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Cancer-Associated Thrombosis: A New Light on an Old Story.

Cancer-associated thrombosis (CAT) is a rising and significant phenomenon, becoming the second leading cause of death in cancer patients. Pathophysiology of CAT differs from thrombosis in the non-cancer population. There are additional risk factors for thrombosis specific to cancer including cancer type, histology, and treatment, such as chemotherapy. Recently developed scoring systems use these risk factors to stratify the degree of risk and encourage thromboprophylaxis in intermediate- to high-risk patients. Anticoagulation is safely used for prophylaxis and treatment of CAT. Both of these h

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… Microvesicles are membrane-enclosed vesicles that are released into the extracellular space by normal, apoptotic or malignant cells [ 4 ]. Tissue factor expressed on the surface of microvesicles is linked to the subsequent acceleration of coagulation and formation of thrombi [ 4 , 20 ]. …

Новый взгляд на механизмы нейродегенерации в экспериментальном аутоиммунном энцефаломелите и многоразовом склерозе: ранняя и критическая роль платец в нейро/аксональной потере.

Множественный склероз (MS) — аутоиммунное расстройство центральной нервной системы (CNS) с ограниченными возможностями лечения. Для этого заболевания характерны различия в патофизиологии между серым веществом (GM) и белым веществом (WM). Преобладающей отличительной чертой ВМ является периваскулярная доска, связанная с потерей функции мозгового барьера (ББД), инфильтрацией лимфоцитов, микроглиальной реактивностью, обезвоживанием и аксонной травмой и должным образом обработанная иммуномодулятивными препаратами. С другой стороны, механизмы, лежащие в основе ущерба ГМ, остаются неясными, что имеет

Mechanisms of Resistance to Chemotherapy in Breast Cancer and Possible Targets in Drug Delivery Systems.

Breast cancer (BC) is one of the most important cancers worldwide, and usually, chemotherapy can be used in an integrative approach. Usually, chemotherapy treatment is performed in association with surgery, radiation or hormone therapy, providing an increased outcome to patients. However, tumors can develop resistance to different drugs, progressing for a more aggressive phenotype. In this scenario, the use of nanocarriers could help to defeat tumor cell resistance, providing a new therapeutic perspective for patients. Thus, this systematic review aims to bring the molecular mechanisms involve

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… This protein can bind to some chemotherapy drugs, such as anthracyclines, taxanes and mitoxantrone, and remove them from the cell interior and release them into the extracellular space [ 22 , 25 , 27 ]. …

Skeletal Site-specific Effects of Zoledronate on in vivo Bone Remodeling and in vitro BMSCs Osteogenic Activity.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been associated with long-term oral or intravenous administration of nitrogen-containing bisphosphonates (BPs). However, the pathogenesis of BRONJ remains unknown, and definitively effective treatment has not yet been established. Bisphosphonate-related osteonecrosis (BRON) tends to occur in maxillofacial bones. Why this occurs is still unclear. Here we show that zoledronate (Zol) treatment suppresses alveolar bone remodeling after tooth typical clinical and radiographic hallmarks of the human BRONJ, whereas enhances peripheral bone q

Physiological functions and pharmacological targeting of transient receptor potential channels.

Transient receptor potential (TRP) channels represent an extensive and diverse protein family fulfilling salient roles as versatile cellular sensors and effectors. The pivotal role of TRP and related ion channels in sensory processes has been well documented. Over the last few years, a new concept has emerged that TRP proteins control an exceptionally broad spectrum of homeostatic physiological functions such as maintenance of body temperature, blood pressure, transmitter release from neurons, mineral and energy homeostasis, and reproduction. This notion is further supported by more than 20 he

Клеточная терапия с мезентичными стволовыми клетками, изготовленными плацентой, для вторичных прогрессивных пациентов с множественным склерозом в а фазы 1 Клинические испытания.

Мезенхимальные стволовые клетки (МСЦ) привлекли значительное внимание к клиническим исследованиям в связи с их иммуномодулятивными свойствами и потенциалом уменьшения воспаления при аутоиммунных расстройствах, таких, как множественный склероз (МС). В настоящем исследовании оценивается безопасность и осуществимость использования МСЦ-В (МСЦ-В) на основе плаценты в five - участники с множественным склерозом второго этапа (СФМ). Основные результаты были сосредоточены на безопасности и терпимости, которые были оценены на основе мониторинга неблагоприятных явлений. six месяцев. Вторичные результаты

Integrated Engineering of CAR-T Cells for Solid Tumours.

