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The Roles of EDA2R in Ageing and Disease.

Ageing is a complex biological process driven, in part, by inflammaging. Recent research identifies the ectodysplasin A2 receptor (EDA2R) as a key regulator of inflammaging and a novel biomarker of ageing, with its expression increasing with age across diverse tissues in humans and animal models. Elevated EDA2R gene expression is associated with accelerated ageing, cellular senescence, frailty, obesity, acne, radiation response and increased levels of inflammatory, renal, cardiac and vascular biomarkers. Similarly, elevated EDA2R protein levels, a critical component of the proteomic ageing clo

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… Finally, Miclea et al. ( 2025 ) found that EDA2R correlated with white matter lesion volume in early multiple sclerosis, pointing to its potential as a biomarker of neuroinflammatory burden. … “Novel Serum Biomarker Associations With 7 Tesla MRI‐Defined Cortical Lesions, Leptomeningeal Enhancement, and Deep Gray Matter Volume in Early Multiple Sclerosis.” Scientific Reports 15, no. 1: 12032. Mikkola, M. L. 2008. “TNF Superfamily in Skin Appendage Development.” …

Резюме ESPR 2013Европейское общество педиатрической радиологии 50th Ежегодное совещание и 36th Курсы для аспирантов. Июнь 3–7 2013. Будапешт, Венгрия.

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… Kassa Darge 17:35–18:10 JESPER LECTURE Chaired by: Sam Stafrace 17:35–18:10 Pediatric multiple sclerosis, ADEM, and other demyelinating diseases: where do we stand? …

Radiolucent lesions of the mandible: a pattern-based approach to diagnosis.

ObjectivesRadiolucent mandibular lesions seen on panoramic radiographs develop from both odontogenic and non-odontogenic structures. They represent a broad spectrum of lesions with a varying degree of malignant potential. The purpose of this review is to illustrate the characteristic imaging findings-as well as the clinical and histological features-of common and uncommon radiolucent lesions of the mandible.MethodsThis review article is based on the retrospective evaluation of 11,725 panoramic radiographs seen in our institution during the past 6 years. It provides a comprehensive, practical a

Sildenafil, a Type-5 Phosphodiesterase Inhibitor, Fails to Reverse Myeloid-Derived Suppressor Cell-Mediated T Cell Suppression in Cells Isolated From Tuberculosis Patients.

Successful TB treatment is hampered by increasing resistance to the two most effective first-line anti-TB drugs, namely isoniazid and rifampicin, thus innovative therapies focused on host processes, termed host-directed therapies (HDTs), are promising novel approaches for increasing treatment efficacy without inducing drug resistance. We assessed the ability of Sildenafil, a type-5 phosphodiesterase inhibitor, as a repurposed compound, to serve as HDT target, by counteracting the suppressive effects of myeloid-derived suppressor cells (MDSC) obtained from active TB cases on T-cell responsivene

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation.

The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribu

Selective IgM Hypogammaglobulinemia and Multiple Sclerosis Treated with Natalizumab and Ofatumumab: A Case Report.

Background: B-cell-depleting drugs targeting the CD20 antigen have been increasingly implemented as an "exit strategy" from natalizumab for relapsing-remitting multiple sclerosis (RRMS) patients due to the increased risk of progressive multifocal leukoencephalopathy. Data on recently approved anti-CD20 drugs, such as ofatumumab serving as a natalizumab "exit strategy", are lacking. Furthermore, due to their immunosuppressive mechanism of action, prolonged use of these "highly effective" drugs is associated with the development of hypogammaglobulinemia and, consequently, a higher risk of infect…

Плазма и вицеральный орган Kynurenin Metabolites Коррелат в Multical Sclerosis Cuprizon Animal Model.

Модель нескольких склерозов (MS) капризона (CPZ) является прекрасной для изучения молекулярных различий, связанных с ущербом, причиненным отравлением. Метаболические различия в кинуреньиновом пути (КП) разложения триптофана (TRP) наблюдаются как в MS, так и в модели мыши CPZ. Наша цель состояла в том, чтобы проанализировать кинуреньин, серотонин и индоловые пути деградации ТРП на периферии, в нейродегенеративных процессах воспаления. В нашем исследовании мыши питались 0,2% токсина CPZ в течение 5 недель. Мы изучили метаболиты на трех путях разрушения ТРП в моче, плазме и соответствующих висцер

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The cuprizone (CPZ) model of multiple sclerosis (MS) is excellent for studying the molecular differences behind the damage caused by poisoning. Metabolic differences in the kynurenine pathway (KP) of tryptophan (TRP) degradation are observed in both MS and a CPZ mouse model. Our goal was to analyze the kynurenine, serotonin, and indole pathways of TRP degrad…

Exploring Human Brain Metabolism via Genome-Scale Metabolic Modeling with Highlights on Multiple Sclerosis.

Cerebral dysfunctions give rise to a wide range of neurological diseases due to the structural and functional complexity of the human brain … L-carnitine and arachidonate as the top reporter metabolites in gray and white matter microglia in multiple sclerosis (MS), respectively. Carbamoyl-phosphate was found to be the top reporter metabolite in primary progressive MS. Taken together, single and integrated iHumanBrain2690 metabolic networks help us elucidate complex metabolism in brain physiology and home …

Protein kinase CK2: a potential therapeutic target for diverse human diseases.

CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (ei

PEX11B Palmitoilation пары пероксисомальная дисфункция с клетками Шванна не работают в диабетической нейропатии.

Диабетическая нейропатия (ДН) является распространенным и болезненным осложнением диабета; однако механизмы, лежащие в основе ее патогенеза, остаются неясными, а эффективные клинические методы лечения отсутствуют. Цель этого исследования заключается в изучении роли пероксисома в клетках Шванна в DN. МЕТОДЫ: Изобилие пероксисома в акустических нервах мышей или клеток Шванна анализировалось с помощью лазерной суперразрешительной съемки и западного пятна. Пробоотборник RPF-GPF-SKL (Ser-Lys-Leu) использовался для оценки уровней пексафагии (пероксисомы-автофагика). Для оценки пальмитоилирования PEX

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BACKGROUND: Diabetic neuropathy (DN) is a prevalent and painful complication of diabetes; however, the mechanisms underlying its pathogenesi … ization) analysis was conducted to investigate the potential causal relationship between DN and MS (Multiple sclerosis). RESULTS: There was a decrease in peroxisomal abundance in the sciatic nerves of diabetic mice, and palmitic acid (PA) induced a reduction in peroxisomal abundance by inhibiting peroxisomal biogenesis in Schwann cells. Mechanistically, PA induced …

Асептический менингит, вызванный моноклональными антителами, используемыми для лечения рака: систематический обзор.

Фон и цель Monoclonal антитела (MAbs) революционизировали лечение рака, но связаны с целым спектром неблагоприятных явлений, включая неврологические осложнения. Понимание механизма и управления осложнениями имеет решающее значение для оптимизации ухода за пациентами. Цель настоящего систематического обзора заключалась в выявлении сообщений о случаях использования МБО для лечения рака, которые привели к появлению асептического менингита (АМ). 2024 (обновлено в мае) 2025). Для оценки качества тематических исследований использовался контрольный перечень критических оценок Института Джоанны Бриггс

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… The patients receiving the reduced doses of alemtuzumab revealed similar adverse immune - related events, whereas the high doses used in multiple sclerosis have not been reported to induce the same effects ( 41 ). Japanese patients are believed to be more predisposed to atezolizumab-induced irAEs. … Infusion-related, short-term, and delayed side effects of rituximab in multiple sclerosis and neuromyelitis optica spectrum disorder. Shiraz E-Med J. 2021;22(3):e101625,1–8. DOI: 10.5812/semj.101625. 48. Graça L, Alves J, Nuak J, Sarmento A. …

Targeting the Endocannabinoidome in Pancreatic Cancer.

Pancreatic Ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, is an aggressive and lethal form of cancer with a very high mortality rate. High heterogeneity, asymptomatic initial stages and a lack of specific diagnostic markers result in an end-stage diagnosis when the tumour has locally advanced or metastasised. PDAC is resistant to most of the available chemotherapy and radiation therapy treatments, making surgery the most potent curative treatment. The desmoplastic tumour microenvironment contributes to determining PDAC pathophysiology, immune response and therapeutic

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… These initial discoveries gave rise to the endocannabinoid system (ECS), a term used to describe the newly discovered endogenous lipid signalling system, which was associated with many pathologies including cancer, chronic pain, inflammation, epilepsy, anxiety, multiple sclerosis, Huntington’s disease … Therefore, understanding the eCBome poses a significant value for the pharmacological treatment of a multitude of pathological conditions including neuropsychiatric diseases such as anxiety and depression, neurological disorders such as multiple sclerosis, nausea induced by chemotherapy, inflammatory …

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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… At present, tolebrutinib is no longer being developed for MG, but research continues in other conditions such as multiple sclerosis, where it has shown promising results in slowing disease progression [ 150 ]. … This “immune reset” model has already been validated in multiple sclerosis, where short treatment cycles of oral cladribine provide durable disease control with limited cumulative toxicity [ 152 , 153 ]. …

Ход работы сессии 28th Европейский конгресс педиатрической ремуматологии (ПСР) 2022) Прага, Чешская Республика. 20-23 сентябрь 2022.

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Insights Into Late-Onset Rheumatoid Arthritis (LORA): Characteristics (Clinical and Imaging), Comorbidities, and Therapeutic Targets.

Late-onset rheumatoid arthritis (LORA) is defined as rheumatoid arthritis (RA) manifesting after the age of 65 years, although the terminology remains somewhat ambiguous. With the advent of a super-aging society and extended life expectancies, a significant increase in the incidence of LORA is anticipated. In comparison to young-onset RA (YORA), LORA is predominantly characterized by a higher incidence of acute onset, augmented disease activity and constitutional symptoms, a propensity for systemic manifestations, increased erythrocyte sedimentation rate at disease onset, reduced seropositivit

Положительная аллостерическая модуляция рецепторов АМПА с помощью PF4778574 приводит к снижению степени демиэлизации и клинической инвалидности в экспериментальных моделях множественного склероза.

