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Small molecule metabolites: discovery of biomarkers and therapeutic targets.

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks of diseases. Metabolite signatures that have close proximity to subject's phenotypic informative dimension, are useful for predicting diagnosis and prognosis of diseases as well as monitoring treatments. The lack of early biomarkers could lead to poor diagnosis and serious outcomes. Therefore, noninvasive diagnosis and monitoring methods with high specificity and selectivity are desperately needed. Small molecule metabolites-based metabolomics has b

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… COVID-19 AlbertoValdés et al. 551 145 Plasma Classification HPLC-MS 3-Hydroxibutirate, linoleic acid, LPC (14:0 and 18:2), LPE (22:6), kynurenic acid Metabolism of carnitines, ketone bodies, fatty acids, and lysophosphatidylcholines Bladder Cancer, Prostate Cancer, Renal Cell Carcinoma Sujin Lee et al … , acetyl-carnitine, tryptophan and lysine selected as potential biomarkers in distinguishing patients. …

Ход работы 34th Симпозиум ESVN-ECVN 23rd-24th сентябрь 2022.

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Твердая неэптическая гипераммония, связанная с уреаплазмой парвума и инфекциями гомини Микопласмы в двойном иммунозапугивании женщины, представляющей как предполагаемый перитональный карциноматоз.

Острая гипераммония, не связанная с гепатической гипераммонией, является редким, но потенциально опасным для жизни заболеванием у пациентов, страдающих иммунокомпромиссной болезнью. Виды Ureaplasma и Mycoplasma являются быстродействующими врожденными организмами, которые генерируют аммиак и могут вызывать распространенную культурно-отрицательную инфекцию. Мы сообщаем о случае 63-year-old Женщина, получающая двойную биологическую терапию, оклелизумаб от множественных склерозов и секукинуумаб от псориаза, которая имела историю стерильности пюрии и симптомов мочи ниже. В течение двух месяцев ее с

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… Total and free carnitine concentrations were mildly reduced, 33 µmol/L (reference range, 37-92 µmol/L) and 22 µmol/L (reference range, 26-90 µmol/L), respectively, with a preserved free-to-total carnitine ratio of 67% (reference, >50%). …

Radioprotectors & mitigators in radiation therapy: Harnessing diverse pathways for optimizing clinical outcomes.

Radioprotectors are agents that protect normal tissues from the harmful effects of radiation during cancer treatment. Combining these protective agents with advanced radiotherapy techniques such as stereotactic body radiotherapy (SBRT) and proton therapy offers a promising strategy to enhance therapeutic efficacy while minimizing normal tissue toxicity. However, despite extensive research and the identification of numerous potential radioprotectors, only a few have made it into clinical practice. It is primarily because the transition from laboratory research to clinical application faces sign

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… , or whole-body irradiation (various doses, e.g. , 8 Gy) | Reduces DNA damage, with Taurine demonstrating antioxidative & detoxification properties, while L-carnitine synergistically inhibits proliferation & osteoblastic differentiation of vascular smooth muscle cells | DMF: Not known | 51 Radiation … The possible mechanisms involved in the protection strategies against radiation-induced cellular damage by carnitines. Int J Clin Med. 2015;6:71–80. doi: 10.4236/ijcm.2015.62011. 52. Rittase WB, McCart EA, Muir JM, Bouten RM, Slaven JE, Mungunsukh O, et al. …

Subject index

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… long-standing type 2 diabetes mellitus, 429–434 pediatric, epidemiology of, 96–101 in pediatric isolated sarcoid granulomatous interstitial nephritis, 411–414 post-coronary artery bypass graft surgery, genetic polymorphisms and, 519–530 randomized controlled trials, 775–779 with rhabdomyolysis, carnitine … Health Study, renal duplex sonography parameters associated with renal parenchymal changes in elderly, 842–850 Cardiovascular risk factors influence of hypertension on mortality in hemodialysis patients and, 112–118 nutrient intake and microalbuminuria in nondiabetic middle age population, 256–266 Carnitine …

Lithium and preventing chemotherapy-induced peripheral neuropathy in breast cancer patients: a placebo-controlled randomized clinical trial.

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of some chemotherapy regimens. Lithium has been suggested for CIPN in some animal studies. We aimed to study lithium's preventive effect on CIPN in breast cancer patients treated with taxanes and platinum-based medications.MethodA double-blind placebo-controlled randomized clinical trial (RCT) was implemented on 36 breast cancer patients in two equal-size groups by block randomization. Participants in both groups consumed daily tablets, either placebo or lithium (300 mg), for 5 days in each course of chemoth

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… Several compounds have been studied to prevent CIPN, including intravenous calcium and magnesium, vitamin E, amifostine, glutathione, glutamine, acetyl-L-carnitine, N-acetyl-cysteine, antiepileptic medicines, and others. … Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. J Clin Oncol. 2013;31(20):2627–2633. doi: 10.1200/JCO.2012.44.8738. 9. …

Ion channels and neuronal hyperexcitability in chemotherapy-induced peripheral neuropathy; cause and effect?

