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Targeting autoimmune mechanisms by precision medicine in Myasthenia Gravis.

Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating weakness and early fatigability of ocular, skeletal and bulbar muscles. Despite being commonly considered a prototypic autoimmune disorder, MG is a complex and heterogeneous condition, presenting with variable clinical phenotypes, likely due to distinct pathophysiological settings related with different immunoreactivities, symptoms' distribution, disease severity, age at onset, thymic histopathology and response to therapies. Cur

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… the follicular hyperplastic MG thymus is characterized by a well-defined chronic inflammatory condition, and presents features of tertiary lymphoid organs, such as sustained over-expression of inflammatory cytokines and chemokines, GC development, and neoangiogenic processes (i.e. high endothelial venule … GCs encircled by high endothelial venules, that are potentially able to recruit peripheral B cells, were identified in the adjacent tissues of a high proportion of MG thymomas, and their number positively correlated with anti-AChR titers ( 41 ). …

Exploring the evolving role of apolipoproteins in oncology: global trends and emerging frontiers.

BackgroundMetabolic reprogramming, especially lipid metabolism, is crucial in cancer progression and treatment resistance. Apolipoproteins are crucial targets for research as they regulate autophagy, oxidative stress, and chemoresistance. A systematic bibliometric and bioinformatics approach is necessary to identify trends and elucidate the molecular mechanisms linking apolipoproteins to cancer.MethodsA systematic bibliometric analysis was conducted using the Web of Science Core Collection and PubMed. VOSviewer, CiteSpace, and the Bibliometrix R package were employed to analyze and visualize c

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… Notably, significant post-treatment upregulation of SELP + high endothelial venules (HEVs) and APOD + myofibroblastic cancer-associated fibroblasts (myCAFs), alongside a decline in STMN1 + capillary endothelial cells (cECs), is specific to the immunochemotherapy cohort. … Notably, significant post-treatment upregulation of SELP + high endothelial venules (HEVs) and APOD + myofibroblastic cancer-associated fibroblasts (myCAFs), alongside a decline in STMN1 + capillary endothelial cells (cECs), is specific to the immunochemotherapy cohort. …

Нейродегенерация коррелирует с повреждениями, связанными с железом, и воспалением лептомеинов в многочисленных клинических подтипах склероза.

ЦЕЛЬ: Цель этого исследования заключалась в изучении существенных последствий различных видов повреждений, которые были оценены QSM (каличественная-приемлемость), а также лептоминговой контрастности в группе пациентов, страдающих релапсирующими и первичными прогрессивными (ПП) MS, и в оценке их связи с клиническими нарушениями и измерением МРТ структурных повреждений головного мозга. МЕТОДЫ: Были выявлены и количественно определены различные виды повреждений белой материи с использованием QSM в 24 РОРМ и 15 ИЦУП (СУП)11 - пациенты с последующим МРТ). Оценка степени контрастности (LMCE; foci) 3

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… Mostly T cells (CD8 T cells) and less B cells infiltrate the lesions and are centered around veins and venules. Mixed active/inactive lesions display an hypocellular lesion center along with a rim of activated macrophages/microglial cells where active demyelination occurs. …

What Has Been Learned from Postmortem Studies?

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… Pulmonary Veno-occlusive Disease Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension that is characterized histopathologically by intimal proliferation and fibrosis of the pulmonary venules and small veins leading to progressive vascular obstruction [ 65 ]. …

Platinum-induced ototoxicity and hearing impairment in children and adolescents.

Platinum compounds play a crucial role in the treatment of solid tumours in paediatric patients, significantly improving survival rates. However, these treatments can result in hearing loss as a side-effect that can significantly impact the quality of life of young cancer survivors. Whilst the therapeutic benefits of platinum compounds in paediatric oncology are indisputable, addressing the challenge of ototoxicity remains a priority. Early and regular auditory function assessments, with tools such as audiometry, otoacoustic emissions and auditory brainstem response testing, are critical durin

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… Direct examination of mesenteric microcirculation demonstrates a progressive reduction in microvascular luminal diameters affecting terminal arterioles, precapillary sphincters and venules. …

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

Pulmonary hypertension in patients with multiple myeloma: A comprehensive review.

