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Curcumol and FTY720 synergistically induce apoptosis and differentiation in chronic myelomonocytic leukemia via multiple signaling pathways.

Chronic myelomonocytic leukemia (CML) is a myeloid tumor characterized by MDS (myelodysplastic syndrome) and MPN (myeloproliferative neoplas … e drug has shown little progress. Fingolimod (FTY720), an FDA-approved drug used to treat relapsing multiple sclerosis, has also shown great potential in the treatment of lymphocytic leukemia. In our study, we find that FTY720 and curcumol have a significant inhibitory effect on K562 cells, K562/ADR cells, and CD34+ cells from CML patients. RNAseq data analysis show …

Potential anti-neuroinflammatory compounds from Australian plants - A review.

Neuroinflammation is a complex response to brain injury involving the activation of glia, release of inflammatory mediators, such as cytokines and chemokines, and generation of reactive oxygen and nitrogen species. Even though it is considered an event secondary to neuronal death or dysfunction, neuro-inflammation comprises a majority of the non-neuronal contributors to the cause and progression of neurodegenerative diseases like Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), Chronic Traumatic Encephalopathy (CTE) and others. As a result of the lack of effectivene…

Epigenetic research in multiple sclerosis: progress, challenges, and opportunities.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. MS likely results from a complex interplay between predisposing causal gene variants (the strongest influence coming from HLA class II locus) and environmental risk factors such as smoking, infectious mononucleosis, and lack of sun exposure/vitamin D. However, little is known about the mechanisms underlying MS development and progression. Moreover, the clinical heterogeneity and variable response to treatment represent additional challenges to a comprehensive understanding and efficient t…

Optic neuritis: experience from a south Indian demyelinating disease registry.

BACKGROUND: Natural history of optic neuritis (OPN) has not been studied in India. AIM: To study consecutive patients with optic neuritis a … ed-up in the clinic. RESULTS: During the follow-up of the 59 patients, 29 (49%) patients developed multiple sclerosis (MS); 3 (5%) patients neuromyelitis optica (NMO); and 13 (22%) patients chronic relapsing inflammatory optic neuritis (CRION), while the remaining 14 (24%) did not either progress or relapse, monophasic OPN. An initial abnormal magnetic resonance im …

Risk factors for deterioration of renal function after donor nephrectomy.

INTRODUCTION: There are few recent studies investigating increased risks for adverse effects leading to chronic kidney disease (CKD) among kidney donors. The aim of this study was to identify factors that protect renal function among actual live kidney donors. MATERIALS AND METHODS: We enrolled 68 individuals who had undergone donor nephrectomy in this study. We assessed donor age, body mass index (BMI), casual blood pressure, preoperative and 3-month follow-up serum creatinines, serum total cholesterol, and several other clinical parameters. The severity of arteriosclerosis in the arteriolar

Assessing optic nerve pathology with diffusion MRI: from mouse to human.

The optic nerve is often affected in patients with glaucoma and multiple sclerosis. Conventional MRI can detect nerve damage, but it does not accurately assess the underlying pathologies. Mean diffusivity and diffusion anisotropy indices derived from diffusion tensor imaging have been shown to be sensitive to a variety of central nervous system white matter pathologies. Despite being sensitive, the lack of specificity limits the ability of these measures to differentiate the underlying pathology. Directional (axial and radial) diffusivities, measuring water diffusion parallel and perpendicular…

Microglial 5-LOX-activating protein antagonism alleviates leukotriene-driven neuroinflammation.

In multiple sclerosis (MS), the chronic, unresolved nature of neuroinflammation within the central nervous system (CNS) remains a major obstacle for effective therapeutic intervention. This challenge arises primarily due to an incomplete understanding of the dysregulated inflammatory and pro-resolving pathways underlying MS lesion progression. Bioactive lipid mediators (LMs), biosynthesized through the coordinated actions of specific enzymes like lipoxygenases (LOX) and cyclooxygenases (COX), are key regulators of both the initiation and resolution of an inflammatory response; however, their s…

[Quality of life in multiple sclerosis and other chronic autoimmune and non-autoimmune diseases].

