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Роман CCL3-HMGB1 Ось сигнала регулирует выражение остеоцита РАНКЛ в множестве миеломы.

Множественная миелома (ММ) — клональная плазменная клетка, вызывающая изнурительное заболевание костей. Остеолитическое разрушение, которое является отличительной чертой MM, вызвано увеличением остеокластного числа и усилившейся ресорбцией костей, главным образом в результате чрезмерного производства RANKL, главного регулятора образования остеокласта, в пределах ниши опухоли. Ранее мы сообщали, что остеоциты, самые изобилие клеток в костной нише, поощряют прогрессию опухоли и поддерживают болезнь костей MM, перепроизводяя RANKL. Однако молекулярные механизмы, лежащие в основе регулирования РАН

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… This increase in osteocyte apoptosis contributes to the upregulation of RANKL and the recruitment and activation of osteoclasts. 5 , 33 , 34 During osteocyte apoptosis, HMGB1 is released into the extracellular space through a passive process. 35 High serum HMGB1 levels are found in MM patients and are … Our data demonstrates that CCL3 induces osteocytes to release HMGB1 through a mechanism that does not involve transcriptional changes in HMBG1 but rather initiates a program for active HMGB1 secretion into the extracellular space. …

Chemotherapy-Mediated Complications of Wound Healing: An Understudied Side Effect.

Significance: Chemotherapy is a primary method to treat cancer. While chemotherapeutic drugs are designed to target rapidly dividing cancer cells, they can also affect other cell types. In the case of dermal cells and macrophages involved in wound healing, cytotoxicity often leads to the development of chronic wounds. The situation becomes even more severe when chemotherapy is combined with surgical tumor excision. Recent Advances: Despite its significant impact on patients' recovery from surgery, the issue of delayed wound healing in individuals undergoing chemotherapy remains inadequately ex

Megakaryocyte Contribution to Bone Marrow Fibrosis: many Arrows in the Quiver.

In Primary Myelofibrosis (PMF), megakaryocyte dysplasia/hyperplasia determines the release of inflammatory cytokines that, in turn, stimulate stromal cells and induce bone marrow fibrosis. The pathogenic mechanism and the cells responsible for progression to bone marrow fibrosis in PMF are not completely understood. This review article aims to provide an overview of the crucial role of megakaryocytes in myelofibrosis by discussing the role and the altered secretion of megakaryocyte-derived soluble factors, enzymes and extracellular matrices that are known to induce bone marrow fibrosis.

Obstructive Intramural Coronary Amyloidosis: Uncommon or Under-Recognized Cause of Microvascular Angina?

BACKGROUND: Obstructive intramural coronary amyloidosis (OICA) can be the unique manifestation of cardiac amyloidosis (CA). The clinical onset may mimic ischemic heart disease as microvascular angina or myocardial infarction. CASE SUMMARY: We report an 83-year-old man with long-standing angina, recurrent ischemic symptoms, and persistently elevated troponin levels despite normal coronary angiographies, negative bone scintigraphy, and nondiagnostic cardiac magnetic resonance. Given the clinical suspicion for CA, endomyocardial biopsy was performed and showed extensive transthyretin amyloid dep

Extracellular vesicles in multiple myeloma-bone marrow niche crosstalk: from cellular dialogue to clinical perspectives.

Multiple myeloma (MM) is a haematological neoplasia defined by the clonal expansion of malignant plasma cells within the intricate and dynamic ecosystem of the bone marrow (BM). Although genetic aberrations intrinsic to tumour cells play a critical role in MM initiation, the advancement and aggressiveness of the disease are heavily influenced by ongoing signalling exchanges and persistent interactions with the surrounding microenvironment. Extracellular vesicles (EVs) are increasingly recognized as essential messengers in this reciprocal communication, acting as membrane-encapsulated vehicles

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… Exosomes are typically derived from the endosomal compartment and released into the extracellular space through the fusion of multivesicular bodies with the plasma membrane [ 43 , 44 ]. … MVs, conversely, are released directly from cells into the extracellular space by outward budding and pinching of the plasma membrane [ 45 , 46 ]. ApoBDs, meanwhile, are primarily produced by cells undergoing apoptosis, thereby encapsulating the residues of dying cells [ 47 , 48 ]. …

Mastocytosis-derived extracellular vesicles deliver miR-23a and miR-30a into pre-osteoblasts and prevent osteoblastogenesis and bone formation.

