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Abstracts of the 5(th) Cachexia Conference, Barcelona, Spain, December 5-8, 2009.

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… Seelaender 1 1 Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; 2 Department of Physiology, Division of Nutrition Physiology, Federal University of São Paulo, São Paulo, Brazil; *in Memoriam The effect of endurance training on hepatic carnitine … In conclusion, endurance training was capable to promote the reestablishment of liver mitochondrial carnitine palmitoyltransferase (CPT) system activity due to a decrease in PGE2 levels in cachectic tumour-bearing animals, preventing steatosis. …

HERV Dys Regulation в деле Myalgic Encephalomyelitis и Multic Sclerosis Responsive to Rituximab.

В этой статье резюмируется случай, когда 30-летний мужчина диагностировал синдром мальгического энцефаломелита/хронического утомительного синдрома (ME/CFS) и его продольный слежение, в результате чего через восемь лет был диагностирован множественный склероз (MS). Наиболее ощутимым результатом стала его реакция на ритуксимаб после систематического отказа в предварительном лечении. Хотя выражение эндогенных ретровирусных белков ассоциируется с автоиммунитетом, пациент не продемонстрировал более широкое выражение токсичного белка HERV (человеческий ретровирус)-W ENV, который является целью текущ

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… Prescribed supplements, including magnesium, NADH, D-ribose, L-carnitine, ubiquinol, melatonin, vitamin B1, alpha-lipoic acid, vitamin D, and LDN (Low-Dose Naltrexone), failed to improve his symptoms. …

Bortezomib-induced aerobic glycolysis contributes to chemotherapy-induced painful peripheral neuropathy.

Chemotherapy-induced painful peripheral neuropathy (CIPN) is the most common toxicity associated with widely used chemotherapeutics. CIPN is the major cause of dose reduction or discontinuation of otherwise life-saving treatment. Unfortunately, CIPN can persist in cancer survivors, which adversely affects their quality of life. Moreover, available treatments are vastly inadequate, warranting a better understanding of the biochemical and metabolic mechanisms that occur in response to chemotherapeutics which would be critical for the development of novel therapies for CIPN. Using extracellular f

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… These trials include lipoic acid which proved to be ineffective in treating CIPN while acetyl-L-carnitine exacerbated pain. 64 Lipoic acid is a cofactor critical for PDH function. 4 However, this study demonstrates that bortezomib enhances the expression of PDHK1 in sensory neurons which in turn phosphorylates … It is well-established that acetyl-L-carnitine potentiates glycolysis, 65 – 68 which might have been the underlying cause of increased paclitaxel-induced pain severity in a clinical trial. 64 A crucial consideration in the development of novel therapies for CIPN is that they must not interfere with …

Molecular Mechanisms Underlying Curcumin-Mediated Therapeutic Effects in Type 2 Diabetes and Cancer.

The growing prevalence of age-related diseases, especially type 2 diabetes mellitus (T2DM) and cancer, has become global health and economic problems. Due to multifactorial nature of both diseases, their pathophysiology is not completely understood so far. Compelling evidence indicates that increased oxidative stress, resulting from an imbalance between production of reactive oxygen species (ROS) and their clearance by antioxidant defense mechanisms, as well as the proinflammatory state contributes to the development and progression of the diseases. Curcumin (CUR; diferuloylmethane), a well-kn

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… In addition, CUR positively affects the activity of lipid-regulating enzymes, including fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and acyl-CoA:cholesterol acyltransferase (ACAT) [ 17 , 18 ]. … ACAT: acyl-CoA:cholesterol acyltransferase; ACC1: acetyl-CoA carboxylase 1; β 3AR: β 3-adrenergic receptor; BAT: brown adipose tissue; CAT: catalase; CD36: fatty acid translocase; ChREBP: carbohydrate response element-binding protein; COX2: cyclooxygenase 2; CPT1: carnitine palmitoyltransferase 1; CRP …

High-Dose Vitamin C in Advanced-Stage Cancer Patients.

