke-induced COPD rat model.

BackgroundChronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease caused by inhalation of cigarette smoke (CS) and other harmful gases and particles.MethodsThis study aimed to explore potential urinary biomarkers for CS-induced COPD based on LC-MS/MS analysis.ResultsA total of 340 urinary proteins were identified, of which 79 were significantly changed (30, 31, and 37 at week 2, 4 and 8, respectively). GO annotation of the differential urinary proteins revealed that acute-phase response, response to organic cyclic compounds, complement activation classical pathway

The advancement and utility of multimodal imaging in the diagnosis of degenerative disc disease.

Degenerative disc disease (DDD) is a common spinal condition characterized by the deterioration of intervertebral discs, leading to chronic back pain and reduced mobility. While magnetic resonance imaging (MRI) has long been the standard for late-stage DDD diagnosis, its limitations in early-stage detection prompt the exploration of advanced imaging methods. Positron emission tomography/computed tomography (PET/CT) using 18F- fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) has shown promise in identifying metabolic imbalances and age-related spinal degeneration, thereby complementing CT

A Case of AL Amyloidosis With Hepatomegaly as the Main Clinical Manifestation.

Light chain (AL) amyloidosis presenting predominantly with hepatomegaly is a rare and frequently misdiagnosed condition. While clinical features are non-specific, elevated ALP/GGT should raise suspicion. A liver biopsy remains the gold standard for diagnosis. Although there is no disease-specific therapy for hepatic amyloidosis, timely chemotherapy initiation-particularly monoclonal antibody-based regimens-can significantly improve prognosis and lead to symptom resolution.

Ущерб от белой материи при нарушении центральной нервной системы.

По мере ускорения процесса старения и улучшения условий жизни болезни центральной нервной системы (СНС) стали одной из основных проблем здравоохранения. Болезни CNS вызывают не только повреждения серых веществ, которые в первую очередь характеризуются потерей нейронов, но и повреждения белых веществ. Однако в большинстве предыдущих исследований основное внимание уделялось травматизму серого вещества (ГМИ), при этом было проведено меньше исследований травматизма белого вещества (ВМИ). В этой статье мы кратко опишем структуру и функцию белого вещества, подытожим патологические изменения ВМИ и со

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… MBP, an intracellular protein and a major structural protein component of myelin, has been shown to bind Aβ and inhibit the formation of Aβ protofibrils in AD, which regulates Aβ in the extracellular space of the brain in AD patients. …