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Antioxidants for female subfertility.

BACKGROUND: A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This … inations of antioxidants, N-acetyl-cysteine, melatonin, L-arginine, myo-inositol, D-chiro-inositol, carnitine, selenium, vitamin E, vitamin B complex, vitamin C, vitamin D+calcium, CoQ10, pentoxifylline and omega-3-polyunsaturated fatty acids versus placebo, no treatment/standard treatment or another antioxidant.Very low-quality evidence suggests that antio …

Processes and therapeutic perspectives of acylation modifications of lysine and cysteine in tumors.

Acylation modification plays a crucial role in tumor progression through altering protein homeostasis and localization. However, a comprehensive summary of these processes is lacking. Protein acylation modifications are comprehensively summarized and categorized based on the amino acids that are modified. This review focuses on modifications of the lysine (acetylation, succinylation, crotonylation, malonylation, and glutarylation) and cysteine (myristoylation and palmitoylation) groups. The key enzymes involved in the occurrence and erasure of different modifications, as well as their effects

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… Carnitine palmitoyltransferase (CPT1A) exhibits the same lysine succinyltransferase activity in vivo and in vitro [ 76 ]. CPT1A mediates the succinylation of the lactate dehydrogenase (LDHA) K222 site [ 77 ]. …

Targeting Metabolic Reprogramming in Acute Myeloid Leukemia.

The cancer metabolic reprogramming allows the maintenance of tumor proliferation, expansion and survival by altering key bioenergetics, biosynthetic and redox functions to meet the higher demands of tumor cells. In addition, several metabolites are also needed to perform signaling functions that further promote tumor growth and progression. These metabolic alterations have been exploited in different cancers, including acute myeloid leukemia, as novel therapeutic strategies both in preclinical models and clinical trials. Here, we review the complexity of acute myeloid leukemia (AML) metabolism

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… Carnitine palmitoyl transferase 1A (CPT1A) and carnitine transporter CT2 (SLC22A16), rate limiting actors of FAO, are overexpressed in AML and constitute novels targets for a subset of AML [ 36 , 37 ] (for a review, see [ 18 ]). … Carnitine transporter CT2 (SLC22A16) is over-expressed in acute myeloid leukemia (AML) and target knockdown reduces growth and viability of AML cells. Apoptosis. 2015;20:1099–1108. doi: 10.1007/s10495-015-1137-x. 38. …

Sudden severe hyperammonemia and status epilepticus -a case report-.

There are various causes to a low level of consciousness in patients in the intensive care unit. Neurological injury, infection, and metabolic disarray are considered as some of the causes. A 39 year-old female patient was transferred to our hospital with septic shock due to ascending colon perforation. The patient had previously received ovarian cancer surgery and a cycle of chemotherapy at another hospital. Emergent operation for colon perforation was successful. After the operation, she was treated in the intensive care unit for infectious and pulmonary complications. She suddenly showed de

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… Hepatic causes of hyperammonemia are well documented and include hepatotoxins, Reye syndrome, or carnitine deficiency [ 6 ]. However, hyperammonemia in the context of unremarkable liver function tests is a challenge for physicians-the differential diagnosis becomes more difficult. …

Microbiota-derived metabolites as modulators of cancer immunotherapy response.

The microbiome is a key regulator of host homeostasis and immune activity, in part through the production of metabolites. These microbiota-derived metabolites can modulate both the innate and adaptive immune system, as well as directly target tumour cells, thereby regulating anti-tumour immunity and response to immunotherapy. Here, we describe the current mechanistic knowledge on how these metabolites exert their effects and outline the methodologies used to detect and assess these metabolites. Finally, we summarize microbiota-targeted therapies capable of improving microbial functionality to

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… . | Diet-microbiota Cross-feeding Trimethylamine derivatives | Trimethylamine N-oxide (TMAO) | Derived from TMA, which is generated by gut microbes from dietary choline, carnitine, or phosphatidylcholine. | Microbiota-host Amino acids | L -Serine, L -Arginine. | Derived from dietary protein and host … Diet-derived choline and L-carnitine are first converted to trimethylamine (TMA) by the gut microbiota through genes such as CutC/D 113 and the gbu operon 114 . Further transport to and oxidation in the liver by flavin-containing monooxygenases is then required to generate TMAO. …

Peripheral Neuropathy under Oncologic Therapies: A Literature Review on Pathogenetic Mechanisms.