Chimeric antigen receptor (CAR) T-cell therapy has achieved durable efficacy in hematologic malignancies but encounters persistent obstacles in solid tumours, including antigen heterogeneity, a suppressive tumour microenvironment (TME), and intrinsic T-cell dysfunction. This review examines the transition from single-axis engineering to an integrated framework that addresses these hurdles in sequence. We delineate how next-generation CAR-T cells are designed for precise spatiotemporal activation through logic-gated and pharmacologically regulatable receptors, while being reinforced by metaboli

Bone Metastasis Pain, from the Bench to the Bedside.

Bone is the most frequent site of metastasis of the most common cancers in men and women. Bone metastasis incidence has been steadily increasing over the years, mainly because of higher life expectancy in oncologic patients. Although bone metastases are sometimes asymptomatic, their consequences are most often devastating, impairing both life quality and expectancy, due to the occurrence of the skeletal-related events, including bone fractures, hypercalcemia and spinal cord compression. Up to 75% of patients endure crippling cancer-induced bone pain (CIBP), against which we have very few weapo

Chest and Mediastinum

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Strategies to overcome the main challenges of the use of CRISPR/Cas9 as a replacement for cancer therapy.

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) shows the opportunity to treat a diverse array of untreated various genetic and complicated disorders. Therapeutic genome editing processes that target disease-causing genes or mutant genes have been greatly accelerated in recent years as a consequence of improvements in sequence-specific nuclease technology. However, the therapeutic promise of genome editing has yet to be explored entirely, many challenges persist that increase the risk of further mutations. Here, we highlighted the main challenges fa

Immune Modulation in the Treatment of Amyotrophic Lateral Sclerosis: A Review of Clinical Trials.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of motor neurons. Though many molecular and genetic causes are thought to serve as predisposing or disease propagating factors, the underlying pathogenesis of the disease is not known. Recent discoveries have demonstrated the presence of inflammation propagating substrates in the central nervous system of patients afflicted with ALS. Over the past decade, this hypothesis has incited an effort to better understand the role of the immune system in ALS and has led to the trial of sever

Biological implant-associated granulomatous inflammation resulting in secondary hypercalcemia and azotemia in a dog.

Implant associated granulomatous inflammation causing hypercalcemia can occur following use of commercial xenogeneic pericardial tissue patches in dogs. Removal of the implant can result in resolution of the hypercalcemia, suggesting a causal relationship between the tissue reaction to a xenogeneic implant and development of hypercalcemia.

Proceedings 27th Symposium ESVN‐ECVN

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Engineered mesenchymal stem cell-derived exosomes: A revolutionary approach to unlocking liver disease treatment.

Exosomes, a specific type of extracellular vesicle with diameters ranging from 30 to 150 nm, play a vital role in coordinating various physiological and pathological processes through direct cell-to-cell communication. These vesicles transport a diverse range of molecules, including proteins, mRNAs, miRNAs, and lipids, that originate from parent cells. Exosomes are released by nearly all cell types, including mesenchymal stem cells (MSCs), and possess significant potential due to their regenerative and immunomodulatory properties. In the context of liver disease treatment, these capabilities o

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… Upon fusion of MVBs with the plasma membrane, exosomes are released into the extracellular space. These exosomes are rich in various bioactive molecules, including proteins, lipids, mRNA, and microRNA, which can modulate cellular functions in recipient cells. …

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions.

The balance between bone forming cells (osteoblasts/osteocytes) and bone resorbing cells (osteoclasts) plays a crucial role in tissue homeostasis and bone repair. Several hormones, cytokines, and growth factors-in particular the members of the TGF-β superfamily such as the bone morphogenetic proteins-not only regulate the proliferation, differentiation, and functioning of these cells, but also coordinate the communication between them to ensure an appropriate response. Therefore, this review focuses on TGF-β superfamily and its influence on bone formation and repair, through the regulation of

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… The sealing zone, characterized by the formation of the bone-apposed ruffled border membrane and the isolated resorption lacuna, segregates the resorptive microenvironment from the general extracellular space ( Figure 1 ) [ 80 , 81 ]. … These antagonist proteins are secreted into the extracellular space and selectively bind to certain members of the TGF-β superfamily, blocking the activation of their receptor and inhibiting the intracellular signaling [ 159 , 203 ]. …

Rhabdomyolysis secondary to COVID-19 infection and vaccination: a review of literature.

