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Autoimmune Neuromuscular Disorders at a Molecular Crossroad: Linking Pathogenesis to Targeted Immunotherapy.

Myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and idiopathic inflammatory myopathies are among the most widely recognized autoimmune neuromuscular disorders. Although they differ in clinical presentation, shared immunopathogenic mechanisms place them at a molecular crossroads. Evidence of overlapping pathways has led to the development of targeted strategies including complement inhibition, FcRn antagonism, B-cell depletion, and the CAR-T cell approach. In this review, we analyze current knowledge regarding pathogenic mechanisms and their link to immunotherapy, extensiv

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… Approximately 80% of anti-SRP patients have antibodies against SRP54, especially its N-terminal or G-central region, with minimal reactivity to the C-terminal region [ 48 , 49 ]. 3-hydroxy-3-methylglutaryl-coenzyme A Reductase (HMGCR) is an endoplasmic reticulum resident enzyme. … Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy Arthritis Rheum. 2011 63 713 721 10.1002/art.30156 21360500 PMC3335400 51. Allenbach Y. Arouche-Delaperche L. Preusse C. Radbruch H. Butler-Browne G. Champtiaux N. …

Expert opinion on screening, diagnosis and management of diabetic peripheral neuropathy: a multidisciplinary approach.

The proposed expert opinion aimed to address the current knowledge on conceptual, clinical, and therapeutic aspects of diabetic peripheral neuropathy (DPN) and to provide a guidance document to assist clinicians for the best practice in DPN care. The participating experts consider the suspicion of the disease by clinicians as a key factor in early recognition and diagnosis, emphasizing an improved awareness of the disease by the first-admission or referring physicians. The proposed "screening and diagnostic" algorithm involves the consideration of DPN in a patient with prediabetes or diabetes

Different Strategies to Overcome Resistance to Proteasome Inhibitors-A Summary 20 Years after Their Introduction.

Proteasome inhibitors (PIs), bortezomib, carfilzomib, and ixazomib, are the first-line treatment for multiple myeloma (MM). They inhibit cytosolic protein degradation in cells, which leads to the accumulation of misfolded and malfunctioned proteins in the cytosol and endoplasmic reticulum, resulting in cell death. Despite being a breakthrough in MM therapy, malignant cells develop resistance to PIs via different mechanisms. Understanding these mechanisms drives research toward new anticancer agents to overcome PI resistance. In this review, we summarize the mechanism of action of PIs and how M

Mechanisms, Mediators, and Moderators of the Effects of Exercise on Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect of neurotoxic antineoplastic agents commonly used to treat cancer. Patients with CIPN experience debilitating signs and symptoms, such as combinations of tingling, numbness, pain, and cramping in the hands and feet that inhibit their daily function. Among the limited prevention and treatment options for CIPN, exercise has emerged as a promising new intervention that has been investigated in approximately two dozen clinical trials to date. As additional studies test and suggest the efficacy of exercise in treating CIPN, it i

Diagnosis and treatment of cystic lung disease.

Cystic lung disease (CLD) is a group of lung disorders characterized by the presence of multiple cysts, defined as air-filled lucencies or low-attenuating areas, bordered by a thin wall (usually < 2 mm). The recognition of CLDs has increased with the widespread use of computed tomography. This article addresses the mechanisms of cyst formation and the diagnostic approaches to CLDs. A number of assessment methods that can be used to confirm CLDs are discussed, including high-resolution computed tomography, pathologic approaches, and genetic/ serologic markers, together with treatment modalities

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… Other potential therapeutic targets include autophagy inhibitors (e.g., chloroquine), MMP inhibitors (e.g., doxycycline), hydroxymethylglutaryl coenzyme A reductase inhibitor (e.g., simvastatin), aromatase inhibitor (e.g., letrozole), cyclooxygenase inhibitor (e.g., aspirin and celecoxib), and tyrosine …

The prince and the pauper. A tale of anticancer targeted agents.

Cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000 to 15 million in 2020. Regarding the pharmacological treatment of cancer, we currently are in the interphase of two treatment eras. The so-called pregenomic therapy which names the traditional cancer drugs, mainly cytotoxic drug types, and post-genomic era-type drugs referring to rationally-based designed. Although there are successful examples of this newer drug discovery approach, most target-specific agents only provide small gains in symptom control and/or survival, whereas others have consiste

Генетические данные о оси печени и мозга: риск липидного метаболизма и нейродегенеративного заболевания.

Ось печени - мозга имеет критическое значение для нейродегенеративных заболеваний (ND), при этом липидный метаболизм влияет на нейроинфламму и микроглиальную функцию. Систематическое исследование генетической связи между липидными метаболическими аномалиями и ND, а именно болезнью Альцгеймера (AD), болезнью Паркинсона (PD), множественным склерозом (MS) и амиотропическим боковым склерозом (ALS), отсутствует. Для оценки потенциальных причинно-следственных связей между ND и шестью липидными параметрами использовалась двухвыборная мендельская случайность (MR). МЕТОДЫ: Для параметров липидов и ND (

Тела эндогенных кетонов связаны с метаболической уязвимостью и инвалидностью при множественном склерозе.

