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Exosomes for angiogenesis induction in ischemic disorders.

Ischaemic disorders are leading causes of morbidity and mortality worldwide. While the current therapeutic approaches have improved life expectancy and quality of life, they are unable to "cure" ischemic diseases and instate regeneration of damaged tissues. Exosomes are a class of extracellular vesicles with an average size of 100-150 nm, secreted by many cell types and considered a potent factor of cells for paracrine effects. Since exosomes contain multiple bioactive components such as growth factors, molecular intermediates of different intracellular pathways, microRNAs and nucleic acids, t

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… MicroRNA‐126 regulates angiogenesis and neurogenesis in a mouse model of focal cerebral ischemia. Mol Ther Nucleic Acids. 2019;16:15‐25. 73. Ye M, Ni Q, Qi H, et al. … MicroRNA‐enriched exosomes from different sources of mesenchymal stem cells can differentially modulate functions of immune cells and neurogenesis. Biomedicine. 2021;10:69. 108. Butreddy A, Kommineni N, Dudhipala N. …

Терапевтический потенциал моделей Purmorphamine через болезни.

Purmorphamine (PUR) — тройная субституция пурина, которая выборочно активирует сгущенный рецептор, тем самым инициируя Sonic Hedgehog (Shhh) сигнализирующий путь, имеющий решающее значение для эмбриональной модели, нейронной спецификации и регенерации тканей в различных системах различных органов. Регулирование сигнала " Шш " причастно к дегенеративным заболеваниям, однако терапевтические меры, направленные на этот путь, по-прежнему ограничены. PUR демонстрирует широкую терапевтическую эффективность различных моделей предклинических заболеваний путем активации как транскрипции с помо

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… . | ↓ Inflammation, astrogliosis, BBB permeability; ↑ neurogenesis & neurovascularization | [ 40 ] ALS | 2022 | Mouse, SOD1G93A | 15 mg/kg every 3 days (from 9 weeks) | i.p. | ↑ Survival & motor performance; PI3K/Akt involvement | [ 20 ] ALS | 2025 | Mouse, hSOD1 | 15 mg/kg every 3 days | i.p. | ↑ FAK … Disruption of Shh signalling has been associated with increased oxidative stress, abnormal neurogenesis and compromised BBB integrity [ 10 , 40 ]. One environmental factor known to perturb this pathway is propionic acid (PPA), a short‐chain fatty acid produced by gut microbiota [ 68 ]. …

Полиморфизм меланкортина - генезиалы с воспалением и болезнями.

Рецепторы Меланокортина (МКР) выполняют различные функции: от пигментации кожи, регулирования аппетита, реакции на стресс и когниции, синтеза стероидов и энергетического баланса до регенерации клеток и иммуномодуляции. Генетический полиморфизм с распределением тканей от мозга, лимбической системы и адренальной коры до нейтрофилов, моноцитов и макрофазов проявляется в MCR. Мутации в генах MC1R, MC2R, MC3R и MC4R связаны с риском меланомы, семейной глюкокортикоидной недостаточности, ожирения и типа 2 Диафиозный сахар, соответственно. Тем временем, MC1R, MC2R и MC5R связаны с риском серьезного де

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… Melanocortin activates crucial signaling pathways and thus promotes neurogenesis, which could be beneficial for conditions where neuronal loss is a prominent feature. … Its ability to enhance neutrophil activity and antipyretic effects is effective in the treatment of stroke, subarachnoid hemorrhage, and Alzheimer’s disease, and it enhances neurogenesis [ 73 ]. …

The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.

Bone metastases represent a major cause of morbidity in advanced cancers, yet the neural regulation of metastatic growth within bone remains largely unexplored. The skeletal system is richly innervated by sensory and sympathetic nerve fibers that influence bone remodeling, hematopoiesis, and immune surveillance. Emerging evidence suggests that disseminated tumor cells exploit these neural circuits to create a growth-permissive microenvironment. Tumor-secreted neurotrophic factors can induce nerve sprouting, while sympathetic activation via β-adrenergic receptors promotes osteoclastogenesis, im

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… Sema4F can cause axonogenesis and perineural invasion in prostate cancer, directly promoting tumor neurogenesis, while class 3 semaphorins often prevent axon development in malignancies [ 63 , 64 ]. … Extracellular vesicles (EVs) generated from tumors contain proteins and miRNAs that reprogram neurons and stromal cells, promoting neurogenesis in premetastatic and metastatic bone niches [ 71 , 72 ]. …

Intranasal administration of aTf protects and repairs the neonatal white matter after a cerebral hypoxic-ischemic event.