AbstractCancer is the second leading cause of death worldwide and is a major global health burden. Significant improvements in survival have been achieved, due in part to advances in adjuvant antineoplastic chemotherapy. The most commonly used antineoplastics belong to the taxane, platinum, and vinca alkaloid families. While beneficial, these agents are frequently accompanied by severe side effects, including chemotherapy-induced peripheral neuropathy (CPIN). While CPIN affects both motor and sensory systems, the majority of symptoms are sensory, with pain, tingling, and numbness being the pre

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… Proposed treatment Strength of evidence Recommendation Benefit(s) Harm(s) a Acetyl-L -carnitine Low Inconclusive Low Moderate Duloxetine Intermediate Moderate for Intermediate Low Gabapentin Intermediate Inconclusive Low Low Lamotrigine Intermediate Moderate against None demonstrated Low Nortriptyline … These recommendations are separate and distinct from the ASCO practice guidelines for the management of chronic pain in survivors of adult cancers. 207 Proposed treatment | Strength of evidence | Recommendation | Benefit(s) | Harm(s) a Acetyl-L -carnitine | Low | Inconclusive | Low | Moderate Duloxetine …

Metabolomic Profiling in the Characterization of Degenerative Bone and Joint Diseases.

Osteoarthritis and inflammatory arthropathies are a cause of significant morbidity globally. New research elucidating the metabolic derangements associated with a variety of bone and joint disorders implicates various local and systemic metabolites, which further elucidate the underlying molecular mechanisms associated with these destructive disease processes. In osteoarthritis, atty acid metabolism has been implicated in disease development, both locally and systemically. Several series of rheumatoid arthritis patients have demonstrated overlapping trends related to histidine and glyceric aci

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… Using a combined proteomic and metabolomic approach, Yang et al. analyzed synovial fluid from 25 RA patients and 10 controls undergoing synovectomy or total joint replacement, and reported significantly increased β-mannosylglycerate, carnitine, diglycerol, lactic acid, and pipecolinic acid in the RA … In a series of pre-symptomatic RA patients, plasma samples were analyzed using a LC-MS and lipid profiling approach and showed elevated levels of lysophospatidylcholines and tryptophan metabolites, as well as reductions in acyl-carnitines and fatty acids [ 26 ]. …

N-Acetylcystine в неврологических расстройствах: систематический обзор клинических и переводческих доказательств по всему миру Seven Расстройства.

N-ацетилцистейн (NAC) — прекурсор глютатиона с установленными антиоксидантами и антивоспалительными свойствами, которые были исследованы в качестве нейрозащитного агента в различных неврологических условиях. В ходе этого систематического обзора систематически составлялся обзор клинических данных по НХД по всем странам. seven Неврологические расстройства. В библиотеке Пубмеда и Кокрана были найдены материалы, опубликованные между 1 Январь 1995 и 31 декабрь 2025. Twenty-three Были проведены следующие исследования: травма головного мозга (TBI, n = 6), болезнь Альцгеймера (AD, n = 5), болезнь Парк

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… NAC = N-acetylcysteine; NAM = N-acetylmethionine; DTT = dithiothreitol; DTE = dithioerythritol; DMSA = meso-2,3-dimercaptosuccinic acid (metal chelator); NF = nutraceutical formulation; SAM = S-adenosyl methionine; ALCAR = acetyl-L-carnitine; DRS = Dementia Rating Scale; MMSE = Mini-Mental State Examination … Scale; IV = intravenous; CSF = cerebrospinal fluid; rs-fMRI = resting-state functional MRI; MACF = Microcog Assessment of Cognitive Functioning; SPECT = single-photon emission computed tomography. * NAC as part of multicomponent supplement including ginkgo, vinpocetine, alpha-lipoic acid, acetyl-l-carnitine …

The Impact of Ketogenic Nutrition on Obesity and Metabolic Health: Mechanisms and Clinical Implications.

The ketogenic diet (KD) has recently gained increasing popularity. This high-fat, adequate-protein, and carbohydrate-poor eating pattern leads to nutritional ketosis. The KD has long been known for its antidiabetic and antiepileptic effects and has been used therapeutically in these contexts. Recently, the KD, due to its effectiveness in inducing weight loss, has also been proposed as a possible approach to treat obesity. Likewise, a KD is currently explored as a supporting element in the treatment of obesity-associated metabolic disorders and certain forms of cancer. Here, we discuss the meta

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… Metabolic disorders | Improved metabolic markers: There are studies showing that a KD may lead to improvements in cardiometabolic markers. 115 , 169 | Carnitine deficiency: The KD may lower carnitine levels, posing issues for individuals with metabolic disorders involving impaired carnitine metabolism … Carnitine levels and the ketogenic diet. Epilepsia. 2001;42:1445-1451. 10.1046/j.1528-1157.2001.18001.x Associated Data Data Availability Statement Not applicable. …

Атлас о факторах риска для множественного склероза: Менделианское исследование случайности.