Цель: Тела кетона могут быть полезными биомаркерами в множестве склероза (МС), поскольку патофизиологические процессы, лежащие в основе развития заболеваний MS, вызывают метаболический стресс. Цель заключалась в оценке связей кетоновых тел с биомаркерами метаболического, подстрекательского и окислительного стресса в MS. Методы: Образцы крови и неврологические оценки были получены от 153 здоровых контрольных приборов (HC), 187 релапсирующих излучающих веществ (RRMS) и 91 пациента с прогрессивным MS (PMS). AcAc, BHB и ацетон измерялись с помощью спектроскопии протонного ядерного магнитного резон

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… Ketone bodies consist of acetoacetate (AcAc), β-hydroxybutyrate (BHB, 3-hydroxybutyrate), and acetone, which are produced by ketogenesis from acetyl coenzyme A (acetyl-CoA) in mitochondria. …

Identification of a novel cuproptosis-related gene signature for multiple myeloma diagnosis.

BackgroundMultiple myeloma (MM) ranks second among the most prevalent hematological malignancies. Recent studies have unearthed the promise of cuproptosis as a novel therapeutic intervention for cancer. However, no research has unveiled the particular roles of cuproptosis-related genes (CRGs) in the prediction of MM diagnosis.MethodsMicroarray data and clinical characteristics of MM patients were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed gene analysis, least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature e

Резюме 18th Неевромускульная научно-исследовательская конференция Соединенного Королевства 15th и 16th апрель 2025.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

A review of mitochondrial dysfunction in diabetic sarcopenia: Mechanisms, diagnosis, and treatment approaches.

Diabetic sarcopenia is a common complication of diabetes, substantially impacting patients' quality of life and prognosis. Its pathogenesis is closely related to energy metabolism, with mitochondria-often referred to as the cellular "powerhouse"-playing a central role in this process. This review focuses on the role of mitochondrial dysfunction in diabetic sarcopenia, emphasizing mechanisms such as energy metabolism imbalance, oxidative stress-induced damage, and abnormalities in mitochondrial biogenesis and dynamics. Additionally, we discussed current research on diagnostic and therapeutic st

Ксантин Оксидореводаза: Меч с двойным отростком в неврологических заболеваниях.

Неинфекционные неврологические расстройства являются второй основной причиной смерти, и их бремя продолжает расти по мере роста и старения населения мира. Окисляющий стресс и воспаление во многом связаны с активацией и развитием множественных склерозов, болезни Альцгеймера, амиотропического бокового склероза, болезни Хантингтона, болезни Паркинсона и даже инсульта. В ходе этого обзора мы изучаем роль деятельности и продуктов &quot; xanthine oxidoreducase &quot; (XOR) во всех вышеупомянутых неврологических заболеваниях. Редоксальный дисбаланс, вызывающий окислительный стресс, может возникнуть и

Oxidative Stress and Cancer: Harnessing the Therapeutic Potential of Curcumin and Analogues Against Cancer.

Reactive oxygen species (ROS) are a class of bioactive molecules that are the by-products of many cellular functions. These molecules are present in normal cells at homeostatic levels but have been studied extensively in cancer due to their dysregulation resulting in pro- and anti-tumorigenic environments. Completely understanding the paradoxical nature of ROS in cancer is imperative to fully realize its modulation as cancer therapy. Studies into ROS have shown far-reaching effects in cancer, including how ROS levels regulate signaling, response to treatment, drug resistance, etc. Many drugs w

Are medication-induced salivary changes the culprit of osteonecrosis of the jaw? A systematic review.

PURPOSE: This systematic review was performed to assess the potential influence of medication-induced salivary changes on the development of medication-related osteonecrosis of the jaw (MRONJ). METHODS: An electronic search was conducted using PubMed, Web of Science, Cochrane, and Embase databases for articles published up to June 2023. A risk of bias assessment was performed according to the modified Newcastle-Ottawa Scale (NOS). Due to the heterogeneity of the selected studies in relation to the type of medications and outcomes evaluated, a meta-analysis could not be performed. RESULTS: Th

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… In addition, IL-6 release is also increased due to the decrease in the enzyme hydroxymethylglutaryl coenzyme A (HMG-CoA), following drug administration. All these changes in the salivary proteins result in a higher occurrence of MRONJ. …

Fanconi syndrome induced by adefovir dipivoxil: a case report and clinical review.

More than 150 cases of Fanconi syndrome (FS) or hypophosphatemia osteomalacia induced by low-dose adefovir dipivoxil (ADV) have been reported since 2002, when ADV was introduced for the long-term treatment of hepatitis B virus (HBV) infection. Because the life expectancy of HBV-infected individuals has increased, the adverse effects of long-term treatment with antiviral therapies are increasingly observed, and nephrotoxicity is one of the most severe adverse effects of ADV. Therefore, the number of cases may be far higher than reported. Moreover, ADV-induced FS is often misdiagnosed or diagnos

Development of a machine learning-based predictive risk model combining fatty acid metabolism and ferroptosis for immunotherapy response and prognosis in prostate cancer.