INTRODUCTION: Diseases that involve the nervous system and the musculoskeletal system are particularly likely to produce different limitations and deficits, and to affect the individual conception of quality of life. AIM: To determine the impact on quality of life generated by chronic autoimmune diseases like multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), ankylosing spondylitis (AS) and chronic musculotendinous diseases like osteoarthritis (OA) and fibromyalgia (FM), using the Short Form 36-item (SF-36) health questionnaire. P…

Infections, Vaccines and Autoimmunity: A Multiple Sclerosis Perspective.

Background: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease that is associated with multiple environmental factors. Among suspected susceptibility events, studies have questioned the potential role of overt viral and bacterial infections, including the Epstein Bar virus (EBV) and human endogenous retroviruses (HERV). Furthermore, the fast development of immunomodulatory therapies further questions the efficacy of the standard immunization policies in MS patients. Topics reviewed: This narrative review will discuss the potential interplay between viral and b…

Probabilistic Clustering Using Multivariate Growth Mixture Model in Clinical Settings-A Scleroderma Example.

BACKGROUND: Scleroderma (systemic sclerosis; SSc) is a chronic autoimmune disease known for wide heterogeneity in patients' disease progression in multiple organ systems. Our goal is to guide clinical care by real-time classification of patients into clinically interpretable subpopulations based on their baseline characteristics and the temporal patterns of their disease progression. METHODS: A Bayesian multivariate growth mixture model was fit to identify subgroups of patients from the Johns Hopkins Scleroderma Center Research Registry who share similar lung function trajectories. We jointly

Imaging the hidden player: Choroid plexus enlargement in multiple sclerosis.

The choroid plexus (CP), one key regulator of cerebrospinal fluid (CSF) production and immune surveillance at the blood-CSF barrier, has recently emerged as a relevant structure in multiple sclerosis (MS) pathophysiology. This review synthesizes current evidence highlighting CP enlargement as measured with magnetic resonance imaging (MRI) as a potential biomarker of neuroinflammation and neurodegeneration in MS. We first outline the basic immunological roles of the CP, emphasizing its function as a dynamic interface facilitating immune cell trafficking and cytokine production within the CNS. A…

Расшифровка Нейропной защиты Bee Venom Peptide Melittin: Insights in Mechanistic Interplay.

Нейродегенеративные заболевания, такие как болезнь Альцгеймера, болезнь Паркинсона и множественный склероз, характеризуются постепенной утратой нейронной структуры и функции. Эти условия часто приводят к когнитивному упадку, дисфункции двигателя и, в конечном счете, к серьезному ухудшению повседневной деятельности. Одной из основных особенностей нейродегенеративных заболеваний является хроническое воспаление, которое приводит к нейронным повреждениям и усугубляет прогрессию заболеваний. Традиционные методы лечения ориентированы главным образом на борьбу с симптомами, а не на устранение коренны

Совпадение в аннотации оригинала
Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, are characterized by progressive loss of neuronal structure and function. These conditions often lead to cognitive decline, motor dysfunction, and ultimately severe impairment of daily activities. A key feature of neurodegenerative diseases is chronic inflam…

Association of Functional Gene Variants in DYSF-ZNF638, MTSS1 and Ferroptosis-Related Genes with Multiple Sclerosis Severity and Target Gene Expression.

Multiple sclerosis (MS) is a chronic inflammatory, neurodegenerative disease with yet-unresolved mechanisms of progression. To address MS severity and neurological deficits, we analyzed seven potentially functional genetic variants and their haplotypes in 845 MS patients. Based on our previous results of targeted RNAseq on ferroptosis-related genes in distinctive MS phenotypes, we selected putative regulatory variants in the top three DEGs (CDKN1A, MAP1B and EGLN2) and investigated their association with gene expression, plasma/serum parameters and disease severity (EDSS, MSSS, gARMSS). The st…

Is There Any Association Between Neurodegenerative Diseases and Periodontitis? A Systematic Review.

