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Индекс Свободных цепей света Каппы и знак центральной веин: два новых биомаркера для многоразового диагностирования склероза.

На последнем совещании Европейского комитета по лечению и исследованиям в области множественного склероза (ECTRIMS) Монтальбан и группа экспертов объявили о пересмотре критериев Макдональда в 2024 году. Среди основных изменений был добавлен зрительный нерв в качестве пятого показателя распространения в космосе (DIS) топографии. Множественный склероз (МС) может диагностироваться у пациентов с радиологически изолированным синдромом (РИС), если к по крайней мере двум из пяти критериев СОП добавляются конкретные биомаркеры. Среди конкретных биомаркеров MS к позитиву будет добавлен индекс свободной

Polymeric micelles loaded with carfilzomib increase tolerability in a humanized bone marrow-like scaffold mouse model.

Carfilzomib-loaded polymeric micelles (CFZ-PM) based on poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) (mPEG-b-p(HPMA-Bz)) were prepared with the aim to improve the maximum tolerated dose of carfilzomib in a "humanized" bone marrow-like scaffold model. For this, CFZ-PM were prepared and characterized for their size, carfilzomib loading and cytotoxicity towards multiple myeloma cells. Further, circulation and tumor & tissue distribution of fluorescently labeled micelles were determined. Tolerability of CFZ-PM versus the clinical approved formulation - Kyprolis® - was assessed

Novel Molecular Therapies and Genetic Landscape in Selected Rare Diseases with Hematologic Manifestations: A Review of the Literature.

Rare diseases affect less than 1 in 2000 people and are characterized by a serious, chronic, and progressive course. Among the described diseases, a mutation in a single gene caused mastocytosis, thrombotic thrombocytopenic purpura, Gaucher disease, and paroxysmal nocturnal hemoglobinuria (KIT, ADAMTS13, GBA1, and PIG-A genes, respectively). In Castleman disease, improper ETS1, PTPN6, TGFBR2, DNMT3A, and PDGFRB genes cause the appearance of symptoms. In histiocytosis, several mutation variants are described: BRAF, MAP2K1, MAP3K1, ARAF, ERBB3, NRAS, KRAS, PICK1, PIK3R2, and PIK3CA. Genes like H

Изучение антивоспламенительных эффектов после экстраполяции в модели мыши R6/2 болезни Хантингтона.

Болезнь Хантингтона - это прогрессивное, неизлечимое нейродегенеративное расстройство, вызванное мутацией в гене Хантингтин. Помимо нейродегенерации, изменённая иммунная активация связана с развитием болезни. Поскольку воспаление центральной нервной системы и дисфункция иммунных клеток признаются в качестве движущей силы, иммуномодуляция может представлять собой дополнительную терапевтическую стратегию. Известно, что короткоцепные жирные кислоты оказывают иммуномодулятивное воздействие на нервно-воспалительные заболевания, такие, как множественный склероз. В этом исследовании R6/2 мышей ежедне

2020 ACVIM Forum On Demand Research Abstract Program.

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Assessment of TSPAN Expression Profile and Their Role in the VSCC Prognosis.

The role and prognostic value of tetraspanins (TSPANs) in vulvar squamous cell carcinoma (VSCC) remain poorly understood. We sought to primarily determine, at both the molecular and tissue level, the expression profile of the TSPANs CD9, CD63, CD81, and CD82 in archived VSCC samples (n = 117) and further investigate their clinical relevance as prognostic markers. Our studies led us to identify CD63 as the most highly expressed TSPAN, at the gene and protein levels. Multicomparison studies also revealed that the expression of CD9 was associated with tumor size, whereas CD63 upregulation was ass

Management of skeletal metastases: An orthopaedic surgeon's guide.

Skeletal metastasis is a common cause of severe morbidity, reduction in quality of life (QOL) and often early mortality. Its prevalence is rising due to a higher rate of diagnosis, better systemic treatment, longer lives with the disease and higher disease burden rate. As people with cancer live longer and with rising sensitivity of body imaging and surveillance, the incidence of pathological fracture, metastatic epidural cord compression is rising and constitutes a challenge for the orthopedic surgeon to maintain their QOL. Metastatic disease is no longer a death sentence condemning patients

Клетки T-бет+CXCR3+B вызывают гиперреактивное взаимодействие клеток B-T в множестве склерозов.