Rhabdomyolysis (RML), characterized by the breakdown of skeletal muscle fibers and the release of muscle contents into the bloodstream, has emerged as a notable complication associated with Coronavirus disease 2019 (COVID-19) infection and vaccination. Studies have reported an increased incidence of RML in individuals with severe COVID-19 infection. However, the exact mechanisms remain unclear and are believed to involve the host's immune response to the virus. Furthermore, RML has been documented as a rare adverse event following COVID-19 vaccination, particularly with mRNA vaccines. Proposed

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… In typical myocytes, Na-K-ATP-ase pumps are inside the cellular membrane, facilitating the active transportation of sodium ions to the extracellular space. This process contributes to establishing a negative membrane potential ( 18 ). …

Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review.

Diffuse large B-cell lymphoma (DLBCL) is a malignancy of immense biological and clinical heterogeneity. Based on the transcriptomic or genomic approach, several different classification schemes have evolved over the years to subdivide DLBCL into clinically (prognostically) relevant subsets, but each leaves unclassified samples. Herein, we outline the DLBCL tumor biology behind the actual and potential drug targets and address the challenges and drawbacks coupled with their (potential) use. Therapeutic modalities are discussed, including small-molecule inhibitors, naked antibodies, antibody-dru

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… Abs are immunoglobulins (IgM, IgG, IgA, IgE, and IgD) that can be inserted in the plasma membrane of B-cells, where they are part of a multiprotein B-cell receptor (BCR) complex, or B-cells secrete them into extracellular space. … BCR is a transmembrane receptor that protrudes from the surface of a B-cell into the extracellular space. BCR comprises a membrane-bound Ig (mIg) and a signal transduction moiety, Igα/β. …

NDP52 и его новая роль в патогенезе.

Автофагика - это процесс, способствующий выживанию, который регулирует деградацию и обновление клеточных компонентов, что делает его важнейшим механизмом для клеточного гомеостазиза. Существуют выборочные формы автофагии, характерные для ряда субстратов, таких, как патогены (бактерии или вирусы), белковые агрегаты или излишние/поврежденные органеллы. Эти процессы включают в себя в качестве ключевых игроков автофагичные рецепторы, которые связывают груз, подлежащий деградации, с автофагическим оборудованием. Среди них NDP52 (известный также как КАКПО2) был охарактеризован как «бридж» между авто

Глубокая стимуляция мозга в гипоталамической области: систематический обзор.

КОЛИЧЕСТВО: Глубокая стимуляция мозга (БРС) успешно используется для лечения циклопатии, включая движение, беспокойство и поведенческие расстройства. Гипоталамус является важнейшим интеграционным центром для многих периферийных и центральных путей, связанных с сердечно - сосудистыми, метаболическими и поведенческими функциями, и представляет собой потенциальную цель нейромодуляции в лечебных условиях. Проведение систематического обзора, изучение гипоталамических целей в ДБС, их признаков и основных клинических результатов.МЕТОДЫ: База данных PubMed, Scopus и Web of Science была подвергнута обы

GD2: hopes and challenges for the treatment of pediatric patients with tumors of the central nervous system.

Pediatric Central Nervous System (CNS) tumors are the leading cause of cancer-related death in children, yet effective treatment options remain limited. The tumor-associated antigen GD2 is a promising target for immunotherapeutic approaches aimed at treating pediatric CNS cancers; however, its heterogeneous expression within and between tumors can complicate the development of effective strategies. Here we review different aspects of GD2 biology, including its structure, synthesis pathway, and cellular and tissue expression, focusing on pediatric CNS tumors. We provide a detailed overview of t

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… Moreover, extending their monosaccharide units into the extracellular space, gangliosides exhibit antigenic properties vital for cell–cell recognition and adhesion, contributing significantly to cellular communication and interactions 7 , 9 , 10 . …