Background: Neurodegenerative diseases are a group of progressive disorders that affect the central nervous system (CNS) such as Alzheimer, Parkinson, and multiple sclerosis. Inflammation plays a critical role in the onset and progression of these injuries. Periodontitis is considered an inflammatory disease caused by oral biofilms around the tooth-supporting tissues, leading to a systemic and chronic inflammatory condition. Thus, this systematic review aimed to search for evidence in the association between neurodegenerative disorders and periodontitis. Methods: This systematic review was reg…

Neuronal and Endothelial Transglutaminase-2 Expression during Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis.

Transglutiminase-2 (TG2) is a multifunctional enzyme that has been implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) using global knockout mice and TG2 selective inhibitors. Previous studies have identified the expression of TG2 in subsets of macrophages-microglia and astrocytes after EAE. The aims of the current investigation were to examine neuronal expression of TG2 in rodent models of chronic-relapsing and non-relapsing EAE and through co-staining with intracellular and cell death markers, provide insight into the putative role of…

Absence of endothelial α5β1 integrin triggers early onset of experimental autoimmune encephalomyelitis due to reduced vascular remodeling and compromised vascular integrity.

Early in the development of multiple sclerosis (MS) and its mouse model experimental autoimmune encephalomyelitis (EAE), vascular integrity is compromised. This is accompanied by a marked vascular remodeling response, though it is currently unclear whether this is an adaptive vascular repair mechanism or is part of the pathogenic process. In light of the well-described angiogenic role for the α5β1 integrin, the goal of this study was to evaluate how genetic deletion of endothelial α5 integrin (α5-EC-KO mice) impacts vascular remodeling and repair following vascular disruption during EAE pathog…

Microglia-derived extracellular vesicles in Alzheimer's Disease: A double-edged sword.

Extracellular vesicles (EVs), based on their origin or size, can be classified as apoptotic bodies, microvesicles (MVs)/microparticles (MPs), and exosomes. EVs are one of the new emerging modes of communication between cells that are providing new insights into the pathophysiology of several diseases. EVs released from activated or apoptotic cells contain specific proteins (signaling molecules, receptors, integrins, cytokines), bioactive lipids, nucleic acids (mRNA, miRNA, small non coding RNAs, DNA) from their progenitor cells. In the brain, EVs contribute to intercellular communication throu

Efficiency of antibody therapy in demyelinating diseases.

Monoclonal antibody therapy is a new treatment strategy for many types of diseases including cancers and autoimmune diseases, realizing a high efficacy and tolerability. In multiple sclerosis (MS) and neuromyelitis optica (NMO) spectrum disorders, several monoclonal antibodies have been suggested to decrease the incidence of clinical relapse and the disease activity. In MS, anti-α4 integrin (natalizumab), anti-CD52 (alemtuzumab), anti-CD25 (daclizumab) and anti-CD20 (ocrelizumab) have been shown to effectively reduce the relapses in randomized controlled trials and have been approved by the Fo…

Multiple Sclerosis: Immunotherapy.

Given our current knowledge, there is a need for the early institution of immunomodulatory therapy, especially for patients with poor progno … imen before irreversible and considerable disability has accumulated. For the majority of patients, multiple sclerosis (MS) is a chronic condition. Therefore, until a curative treatment has been developed, the available repertoire of immunosuppressive or immunomodulatory treatments should be assessed with respect to the possibility of long-term use. This is particul …

Cytomegalovirus Drives the Development of Cytotoxic CD4+ T Cells in Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Chronic immune activation is a hallmark of latent viral infections and autoimmune disorders, profoundly shaping i … althy cytomegalovirus (CMV)-seropositive donors, patients with CMV-seronegative relapsing-remitting multiple sclerosis (RR-MS) (autoimmune trigger), and patients with CMV-seropositive RR-MS (combination of viral and autoimmune trigger). RESULTS: Our findings reveal that the heterogeneous pool of CD4 CTL encompasses distinct subsets with divergent expression of proi …