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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.

Another Weapon against Cancer and Metastasis: Physical-Activity-Dependent Effects on Adiposity and Adipokines.

Physically active behavior has been associated with a reduced risk of developing certain types of cancer and improved psychological conditions for patients by reducing anxiety and depression, in turn improving the quality of life of cancer patients. On the other hand, the correlations between inactivity, sedentary behavior, and overweight and obesity with the risk of development and progression of various cancers are well studied, mainly in middle-aged and elderly subjects. In this article, we have revised the evidence on the effects of physical activity on the expression and release of the ad

Изучение точных терапевтических средств: вычислительная разработка антисенсовых олигонуклеотидов, предназначенных для использования в патрубках генов AXL в управлении несколькими склерозами.

Множественный склероз (MS) — хроническое аутоиммунное заболевание, характеризующееся обезвоживанием, нейродегенерацией и воспалением в центральной нервной системе. Ген AXL, который кодирует рецепторную тиросину киназы, стал многообещающей терапевтической целью в связи с его участием в нейроинфламмации и дисфункции олигодендроцита. В текущем исследовании мы использовали силико-методы для разработки антисенсе олигонуклеотидов (АСО), которые выборочно нацелены на транскрипцию генов AXL, чтобы модифицировать экспрессию AXL и смягчать патологию MS. Три ASO, A1, A2 и A3 были предназначены для конкре

Harnessing the Therapeutic Potential of Mesenchymal Stem Cells in Cancer Treatment.

Cancer, as a complicated disease, is considered to be one of the major leading causes of death globally. Although various cancer therapeutic strategies have been established, however, some issues confine the efficacies of the treatments. In recent decades researchers for finding efficient therapeutic solutions have extensively focused on the abilities of stem cells in cancer inhibition. Mesenchymal stem cells (MSCs) are multipotent stromal cells that can the most widely extracted from various sources such as the bone marrow (BM), placenta, umbilical cord (UC), menses blood, Wharton's jelly (WJ

ISEV2020 Резюме

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Воздействие метаболического синдрома на нейроинфламму и мозговой барьер.

Метаболический синдром, который включает диабет и ожирение. one из самых распространенных медицинских заболеваний. Она вызывает системное воспаление, приводящее к далеко идущим последствиям для тела, которое все еще обнаруживается. Neuropathology, вызванная метаболическим синдромом, часто является результатом повышения проницаемости кровеносного мозга (ББД). ББД, система, предназначенная для ограничения проникновения токсинов, иммунных клеток и патогенов в мозг, имеет жизненно важное значение для надлежащей нейронной функции. Местное и системное воспаление, вызванное ожирением или типом 2 Мели

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… LAMs expressed by ECs include P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) ( Su et al., 2012 ). The selectins bind to P-selectin glycoprotein ligand (PSGL-1), while ICAM-1 and VCAM-1 bind to α4-integrins on leukocytes. …

Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19.

Defibrotide, which is approved for treating hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), exhibits pleiotropic anti-inflammatory, anti-thrombotic, and fibrinolytic properties, conferring broad endothelial protective effects. Given these mechanisms, defibrotide has potential utility in various conditions involving endothelial injury or activation. In this review we outline the endothelial-protective mechanisms of defibrotide and comprehensively summarize current evidence supporting its applications in hematologic malignancies, including the prevention and treatment

Monoclonal Gammopathies and the Bone Marrow Microenvironment: From Bench to Bedside and Then Back Again.

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by a multistep evolutionary pathway, with an initial phase called monoclonal gammopathy of undetermined significance (MGUS), potentially evolving into the symptomatic disease, often preceded by an intermediate phase called "smoldering" MM (sMM). From a biological point of view, genomic alterations (translocations/deletions/mutations) are already present at the MGUS phase, thus rendering their role in disease evolution questionable. On the other hand, we currently know that changes in the bone marrow microenvironment (TM

Past, Present, and a Glance into the Future of Multiple Myeloma Treatment.

Multiple myeloma (MM) is a challenging hematological cancer which typically grows in bone marrow. MM accounts for 10% of hematological malignancies and 1.8% of cancers. The recent treatment strategies have significantly improved progression-free survival for MM patients in the last decade; however, a relapse for most MM patients is inevitable. In this review we discuss current treatment, important pathways for proliferation, survival, immune suppression, and resistance that could be targeted for future treatments.

Different origin-derived exosomes and their clinical advantages in cancer therapy.

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to ac

Modulating CD8⁺ T cell immunity through exercise: mechanistic insights and implications for precision immunotherapy.

CD8⁺ T lymphocytes are pivotal effectors of adaptive immunity, executing cytotoxic mechanisms essential for pathogen clearance, tumor surveillance and tissue protection. Their activity is shaped by antigenic stimulation, cytokine networks and the metabolic and structural architecture of the tissue microenvironment. Physical exercise has emerged as a potent, non-pharmacological modulator of CD8⁺ T cell biology, capable of influencing recruitment, activation, differentiation and functional persistence. Acute exercise mobilizes effector and memory subsets, enhances trafficking to peripheral tissu

Exploring new drug treatment targets for immune related bone diseases using a multi omics joint analysis strategy.