Multiple myeloma (MM) is a common hematological malignancy resulting from clonal proliferation of plasma cells and is defined by criteria set forth by the international myeloma working group. Pulmonary hypertension (PH) is defined by an elevated mean pulmonary artery pressure >20 mmHg measured during right heart catheterization. Echocardiography-diagnosed PH is relatively common in patients with MM and has been associated with increased mortality, morbidity, and poor stem cell transplant outcomes. PH in patients with MM (PH-MM) is usually multifactorial in origin. MM disease-specific factors,

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… PVOD (pulmonary veno occlusive disease) : PVOD is a rare but devastating cause of PH characterized by preferential remodeling of the pulmonary venules and capillaries. RHC findings in patients with PVOD are similar to PAH and the PAWP is normal. …

Immunological Targets in Generalized Myasthenia Gravis Treatment: Where Are We Going Now?

BackgroundGeneralized myasthenia gravis (gMG) is a heterogeneous autoimmune disorder marked by antibody-mediated disruption of neuromuscular transmission. Despite advancements in immunosuppressive therapies and biologics, a subset of patients remains refractory, necessitating more targeted and personalized treatment strategies.ObjectiveThis review aims to synthesize current knowledge of the immunopathological mechanisms across gMG subtypes and to explore emerging therapeutic targets tailored to these diverse disease phenotypes.MethodsA narrative review was conducted, integrating recent finding

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… The medullary region may also show distinctive features in TAMG compared to thymoma without MG, characterized by a specific chemokine pattern and immune cell composition, including migratory dendritic cells, Treg cells, high endothelial venules, and GCs, similar to what is observed in the thymic hyperplasia … The presence of GCs and high endothelial venules is associated not only with MG but also with younger age at MG symptom onset and higher levels of anti-AChR autoantibodies [ 63 ]. …

EMD originates from hyaluronan-induced homophilic interactions of CD44 variant-expressing MM cells under shear stress.

Extramedullary disease (EMD) is known to be associated with chemoresistance and poor prognosis in multiple myeloma (MM); however, the mechanisms of its development are not fully understood. Elucidating the mechanism of EMD development and its therapeutic targeting would greatly contribute to further improvement of treatment outcome in patients with MM. Here, we show that bone marrow stroma cell-derived hyaluronan (HA) elicits homophilic interactions of MM cells by binding to surface CD44, especially long-stretch variants, under physiological shear stress and generates cell clusters that might

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… Hematopoietic cells are constantly exposed to shear stress at 2.5 to 20 dyne/cm 2 from blood flow in BM venules. 32 , 33 We rotated culture flasks at 60 rpm on a horizontal rotator, which generates 10 dyne/cm 2 , to reproduce physiological shear stress in vitro. …

Targeting Selectins and Their Ligands in Cancer.

Aberrant glycosylation is a hallmark of cancer cells with increased evidence pointing to a role in tumor progression. In particular, aberrant sialylation of glycoproteins and glycolipids has been linked to increased immune cell evasion, drug evasion, drug resistance, tumor invasiveness, and vascular dissemination, leading to metastases. Hypersialylation of cancer cells is largely the result of overexpression of sialyltransferases (STs). Differentially, humans express twenty different STs in a tissue-specific manner, each of which catalyzes the attachment of sialic acids via different glycosidi

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… Blood ( 2014 ) 123 : 1361 – 71 . 10.1182/blood-2013-11-538694 24394666 PMC3938148 60 Lafouresse F Bellard E Laurent C Moussion C Fournie JJ Ysebaert L L-selectin controls trafficking of chronic lymphocytic leukemia cells in lymph node high endothelial venules in vivo . …

Multiple cystic lung disease.