Osteoporosis and other manifestations of bone disease are frequent in patients with systemic mastocytosis (SM) in association with the presence of mast cell infiltrates in bone marrow, although the mechanisms behind bone disease remain poorly understood. We find that extracellular vesicles (EVs) released by neoplastic mast cells and present in the serum of patients with SM (SM-EVs) block osteoblast differentiation and mineralization in culture, and when injected into mice diminish the expression of osteoblast markers, and trabecular bone volume and microarchitecture. We demonstrate that miRNA-

Схемы проявления автоантибиоза в множестве склероза, выявленные благодаря разработке технологии обнаружения автоантигенов.

Множественный склероз (MS) — изнурительное аутоиммунное заболевание CNS, которое характеризуется демиэлированием и аксонной травмой и которому часто предшествует демиелионирующее явление, называемое клинически изолированным синдромом (CIS). Несмотря на важность клеток B и автоантител в патологии MS, их целевые особенности остаются в значительной степени неизвестными. Для агностической и всеобъемлющей оценки автоантител в MS мы разработали и использовали то, что мы считаем новой автоантигенной технологией открытия, Антигеномной платформой. Эта Платформа представляет собой высокопроизводительный

Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core.

Engineering of a "smart" drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer surface biomarker are critical for a targeted treatment to work. Currently, the available delivery systems use a two-dimensional monolayer of cancer cells to test the efficacy of the drug delivery system, but designing a "smart" drug delivery system to be specific for a tumour in vivo and to penetrat

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… The mechanism of FA-SMA loaded curcumin nanoparticles transported through tumour spheroid mass by free diffusion in extracellular space may be facilitated by cyclo-RGDfK (TPP) and α5β1 integrin interactions as depicted in Figure 10 and described by Sugahara et al. [ 7 ]. … FA-SMA loaded curcumin nanoparticles are transported through tumour spheroid mass by free diffusion in extracellular space. …

Machine Learning: A New Prospect in Multi-Omics Data Analysis of Cancer.

Cancer is defined as a large group of diseases that is associated with abnormal cell growth, uncontrollable cell division, and may tend to impinge on other tissues of the body by different mechanisms through metastasis. What makes cancer so important is that the cancer incidence rate is growing worldwide which can have major health, economic, and even social impacts on both patients and the governments. Thereby, the early cancer prognosis, diagnosis, and treatment can play a crucial role at the front line of combating cancer. The onset and progression of cancer can occur under the influence of

Иммуноэксциотоксичность как возможная основная патофизиология, лежащая в основе множественного склероза и других аутоиммунных расстройств.

Аутоиммунные расстройства представляют собой разрушительные процессы, которые считаются атакой на «само» антигены иммунной системы CD+4 T-клеток, которые направлены на антигены, в случае множественного склероза (MS), особенно миелиновых антигенов. Тем не менее все больше фактов свидетельствует о том, что основные разрушительные явления в MS, а также другие аутоиммунные расстройства нецентральной нервной системы (КНС) представляют собой гораздо больше, чем иммунную атаку на CNS, вызванную неправильно управляемой иммунной системой, которая нападает на « само » антиген или антигены в результате п

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… Astrocytes, along with microglia, utilize a group of 5 glutamate transporters (EAAT 1–5) to keep extracellular levels of glutamate low, as high concentrations in the extracellular space (ECS) can be quite destructive. …

A review of recent clinical trials to evaluate disease-modifying therapies in the treatment of cardiac amyloidosis.