High-dose intravenously administered vitamin C (IVC) is widely used in cancer patients by complementary and alternative medicine practitioners. The most frequent indications for IVC therapy result from the belief in its effectiveness as a potent anti-cancer agent which additionally enhances chemosensitivity of cancer cells and reduces chemotherapy-related toxicities and fatigue intensity. In this narrative review, we decided to deal with this issue, trying to answer the question whether there is any scientific evidence supporting the rationale for application of high-dose IVC therapy in advanc

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… Ascorbate participates in the stabilization of collagen tertiary structure, carnitine biosynthesis, and biosynthesis of some hormones (corticosteroids, aldosterone) as well as amino acids [ 33 ]. … Therefore, the impaired carnitine metabolism (because of insufficient vitamin C supplementation or excessive use in states of pathology) can be responsible for weakness [ 108 ]. …

Genetic and Epigenetic Regulation of the Innate Immune Response to Gout.

Gout is a disease caused by uric acid (UA) accumulation in the joints, causing inflammation. Two UA forms - monosodium urate (MSU) and solub … tation factor-like effector family; CKD: chronic kidney disease; CNV: copy number variation; CPT1A: carnitine palmitoyl transferase - type 1a; CXCL1: chemokine (CXC motif) ligand 1; DAMPs: damage associated molecular patterns; DC: dendritic cells; DNMT(1): maintenance DNA methyltransferase; eQTL: expression quantitative trait loci; ERK1: extracellular signa …

Toxicity studies of WY-14,643 (CAS No. 50892-23-4) administered in feed to male Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters.

Wy-14,643 was selected for inclusion in a series of studies on peroxisome proliferators because it is known to produce considerable peroxiso … rease in peroxisomal enzyme activity occurred in 10 ppm mice; increases in peroxisomal $-oxidation, carnitine acetyltransferase, catalase, and acyl CoA oxidase occurred in all exposed mice compared to controls. Significantly increased BrdU-labeled hepatocyte percentages occurred in 100 and 1,000 ppm mice and 500 and 5,000 ppm hamsters; peroxisomal $-oxidati …

Breaking the Feedback Loop: A Model of Vicious Cycle for CIPN and Acupuncture-Medication Combination.

Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and often debilitating complication of cancer therapy, whose chronicity and refractoriness cannot be adequately explained by traditional linear etiological models. This review proposes and organizes a "vicious cycle" model as a hypothesis: initial neuronal injury caused by chemotherapeutic agents initiates a self-sustaining positive feedback loop in which mitochondrial dysfunction and oxidative stress reciprocally amplify each other, thereby activating neuroinflammation and ion channel remodeling. These processes collectively dri

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… ameliorates oxidative stress and sustains mitochondrial function upon activation. 24 Vinpocetine enhances mitochondrial biogenesis via the PGC-1α–NRF1–TFAM pathway, reducing mitochondrial ROS generation. 41 Alpha-lipoic acid (ALA) exhibits robust antioxidant and anti-inflammatory properties, while acetyl-L-carnitine … Natural products - alpha-lipoic acid and acetyl-L-carnitine - in the treatment of chemotherapy-induced peripheral neuropathy . Eur Rev Med Pharmacol Sci . 2018 ; 22 ( 14 ): 4739 – 4754 . doi: 10.26355/eurrev_201807_15534 30058711 43. Jonathan A , Vitória S , Raquel N , et al. …

Modulation of Lonp1 Activity by Small Compounds.

The Lon protease homolog 1 (LONP1) is an ATP-dependent mitochondrial protease essential for maintaining proteostasis, bioenergetics, and cellular homeostasis. LONP1 plays a pivotal role in protein quality control, mitochondrial DNA maintenance, and oxidative phosphorylation system (OXPHOS) regulation, particularly under stress conditions. Dysregulation of LONP1 has been implicated in various pathologies, including cancer, metabolic disorders, and reproductive diseases, positioning it as a promising pharmacological target. This review examines compounds that modulate LONP1 activity, categorizin

