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Выражение Brd4 в CD4 T клеток и в микроглии поощряет нейроинфламмацию в экспериментальном аутоиммунном энцефаломиелите.

Микроглии являются постоянными врожденными иммунными клетками центральной нервной системы (СНС), которые обеспечивают антимикробную защиту, но также способствуют нейроинфламмации. BRD4 — читатель хроматинов, связывающий себя с ацетилированными гистонами и направляющий транскрипцию множества генов. Однако неизвестно, регулирует ли и каким образом БРД4 функцию микроглии. Мы рассмотрели роль микроглии и BRD4 в нейро-воспалительном заболевании, экспериментальном аутоиммунном энцефаломиелите (EAE), модели мыши для множественных склерозов. Ранее сообщалось, что в EAE при первоначальной активации Т к

MSC-EV therapy for bone/cartilage diseases.

Mesenchymal stromal cells (MSCs) have been utilized in cell therapy for various diseases. Recent studies have demonstrated that extracellular vesicles (EVs) released by MSCs play an important role in their therapeutic activities. EVs contain a variety of bioactive molecules such as proteins, messenger RNAs (mRNAs), and micro RNAs (miRNAs) and modify the function of the recipient cells by transferring these molecules. Despite the promising potential of EV therapy as a substitute for MSC therapy, there are challenges that need to be addressed for the clinical success of EV therapy. EV quality ha

Препятствия и факторы, способствующие реформированию системы здравоохранения.

ВВЕДЕНИЕ: Системы здравоохранения во всем мире сталкиваются с растущим давлением, обусловленным растущим бременем неинфекционных заболеваний и старением населения, а также хронической нехваткой рабочей силы, инфраструктурными ограничениями и структурными дисгармониями между моделями ухода, предназначенными для лечения острых заболеваний, и долгосрочными потребностями сложных пациентов. Многие страны предпринимают комплексные усилия по преобразованию, включая перенос ухода ближе к дому, улучшение раннего выявления заболеваний и решение проблем, связанных с рабочей силой. Цель этого исследования

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… Denmark's nationally coordinated adoption of home fetal monitoring illustrates how system-wide alignment reduces duplication and ensures that community and home-based services can safely substitute for hospital-based care ( 35 ). … Home-based fetal monitoring, chronic disease self-management programmes, and hospital-at-home services are sustained in part because patients perceive greater convenience, continuity, and autonomy compared with hospital-based care ( 32 , 35 , 38 ). …

Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease.

Patients with multiple myeloma, an incurable malignancy of plasma cells, frequently develop osteolytic bone lesions that severely impact quality of life and clinical outcomes. Eliglustat, a U.S. Food and Drug Administration-approved glucosylceramide synthase inhibitor, reduced osteoclast-driven bone loss in preclinical in vivo models of myeloma. In combination with zoledronic acid, a bisphosphonate that treats myeloma bone disease, eliglustat provided further protection from bone loss. Autophagic degradation of TRAF3, a key step for osteoclast differentiation, was inhibited by eliglustat as ev

Gene regulation by non-Coding RNAs in infertility: a mechanistic review.

Infertility is a significant global health issue affecting millions of couples, with noncoding RNAs (ncRNAs) emerging as pivotal regulators in reproductive biology. This review explores the roles of various ncRNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), PIWI-interacting RNAs (piRNAs), and circular RNAs (circRNAs) in male and female infertility. These ncRNAs modulate critical processes such as spermatogenesis, oogenesis, follicular development, and embryo implantation through mechanisms like post-transcriptional regulation, chromatin remode

Clinical Treatment Guidelines for Tafasitamab Plus Lenalidomide in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 24% of new cases of B-cell non-Hodgkin lymphoma in the US each year. Up to 50% of patients relapse or are refractory (R/R) to the standard first-line treatment option, R-CHOP. The anti-CD19 monoclonal antibody tafasitamab, in combination with lenalidomide (LEN), is an NCCN preferred regimen for transplant-ineligible patients with R/R DLBCL and received accelerated approval in the US (July 2020) and conditional marketing authorization in Europe (August 2021) and other countries, based on data from the L-MIND study. The recommended

Adaptive NK cells undergo a dynamic modulation in response to human cytomegalovirus and recruit T cells in in vitro migration assays.