Cardiac amyloidosis (CA) is a serious condition that results in infiltrative cardiomyopathy and heart failure with preserved ejection fraction (HFpEF) that is caused by the extracellular deposition of amyloid fibrils within heart tissue. While many important features of CA have been known for years, its prevalence in elderly patients with HF is increasingly being recognized. Plasma cells produce monoclonal immunoglobulin light chains which results in the formation and aggregation of amyloid fibrils that are responsible for AL amyloidosis. CA is classified as originating from either transthyret

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… Amyloid deposits into extracellular space of the myocardium results in thickening and stiffening of ventricular walls with resultant heart failure and conductive dysfunction. Senile ATTR amyloidosis is similar to familial ATTR amyloidosis, except that the non-mutated TTR protein is deposited. … Deposition of these fibrils in the extracellular space leads to the stiffening of the myocardium and depressed cardiac function. This deposition primarily affects diastolic function until late in the disease when left ventricular systolic function is also affected. …

Mesenchymal-Stem-Cell-Based Therapy against Gliomas.

Glioblastoma is the most aggressive, malignant, and lethal brain tumor of the central nervous system. Its poor prognosis lies in its inefficient response to currently available treatments that consist of surgical resection, radiotherapy, and chemotherapy. Recently, the use of mesenchymal stem cells (MSCs) as a possible kind of cell therapy against glioblastoma is gaining great interest due to their immunomodulatory properties, tumor tropism, and differentiation into other cell types. However, MSCs seem to present both antitumor and pro-tumor properties depending on the tissue from which they c

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… Exosomes Derived from MSCs The secretome of MSCs is formed by a set of proteins expressed by MSCs and secreted into the extracellular space. Cytokines, chemokines, growth factors, and extracellular vesicles (EV) belong to this group. … They can fuse with lysosome to be degraded, or they can fuse with the plasma membrane to release their cargo into the extracellular space (exosomes). …

Recent advances in drug repositioning for the discovery of new anticancer drugs.

Drug repositioning (also referred to as drug repurposing), the process of finding new uses of existing drugs, has been gaining popularity in recent years. The availability of several established clinical drug libraries and rapid advances in disease biology, genomics and bioinformatics has accelerated the pace of both activity-based and in silico drug repositioning. Drug repositioning has attracted particular attention from the communities engaged in anticancer drug discovery due to the combination of great demand for new anticancer drugs and the availability of a wide variety of cell- and targ

Tumor Targeting with Peptide-Drug Conjugates: Showcasing Key Progress and Hurdles.

Peptide-drug conjugates (PDCs) are modular, targeted therapeutics composed of a homing peptide linked to a cytotoxic or modulating drug payload via a cleavable/non-cleavable linker. PDCs utilize peptide targeting to enhance the delivery of potent drugs to tumors, providing advantages such as superior tissue penetration, reduced immunogenicity, and simpler manufacture compared to antibody-drug conjugates (ADCs). A comparison of PDCs versus ADCs highlights that PDCs' small size (~1-3 kDa) enables deeper tumor penetration and faster clearance, whereas ADCs (~150 kDa) benefit from prolonged circul

Drug delivery for age-related bone diseases: From therapeutic targets to common and emerging therapeutic strategies.

With the accumulation of knowledge on aging, people have gradually realized that among the many factors that cause individual aging, the accumulation of aging cells is an essential cause of organ degeneration and, ultimately, age-related diseases. Most cells present in the bone microenvironment gradually age over time, leading to an imbalance of osteogenesis, osteoclastogenesis, adipogenesis, and chondrogenesis. This imbalance contributes to age-related bone loss and the development of age-related bone diseases, such as osteoporosis. Bone aging can prolong the lifespan and delay the developmen

Техническое обслуживание дисмиелинических небольших диаметровых аксонов 14-3-3s в центральной нервной системе.

