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Аккумулирование опустошающих липидов в Arf1-Ablanted Neurorons способствует нейродегенерации с помощью mtDNA и активации воспаляющих путей в Микроглии.

В нейронах и глиальных клетках были обнаружены липидные метаболические расстройства у пациентов с нейродегенеративной (ND) и животных. Однако патологическая связь между липидными капельками и НУ остается слабой. Недавняя работа высветила полезность модели мыши Arf1-knockout с учетом особенностей нейронов и соответствующих клеток для разъяснения связи между расстройствами липидного метаболизма и амиотропическим боковым склерозом (ALS) и множественным склерозом (MS). В этом исследовании было установлено, что недостача арф1 вызвала первичный синтез избытка жирной кислоты через ось АКТ-mTORC1-SREB

Последние достижения в области мезенхимической стволовой клеточной терапии для множественных склерозов: клинические виды применения и проблемы.

Множественный склероз (MS), хроническое аутоиммунное расстройство центральной нервной системы (CNS), характеризуется воспалением, обезвоживанием и нейродегенерацией, что приводит к различным клиническим проявлениям, таким, как усталость, сенсорное расстройство и когнитивная дисфункция. Текущее фармакологическое лечение направлено прежде всего на иммунную модуляцию, но не позволяет остановить прогрессию заболеваний или полностью обратить на нет повреждения CNS. Лечение стволовыми клетками (MSC) является многообещающей альтернативой, используя иммуномудуляторы, нейрозащиту и регенеративные спосо

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… Initially, they are formed by endosomal membrane intraparticles to generate multivesicular bodies. … Throughout this phase, the invagination process generates intraluminal vesicles (ILVs), leading to the formation of multivesicular bodies (MVBs). …

Extracellular Vesicles in Multiple Myeloma-Cracking the Code to a Better Understanding of the Disease.

Multiple myeloma (MM) is a plasma cell-derived malignancy that stands for around 1.5% of newly discovered cancer cases. Despite constantly improving treatment methods, the disease is incurable with over 13,000 deaths in the US and over 30,000 in Europe. Recent studies suggest that extracellular vesicles (EVs) might play a significant role in the pathogenesis and evolution of MM. Further investigation of their role could prove to be beneficial in establishing new therapies and hence, improve the prognosis of MM patients. What is more, EVs might serve as novel markers in diagnosing and monitorin

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… Therefore, three groups are distinguished: exosomes are the EVs created by a fusion of multivesicular bodies (MVB) with the plasma membrane (PM); microvesicles (MVs) are established by direct budding from the PM; and apoptotic extracellular vesicles (ApoEVs) are the result of apoptosis ( Table 1 ). … body MVs microvesicles NFkB nuclear factor kappa-light-chain-enhancer of activated B cells NK natural killer NKG2DLs natural-killer group 2, member D OBs osteoblasts OCs osteoclasts OPG osteoprotegerin PDGF-BB platelet-derived growth factor-BB PGE2 prostaglandin E2 Pgp P-glycoprotein PI3K phosphoinositide …

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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… ESCRT Machinery/MVB Biogenesis Alix, TSG-101, Gag Essential in the formation of multivesicular bodies (MVBs) and exosome biogenesis through the endosomal sorting complex required for transport (ESCRT). … ESCRT Machinery/MVB Biogenesis Alix, TSG-101, Gag Essential in the formation of multivesicular bodies (MVBs) and exosome biogenesis through the endosomal sorting complex required for transport (ESCRT). …

Fate of hematopoietic stem cells determined by Notch1 signaling (Review).

Regulation of the fate of hematopoietic stem cells (HSCs), including silencing, self-renewal or differentiation into blood line cells, is crucial to maintain the homeostasis of the human blood system and prevent leukemia. Notch1, a key receptor in the Notch signaling pathway, plays an important regulatory role in these properties of HSCs, particularly in the maintenance of the stemness of HSCs. In recent decades, the ubiquitination modification of Notch1 has been gradually revealed, and also demonstrated to affect the proliferation and differentiation of HSCs. Therefore, a detailed elucidation

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… Finally, multiple MEs fuse to form multivesicular bodies (MVBs). In this step, Notch1 has the three distinct aforementioned fates, specifically, it either returns to the membrane by circulating endosomes, remains in MVBs, or activates the Notch1 signaling. … Cargo ubiquitination is essential for multivesicular body intralumenal vesicle formation. EMBO Rep. 2012;13:331–338. doi: 10.1038/embor.2012.18. 90. Perry JM, Li L. Self-renewal versus transformation: Fbxw7 deletion leads to stem cell activation and leukemogenesis. …

MicroRNAs and Osteolytic Bone Metastasis: The Roles of MicroRNAs in Tumor-Induced Osteoclast Differentiation.