In the field of treatment and prevention of immune-related bone diseases, significant challenges persist, necessitating the urgent exploration of new and effective treatment methods. However, most existing Mendelian randomization (MR) studies are confined to a single analytical approach, which limits the comprehensive understanding of the pathogenesis and potential therapeutic targets of these diseases. In light of this, we propose the hypothesis that genetic variations in specific plasma proteins have a causal relationship with immune-related bone diseases through the MR mechanism, and that k

Skin Telocytes Could Fundament the Cellular Mechanisms of Wound Healing in Platelet-Rich Plasma Administration.

For more than 40 years, autologous platelet concentrates have been used in clinical medicine. Since the first formula used, namely platelet-rich plasma (PRP), other platelet concentrates have been experimented with, including platelet-rich fibrin and concentrated growth factor. Platelet concentrates have three standard characteristics: they act as scaffolds, they serve as a source of growth factors and cytokines, and they contain live cells. PRP has become extensively used in regenerative medicine for the successful treatment of a variety of clinical (non-)dermatological conditions like alopec

Dendritic cell biology and its role in tumor immunotherapy.

As crucial antigen presenting cells, dendritic cells (DCs) play a vital role in tumor immunotherapy. Taking into account the many recent advances in DC biology, we discuss how DCs (1) recognize pathogenic antigens with pattern recognition receptors through specific phagocytosis and through non-specific micropinocytosis, (2) process antigens into small peptides with proper sizes and sequences, and (3) present MHC-peptides to CD4+ and CD8+ T cells to initiate immune responses against invading microbes and aberrant host cells. During anti-tumor immune responses, DC-derived exosomes were discovere

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… The human DC-specific intercellular adhesion molecule-1 grabbing nonintegrin (DC-SIGN or CD209) is thought to be a canonical of the C-type lectin receptor expressed on both macrophages and DCs [ 15 ]. It is a type 2, mannose-specific C-type lectin that also works as a cytosolic DNA-sensor. …

Biomimetic materials for medical applications.

AbstractRecent advances in biomedical research have facilitated the exploration of biomimetic materials and their potential for diagnosing and treating diseases. This review synthesizes reports of recent research into biomimetic materials and provides a focused analysis of their therapeutic and diagnostic efficacy across multiple physiological systems, including the locomotor, digestive, respiratory, urinary, endocrine, nervous, integumentary, hematopoietic, and circulatory systems. These findings highlight the transformative potential of these materials in the management of systemic diseases.

Disorders of the Gastrointestinal System

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Old Player-New Tricks: Non Angiogenic Effects of the VEGF/VEGFR Pathway in Cancer.

Angiogenesis has long been considered to facilitate and sustain cancer growth, making the introduction of anti-angiogenic agents that disrupt the vascular endothelial growth factor/receptor (VEGF/VEGFR) pathway an important milestone at the beginning of the 21st century. Originally research on VEGF signaling focused on its survival and mitogenic effects towards endothelial cells, with moderate so far success of anti-angiogenic therapy. However, VEGF can have multiple effects on additional cell types including immune and tumor cells, by directly influencing and promoting tumor cell survival, pr

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… adhesion molecule-1; VCAM1: vascular cell adhesion molecule-1; Th(1/2): T helper cell (1/2); Lag3: lymphocyte activation gene 3 protein; Tim3: T-cell immunoglobulin mucin receptor 3; PD-1: programmed cell death protein 1; CTLs: cytotoxic T-lymphocytes; Tregs: T-regulatory cells; MDSCs: myeloid derived … Extravasation into the tumor tissue is dependent upon interactions with adhesion molecules expressed on the immune cells themselves and the luminal surface of the tumors’ endothelial lining such as E-cadherin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) [ …

Bone Metastases: An Overview.

Bone is a frequent site of metastases and typically indicates a short-term prognosis in cancer patients. Once cancer has spread to the bones it can rarely be cured, but often it can still be treated to slow its growth. The majority of skeletal metastases are due to breast and prostate cancer. Bone metastasis is actually much more common than primary bone cancers, especially in adults. The diagnosis is based on signs, symptoms and imaging. New classes of drugs and new interventions are given a better quality of life to these patients and improved the expectancy of life. It is necessary a multid

Cytokines in CAR T Cell-Associated Neurotoxicity.

Chimeric antigen receptor (CAR) T cells provide new therapeutic options for patients with relapsed/refractory hematologic malignancies. However, neurotoxicity is a frequent, and potentially fatal, complication. The spectrum of manifestations ranges from delirium and language dysfunction to seizures, coma, and fatal cerebral edema. This novel syndrome has been designated immune effector cell-associated neurotoxicity syndrome (ICANS). In this review, we draw an arc from our current understanding of how systemic and potentially local cytokine release act on the CNS, toward possible preventive and

Retinal Vein Occlusion-Background Knowledge and Foreground Knowledge Prospects-A Review.

Thrombosis of retinal veins is one of the most common retinal vascular diseases that may lead to vascular blindness. The latest epidemiological data leave no illusions that the burden on the healthcare system, as impacted by patients with this diagnosis, will increase worldwide. This obliges scientists to search for new therapeutic and diagnostic options. In the 21st century, there has been tremendous progress in retinal imaging techniques, which has facilitated a better understanding of the mechanisms related to the development of retinal vein occlusion (RVO) and its complications, and conseq