Our previous studies showed that the intracerebral injection of apotransferrin (aTf) attenuates white matter damage and accelerates the remyelination process in a neonatal rat model of cerebral hypoxia-ischemia (HI) injury. However, the intracerebral injection of aTf might not be practical for clinical treatments. Therefore, the development of less invasive techniques capable of delivering aTf to the central nervous system would clearly aid in its effective clinical use. In this work, we have determined whether intranasal (iN) administration of human aTf provides neuroprotection to the neonata

Spontaneous activity promotes synapse formation in a cell-type-dependent manner in the developing retina.

Spontaneous activity is thought to regulate synaptogenesis in many parts of the developing nervous system. In vivo evidence for this regulation, however, is scarce and comes almost exclusively from experiments in which normal activity was reduced or blocked completely. Thus, whether spontaneous activity itself promotes synaptogenesis or plays a purely permissive role remains uncertain. In addition, how activity influences synapse dynamics to shape connectivity and whether its effects among neurons are uniform or cell-type-dependent is unclear. In mice lacking the cone-rod homeobox gene (Crx),

Ageing, Cellular Senescence and Neurodegenerative Disease.

Ageing is a major risk factor for developing many neurodegenerative diseases. Cellular senescence is a homeostatic biological process that has a key role in driving ageing. There is evidence that senescent cells accumulate in the nervous system with ageing and neurodegenerative disease and may predispose a person to the appearance of a neurodegenerative condition or may aggravate its course. Research into senescence has long been hindered by its variable and cell-type specific features and the lack of a universal marker to unequivocally detect senescent cells. Recent advances in senescence mar

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… Although the role of adult neurogenesis in AD remains contentious, studies from animal models indicate that ablation of adult neurogenesis exacerbates memory deficits and upregulates hyperphosphorylated tau [ 111 ], whereas implantation of human neural stem cells alleviates memory deficits and AD pathology … In addition, a shift towards an interferon I-dependent expression profile is seen with ageing in human and mouse choroid plexus, which may adversely affect cognitive function and hippocampal neurogenesis [ 135 ]. …

Effects of physical exercise during adjuvant chemotherapy for breast cancer on long-term tested and perceived cognition: results of a pragmatic follow-up study.

PurposeCancer-related cognitive impairment (CRCI) following chemotherapy is commonly reported in breast cancer survivors, even years after treatment. Data from preclinical studies suggest that exercise during chemotherapy may prevent or diminish cognitive problems; however, clinical data are scarce.MethodsThis is a pragmatic follow-up study of two original randomized trials, which compares breast cancer patients randomized to exercise during chemotherapy to non-exercise controls 8.5 years post-treatment. Cognitive outcomes include an online neuropsychological test battery and self-reported cog

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… Rodent studies describe various pathways via which exercise can benefit cognition, such as stimulating hippocampal neurogenesis [ 11 , 12 ]. … Liu PZ, Nusslock R (2018) Exercise-mediated neurogenesis in the hippocampus via BDNF. Front Neurosci 12. 10.3389/FNINS.2018.00052 10.3389/fnins.2018.00052 PMC5808288 29467613 12. …

Association between miR-182 rs76481776 Polymorphism and Antidepressant Treatment Response in Patients with Depression.