Peripheral neurologic complications are frequent adverse events during oncologic treatments and often lead to dose reduction, administration delays with time elongation of the therapeutic plan and, not least, worsening of patients' quality of life. Experience skills are required to recognize symptoms and clinical evidences and the collaboration between different health professionals, in particular oncologists and hospital pharmacists, grants a correct management of this undesirable occurrence. Some classes of drugs (platinates, vinca alkaloids, taxanes) typically develop this kind of side effe

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… Antioxidants, vitamins A, B, and E, herbal medicines such as Goshajinkigan, acetyl-l-carnitine, Ca 2+ -Mg 2+ infusions, acupuncture, have been tested for the treatment of TIPN [ 15 , 147 ], but they failed to produce either neuroprotection or alleviation of symptoms [ 57 , 148 ]. … 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 2627 2633 10.1200/JCO.2012.44.8738 23733756 PMC3699727 58. Zheng H. Xiao W.H. Bennett G.J. …

Диет с высоким содержанием жира с низким содержанием карбогидрата связан с защитой автономного иммунитета CNS.

Множественный склероз (MS) является воспалительным и нейродегенеративным заболеванием центральной нервной системы (КНС), которое, как считается, вызвано аутоиммунными механизмами. Генетические и экологические факторы связаны с развитием НР, и среди них диеты и питательные вещества становятся потенциальными важнейшими факторами. Вместе с тем отсутствует полное понимание их последствий и соответствующих механизмов. Применяя самые современные методы анализа геометрии питания, впервые становится очевидным, что увеличение предложения углеводов в глобальном масштабе связано с увеличением бремени бол

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… Carnitine palmitoyltransferase 1A (CPT1A) is involved in fatty acid oxidation, associated both with immune activation [ 32 , 33 ] and tolerance. [ 63 ] Higher CPT1A levels in T cells and cDCs were found in HC group with more severe symptoms (Figure  3F ), consistent with enhanced … MetFlow Staining MetFlow markers were obtained from previous published study. [ 17 ] In brief, HK1 (hexokinase 1) was chosen as a marker for glycolysis, and CPT1A (carnitine palmitoyl‐transferase 1A) was selected as marker for fatty acid oxidation. …

Palliative Care and the Management of Common Distressing Symptoms in Advanced Cancer: Pain, Breathlessness, Nausea and Vomiting, and Fatigue.

Good symptom management in oncology is associated with improved patient and family quality of life, greater treatment compliance, and may even offer survival advantages. With population growth and aging, the proportion of patients with multiple symptoms-both related and unrelated to their cancer-is anticipated to increase, supporting calls for a more routine and integrated approach to symptom management. This article presents a summary of the literature for the use of symptom assessment tools and reviews the management of four common and distressing symptoms commonly experienced by people with

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… factor erythropoietin reduces fatigue (SMD, −0.36; 95% CI, −0.46 to −0.26), whereas evidence for darbepoetin is less consistent. 145 Single trials support short-term use of dexamethasone, although efficacy and safety beyond 2 weeks are undetermined. 146 There is currently no evidence of benefit from l -carnitine … L-carnitine supplementation for the management of fatigue in patients with cancer: An Eastern Cooperative Oncology Group phase III, randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2012;30:3864–3869. doi: 10.1200/JCO.2011.40.2180. 148. Higginson IJ, Evans CJ. …

Neurology

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CSI position statement on management of heart failure in India.

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Hypertrophic Cardiomyopathy Phenocopies: Classification, Key Features, and Differential Diagnosis.