Prostate cancer (PCa) remains a leading cause of cancer-related mortality, necessitating robust prognostic models and personalized therapeutic strategies. This study integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics to construct a prognostic model based on genes shared between ferroptosis and fatty acid metabolism (FAM). Using the TCGA-PRAD dataset, we identified 73 differentially expressed genes (DEGs) at the intersection of ferroptosis and FAM, of which 19 were significantly associated with progression-free survival (PFS). A machine learning-

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… Sen U Coleman C Sen T Stearoyl coenzyme A desaturase-1: multitasker in cancer, metabolism, and ferroptosis Trends Cancer 2023 9 480 489 10.1016/j.trecan.2023.03.003 37029018 Sen U, Coleman C, Sen T. Stearoyl coenzyme A desaturase-1: multitasker in cancer, metabolism, and ferroptosis. …

Ferroptosis: Frenemy of Radiotherapy.

Recently, it was established that ferroptosis, a type of iron-dependent regulated cell death, plays a prominent role in radiotherapy-triggered cell death. Accordingly, ferroptosis inducers attracted a lot of interest as potential radio-synergizing drugs, ultimately enhancing radioresponses and patient outcomes. Nevertheless, the tumor microenvironment seems to have a major impact on ferroptosis induction. The influence of hypoxic conditions is an area of interest, as it remains the principal hurdle in the field of radiotherapy. In this review, we focus on the implications of hypoxic conditions

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… Acyl coenzyme A (CoA) derivatives of these PUFAs are produced by acyl-coenzyme A synthetase long-chain family member 4 (ACSL4). After the production of these PUFA-CoA, lysophosphatidylcholine acyltransferase 3 (LPCAT3) esterifies them into phospholipids [ 27 , 28 , 29 ]. …

Opportunities and Challenges of Small Molecule Induced Targeted Protein Degradation.

Proteolysis targeting chimeras (PROTAC) represents a new type of small molecule induced protein degradation technology that has emerged in recent years. PROTAC uses bifunctional small molecules to induce ubiquitination of target proteins and utilizes intracellular proteasomes for chemical knockdown. It complements the gene editing and RNA interference for protein knockdown. Compared with small molecule inhibitors, PROTAC has shown great advantages in overcoming tumor resistance, affecting the non-enzymatic function of target proteins, degrading undruggable targets, and providing new rapid and

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… PROTAC Provides Tools to Rapid Knockout of the HMGCR 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase (HMGCR) is the rate-limiting enzyme in the cholesterol synthesis pathway. … Degradation versus inhibition: development of proteolysis-targeting chimeras for overcoming statin-induced compensatory upregulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase. J. Med. Chem. 63 4908–4928. 10.1021/acs.jmedchem.0c00339 Li Z. Q., Razavi P., Li Q., Toy W. …

Митохондриальная дисфункция, накопление железа, пероксидация липидов и воспаленная активация в клеточных моделях, полученных от пациентов с множественным склерозом.

Множественный склероз (MS) является воспалительным заболеванием центральной нервной системы (CNS). Несмотря на успехи в борьбе с вновь возникающими активными заболеваниями, эффективное лечение необратимого постепенного сокращения НР остается ограниченным. Исследования с использованием фибробатластов кожи, полученные от пациентов с неврологическими расстройствами, выявили изменения в путях клеточного стресса и биоэнергетики. Однако исследований с использованием моделей клеток MS, разработанных пациентами, мало. В этом исследовании мы собрали фибробласты из two Пациенты MS для изучения клеточных

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… Furthermore, it has been demonstrated that several ferroptosis-related genes, such as Ataxia Telangiectasia Mutated ( ATM ), Glycogen Synthase Kinase 3 Beta ( GSK3B) , 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase ( HMGCR ), Kruppel-Like Factor 2 ( KLF2 ), Mitogen-Activated Protein Kinase …

IL-6 and NFE2L2: A putative role for the hepatoprotective effect of N. Sativa, P. Ginseng and C. Sempervirens in AFB-1 induced hepatocellular carcinoma in rats.

In this study, we investigated possible hepato-protective effects of N. Sativa, P. Ginseng, and C. Sempervirens in Aflatoxin B1 (AFB-1) induced hepatocellular carcinoma rat model. Fifty-four male albino rats were randomly assigned to experimental groups. Alcoholic extracts of aforementioned herbs were administered orally for 28 days at different doses. IL-6, hs-CRP, MDA, SOD and NFE2L2 were determined using ELISA. Histopathological changes in treated groups were examined. Herbal treatment significantly reduced IL-6, hs-CRP, and MDA (P C. Sempervirens 600 and N. Sativa 1000 increased NFE2L2 lev