ObjectiveThe efficacy of antidepressants is influenced by a combination of genetic, individual, and environmental factors. This study aimed to investigate the association between the miR-182 rs76481776 polymorphism and the response to antidepressant treatment in major depressive disorder (MDD) patients, and its underlying molecular mechanisms.MethodsThis study enrolled 180 MDD patients and 180 healthy controls. The rs76481776 genotype was determined using TaqMan-based qPCR. The severity of depression and treatment response were assessed using the Hamilton Depression Rating Scale (HAMD). The ex

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… Furthermore, miR-182-5p has been linked to depression-like behaviors [ 18 ]; knockout of miR-182-5p can alleviate chronic social defeat stress (CSDS)-induced depression-like behaviors in mice and inhibit neurogenesis [ 19 ]. … Furthermore, in a mouse model of CSDS, administration of a miR-182-5p agonist significantly prolonged immobility time and exacerbated impairments in neurogenesis [ 19 ]. …

Изменения лакта и лактилации в неврологических расстройствах.

Значительное внимание стало уделяться изучению изменений в лактилации различных целевых органов как в области здравоохранения, так и в области болезней. Многие жизненно важные процессы и начало болезней связаны не только с избытком белков, но и в первую очередь регулируются различными посттрансляционными изменениями белков. Лактат, который раньше считался лишь побочным продуктом анаэробного метаболизма, превратился в важнейшую энергетическую субстрату и сигнализирующую молекулу, связанную как с физиологическими, так и патологическими процессами в нервной системе. Кроме того, в недавних исследо

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… Additionally, in 2019, Wang et al. confirmed in mice that brain endothelial cells play a crucial role in maintaining lactate homeostasis and regulating adult hippocampal neurogenesis. … Furthermore, overexpression of MCT1 in the brain vasculature or the loss of protein kinase B1 can restore MCT1 expression in phosphatase and tensin homolog mutant mice, reduce lactate levels, and normalize hippocampal neurogenesis and cognitive function. …

CHI3L1 в Множественном склерозе-от скамьи до клиники.

Множественный склероз (MS) — хроническое демиелинирующее заболевание центральной нервной системы (CNS) с сложным и не вполне понятным этиопатологическим фоном, предусматривающим воспалительные и нейродегенеративные процессы. CHI3L1 был замешан в таких патологических условиях, как воспаление, повреждение и нейродегенерация, и, вероятно, будет играть определенную роль в физиологическом развитии CNS. CHI3L1 производится главным образом макрофагами CNS, микроглией и активированными астроцитами. Структура выражения CHI3L1 при поражениях MS может поддержать важную роль астроцитов в модуляции подстре

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… In neurodegenerative diseases, CHI3L1-RAGE interactions influence neurogenesis by affecting neural stem cell proliferation and differentiation [ 54 , 55 ]. … Several studies have shown CHI3L1 involvement in neurogenesis and neuronal function, plasticity, and regeneration via engagement in the signaling pathways of neurotrophic factors [ 33 , 70 , 78 ]. …

Роль и функции " Ирисина " : перспективы последних изменений и неевродегенеративных заболеваний.

Irisin — пептид, полученный из фибронектина типа III, содержащего домен белка 5 (FNDC5) и производимый главным образом мышечными волокнами в соответствии с регулированием пероксисомных прорациатрированных рецепторов гамма-коативатора 1-альфа (PGC1α) во время упражнения. Ирисин стал объектом обширных исследований в силу его потенциала как метаболического регулятора и его антиоксидантных свойств. В частности, она связана с защитными действиями в мозгу. Несмотря на растущий интерес, остается много вопросов относительно молекулярных механизмов, лежащих в основе их воздействия. В настоящем обзоре р

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… In this context, it should also be noted that irisin is one of the few known stimuli capable of inducing de novo neurogenesis [ 42 , 76 , 77 ], which also attenuates neuronal damage and synaptic loss [ 78 , 79 , 80 , 81 , 82 , 83 ]. … Additionally, some evidence suggests that irisin functions in vivo as a neuroprotective agent, promoting synaptic plasticity and neurogenesis, enhancing memory performance, and regulating the production of BDNF [ 74 , 273 ]. …

Review of the Current Knowledge on the Role of Stem Cell Transplantation in Neurorehabilitation.

