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Acetyl-l-carnitine prevents homocysteine-induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells.

Previous studies have revealed that high levels of serum homocysteine (Hcy) are closely associated with the development of juvenile and age-related cataracts. An increased concentration of Hcy is likely to induce gene specific demethylation in DNA promoter regions. The aim of the present study was to prevent this demethylation by administering acetyl-l-carnitine (ALCAR) to human lens epithelial cells (HLECs). Different concentrations of Hcy were used to treat HLECs for 3, 6, 12 and 24 h and the findings were used to determine the optimum dose to induce endoplasmic reticulum (ER) stress. Simila

Repeated acetyl-l-carnitine administration increases phospho-Thr34 DARPP-32 levels and antagonizes cocaine-induced increase in Cdk5 and phospho-Thr75 DARPP-32 levels in rat striatum.

Abstract Acute cocaine administration increases phosphorylation of dopamine and cAMP-regulated phosphoprotein (M(r) 32 kDa) (DARPP-32) at threonine (Thr)-34, whereas repeated cocaine administration increases DARPP-32 phosphorylation at Thr-75 in Sprague-Dawley rat striatum. Repeated acetyl-l-carnitine (ALCAR) administration persistently increases dopamine outflow in the nucleus accumbens. The present study examined the effect of repeated ALCAR administration on the DARPP-32 phosphorylation pattern in the nucleus accumbens and caudate-putamen. ALCAR increased phosphoThr-34 DARPP-32 levels and d

Inhibitory effects of alcohol on glucose transport across the blood-brain barrier leads to neurodegeneration: preventive role of acetyl-L: -carnitine.

PURPOSE: Evidence shows that alcohol intake causes oxidative neuronal injury and neurocognitive deficits that are distinct from the classical Wernicke-Korsakoff neuropathy. Our previous findings indicated that alcohol-elicited blood-brain barrier (BBB) damage leads to neuroinflammation and neuronal loss. The dynamic function of the BBB requires a constant supply and utilization of glucose. Here we examined whether interference of glucose uptake and transport at the endothelium by alcohol leads to BBB dysfunction and neuronal degeneration. MATERIAL AND METHODS: We tested the hypothesis in cell

Mass spectrometry-based proteomics and metabolomics in multiple myeloma: a systematic review of prognostic biomarkers and minimal residual disease monitoring.

INTRODUCTION: Current multiple myeloma (MM) risk stratification, anchored on the Revised International Staging System (R-ISS), provides a static snapshot of disease but fails to capture its dynamic biological evolution, functional tumor-microenvironment crosstalk, and real-time treatment response. Mass spectrometry (MS)-based proteomic and metabolomic profiling has emerged as a high-sensitivity tool for both novel biomarker discovery and minimal residual disease (MRD) monitoring. This systematic review evaluates the independent prognostic value and clinical utility of quantitative MS-based pro

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… , fatty acids | R-ISS | Staging, prognosis | Metabolites showed significant differences between R-ISS grades ( p < 0.001 for trend); acetylcarnitine progressively decreased with stage Da Silva et al. ( 17 ) | Case–Control; MM at diagnosis ( n = 109) | Plasma | Targeted ESI-MS/MS | Acylcarnitines (↑), … Specifically, acylcarnitines (e.g., acetylcarnitine) were elevated in association with higher-risk disease in two studies ( 17 , 20 ). …

SECURE study: baseline findings from a UK prospective cohort of incidentally detected MGUS.

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… Exploratory endpoints focus on biochemical, proteomics, and genomic predictors, such as metabolite signatures (sphingosine-1-phosphate, acetylcarnitine), post-translational modifications of serum free light-chains, and ctDNA dynamics, linked to progression. …

Epigenetic Mechanisms Involved in the Cardiovascular Toxicity of Anticancer Drugs.

The cardiovascular toxicity of anticancer drugs promotes the development of cardiovascular diseases. Therefore, cardiovascular toxicity is an important safety issue that must be considered when developing medications and therapeutic applications to treat cancer. Among anticancer drugs, members of the anthracycline family, such as doxorubicin, daunorubicin and mitoxantrone, are known to cause cardiotoxicity and even heart failure. Using human-induced pluripotent stem cell-derived cardiomyocytes in combination with "Omic" technologies, we identified several cardiotoxicity mechanisms and signal t

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… DOX can suppress the expression of genes required for oxidation of beta fatty acids and ATP-producing mitochondrial enzymes, explaining the reduced formation of epigenetic modifiers of mitochondrial metabolites, such as acetyl-CoA, acetylcarnitine and ATP ( 3 ). …

Applied information retrieval and multidisciplinary research: new mechanistic hypotheses in complex regional pain syndrome.