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… In addition, artemisinin appears to modulate the acetyl-transferase activity of specific variants of the mitochondrial carnitine O-acetyl transferase (CRAT), associated with a case of early-onset Leigh syndrome, either on recombinant proteins or on patient cell lysates [ 110 ]. … Combined in silico/in vitro approaches for identifying modulators of the activity of the p.Tyr110Cys Carnitine O-Acetyltransferase (CRAT) variant associated to an early onset case of Leigh syndrome. Acta Pharmacol. Sin. 2025;46:1123–1136. doi: 10.1038/s41401-024-01435-0. 111. …

Гут Микробиом и мальгический энцефаломилит/хронический синдром утомления (ME/CFS): Понимание механизмов борьбы с заболеваниями.

Myalgic Encephalomyelitis/Chronic Fatige (ME/CFS) — клиническая болезнь, характерная особенность которой заключается в постэкспертальной болезни (PEM). Она может влиять на многие органы и системы, что приводит к серьезному ухудшению качества жизни пациентов. Несмотря на многочисленные постинфекционные, иммунологические, неврологические, метаболические и эндокринные изменения, не существует ни окончательного диагностического маркера, ни утвержденного лечения. Этиология и патофизиология по-прежнему не до конца понимаются; однако появляющиеся данные свидетельствуют о том, что кишечная микробиомия

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… Association between Fatigue, Peripheral Serotonin, and L-Carnitine in Hypothyroidism and in Chronic Fatigue Syndrome Front. Endocrinol. 2024 15 1358404 10.3389/fendo.2024.1358404 PMC10948554 38505756 112. Chojnacki M. Błońska A. Kaczka A. Chojnacki J. Walecka-Kapica E. Romanowska N. … Indoleamine 2,3-Dioxygenase, by Degrading L-Tryptophan, Enhances Carnitine Palmitoyltransferase i Activity and Fatty Acid Oxidation, and Exerts Fatty Acid-Dependent Effects in Human Alloreactive CD 4+ T-Cells Int. J. Mol. Med. 2016 38 1605 1613 10.3892/ijmm.2016.2750 27667153 114. Kashi A.A. …

The Metabolic Features of Osteoblasts: Implications for Multiple Myeloma (MM) Bone Disease.

The study of osteoblast (OB) metabolism has recently received increased attention due to the considerable amount of energy used during the bone remodeling process. In addition to glucose, the main nutrient for the osteoblast lineages, recent data highlight the importance of amino acid and fatty acid metabolism in providing the fuel necessary for the proper functioning of OBs. Among the amino acids, it has been reported that OBs are largely dependent on glutamine (Gln) for their differentiation and activity. In this review, we describe the main metabolic pathways governing OBs' fate and functio

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… Abbreviations: αKG: α-ketoglutarate; AMPK: AMP-activated protein kinase; Arg: arginine; Asn: asparagine; ASNS: asparagine synthetase; Asp: aspartate; ATP: adenosine triphosphate; CPT1/2: carnitine palmitoyltransferase 1/2; FZD: frizzled; GLS: glutaminase; GSH: glutathione; GLUT1/3/4: glucose transporter … Once inside the cell, the fatty acids are transported to the mitochondria via a shuttle formed by carnitine palmitoyltransferase 1 (CPT1) situated on the outer mitochondrial membrane and CPT2 placed on the inner membrane [ 71 ]. …

The future of NMR metabolomics in cancer therapy: towards personalizing treatment and developing targeted drugs?

There has been a recent shift in how cancers are defined, where tumors are no longer simply classified by their tissue origin, but also by their molecular characteristics. Furthermore, personalized medicine has become a popular term and it could start to play an important role in future medical care. However, today, a "one size fits all" approach is still the most common form of cancer treatment. In this mini-review paper, we report on the role of nuclear magnetic resonance (NMR) metabolomics in drug development and in personalized medicine. NMR spectroscopy has successfully been used to evalu

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… Patient outcome after chemotherapy has also been found to correlate to the abundance of carnitine and acetyl carnitine in multiple myeloma patients [ 93 ]. …

Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series.