Multiple cystic lung disease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main dise

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… Late in the course of PLCH, patients may develop secondary pulmonary arterial hypertension, because pulmonary vascular lesions tend to predominate in the venules and may produce a picture reminiscent of pulmonary veno-occlusive disease [ 52 ]. …

Targeting hematologic malignancies by inhibiting E-selectin: A sweet spot for AML therapy?

E-selectin, a cytoadhesive glycoprotein, is expressed on venular endothelial cells and mediates leukocyte localization to inflamed endothelium, the first step in inflammatory cell extravasation into tissue. Constitutive marrow endothelial E-selectin expression also supports bone marrow hematopoiesis via NF-κB-mediated signaling. Correspondingly, E-selectin interaction with E-selectin ligand (sialyl Lewisx) on acute myeloid leukemia (AML) cells leads to chemotherapy resistance in vivo. Uproleselan (GMI-1271) is a carbohydrate analog of sialyl Lewisx that blocks E-selectin binding. A Phase 2 tri

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… E-selectin binds leukocytes to activated endothelium, whereas P-selectin binds leukocytes to platelet-activated endothelium and platelets, and L-selectin binds leukocytes to lymph node high endothelial venules (HEVs). …

Primary Gastric Lymphoma, Epidemiology, Clinical Diagnosis, and Treatment.

Primary gastric lymphoma (PGL) is the most common extranodal non-Hodgkin lymphoma and represents a wide spectrum of disease, ranging from indolent low-grade marginal zone lymphoma or mucosa-associated lymphoid tissue (MALT) lymphoma to aggressive diffuse large B-cell lymphoma. The PGL is a relatively rare cancer and easily misdiagnosed due to its unspecific symptoms of the digestive tract. The medical literature and ongoing clinical trials were reviewed on the clinical presentation, diagnosis, prognosis, prevention, and treatment of PGL. Primary gastric lymphoma is an event in the course of ca

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… It has been shown that lymphocytes interact with endothelial venules, mediated by receptor molecules (lymphocytic and integrins). 23 B lymphocytes of the marginal zone are the origin of MALT lymphoma and are characterized by a cellular population that is heterogeneous with a predominant presence of …

MR and CT angiography in the diagnosis of vasculitides.

Vasculitides represent the wide-ranging series of complex inflammatory diseases that involve inflammation of blood vessel walls. These conditions are characterized according to the caliber of the predominantly involved vessels. The work-up of vasculitides often includes imaging to narrow a differential diagnosis and guide management. Findings from CT and MR angiography in conjunction with a thorough history and physical exam are of utmost importance in making an accurate diagnosis. Further, imaging can be used for follow-up, in order to monitor disease progression and response to treatment. Th

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… ANCA-associated vasculitis A group of patients with small-vessel vasculitis, involving arterioles, capillaries, and venules, and glomerulonephritis have serum anti-neutrophil cytoplasmic antibodies (ANCA). 56 ANCA are produced by T cells and activate leukocytes and monocytes, which result in damage …

Skin manifestations associated with systemic diseases - Part I.

The skin demonstrates what is happening in the body in many diseases, as it reflects some internal processes on the surface. In this sense, skin as an organ, goes beyond its protective and barrier functions, as it provides clues for the identification of some systemic diseases. The dermatologist then raises diagnostic hypotheses for conditions related to all systems and refers them to the appropriate specialty. With easy access to examination by trained eyes and biopsies, the skin can present specific or non specific alterations on histopathology. In the first case this combination establishes

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… gangrene, periorbital ecchymosis, face and neck edema, nodules, and granuloma annulare have been described. 33 Polyarteritis nodosa Systemic polyarteritis nodosa (PAN) is a necrotizing vasculitis of small or medium-sized arteries without glomerulonephritis or vasculitis of arterioles, capillaries or venules …

Primary cutaneous lymphomas: diagnosis and treatment.