В центральной нервной системе миелин, образующийся вокруг нервных аксонов олигодендроцитом, позволяет эффективно проводить потенциалы действий и поддерживает аксонный гомеостаз. Таким образом, в случае демиелинизирующих заболеваний, таких, как множественный склероз (MS), наблюдается аксональное дегенерация и потеря, особенно в аксонах малых диаметров. Teneurin-4 Недостатки (недостатки)Ten-4 -) Мыши демонстрируют сильное дисмиэлирование микродиаметровых аксонов, но выживают больше года. Здесь мы хотели прояснить механизм выживания аксонов малого диаметра без миелина с помощью Ten-4 - Мыши. Имму

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… In these cases, dysfunctional myelin acts as a physical barrier that does not allow axons to take up metabolites from the extracellular space. …

Нанозимы: инновационная терапия в борьбе с нейродегенеративными заболеваниями.

Нейродегенеративные заболевания, включая болезнь Альцгеймера (AD), болезнь Паркинсона (PD), множественный склероз (MS), амиотропический боковой склероз (ALS) и болезнь Хантингтона (HD), представляют собой серьезную проблему для здоровья населения мира из-за их прогрессивного характера и отсутствия лечения. Эти расстройства характеризуются окислительным стрессом, завязыванием белка и нейроинфламмацией, которые в совокупности приводят к нервным повреждениям и смерти. Последние достижения в нанотехнологии позволили внедрить нанозменные наноматериалы, которые имитируют деятельность, похожую на фер

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… However, enzymes are largely absent in extracellular spaces, except for EC-SOD, making enzyme mimics a potentially valuable solution for providing effective protection. 2.2.1. …

Cancer Stem Cells (CSCs), Circulating Tumor Cells (CTCs) and Their Interplay with Cancer Associated Fibroblasts (CAFs): A New World of Targets and Treatments.

The importance of defining new molecules to fight cancer is of significant interest to the scientific community. In particular, it has been shown that cancer stem cells (CSCs) are a small subpopulation of cells within tumors with capabilities of self-renewal, differentiation, and tumorigenicity; on the other side, circulating tumor cells (CTCs) seem to split away from the primary tumor and appear in the circulatory system as singular units or clusters. It is becoming more and more important to discover new biomarkers related to these populations of cells in combination to define the network am

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… Indeed, the definition of new actors in cancer, as for example CSCs or in blood the CTCs and extracellular vesicles (EVs), lipid bound vesicles secreted by cells into the extracellular space and that can transport cargo—including DNA, RNA, and proteins—between cells as a form of intercellular communication …

Targeting fibrosis, mechanisms and cilinical trials.

Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response. Multiple organs can develop fibrosis, including the liver, kidney, heart, and lung. Fibrosis such as liver cirrhosis, idiopathic pulmonary fibrosis, and cystic fibrosis caused substantial disease burden. Persistent abnormal activation of myofibroblasts mediated by various signals, such as transforming growth factor, platelet-derived growth factor, and fibroblast growh factor, has been recongized as a major event in the occurrence and progression of fibrosi

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… This TGF-β/LAP/LTBP complex binds to the ECM in the extracellular space and inactivates TGF-β 101 . The complex can be cleaved by various proteases to release active TGF-β 102 . Activated TGF-βs bind to TGFβR2 and TGFβR1 100 . …

Analysis of factors influencing the increase of extracellular water ratio in tumor patients without edema signs.

ObjectiveThis study aims to examine the factors contributing to the increase in extracellular water to total body water ratio (ECW/TBW) among tumor patients without visible edema, and to offer insights into the diagnosis and prompt management of early water retention in such patients.MethodsA cohort of 274 tumor patients admitted to Anqing First People's Hospital, affiliated with Anhui Medical University between December 2020 and December 2022, were selected, excluding those with clinically observable edema. General clinical data, main laboratory test outcomes, and body composition indices wer