Osteolytic bone metastasis frequently occurs in the later stages of breast, lung, and several other cancers. Osteoclasts, the only cells that resorb bone, are hijacked by tumor cells, which break down bone remodeling systems. As a result, osteolysis occurs and may cause patients to suffer bone fractures, pain, and hypercalcemia. It is important to understand the mechanism of bone metastasis to establish new cancer therapies. MicroRNAs are small, noncoding RNAs that are involved in various biological processes, including cellular differentiation, proliferation, apoptosis, and tumorigenesis. Mic

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… Exosomes are 40 to 100 nm in diameter and are derived from multivesicular bodies [ 43 , 44 , 45 ]. Two principal methods of collecting EVs are currently used: with and without ultracentrifugation [ 6 , 45 ]. However, the techniques are inadequate for collecting each type of EV [ 44 , 45 ]. …

Extracellular Vesicle-Associated miRNAs and Chemoresistance: A Systematic Review.

Cancer is a leading public health issue globally, and diagnosis is often associated with poor outcomes and reduced patient survival. One of the major contributors to the fatality resultant of cancer is the development of resistance to chemotherapy, known as chemoresistance. Furthermore, there are limitations in our ability to identify patients that will respond to therapy, versus patients that will develop relapse, and display limited or no response to treatment. This often leads to patients being subjected to multiple futile treatment cycles, and results in a reduction in their quality of lif

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… In the context of exosomes, these are mainly identified by the presence of tetraspanins, such as CD81 and CD9, or proteins associated with the key mediators of multivesicular body biogenesis, known as the endosomal sorting complex required for transport (ESCRT) pathway, which includes proteins such as … Furthermore, resistance to chemotherapy can be promoted through the transfer of miRNAs, which are specifically sorted into intraluminal vesicles (ILV), present in multivesicular bodies (MVB) within the donor cell. …

Использование естественных экзоцитозных везикул для борьбы с возрастными заболеваниями: от возрастных драйверов до терапевтических возможностей.

Старение — это сложный биологический процесс, приводящий к увеличению нагрузки возрастных заболеваний (ARD). Клеточная старость, включающая необратимое остановку клеточного цикла и выделение фенотипа секреторной активности при старении (SASP), играет центральную роль в старении и развитии ARD. Естественные экзоцитические везикулы (NEVs) — это везикулы, полученные из клеток, органов и тканей без искусственных вмешательств. В последние годы NEVs привлекли внимание как медиаторы межклеточной коммуникации, и показали многофункциональный потенциал в регулировании клеточной старости и ARD. С одной с

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… Animal NEVs form via the multivesicular body (MVB) pathway, creating exosomes and outer budding, forming ectosomes. Plant NEVs use the MVB and EXPO pathways to produce extracellular vesicles (EVs). Bacterial NEVs differ between gram-negative and gram-positive bacteria. … Over time, these ILVs accumulate within larger structures known as multivesicular bodies (MVBs). …

Exploiting the message from cancer: the diagnostic value of extracellular vesicles for clinical applications.

Liquid biopsy is indispensable for the resolution of current medical issues, such as the cost of developing new drugs and predicting responses of patients to drugs. In this sense, not only the technology for liquid biopsy but also the target biomolecules for biomarkers need to be identified. Extracellular vesicles (EVs), which contain various proteins, including membrane-bound proteins, and RNAs, including mRNA and long/short noncoding RNAs, have emerged as ideal targets for liquid biopsy. These complex biomolecules are covered by a lipid bilayer, which can protect them from degradation. In th

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… Heijnen HF Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules Blood 1999 94 3791 3799 10572093 23. …

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

Multiple Myeloma Cell-Derived Exosomes: Implications on Tumorigenesis, Diagnosis, Prognosis and Therapeutic Strategies.

Multiple myeloma (MM) is a hematological disease that is still not curable. The bone marrow milieu, with cellular and non-cellular elements, participate in the creation of a pro-tumoral environment enhancing growth and survival of MM plasma cells. Exosomes are vesicles oscillating in dimension between 50 nm and 100 nm in size that can be released by various cells and contribute to the pathogenesis and progression of MM. Exosomes enclose proteins, cytokines, lipids, microRNAs, long noncoding RNAs, and circular RNAs able to regulate interactions between MM plasma cells and adjacent cells. Throug

The role of MSCs and CAR-MSCs in cellular immunotherapy.