Primary cutaneous lymphomas (CLs) are a heterogeneous group of lymphoproliferative neoplasms, with lymphatic proliferation limited to the skin with no involvement of lymph nodes, bone marrow or viscera at the diagnosis. Cutaneous lymphomas originate from mature T-lymphocytes (65% of all cases), mature B-lymphocytes (25%) or NK cells. Histopathological evaluation including immunophenotyping of the skin biopsy specimen is the basis of the diagnosis, which must be complemented with a precise staging of the disease and identification of prognostic factors, to allow for the choice of the best treat

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… CLA-expressing skin-homing T cells can interact with the receptor E-selectin on dermal postcapillary venules. Furthermore, MF lesions can express high levels of CCL17 and CCL22 [ 3 ]. The proliferation of T cells is inevitably related to stimulation via CD28. …

Пути к прогрессивной инвалидности при множественном склерозе: роль глиальных клеток в хроническом воспалении CNS.

Множественный склероз (MS) является наиболее распространенным неинфекционным воспалительным заболеванием CNS, характеризующимся прогрессивным нейродегенерацией и точечными демиелинированными повреждениями. Традиционно считается аутоиммунным заболеванием, MS движет атака иммунной системы на CNS Myelin, что приводит к кумулятивной инвалидности. Однако традиционные методы борьбы с воспламенением часто не позволяют предотвратить постепенное ухудшение состояния, особенно при отсутствии открытого воспаления, что подчеркивает необходимость более глубокого понимания его патогенеза. Недавние исследован

CAR-T cell therapy for the treatment of adult high-grade gliomas.

Treatment for malignant primary brain tumors, including glioblastoma, remains a significant challenge despite advances in therapy. CAR-T cell immunotherapy represents a promising alternative to conventional treatments. This review discusses the landscape of clinical trials for CAR-T cell therapy targeting brain tumors, highlighting key advancements like novel target antigens and combinatorial strategies designed to address tumor heterogeneity and immunosuppression, with the goal of improving outcomes for patients with these aggressive cancers.

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… Diapedesis of mononuclear cells across cerebral venules during experimental autoimmune encephalomyelitis leaves tight junctions intact. Acta Neuropathol. 109 , 181–190 (2005). 66. Reese, T. S. & Karnovsky, M. J. Fine structural localization of a blood–brain barrier to exogenous peroxidase. J. …

The inflammatory and metabolic status of patients with sudden-onset sensorineural hearing loss.

IntroductionSudden sensorineural hearing loss (SSNHL) is a common emergency symptom in otolaryngology that requires immediate diagnosis and treatment. SSNHL has a multifactorial etiology, and its pathophysiologic mechanisms may be associated with inflammatory and metabolic changes that may affect the cochlear microenvironment or its nervous component, thus triggering the process or hindering hearing recovery. Therefore, the aim of this study was to assess metabolic and inflammatory changes to identify systemic parameters that could serve as prognostic factors for hearing recovery in patients w

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… Interleukin-2 activates the endothelial cells of the modiolar spiral vein in the area of the cochlea so that they increasingly express ICAM-1 and take on the characteristics of high endothelial venules. …

Therapeutic Antibodies in Cancer Treatment in the UK.

The growing understanding of the molecular mechanisms of carcinogenesis accelerated the development of monoclonal therapeutic antibodies to specifically target multiple cancer pathways. Recombinant protein therapeutics now constitute a large proportion of yearly approved medicines. Oncology, autoimmune diseases and to a smaller degree the prophylaxis of organ transplant rejection are their main application areas. As of the date of this review, 37 monoclonal antibody products are approved for use in cancer treatments in the United Kingdom. Currently, the antibody therapeutics market is dominate

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… These cells co-express Cutaneous lymphocytes antigen (CLA) along with CCR4 both of which binds to ligands such as E-selectin on the dermal venules, CC-chemokine ligand 17 and CCL22 [ 90 ]. These interactions are essential in allowing the T-cells and to enter in the dermis and epidermis layers. …