Множественный склероз (MS) — аутоиммунное заболевание центральной нервной системы (CNS). Одним из ключевых механизмов в НР является автораспространение (АП) ячеек В и Т, основанное на самопропитании. Здесь мы показываем, что про-воспаление B-T-обогащенные клетки клеток (BTEC) формируются во время AP и зеркальные особенности реакции микроцентра. T-bet+CXCR3+B — основной подмножество клеток, усиливающих и поддерживающих свои параллельные клетки TH1 с помощью интерферона (IFN)-__, и присутствуют в сильно воспламенённой менингетной ткани. Фундаментальная сигнатура активации клеток В находит свое о

Inhibition of EIF2α Dephosphorylation Decreases Cell Viability and Synergizes with Standard-of-Care Chemotherapeutics in Head and Neck Squamous Cell Carcinoma.

Drug resistance is a common cause of therapy failure in head and neck squamous cell carcinoma (HNSCC). One approach to tackling it is by targeting fundamental cellular processes, such as translation. The eukaryotic translation initiation factor 2α (EIF2α) is a key player in canonical translation initiation and integrates diverse stress signals; when phosphorylated, it curbs global protein synthesis. This study evaluates EIF2α expression and phosphorylation in HNSCC. A small-molecule inhibitor of EIF2α dephosphorylation, salubrinal, was tested in vitro, followed by viability assays, flow cytome

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

CD45dimCD34+CD38-CD133+ cells have the potential as leukemic stem cells in acute myeloid leukemia.

BackgroundLeukemia stem cells (LSCs) in play an important role in the initiation, relapse, and progression of acute myeloid leukemia (AML), and in the development of chemotherapeutic drug resistance in AML. Studies regarding the detection of LSCs and the development of novel therapies for targeting them are extensive. The identification of LSCs and targeting therapies for them has been continuously under investigation.MethodsWe examined the levels of CD45dimCD34+CD38-CD133+ cells in bone marrow samples from patients with hematological malignancies and healthy controls, using four-color flow cy

Bortezomib (PS-341) treatment decreases inflammation and partially rescues the expression of the dystrophin-glycoprotein complex in GRMD dogs.

Golden retriever muscular dystrophy (GRMD) is a genetic myopathy corresponding to Duchenne muscular dystrophy (DMD) in humans. Muscle atrophy is known to be associated with degradation of the dystrophin-glycoprotein complex (DGC) via the ubiquitin-proteasome pathway. In the present study, we investigated the effect of bortezomib treatment on the muscle fibers of GRMD dogs. Five GRMD dogs were examined; two were treated (TD- Treated dogs) with the proteasome inhibitor bortezomib, and three were control dogs (CD). Dogs were treated with bortezomib using the same treatment regimen used for multip

Synergistic Effects of Olfactory Ecto-Mesenchymal Stem Cell Supernatant and Ellagic Acid on Demyelination and Glial Modulation in a Chronic Multiple Sclerosis Model.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Stem cells as a source of neurotrophic factors and ellagic acid (EA) as an antioxidant reduce the progression of neurodegenerative diseases. In this study, we evaluated the effect of olfactory ecto-mesenchymal stem cell (EMSC) supernatant and EA on A1 astrocytes, M1 microglia, and demyelination in cuprizone model. To induce the chronic demyelination model, mice received a diet containing 0.2% cuprizone/kg of food for 12 weeks. EMSC supernatant was injected into the lateral ventricle of mice. EA was

Unc-51 like kinase 3 (ULK3) contributes to autophagy and cell survival in multiple myeloma.

Despite effective therapies such as proteasome inhibitors, multiple myeloma (MM) patients relapse with refractory disease. Analysis of RNA sequencing data from CD138 + MM patient cells (n = 813) across disease stages identifies an autophagy gene signature. Particularly elevated ULK3 expression is strongly associated with disease progression. Functional studies reveal that ULK3 supports MM cell survival via the ULK-ATG13-FIP200 complex. We generate small-molecule kinase inhibitors (SG3-014/MA9-060) exhibiting nanomolar potency against ULK3, with binding confirmed by co-crystallization. While ex

Clinicopathologic Features of Antibrush Border Antibody Disease.