Chimeric antigen receptors (CARs) are widely used by T cells (CAR-T cells), natural killer cells dendritic cells and macrophages, and they are of great importance in cellular immunotherapy. However, the use of CAR-related products faces several challenges, including the poor persistence of cells carrying CARs, cell dysfunction or exhaustion, relapse of disease, immune effector cell-associated neurotoxicity syndrome, cytokine release syndrome, low efficacy against solid tumors and immunosuppression by the tumor microenvironment. Another important cell therapy regimen involves mesenchymal stem c

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… Exosomes are secreted by the fusion of multivesicular bodies (MVBs) with the plasma membrane. MVBs are formed by inward budding from the external membrane of late endosomes and successive pinching off of budding vesicles into the lumenal space of late endosomes [ 62 ]. … Exosome: From internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci. 2000;113(Pt 19):3365–3374. doi: 10.1242/jcs.113.19.3365. 63. Calvo V, Izquierdo M. T lymphocyte and CAR-T cell-derived extracellular vesicles and their applications in cancer therapy. …

Therapeutic Applications of Stem Cells and Extracellular Vesicles in Emergency Care: Futuristic Perspectives.

Regenerative medicine (RM) is an interdisciplinary field that aims to repair, replace or regenerate damaged or missing tissue or organs to function as close as possible to its physiological architecture and functions. Stem cells, which are undifferentiated cells retaining self-renewal potential, excessive proliferation and differentiation capacity into offspring or daughter cells that form different lineage cells of an organism, are considered as an important part of the RM approaches. They have been widely investigated in preclinical and clinical studies for therapeutic purposes. Extracellula

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… Briefly, exosomes are 40-120 nm sized vesicles resulting from intraluminal budding of multivesicular bodies and fusion of these multivesicular bodies with cell membrane via the endolysosomal pathway. …

Beyond Formulation: Contributions of Nanotechnology for Translation of Anticancer Natural Products into New Drugs.

Nature is the largest pharmacy in the world. Doxorubicin (DOX) and paclitaxel (PTX) are two examples of natural-product-derived drugs employed as first-line treatment of various cancer types due to their broad mechanisms of action. These drugs are marketed as conventional and nanotechnology-based formulations, which is quite curious since the research and development (R&D) course of nanoformulations are even more expensive and prone to failure than the conventional ones. Nonetheless, nanosystems are cost-effective and represent both novel and safer dosage forms with fewer side effects due to m

Application of cell-derived exosomes in the hematological malignancies therapy.

Exosomes are small membrane vesicles of endocytic origin that are produced by both tumor and normal cells and can be found in physiological fluids like plasma and cell culture supernatants. They include cytokines, growth factors, proteins, lipids, RNAs, and metabolites and are important intercellular communication controllers in several disorders. According to a vast amount of research, exosomes could support or inhibit tumor start and diffusion in a variety of solid and hematological malignancies by paracrine signaling. Exosomes are crucial therapeutic agents for a variety of illnesses, such

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… Formation of Multivesicular Bodies (MVBs): late endosomes containing ILVs are referred to as MVBs. MVBs can further undergo two distinct pathways: the recycling pathway or the pathway leading to exosome release ( Rainero and Norman, 2013 ; Raudenska et al., 2021 ). … The biogenesis of exosomes involves three distinct endosomal processes: the formation of endocytic vesicles, the generation of multivesicular bodies (MVBs), and the release of exosomes ( Abels et al., 2016 ; Boriachek et al., 2018 ). …

Extracellular vesicles: a new frontier in diagnosing and treating graft-versus-host disease after allogeneic hematopoietic cell transplantation.

Graft-versus-host disease (GvHD) is a prevalent complication following allogeneic hematopoietic stem cell transplantation (HSCT) and is characterized by relatively high morbidity and mortality rates. GvHD can result in extensive systemic damage in patients following allogeneic HSCT (allo-HSCT), with the skin, gastrointestinal tract, and liver frequently being the primary target organs affected. The severe manifestations of acute intestinal GvHD often indicate a poor prognosis for patients after allo-HSCT. Endoscopy and histopathological evaluation remain employed to diagnose GvHD, and auxiliar

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… Exosomes are vesicles formed by the fusion of multivesicular bodies (MVBs) and the plasma membrane. Microvesicles are vesicles formed by the plasma membrane directly to the outgoing bud, and apoptotic bodies are vesicles released by apoptosis [ 52 ]. … ER, Endoplasmic reticulum; Golgi, Golgi apparatus; ESCRT, Endosomal sorting complex required for transport; MVBs, Multivesicular bodies After in-depth studies over the past decades, various biological effects of EVs have gradually emerged, including mediating intercellular signaling, antigen presentation …

Exosomes derived from BMSCs ameliorate cyclophosphamide-induced testosterone deficiency by enhancing the autophagy of Leydig cells via the AMPK-mTOR signaling pathway.