ВВЕДЕНИЕ: Множественный склероз (МС) — расстройство центральной нервной системы (КНС), характеризующееся воспалением, обезвоживанием и нейронным дегенерацией. Несмотря на достижения в области иммуномодуляционного лечения, нейрозащитные или восстановительные стратегии по-прежнему являются неадекватными. Наши исследования сосредоточены на потенциале позитивного аллостерического модулятора рецепторов AMPA (AMPA-PAM), PF4778574, в борьбе с симптомами MS. Мы использовали MOG35-55 Продуктированная экспериментальная аутоиммунная энцефаломиелитная модель (EAE) в мышах C57BL6J для изучения терапевтичес

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INTRODUCTION: Multiple Sclerosis (MS), a debilitating central nervous system (CNS) disorder, is characterized by inflammation, demyelination, and neuronal degeneration. Despite advancements in immunomodulatory treatments, neuroprotective or restorative strategies remain inadequate. Our research is focusing on the potential of the positive allosteric modulato…

From Sjögren syndrome to Sjögren disease: rethinking classification and diagnostic complexity.

Sjögren syndrome (SS), traditionally regarded as a sicca-predominant condition, is now recognized as a systemic autoimmune disease characterized by type I interferon activation, B-cell hyperactivity, and periepithelial lymphocytic infiltration. This conceptual shift has prompted changes in terminology, with "SS" increasingly replaced by "Sjögren disease (SjD)" and "secondary SS" by "associated SjD," reflecting the concept of polyautoimmunity and ensuring equal clinical standing. In this review, we trace the historical evolution of SS classification criteria and examine their limitations in rea

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… Peripheral or central neurologic manifestations, including polyneuropathy, optic neuritis, or multiple sclerosis-like features, may occur. However, widespread or intraoral neuropathic pain is negatively associated with SjD [ 109 ]. In such cases, alternative diagnoses should be prioritized. …

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges.

Uncontrolled inflammation is a salient factor in multiple chronic inflammatory diseases and cancers. In this review, we provided an in-depth analysis of the relationships and distinctions between uncontrolled inflammation, fibrosis and cancers, while emphasizing the challenges and opportunities of developing novel therapies for the treatment and/or management of these diseases. We described how drug delivery systems, combination therapy and the integration of tissue-targeted and/or pathways selective strategies could overcome the challenges of current agents for managing and/or treating chroni

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… DMF has been approved for the treatment of relapsing multiple sclerosis and psoriasis while clinical trials evaluating its potential application in other inflammatory diseases and cancer are ongoing [ 255 ]. …

Polypharmacy and medication use in patients with chronic kidney disease with and without kidney replacement therapy compared to matched controls.

BackgroundThis study aims to examine polypharmacy (PP) prevalence in patients with chronic kidney disease (CKD) Stage G4/G5 and patients with kidney replacement therapy (KRT) compared with matched controls from the general population. Furthermore, we examine risk factors for PP and describe the most commonly dispensed medications.MethodsDutch health claims data were used to identify three patient groups: CKD Stage G4/G5, dialysis and kidney transplant patients. Each patient was matched to two controls based on age, sex and socio-economic status (SES) score. We differentiated between 'all medic

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… DDDs for central nervous system disorders: multiple sclerosis milIU, million international units. ATC code | Oral | Parenteral L03AB07 | – | 4.3 mg L03AB08 | – | 4 milIU L03AB13 | – | 8.9 μg L03AX13 | – | 20 μg L04AA27 | 0.5 mg | – L04AA31 | 14 mg | – N07XX09 | 480 mg | – Table A7. … DDDs for central nervous system disorders: other Restriction: only if there is no ATC code for central nervous system disorders: multiple sclerosis ATC code | Oral | Parenteral A07AA11 | 600 mg | – M03BX01 | 50 mg | 0.55 mg M03BX02 | 12 mg | – N07XX02 | 0.1 g | – Table A8. …

HMGB1: новая биомаркировка и лечебная цель аутоиммунной и аутовоспалительной кожных заболеваний.

Вставка 1 группы высокой подвижности (HMGB1) выражена почти во всех человеческих клетках. Во время активации клеток и клеточной смерти нуклеопротеин HMGB1 может перемещаться в внеклеточное пространство, тем самым посредничая ранним подстрекательским ответом как сигнализация или молекулярный рисунок, связанный с повреждением (DAMP). Внешнеклеточный HMGB1 взаимодействует с иммунными клетками, связываясь с системой распознавания рецепторов Toll-подобных (TLR), включая TLR2 и TLR4, и рецептором для современных продуктов для гликации (RAGE), тем самым содействуя иммунной реакции для защиты хоста от

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High-mobility group box 1 (HMGB1) is expressed in almost all human cells. During cell activation and cell death, the nucleoprotein HMGB1 can … for monitoring disease activity in several chronic inflammatory or autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus and vitiligo. Additionally, the inhibition of HMGB1 expression or its activity has beneficial effects on disease activity in animal models of autoimmune diseases. Thus, …