ЦЕЛИ: Мы провели систематический обзор и широкомасштабное исследование на предмет случайной менделизации (MR) для изучения связи между возможными факторами риска и множественным склерозом (MS). Мы использовали анализ MR для оценки связей между 65 возможные факторы риска и НР с использованием данных, полученных в результате исследования, проведенного в масштабах всего генома, включая 14 498 случаи и случаи 24 091 контроль за европейским происхождением. Для 18 Мы провели систематический обзор воздействия, не подходящего для анализа МР, с целью получения последних данных метаанализа их связей с Н

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… NA NA 26414677 Other factors  Migraine 59 674 316 078 European 33 33 4.4 d 524 27322543  Migraine without aura 2326 4580 European 6 7.8 d 97 22683712  Estimated bone mineral density 426 824 NA European 993 786 20.7 e 112 30598549  Uric acid a 288 649 NA European 123 94 5.3 e 131 31578528 Amino acid  Carnitine … 0.838  Migraine without aura 1.03 0.93–1.14 0.574 1.02 0.91–1.14 0.789 0.180  Estimated bone mineral density 1.02 0.95–1.10 0.569 1.11 0.98–1.25 0.089 1.05 0.98–1.12 0.164 1340.7  < 0.001 0.633  Uric acid 1.03 0.92–1.14 0.633 1.00 0.92–1.09 0.952 1.01 0.93–1.10 0.743 265.7  < 0.001 0.621 Amino acid  Carnitine …

Болезнь Альцгеймера (AD) в множестве склерозов (MS): систематический обзор опубликованных случаев, механистические связи между AD и MS и возможная клиническая оценка AD в MS.

Фон: Болезнь Альцгеймера (AD) и множественный склероз (MS) являются двумя неврологическими расстройствами, которые могут создавать огромное бремя для качества жизни человека. В связи с появлением новых методов лечения, которые существенно увеличивают продолжительность жизни, возможно, наблюдается рост распространенности АД среди пожилых пациентов с НР. Цель: На основе предыдущего обзора, посвященного сосуществованию MS-AD, этот обзор был направлен не только на расширение круга поиска литературы, но и на изучение возможных механистических связей между клиническими маркерами MS и AD. Методы: мы

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… Biomarkers for MS included oligoclonal bands, free carnitine, lipids containing choline, acylcarnitines, and some amino acids. This study provided interesting data and new insights for improving clinical outcomes for patients with neurodegenerative diseases. … The markers hydroxylysine—H2O, glutamine-carnitine, and glucosyl galactosyl were used to identify AD and PP patients. Phenylalanyl-proline and alanyl-phenylalanine were the most effective in differentiating between the AD and MCI groups. …

Role of Protein Kinase CK2 in Aberrant Lipid Metabolism in Cancer.

Uncontrolled proliferation is a feature defining cancer and it is linked to the ability of cancer cells to effectively adapt their metabolic needs in response to a harsh tumor environment. Metabolic reprogramming is considered a hallmark of cancer and includes increased glucose uptake and processing, and increased glutamine utilization, but also the deregulation of lipid and cholesterol-associated signal transduction, as highlighted in recent years. In the first part of the review, we will i) provide an overview of the major types of lipids found in eukaryotic cells and their importance as med

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… acyltransferase 1A the enzyme catalyzing the formation of acyl-carnitine [ 57 ]. … Phosphatidylinositol 3-kinase-dependent modulation of carnitine palmitoyltransferase 1A expression regulates lipid metabolism during hematopoietic cell growth. J. Biol. Chem. 2006;281:37372–37380. doi: 10.1074/jbc.M608372200. 58. …

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

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… Although exercise also has mitogenic effects, these mechanisms may differ from the effects of acetyl-L-carnitine if exercise proves to be beneficial as acetyl-L-carnitine was shown to be harmful for CIPN. Further analysis of this outcome could elucidate the role of exercise in treating CIPN. … Two-Year Trends of Taxane-Induced Neuropathy in Women Enrolled in a Randomized Trial of Acetyl-L-Carnitine (SWOG S0715) J. Natl. Cancer Inst. 2018;110:669–676. doi: 10.1093/jnci/djx259. 5. …

Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN).