Cyclophosphamide-induced testosterone deficiency (CPTD) during the treatment of cancers and autoimmune disorders severely influences the quality of life of patients. Currently, several guidelines recommend patients suffering from CPTD receive testosterone replacement therapy (TRT). However, TRT has many disadvantages underscoring the requirement for alternative, nontoxic treatment strategies. We previously reported bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exos) could alleviate cyclophosphamide (CP)-induced spermatogenesis dysfunction, highlighting their role in the treatment

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… [Cytochemical studies on the formation of multivesicular bodies in Leydig cells. Shi Yan Sheng Wu Xue Bao. 1990;23:453–63. [Article in Chinese] 32. Tang XM, Zhang HX, Yi J. [Leydig cells – a normal cell model of cellular autophagy. Shi Yan Sheng Wu Xue Bao. 1992;25:39–47. [Article in Chinese] 33. …

Exosomes: innovative biomarkers leading the charge in non-invasive cancer diagnostics.

Exosomes, nanoscale extracellular vesicles secreted by diverse cell types, have emerged as promising biomarkers for non-invasive tumor diagnostics, offering significant advantages over traditional methods. These vesicles, typically ranging from 30 to 150 nanometers in size, carry a diverse cargo of proteins, lipids, RNA, and microRNAs, which reflect the molecular alterations occurring within their parent cells. Notably, exosomes can be isolated from easily accessible biofluids such as blood, urine, and saliva, making them ideal candidates for liquid biopsy applications. This review explores th

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… Biogenesis of exosomes Exosome biogenesis is a highly regulated, multi-step process involving the formation, maturation, and release of multivesicular bodies (MVBs), which are key intermediates in exosome production. … Exosome biogenesis is primarily centered around the formation of multivesicular bodies (MVBs). These structures are typically derived from the process of endocytosis, during which various mechanisms facilitate the inward budding of the plasma membrane, leading to the creation of early endosomes. …

Exosomal circRNAs: Deciphering the novel drug resistance roles in cancer therapy.

Exosomal circular RNA (circRNAs) are pivotal in cancer biology, and tumor pathophysiology. These stable, non-coding RNAs encapsulated in exosomes participated in cancer progression, tumor growth, metastasis, drug sensitivity and the tumor microenvironment (TME). Their presence in bodily fluids positions them as potential non-invasive biomarkers, revealing the molecular dynamics of cancers. Research in exosomal circRNAs is reshaping our understanding of neoplastic intercellular communication. Exploiting the natural properties of exosomes for targeted drug delivery and disrupting circRNA-mediate

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… Subsequently, these endosomes internally develop into multivesicular bodies, which are aggregates of small vesicles formed by the invagination of the endosomal membrane. … Ultimately, the multivesicular bodies fuse with the plasma membrane, releasing the contained vesicles—known as exosomes—into the extracellular space [ 35 ]. …

Role of Exosomal Non-Coding RNAs in Bone-Related Diseases.

Bone-related diseases seriously affect the lives of patients and carry a heavy economic burden on society. Treatment methods cannot meet the diverse clinical needs of affected patients. Exosomes participate in the occurrence and development of many diseases through intercellular communication, including bone-related diseases. Studies have shown that exosomes can take-up and "package" non-coding RNAs and "deliver" them to recipient cells, thereby regulating the function of recipient cells. The exosomal non-coding RNAs secreted by osteoblasts, osteoclasts, chondrocytes, and other cells are invol

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… Then, under the regulation of endosomal transport complexes and some related proteins, these early endosomes “sprout” and form multivesicular bodies. The latter can release vesicles after fusion with the plasma membrane, and exosomes are formed ( Simons and Raposo, 2009 ; Soekmadji et al., 2013 ). … As the endocardium of the early endosome forms a vesicle into the inner bud, an exosome begins to form and then transform into multivesicular bodies. The latter can release vesicles after fusion with the plasma membrane, and are then known as “exosomes.” …