BackgroundCollaborative efforts of physicians and basic scientists are often necessary in the investigation of complex disorders. Difficulties can arise, however, when large amounts of information need to reviewed. Advanced information retrieval can be beneficial in combining and reviewing data obtained from the various scientific fields. In this paper, a team of investigators with varying backgrounds has applied advanced information retrieval methods, in the form of text mining and entity relationship tools, to review the current literature, with the intention to generate new insights into th

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… cells Cancer Res 2000 60 4610 4616 10969814 Chiechio S Copani A De Petris L Morales ME Nicoletti F Gereau RW Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine …

Chemotherapy-Mediated Complications of Wound Healing: An Understudied Side Effect.

Significance: Chemotherapy is a primary method to treat cancer. While chemotherapeutic drugs are designed to target rapidly dividing cancer cells, they can also affect other cell types. In the case of dermal cells and macrophages involved in wound healing, cytotoxicity often leads to the development of chronic wounds. The situation becomes even more severe when chemotherapy is combined with surgical tumor excision. Recent Advances: Despite its significant impact on patients' recovery from surgery, the issue of delayed wound healing in individuals undergoing chemotherapy remains inadequately ex

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… Based on existing data, a weak recommendation for Duloxetine can be suggested. 50 The use of vitamin B complex and nutraceuticals, alpha-lipoic acid, L-acetylcarnitine, vitamin E, and Coenzyme Q is reported in treating polyneuropathies. 59 The neurotoxic effects of selected chemotherapeutics are summarized …

Multi-omics tumor profiling technologies to develop precision medicine in multiple myeloma.

Multiple myeloma (MM), the second most common hematologic cancer, is caused by accumulation of aberrant plasma cells in the bone marrow. Its molecular causes are not fully understood and its great heterogeneity among patients complicates therapeutic decision-making. In the past decades, development of new therapies and drugs have significantly improved survival of MM patients. However, resistance to drugs and relapse remain the most common causes of mortality and are the major challenges to overcome. The advent of high throughput omics technologies capable of analyzing big amount of clinical a

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… Using nanoflow ultraperformance LC coupled to high-resolution orbitrap MS, carnitine and acetylcarnitine were identified as potential biomarkers for NDMM and relapsed MM [ 318 ]. …

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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… Proton NMR-based metabolite analyses of archived serial paired serum and urine samples from myeloma patients at different stages of disease activity identifies acetylcarnitine as a novel marker of active disease. PloS One. 2013;8:e56422. doi: 10.1371/journal.pone.0056422. 94. …

Design and Rationale of Prolonged Nightly Fasting for Multiple Myeloma Prevention (PROFAST): Protocol for a Randomized Controlled Pilot Trial.

BACKGROUND: Obesity is an established, modifiable risk factor of multiple myeloma (MM); yet, no lifestyle interventions are routinely recommended for patients with overweight or obesity with MM precursor conditions. Prolonged nightly fasting is a simple, practical dietary regimen supported by research, suggesting that the synchronization of feeding-fasting timing with sleep-wake cycles favorably affects metabolic pathways implicated in MM. We describe the design and rationale of a randomized controlled pilot trial evaluating the efficacy of a regular, prolonged nighttime fasting schedule among

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… Proton NMR-based metabolite analyses of archived serial paired serum and urine samples from myeloma patients at different stages of disease activity identifies acetylcarnitine as a novel marker of active disease. …

Integrated Medicine for Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of typical chemotherapeutics among cancer survivors. Despite the recent progress, the effective prevention and treatment strategies for CIPN remain limited. Better understanding of the pathogenesis of CIPN may provide new niches for developing a new ideal therapeutic strategy. This review summarizes the current understanding of CIPN and current recommendations along with completed/active clinical trials and aims to foster translational research to improve the development of effective strategies for managing CIPN.

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… chemotherapy in patients with cancer | NCT00068445 | Alliance for Clinical Trials in Oncology | Phase 3 | Taxanes, Platinum, Vinca Alkaloids | NS | Lamotrigine vs. placebo Clinical study on acetyl-l-carnitine | NCT01526564 | Lee's Pharmaceutical Limited | Phase 3 | Taxoids, Satraplatin and Vincristine | NS | Acetylcarnitine …

Mass spectrometry-based metabolomics in health and medical science: a systematic review.

Metabolomics is the study of the investigation of small molecules derived from cellular and organism metabolism, which reflects the outcomes of the complex network of biochemical reactions in living systems. As the most recent member of the omics family, there has been notable progress in metabolomics in the last decade, mainly driven by the improvement in mass spectrometry (MS). MS-based metabolomic strategies in modern health and medical science studies provide innovative tools for novel diagnostic and prognostic approaches, as well as an augmented role in drug development, nutrition science

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… Chen et al. recruited four cohorts of 2155 participants to screen potential early CKD biomarkers using MS-based metabolomics. 46 A variety of statistical analysis methods were used, and five metabolites, 5-methoxytryptophan, canavaninosuccinate, acetylcarnitine, tiglylcarnitine, and taurine, can be used …

Биомаркеры по исследованиям в области клинической медицины: исследование литературы в базе данных PubMed и критическая оценка.