Human cytomegalovirus (HCMV) reactivation remains a relevant complication after hematopoietic stem cell transplantation (HSCT) despite the great progress made in prophylaxis and treatment. Adaptive Natural Killer (NK) cells undergo a persistent reconfiguration in response to HCMV reactivation however, the exact role of adaptive NK cells in HCMV surveillance is currently unknown. We studied the relationship between HCMV reactivation and adaptive NK cells in 70 patients monitored weekly until day +100 after HSCT. Absolute cell counts of adaptive NK cells increased significantly after resolution

Alpha-mangostin Amliorates Apoptosis, воспаление и окисляющий стресс в результате разложения Cuprizon в C57BL/6 Мыши.

ВВЕДЕНИЕ: Согласно сообщениям, альфа-мангостин (α-MG), самый изобилийный ксантон, найденный в Гарцинии Мангостана Линн, обладает мощными антиоксидантами и антивоспламеняющимися свойствами. Цель этого исследования заключалась в изучении нейрозащитного воздействия α-MG на вызванную кубической зоной (CZ) демиелинизацию в корпусе каллосум (CC) мышей, ставшей установившейся моделью животных для множественного склероза (MS). МЕТОДЫ: Взрослая женщина C57BL/6 Мыши были накормлены чау, в котором содержится 0.4% (w/w) CZ для 5 недель. Животные были произвольно назначены six группы: (1) контрольная групп

World Trade Center Health Program: First Decade of Research.

The terrorist attacks on 11 September 2001 placed nearly a half million people at increased risk of adverse health. Health effects research began shortly after and continues today, now mostly as a coordinated effort under the federally mandated World Trade Center (WTC) Health Program (WTCHP). Established in 2011, the WTCHP provides medical monitoring and treatment of covered health conditions for responders and survivors and maintains a research program aimed to improve the care and well-being of the affected population. By 2020, funds in excess of USD 127 M had been awarded for health effects

Discovery and validation of surface N-glycoproteins in MM cell lines and patient samples uncovers immunotherapy targets.

BackgroundMultiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow. While recent advances in treatment for MM have improved patient outcomes, the 5-year survival rate remains ~50%. A better understanding of the MM cell surface proteome could facilitate development of new directed therapies and assist in stratification and monitoring of patient outcomes.MethodsIn this study, we first used a mass spectrometry (MS)-based discovery-driven cell surface capture (CSC) approach to map the cell surface N-glycoproteome of MM cell lines. Next, we developed t

Pamidronate disodium for palliative therapy of feline bone-invasive tumors.

This study sought to quantify in vitro antiproliferative effects of pamidronate in feline cancer cells and assess feasibility of use of pamidronate in cats by assessing short-term toxicity and dosing schedule in cats with bone-invasive cancer. A retrospective pilot study included eight cats with bone invasive cancer treated with intravenous pamidronate. In vitro, pamidronate reduced proliferation in feline cancer cells (P < 0.05). One cat treated with pamidronate in combination with chemotherapy and two cats treated with pamidronate as a single agent after failing prior therapy had subjective

Conjunctival HLA-DR and CD8 expression detected by impression cytology in ocular graft versus host disease.

PurposeTo assess the expression of human leucocyte antigen (HLA)-DR in epithelial cells and cluster of differentiation (CD8)-positive lymphocytes as possible markers of chronic ocular graft versus host disease (cGvHD) after hematological stem cell transplantation (HSCT).MethodsTwenty-seven consecutive patients with dry-eye symptoms following HSCT (24 [89%] with peripheral blood stem cell transplantation and 3 [11%] with bone marrow transplants; 17 [63%] familiar allogenic grafts) and 19 age-matched controls were included. Conjunctival impression cytology specimens were stained for HLA-DR, cyto

Nanogel-Based Precision Bone Regeneration: Rational Design, Biological Barrier Penetration, and Osteoporotic Microenvironment Remodeling.