Among cardiomyopathies, the hypertrophic phenotype is the most common, and hypertrophic cardiomyopathy (HCM) phenocopies represent a heterogeneous group of conditions. They are defined by a left ventricular wall thickness ≥15 mm in the absence of other causes such as loading conditions, ischemia, or valvular disease. Although they mimic similar clinical and morphological features, their etiologies are distinct and include genetic, metabolic, and infiltrative mechanisms. Therefore, accurate classification and differential diagnosis are crucial for effective management and treatment. Sarcomeric

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… Among these, very long-chain acyl-CoA dehydrogenase deficiency (VLCADD, OMIM 201475), carnitine palmitoyltransferase II deficiency (CPTII, OMIM 255110), and multiple acyl-CoA dehydrogenase deficiency (MADD, OMIM 231680) are most frequently associated with an HCM phenotype. … Treatment consists of standard heart failure therapy and dietary supplements aiding mitochondrial biogenesis and function, such as creatine, carnitine, and coenzyme Q10. Furthermore, mitochondrial replacement therapies and gene therapy approaches are under investigation [ 70 ]. 8. …

Lomitapide repurposing for treatment of malignancies: A promising direction.

The development of novel drugs from basic science to clinical practice requires several years, much effort, and cost. Drug repurposing can promote the utilization of clinical drugs in cancer therapy. Recent studies have shown the potential effects of lomitapide on treating malignancies, which is currently used for the treatment of familial hypercholesterolemia. We systematically review possible functions and mechanisms of lomitapide as an anti-tumor compound, regarding the aspects of apoptosis, autophagy, and metabolism of tumor cells, to support repurposing lomitapide for the clinical treatme

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… The released free fatty acids will be transported to mitochondria by carnitine palmitoyltransferase 1 (CPT1), which can be inhibited by the products of ACC [ [100] , [101] , [102] ]. … Carnitine palmitoyltransferase I. The site of inhibition of hepatic fatty acid oxidation by malonyl-CoA. J. Biol. Chem. 1978;253(12):4128–4136. 101. McCubrey J.A., Lahair M.M., Franklin R.A. Reactive oxygen species-induced activation of the MAP kinase signaling pathways. …

Targeting the epigenome to treat neurodegenerative diseases or delay their onset: a perspective.

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… Similarly, formulations including SAM, folic acid, vitamin B12, and nutraceuticals such as alpha-tocopherol, N-acetyl cysteine, and acetyl-L-carnitine, have been investigated in AD patients and showed some improvement of cognitive symptoms. …

Decoding chemotherapy-induced peripheral neuropathy: ion channels, disease models, and future directions.

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of cancer treatments like paclitaxel and oxaliplatin, impacting patient quality of life (QoL). Despite much research, its underlying mechanisms remain unclear and effective therapies are lacking. This review evaluates whether current experimental models accurately reflect CIPN, emphasizing recent molecular and cellular findings, especially the role of sensory ion channels. We outline limitations of existing models and propose more translational preclinical approaches to better capture disease complexity and patient

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… For instance, while compounds such as acetyl-L-carnitine, nimodipine, and glutamine elicited a reduction in neuropathy in rodent studies, they did not yield substantial outcomes for patients ( Ghirardi et al., 2005 ; Loprinzi et al., 2020 ). … Chemotherapy-induced allodinia: neuroprotective effect of acetyl-L-carnitine. Vivo (Brooklyn) 19, 631–637. Giorgi S., Lamberti A., Butrón L., Gross-Amat O., Alarcón-Alarcón D., Rodríguez-Cañas E., et al. (2023). …

Post-transplant cyclophosphamide-induced cardiotoxicity: A comprehensive review.

Cyclophosphamide-induced cardiotoxicity, associated with its toxic metabolite acrolein, is a significant concern and unresolved issue, especially when cyclophosphamide is administrated in high doses. However, cardiotoxicity following low-dose cyclophosphamide has been also documented, especially in post-hematopoietic stem cell transplantation (post-HSCT) settings. Despite the involvement of multiple signaling pathways in cyclophosphamide-induced cardiomyopathy, the exact underlying mechanisms remain to be fully elucidated. This review outlines the current challenges of cyclophosphamide therapy

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… Furthermore, cyclophosphamide affects the β-oxidation levels in the mitochondrial matrix, which is mediated by malonyl-CoA increasing, derived from acetyl CoA, and carnitine palmitoyl transferase-I (CPT-1) decreasing, ultimately resulting in cytosol FFA and Ca2 + accumulation. 28 Therefore, the energy … Abbreviations: APAF-1, Apoptotic Protease Activating Factor 1; ATP, Adenosine triphosphate; BAD, BCL2 associated agonist of cell death; BAX, Bcl-2-associated X-protein; Caspase, cysteine-dependent, aspartate-specific peptidase; CoA, coenzyme A; COX-2, cyclooxygenase-2; CPT-1, Carnitine palmitoyltransferase …

Bortezomib in the management of multiple myeloma.