Palmitoylethanolamide (PEA), an endogenous fatty acid amide, has been demonstrated to bind to a receptor in the cell nucleus - the peroxisome proliferator-activated receptor - and performs a great variety of biological functions related to chronic and neuropathic pain and inflammation, as has been demonstrated in clinical trials. These include peripheral neuropathies such as diabetic neuropathy, chemotherapy-induced peripheral neuropathy, carpal tunnel syndrome, sciatic pain, osteoarthritis, low-back pain, failed back surgery syndrome, dental pains, neuropathic pain in stroke and multiple scle

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… The addition of other prescribed supplements, such as acetyl- l -carnitine, did not decrease pain either. She is presented as a nonresponder. One of the reasons for this might have been advanced age combined with a nonspecific chronic pain. …

Energy metabolism in health and diseases.

Energy metabolism is indispensable for sustaining physiological functions in living organisms and assumes a pivotal role across physiological and pathological conditions. This review provides an extensive overview of advancements in energy metabolism research, elucidating critical pathways such as glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism, along with their intricate regulatory mechanisms. The homeostatic balance of these processes is crucial; however, in pathological states such as neurodegenerative diseases, autoimmune disorders, and cancer, exten

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… After activation, the fatty acids are transferred from the cytoplasm to the mitochondrial matrix through Carnitine palmitoyltransferase I (CPT1). The fatty acids undergo a series of β-oxidation cycles, resulting in the production of acetyl-CoA and NADH. … This is achieved by alleviating the inhibition of carnitine palmitoyltransferase 1 (CPT1), which is mediated by the local production of malonyl-CoA at the outer membrane of the mitochondria, via ACC2. Notably, the amino terminus of ACC2 contains a sequence that targets it to the mitochondria. …

Cardiovascular Biomarkers in Cardio-Oncology: Antineoplastic Drug Cardiotoxicity and Beyond.

Serum biomarkers represent a reproducible, sensitive, minimally invasive and inexpensive method to explore possible adverse cardiovascular effects of antineoplastic treatments. They are useful tools in risk stratification, the early detection of cardiotoxicity and the follow-up and prognostic assessment of cancer patients. In this literature review, we aim at describing the current state of knowledge on the meaning and the usefulness of cardiovascular biomarkers in patients with cancer; analyzing the intricate relationship between cancer and cardiovascular disease (especially HF) and how this

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… They established a predictive model characterized by L-carnitine, 19-hydroxydeoxycorticosterone, lysophosphatidylcholine (LPC) (14:0) and LPC (20:2) [ 140 ]. … In both serum and tissue specimens, the levels of many amino acids (including arginine and citrulline), biogenic amines, acylcarnitines (carnitine) and tricarboxylic acid cycle (TCA)-related metabolites (e.g., lactate, succinate) were found to be altered [ 141 ]. …

How I treat elderly patients with plasma cell dyscrasias.

Plasma cell dyscrasias are a rare heterogeneous group of hematological disorders which are more prevalent in the older part of the population. The introduction of novel agents, improved understanding of disease biology and better supportive management have improved outcomes considerably and in the era of the aging population the question of how to best manage older patients with plasma cell dyscrasias has never been more relevant. Data on how to treat these patients comes mostly from subgroup analysis as they are underrepresented in clinical trials. This review will cover issues, available evi

Non-Hematologic Toxicity of Bortezomib in Multiple Myeloma: The Neuromuscular and Cardiovascular Adverse Effects.

The overall approach to the treatment of multiple myeloma (MM) has undergone several changes during the past decade. and proteasome inhibitors (PIs) including bortezomib, carfilzomib, and ixazomib have considerably improved the outcomes in affected patients. The first-in-class selective PI bortezomib has been initially approved for the refractory forms of the disease but has now become, in combination with other drugs, the backbone of the frontline therapy for newly diagnosed MM patients, as well as in the maintenance therapy and relapsed/refractory setting. Despite being among the most widely

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… However, single small-sized studies that evaluated the efficacy of acetyl-L-carnitine, methylcobalamin, and a nutraceutical compound (docosahexaenoic acid, α-lipoic acid, vitamin C, and vitamin E) for the prevention of bortezomib-related peripheral neuropathy do not allow to draw firm conclusions on … Acetyl-L-carnitine (ALCAR) for the prevention of chemotherapy-induced peripheral neuropathy in patients with relapsed or refractory multiple myeloma treated with bortezomib, doxorubin and low-dose dexamethasone: A study from the Wisconsin Ocology Network Cancer Chemother. …

Bortezomib-induced peripheral neuropathy: from molecular mechanisms to clinical management.