The pathogenesis of osteoporosis is primarily associated with impaired communication between osteoblasts and osteoclasts, leading to disrupted bone homeostasis. Conventional biomaterials mainly rely on macroscopic structural support and are limited in their ability to precisely regulate the complex bone microenvironment and overcome biological barriers. As representative soft matter nanoplatforms, nanogels possess unique viscoelastic mechanical properties and adaptive biointerfacial properties, offering new opportunities to overcome physical barriers within bone tissues. Moving beyond previous

The European Medicines Agency Review of Carfilzomib for the Treatment of Adult Patients with Multiple Myeloma Who Have Received at Least One Prior Therapy.

On November 19, 2015, a marketing authorization valid through the European Union was issued for carfilzomib in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy.In a phase III trial in patients with relapsed MM, median progression-free survival (PFS) for patients treated with carfilzomib in combination with lenalidomide and dexamethasone (CRd) was 26.3 months versus 17.6 months for those receiving lenalidomide and dexamethasone alone (hazard ratio = 0.69; 95% confidence interval, 0.57-0.83

Placental expanded mesenchymal-like cells (PLX-R18) for poor graft function after hematopoietic cell transplantation: A phase I study.

Persistent cytopenia in the post-hematopoietic cell transplantation (HCT) setting can occur despite adequate engraftment of donor cells. PLX-R18, a placental-derived mesenchymal-like cell product, is expanded ex vivo in a 3-dimensional environment. PLX-R18 cells secrete a large array of hematopoietic factors, which promote regeneration, maturation, and differentiation of hematopoietic cells and stimulate their migration to peripheral blood. This phase 1, first-in-human study (NCT03002519), included 21 patients with incomplete hematopoietic recovery post-HCT. Patients were treated with escalati

Эволюционно сохраненная созвездие функциональных резинов программирует реагирующую на вирус судьбу человека (эпи)генома.

Здоровье человека зависит от запутанной защитной клеточной реакции на микробные патогены, такие как вирусы. Несмотря на предпринятые значительные усилия, (эпи)геномические механизмы, используемые клетками человека для адаптации программ защитного генного экспрессия к микробным атакам, по-прежнему недостаточно изучены, главным образом из-за значительного отсутствия регистрации в vivo функциональных модулей резного регулирования (КРМ) генома человека. Здесь мы представляем реагирующую на вирус судьбу человека (эпи)генома, описываемого в наивных и инфицированных клетках функциональными геномами,

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

Совершенствование иммунотерапии клеток ИНКТ путем интеграции оптимизированных эндодоменов ЦАР и участников ИНКТ.

Клетки ИНКТ становятся весьма перспективной платформой иммунотерапии для лечения рака. Чтобы максимально увеличить антираковую активность CAR-INKT против рака крови, мы изучили оптимальные конструкции CAR и их комбинацию с новыми специфичными участниками INKT. Мы находим, что среди пяти различных эндодомен ЦАР, подкрепляемых возросшей вспыльчивостью и перекрестным разговором между Plexin D1 на CAR-INKT и Semaphorin 4 A на клетках миэломы, BCMA CD28z CAR-INKT проявляет наибольшую активность против миэломы. В частности, CD28z CAR-INKT опережает их коллег CAR-T. В целях расширения потенциала CAR-

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidiscip

Upregulation of CD19 by low-dose chidamide promotes CAR T cells functionality in B-cell non-Hodgkin lymphoma.

B-cell non-Hodgkin lymphoma (B-NHL) is a highly heterogeneous group of lymphopoietic malignancies that account for 85% to 90% of all non-Hodgkin lymphomas. In recent years, CD19 Chimeric antigen receptor T (CAR T) cell immunotherapy has significantly improved the cure rate of B-NHL patients, but there are still some patients who cannot achieve remission after treatment, or relapse after remission. Therefore, it is of great importance to overcome the drug resistance of CD19 CAR T cells after B-NHL treatment and reduce the recurrence rate of CD19 CAR T cells after B-NHL treatment. We found that