The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN). This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG) neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased react

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… Moreover, they observed that a prophylactic treatment with Acetyl-L-Carnitine (ALC) is able not only to inhibit the onset of paclitaxel-induced peripheral neuropathy and neuropathic pain but also to prevent mitochondria energy failure. … Chemotherapy-evoked neuropathic pain: Abnormal spontaneous discharge in A-fiber and C-fiber primary afferent neurons and its suppression by acetyl-L-carnitine Pain 2008 135 262 270 10.1016/j.pain.2007.06.001 17659836 PMC2689385 42. Bennett G.J. Doyle T. Salvemini D. …

Short-chain acyl post-translational modifications in cancers: Mechanisms, roles, and therapeutic implications.

Post-translational modifications (PTMs) play a pivotal role in epigenetic regulation and are key pathways for modulating protein functionality. PTMs involve the covalent attachment of distinct chemical groups, such as succinyl, crotonyl, and lactyl, at specific protein sites, which alter protein structure, function, stability, and activity, ultimately influencing biological processes. Recently, metabolically derived short-chain acylation modifications (with acyl groups containing fewer than six carbon atoms) have been progressively identified, such as butyrylation, succinylation, crotonylation

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… protein cyclin B1 cyclin E2 C‐C motif chemokine receptor 8 cluster of differentiation 39 cluster of differentiation 73 cadherin 1 cyclin‐dependent kinase inhibitor 2B chromodomain Y‐like 1 chromosome region candidate 2 proto‐oncogene c‐Jun chaperone‐mediated autophagy cyclooxygenase 2 carnitine … In ovarian cancer, carnitine palmitoyltransferase 1A (CPT1A) promotes the succinylation of mitochondrial fission factor (MFF) at K302, hindering Parkin‐mediated ubiquitin‐proteasome degradation of MFF. …

WITHDRAWN: Interventions for fatigue and weight loss in adults with advanced progressive illness.

BACKGROUND: Fatigue and unintentional weight loss are two of the commonest symptoms experienced by people with advanced progressive illness. … c reviews (23 studies and 1502 participants); the pharmacological interventions were amantadine and carnitine. The non pharmacological interventions were diet, exercise and occupational therapy.Mixed conditions in advanced stages of illness - we identified one systematic review (five studies and 453 participants); the intervention was medically assisted hyd …

Interventions for fatigue and weight loss in adults with advanced progressive illness.

BACKGROUND: Fatigue and unintentional weight loss are two of the commonest symptoms experienced by people with advanced progressive illness. … c reviews (23 studies and 1502 participants); the pharmacological interventions were amantadine and carnitine. The non pharmacological interventions were diet, exercise and occupational therapy.Mixed conditions in advanced stages of illness - we identified one systematic review (five studies and 453 participants); the intervention was medically assisted hyd …

Centralizing the Knowledge and Interpretation of Pain in Chemotherapy-Induced Peripheral Neuropathy: A Paradigm Shift towards Brain-Centric Approaches.

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of cancer treatment, often linked with pain complaints. Patients report mechanical and thermal hypersensitivity that may emerge during chemotherapy treatment and may persist after cancer remission. Whereas the latter situation disturbs the quality of life, life itself may be endangered by the appearance of CIPN during cancer treatment. The causes of CIPN have almost entirely been ascribed to the neurotoxicity of chemotherapeutic drugs in the peripheral nervous system. However, the central consequences of peripheral neuropathy a

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… For example, the administration of acetyl-L-carnitine decreases mitochondrial dysfunctions and prevents paclitaxel-, oxaliplatin-, and bortezomib-induced peripheral neuropathy [ 68 , 69 , 70 , 71 ]. … However, a randomized controlled trial enrolling 409 patients found that acetyl-l-carnitine aggravated CIPN [ 72 , 73 ]. …

The Evolving Pharmacotherapeutic Landscape for the Treatment of Sickle Cell Disease.

Sickle cell disease (SCD) is an extremely heterogeneous disease that has been associated with global morbidity and early mortality. More effective and inexpensive therapies are needed. During the last five years, the landscape of the pharmacotherapy of SCD has changed dramatically. Currently, 54 drugs have been used or under consideration to use for the treatment of SCD. These fall into 3 categories: the first category includes the four drugs (Hydroxyurea, L-Glutamine, Crizanlizumab tmca and Voxelotor) that have been approved by the United States Food and Drug Administration (FDA) based on suc

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… Acetyl-l-carnitine is an essential nutrient that facilitates the entry of long-chain fatty acids into the mitochondria and decreases lipid peroxidation in tissue. α-Lipoic acid and acetyl-L-carnitine have a synergistic antioxidant effect. 143 A recent Phase II trial combining antioxidants enrolled 42 … patients to determine whether α-lipoic acid and acetyl-L-carnitine will lower systemic inflammation in patients with SCD. …