The management involving stem cell (SC) therapy along with physiotherapy offers tremendous chance for patients after spinal cord injury (SCI), traumatic brain injury (TBI), stroke, etc. However, there are still only a limited number of reports assessing the impact of stem cells (SCs) on the rehabilitation process and/or the results of the simultaneous use of SC and rehabilitation. Additionally, since there is still not enough convincing evidence about the effect of SCT on humans, e.g., in stroke, there have been no studies conducted concerning rehabilitation program formation and expected outc

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… Previously, Joseph Altman (PhD) of the Massachusetts Institute of Technology (MIT) discovered neuronal generation (neurogenesis) in rats in 1962. … Moreover, these data suggest that implants of exogenous NSCs may promote regeneration in aging organisms through stimulation of endogenous neurogenesis [ 4 , 5 ]. Recently, the molecular mechanisms involved in the process of differentiation of the NSCs have been described [ 6 ]. …

Эгоистические нейрофармацевтики: открытие кровеносного барьера для лечения следующего поколения.

Блокирование мозга крови (ББД) представляет собой огромную проблему в нейрофармакологии, ограничивая доставку терапевтических агентов в мозг. Экзосомы, нанокарьеры природы, стали многообещающим решением из-за их биосовместимости, низкой иммуногенности и врожденной способности пересекать ББД. Тщательное изучение анатомии и физиологии ББД свидетельствует о сложности доставки неврологических наркотиков и подчеркивает ограниченность традиционных методов. В настоящем обзоре изучается потенциал нейрофармацевтики с экзосомной силой, при этом особое внимание уделяется их структурным и функциональным с

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… In a streptozotocin (STZ)-induced AD rat model, CoQ10-loaded exosomes improved spatial memory, increased hippocampal neuron density, and elevated brain-derived neurotrophic factor (BDNF) and SRY-related HMG-box 2 (SOX2) expression, highlighting their role in neuroprotection and neurogenesis [ 126 ]. …

Gut microbiota and microbial metabolites for osteoporosis.

Osteoporosis is an age-related bone metabolic disease. As an essential endocrine organ, the skeletal system is intricately connected with extraosseous organs. The crosstalk between bones and other organs supports this view. In recent years, the link between the gut microecology and bone metabolism has become an important research topic, both in preclinical studies and in clinical trials. Many studies have shown that skeletal changes are accompanied by changes in the composition and structure of the gut microbiota (GM). At the same time, natural or artificial interventions targeting the GM can

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… physical contact appears to be crucial to experiencing the positive effects of social interaction. 95 In addition, studies have suggested that social interaction rescues memory deficits in animal models of Alzheimer’s disease by increasing brain-derived neurotrophic factor (BDNF)-dependent hippocampal neurogenesis … | C57BL/6 mice (24 months) | Young GF mice (5–6 weeks) | However, recipient mice transplanted with gut microbes from old mice may have advantages in hippocampal neurogenesis, intestinal surface area expansion, and butyrate metabolism compared with recipient mice transplanted with gut microbes from young …

Читинас-3-подобный-1: многообразный игрок в нейроинфламмации и дегенеративной патологии с терапевтическими последствиями.

Читинас-3-подобный-1 (CHI3L1) — эволюционно сохранившийся белок, содержащийся в ключевых биологических процессах, включая реконструирование тканей, ангиогенез и нейроинфламмацию. Она стала важным игроком в различных нейродегенеративных заболеваниях и расстройствах мозга. Повышенные уровни CHI3L1 наблюдались в таких неврологических условиях, как травматическое повреждение мозга (TBI), болезнь Альцгеймера (AD), болезнь Паркинсона (PD), амиотропический боковой склероз (ALS), болезнь Креуцфельда-Якоба (CJD), множественный склероз (MS), оптика нейромиелита (NMO), вызванная ВИЧ деменция (HAD), цереб

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… Recent findings further expand CHI3L1’s role in NMO-related neuroinflammation by implicating its signaling in hippocampal neurogenesis and cognitive function. … This novel mechanism involves CHI3L1 engaging the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), leading to the suppression of β-catenin signaling, which is crucial for neurogenesis [ 31 ]. …

Long-Term Outcomes of Pituitary Gland Preservation in Pituitary Macroadenoma Apoplexy: Case Series and Review of the Literature.