Bortezomib (BTZ) is a first-generation proteasome inhibitor that has shown significant efficacy in the treatment of multiple myeloma (MM), providing significant therapeutic benefits without severely compromising overall patient health. However, one of the most common and debilitating side effects associated with BTZ therapy is bortezomib-induced peripheral neuropathy (BIPN). This condition is the leading complication observed in patients undergoing BTZ treatment and has a profound impact on treatment regimens, often necessitating dose reductions or alterations in the dosing schedule. Despite t

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… Antioxidants Glutathione | MM patients | Preventive: Glutathione (2.4 g, i.v.) was administered once daily starting from the 2–3 days before chemotherapy, until the end of the chemotherapy cycle. | Reduced oxidative stress | Reduced the incidence and severity of CIPN | Huang et al. (2021) Acetyl-L-carnitine … Acetyl L-carnitine reverses mitochondrial dysfunction and the progression of sensory neuropathy in BIPN model rats ( Zheng et al., 2012 ). The active oxygen scavenger phenyl‐N‐tert‐butylnitrone prevents and reverses BTZ-induced pain abnormalities ( Duggett and Flatters, 2017 ). …

Defining neuroblastoma: From origin to precision medicine.

Neuroblastoma (NB), a heterogenous pediatric tumor of the sympathetic nervous system, is the most common and deadly extracranial solid malignancy diagnosed in infants. Numerous efforts have been invested in understanding its origin and in development of novel curative targeted therapies. Here, we summarize the recent advances in the identification of the cell of origin and the genetic alterations occurring during development that contribute to NB. We discuss current treatment regimens, present and future directions for the identification of novel therapeutic metabolic targets, differentiation

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… proliferation, and, in some cases, also in induction of differentiation. 2-DG: 2-deoxyglucose; 3-BrOP: 3-bromo-2-oxopropionate-1-propyl ester; HK2: hexokinase 2; PFKL: phosphofructokinase, liver type; LDHA: lactate dehydrogenase A; FATP2: fatty acid transport protein 2; GPX4: glutathione peroxidase 4; CPT1: carnitine … We also showed that inhibition of carnitine/palmitoyl-transferase 1 (CPT1), the rate-limiting enzyme of FAO, reduced proliferation in vitro and tumor growth in vivo. 80 Moreover, inhibition of MYCN impaired β-oxidation of fatty acids leading to the accumulation of lipid droplets. 98 Tao et al., reported …

Left Ventricular Hypertrophy: Etiology-Based Therapeutic Options.

Determining the etiologies of left ventricular hypertrophy (LVH) can be challenging due to the similarities of the different manifestations in clinical presentation and morphological features. Depending on the underlying cause, not only left ventricular mass but also left ventricular cavity size, or both, may increase. Patients with LVH remain asymptomatic for a few years, but disease progression will lead to the development of systolic or diastolic dysfunction and end-stage heart failure. As hypertrophied cardiac muscle disrupts normal conduction, LVH predisposes to arrhythmias. Distinguishin

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… NCT02842242 ) [ 78 ] • Phase III trial-oHCM (EXPLORER-HCM) [ 79 ] CK-274 (Cytokinetics, Inc., South San Francisco, CA, USA) | • Is currently under development | • Ongoing phase II clinical trial in obstructive HCM Myocardial energetics Perhexiline | • Used as an antianginal therapy • Oral inhibitor of carnitine … Perhexiline inhibits carnitine palmitoyltransferase I (CPT-1) and reduces fatty acid uptake into mitochondria, resulting in greater cellular dependence on carbohydrates for ATP production. …