IntroductionAntibrush border antibody disease (ABBA) is an autoimmune tubulointerstitial kidney disease that primarily affects older individuals and results in progressive kidney failure. It is rare with only 20 reported cases. Here, we describe a case series to further define the clinicopathologic spectrum and natural history, and to inform management.MethodsWe identified 67 patients with ABBA who underwent kidney biopsy, including 65 native and 2 transplants. Demographics, clinical findings, and laboratory data were obtained. Histopathologic data included light microscopy, immunofluorescence

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… Frozen sections were stained with fluorescein-tagged polyclonal rabbit antihuman antibodies to IgG, IgA, IgM, C3, C1q, albumin, fibrinogen, and kappa and lambda light chains and evaluated with a semiquantitative 0 to 3+ scale. For cases with sufficient tissue, IgG subclass staining was performed. … For serologic testing, 4 μm frozen sections of normal human kidney were washed with Flex PBS buffer (Dako Corp., Carpinteria, CA) and patient serum was applied to tissue sections at 1:10 dilution in PBS-Tween-20 solution for 30 minutes at room temperature. …

Multiple myeloma presenting as a cervical intraforaminal tumor: A case report and review of literature.

Multiple myeloma (MM) is a hematological malignancy with characteristic clonal plasma cell proliferation and production of monoclonal immunoglobulins. Although it can often metastasize to the bony spine, completely extravertebral and extra-/intradural manifestations are exceedingly rare. In this case report, we describe a 51-year-old male patient with cervical extradural and intraforaminal MM who was surgically treated in our department. Clinical findings and radiological images were retrieved from medical records and an imaging system. This unusual localization of MM and similar cases in the

Возраст и стадия созревания связаны с последствиями фибриногена для человека Олигодендроголии.

Фибриноген — это протеин, полученный из крови и содержащийся в коагуляции, и он может проникнуть в центральную нервную систему (КНС) после разрушения мозгового барьера. Эта молекула была связана с множественным склерозом (MS), заболеванием, отмеченным воспалением и обезвоживанием в CNS. Однако воздействие этой молекулы не изучалось на миелионирующих клетках человека. В этом исследовании рассматривается вопрос о том, как фибриноген влияет на родственные клетки человека олигодендроцита (OL) на различных этапах развития. Используя индуцированные плюрипотентные стволовые клетки (iPSC) прекурсоры O

DNA Methylation Cancer Biomarkers: Translation to the Clinic.

Carcinogenesis is accompanied by widespread DNA methylation changes within the cell. These changes are characterized by a globally hypomethylated genome with focal hypermethylation of numerous 5'-cytosine-phosphate-guanine-3' (CpG) islands, often spanning gene promoters and first exons. Many of these epigenetic changes occur early in tumorigenesis and are highly pervasive across a tumor type. This allows DNA methylation cancer biomarkers to be suitable for early detection and also to have utility across a range of areas relevant to cancer detection and treatment. Such tests are also simple in

Biopsy Techniques for Musculoskeletal Tumors: Basic Principles and Specialized Techniques.

Biopsy is a pivotal component in the diagnostic process of bone and soft tissue tumors. The objective is to obtain adequate tissue without compromising local tumor dissemination and the patient's survival. This review explores contemporary principles and practices in musculoskeletal biopsies, emphasizing the critical role of diagnostic accuracy while also delving into the evolving landscape of liquid biopsies as a promising alternative in the field. A thorough literature search was done in PubMed and Google Scholar as well as in physical books in libraries to summarize the available biopsy tec

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… The pathologist and surgeon may be more assured of a diagnosis of metastasis made on frozen section analysis if supported by the preoperative evaluation. … Can be used with frozen sections. Use the smallest incision that is compatible with obtaining adequate specimen. Careful hemostasis (use tourniquet; very rarely use drains). …

Association between nutritional status and biochemical markers among hematopoietic stem cell transplant candidates: a cross-sectional study.

AimCandidates of Hematopoietic Stem Cell Transplantation (HSCT) may be at nutritional risk due to decreased oral intake, high nutritional requirements and nutrient malabsorption. The aim of this study was to evaluate the association between nutritional status and blood biomarkers in candidates of HSCT.MethodsA total of 278 patients aged 18-65 years old were recruited and their baseline demographic and clinical characteristics were recorded. All subjects underwent nutritional status analysis using Nutritional Risk Screening (NRS-2002). Blood biomarkers including C-reactive protein (CRP), Erythr