Introduction  For patients presenting with neurological changes from pituitary tumor apoplexy, urgent surgical intervention is commonly performed for diagnosis, tumor resection, and optic apparatus decompression. Although identification and preservation of the pituitary gland during the time of surgery can be challenging, it may lead to improve endocrine outcomes. Methods  A retrospective case series of all patients with macroadenomas presenting with apoplexy at Loyola University Medical Center from 2016 to 2018 was studied. Demographic, radiographic, and intraoperative characteristics were co

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… , thus resulting in less or no dysfunction in adult neurogenesis and associated functions, such as memory. 44 Finally, tapentadol shows minimal serotoninergic activity, which is important in the prolonged management of patients, since serotoninergic pathways may promote pain and nausea. 39 Figure 1 Schematic … Opiate analgesics as negative modulators of adult hippocampal neurogenesis: potential implications in clinical practice . Front Pharmacol . 2017 ; 8 : 254 . doi: 10.3389/fphar.2017.00254 28536527 PMC5422555 45. Kress HG , Ahlbeck K , Aldington D , et al. …

От ожирения до митохондриальной дисфункции в периферальных тканях и в центральной нервной системе.

Ожирение - это состояние хронического низкосортного воспаления, затрагивающего периферийные органы тела, а также центральную нервную систему. Дефункция жировой ткани, возникающая в условиях ожирения, является ключевым фактором возникновения и развития различных заболеваний, включая нейродегенеративные расстройства. Митохондрия, ключевые органеллы в производстве клеточной энергии, играет важную роль в этой дисфункции тканей. В многочисленных исследованиях подчеркивается тесная связь между ожирением и дисфункцией митохондриалов адипоцита, что приводит к чрезмерному производству ROS и воспалению

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… When the BBB is damaged, peripheral inflammatory cytokines and leukocytes migrate into the brain, resulting in reduced synaptic plasticity and impaired neurogenesis [ 17 ]. Thus, in obesity, peripheral immune cells can be recruited into the CNS like macrophages in white adipose tissue. … Furthermore, a high-fat diet compromised neurogenesis in the rodent hippocampus, a brain structure related to cognition, memory, learning, and emotions [ 22 ], enhanced lipid peroxidation, and reduced levels of brain-derived neurotrophic factor (BDNF). …

Терапевтическая ориентация на нейроинфламацию, вызванную ожирением, и нейродегенерацию.

Ожирение является одним из основных из изменяемых факторов риска, ведущих к нейроинфламмации и нейродегенерации. Чрезмерное содержание жира в ожирении способствует постепенному проникновению иммунных клеток в жировые ткани, что приводит к высвобождению провоспалительных факторов, таких, как цитокины и адипокины. Эти подстрекательские посредники циркулируют по кровотоку, пропагандируя воспаление как на периферии, так и в центральной нервной системе. Гут дисбиоз, который приводит к утечке кишечного барьера, усугубляет воспаление и играет важную роль в увязке ожирения с патогенезом нейроинфламмац

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… In the brain, obese mice treated with TAK-242 exhibited a significant reduction in microglial activation, improved levels of neurogenesis, and inhibition of soluble amyloid beta (Aβ) levels ( 29 ). … Interestingly, when comparing between the effects of caloric restriction and exercise on HFD rats, it was shown that long-term caloric restriction (16-weeks) has the greater systemic metabolic benefit, including improved synaptic function, neuronal insulin signaling, neurogenesis and increased mitochondrial …

IGF-1 defends against chronic-stress induced depression in rat models of chronic unpredictable mild stress through the PI3K/Akt/FoxO3a pathway.

This study aims to investigate the role of IGF-1 in chronic-stress induced depression through the PI3K/Akt/FoxO3a pathway. A rat model of chronic unpredictable mild stress (CUMS) was established. In total, 48 rats were randomized into control (normal rats), CUMS (CUMS modeled rats) and CUMS + IGF-1 (injection of IGF-1 before CUMS modeling) groups. Body weight, horizontal (number of horizontal crossing) and vertical activity (rearing times), and sucrose consumption were identified one day before and after the open-field test. The mRNA and protein expression of PI3K, Akt, FoxO3a and Bim in the h

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… Accumulating evidence shows that the pathology of depression is associated with neuronal inflammation and can be alleviated by neurogenesis [7] . … The pathology of depression is reported to be associated with neuronal inflammation, while depression is believed to be alleviated by neurogenesis [7] . …