Биомаркер, короткая форма "биологического маркера", появилась в научной литературе в 1940-х годах. С тех пор было предложено множество различных определений, однако общеприменимое объяснение термина &quot; биомаркер &quot; в науке является чрезвычайно сложным. Слово "биомаркер" встречается в 1.3 million статьи в научной базе данных PubMed , которая в настоящее время включает более 39 million Ссылки на биомедицинскую литературу. Биомаркеры тесно связаны со здоровьем и болезнями человека. В настоящей статье делается попытка подойти к многогранному термину "биомаркет" и оценить его с клинической

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… The authors reported AUC values above 0.75 for 2-hydroxybutyric acid, itaconic acid, O -acetylcarnitine, glutathione disulfide, p -cresol sulfate, 2-furoic acid, L-asparagine, d-biotin, choline and homovanillic acid. …

Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma.

Pathways that govern cellular bioenergetics are deregulated in tumor cells and represent a hallmark of cancer. Tumor cells have the capacity to reprogram pathways that control nutrient acquisition, anabolism and catabolism to enhance their growth and survival. Tumorigenesis requires the autonomous reprogramming of key metabolic pathways that obtain, generate and produce metabolites from a nutrient-deprived tumor microenvironment to meet the increased bioenergetic demands of cancer cells. Intra- and extracellular factors also have a profound effect on gene expression to drive metabolic pathway

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… Eight metabolites, i.e., free carnitine, acetylcarnitine, glutamate, asymmetric dimethylarginine and phosphatidylcholine species, differed between MGUS and NDMM patients, supporting the notion that metabolic changes occur during myelomagenesis. …

Dietary Supplements in Chemotherapy-Induced Peripheral Neuropathy: A New Hope?

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the main and most prevalent side effects of chemotherapy, significantly affecting the quality of life of patients and the course of chemotherapeutic treatment. Nevertheless, despite its prevalence, the management of the CIPN is considered particularly challenging, with this condition often being perceived as very difficult or even impossible to prevent with currently available agents. Therefore, it is imperative to find better options for patients diagnosed with this condition. While the search for the new agents must continue, anothe

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… Effects of L-Carnitine, L-Acetylcarnitine and Gangliosides on the Regeneration of the Transected Sciatic Nerve in Rats. Neurol. Res. 1989;11:57–62. doi: 10.1080/01616412.1989.11739863. 35. …

Genetic Syndromes, Maternal Diseases and Antenatal Factors Associated with Autism Spectrum Disorders (ASD).

Autism spectrum disorder (ASD) affecting about 1% of all children is associated, in addition to complex genetic factors, with a variety of prenatal, perinatal, and postnatal etiologies. In addition, ASD is often an important clinical presentation of some well-known genetic syndromes in human. We discuss these syndromes as well as the role of the more important prenatal factors affecting the fetus throughout pregnancy which may also be associated with ASD. Among the genetic disorders we find Fragile X, Rett syndrome, tuberous sclerosis, Timothy syndrome, Phelan-McDermid syndrome, Hamartoma tumo

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… Acetylcarnitine (LAC) was proven beneficial among fragile x patients with ADHD (Wadell et al., 2013 ). Rett syndrome and MECP2 mutations Rett syndrome, an X linked disease that affects girls, is characterized by neurodevelopmental delay, ASD and seizures. …

Genetic and Mechanistic Insights Inform Amyotrophic Lateral Sclerosis Treatment and Symptomatic Management: Current and Emerging Therapeutics and Clinical Trial Design Considerations.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both upper and lower motor neurons. ALS is classically characterized by painless progressive weakness, causing impaired function of limbs, speech, swallowing, and respiratory function. The disease is fatal within 2-4 years, often the result of respiratory failure. The pathologic hallmark for a majority of ALS cases is aberrant cytoplasmic accumulations of the nuclear protein TAR-DNA binding protein (TDP-43). A total of 10-15% of ALS can be attributed to a single gene mutation, known as genetic or "familia

Curcumin Formulations for Better Bioavailability: What We Learned from Clinical Trials Thus Far?

Curcumin has been credited with a wide spectrum of pharmacological properties for the prevention and treatment of several chronic diseases such as arthritis, autoimmune diseases, cancer, cardiovascular diseases, diabetes, hemoglobinopathies, hypertension, infectious diseases, inflammation, metabolic syndrome, neurological diseases, obesity, and skin diseases. However, due to its weak solubility and bioavailability, it has limited potential as an oral medication. Numerous factors including low water solubility, poor intestinal permeability, instability at alkaline pH, and fast metabolism contri

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… formulation increased intratumor pH and inorganic phosphate levels in glioblastoma patients with minor side effects. 162 In another study, this formulation was shown to reduce creatinine kinase MB (CK-MB) in myocardial infarction patients. 163 Another phospholipidic formulation FLAVOMEGA containing acetylcarnitine …

Всемирный конгресс молекулярного воображения 2022.

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