Multiple myeloma (MM) is a B-cell malignancy characterized by clonal expansion of plasma cells within the bone marrow, the presence of a serum and/or urine monoclonal protein, lytic bone lesions, and anemia. On a cellular level, the disease is characterized by complex interactions between tumor cells and the surrounding bone marrow microenvironment. Understanding of the relationship between malignant plasma cells and the microenvironment has sparked ongoing efforts to develop targeted therapeutic agents for treatment of this disease. The successful development of the first-in-class small-molec

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… that possesses antioxidant properties and modulates glucose uptake, has been used for prevention of diabetic peripheral neuropathy and may be beneficial for MM patients who receive bortezomib, although this intervention requires further study in bortezomib-treated MM patients. 60 Similarly, acetyl-L-carnitine … Acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy: a short review. CNS Drugs. 2007;21(Suppl 1):39–43. doi: 10.2165/00023210-200721001-00006. discussion 5–6. 62. Colvin LA, Johnson PR, Mitchell R, Fleetwood-Walker SM, Fallon M. …

Dietary interventions for multiple sclerosis-related outcomes.

BackgroundMultiple sclerosis (MS) is a common demyelinating disease of the central nervous system. Although the exact pathogenesis remains u … upplements (10 trials); dietary programmes (3 trials); and other dietary supplements (e.g. acetyl L-carnitine, biotin, creatine, palmitoylethanolamide, probiotic, riboflavin) (6 trials). In three trials comparing PUFAs with monounsaturated fatty acids (MUFAs), the evidence was very uncertain concerning difference in relapses (risk ratio (RR) 1.02, 95% confi …

Histone deacetylase in inflammatory bowel disease: novel insights.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is characterized by chronic nonspecific intestinal inflammation. Despite considerable efforts, IBD remains a heavy burden on society and human health, with increasing morbidity. Posttranslational modification, especially histone acetylation, is a key process in controlling DNA transcriptional activity. Histone deacetylases (HDACs) play a vital role in the mechanism of IBD pathogenesis through histone and nonhistone protein deacetylation. Herein, we present a summary of different categories of HDACs as well as H

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… BMDM, bone marrow-derived macrophages; CPT1, carnitine palmitoyltransferase 1; DSS, dextran sulfate sodium; FBA, N-(1-carbamoyl-2-phenylethyl) butyramide; HCEC, human colon epithelial cells; HDAC, histone deacetylase; HDACi, HDAC inhibitor; IBD, inflammatory bowel disease; iTreg, inducible regulatory … suppressing IFN-γ-induced STAT1 activation and inflammation. 75 Furthermore, butyrate can also induce IL-22 production in CD4 + T cells and innate lymphoid cells through increasing the H3K9 acetylation of the hypoxia response element on the IL-22 promoter, thus inhibiting colitis. 76 Butyrate also enhances carnitine …

Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.

Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Unders

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… In AML, rate-limiting enzymes such as carnitine palmitoyl transferase 1a (CPT1a) and carnitine transporter 2 SLC22A16 (CT2) are often overexpressed and are validated therapeutic targets [ 4 ]. … palmitoyl transferase 1a CT2 | Carnitine transporter 2 D2HG | D-2-hydroxyglutarate DHFHR | Dihydrofolate reductase ECAR | Extracellular acidification rate EFS | Event-free survival ETC | Electron transport chain FA | Fatty acids FAO | Fatty acid oxidation FASN | Fatty acid synthase gene FIS1 | Mitochondrial …

Noncanonical SQSTM1/p62-Nrf2 pathway activation mediates proteasome inhibitor resistance in multiple myeloma cells via redox, metabolic and translational reprogramming.

Multiple Myeloma (MM) is a B-cell malignancy characterized by the accumulation of clonal plasma cells in the bone marrow, with drug resistance being a major cause of therapeutic failure. We established a carfilzomib-resistant derivative of the LP-1 MM cell line (LP-1/Cfz) and found that the transcription factor NF-E2 p45-related factor 2 (Nrf2; gene symbol NFE2L2) contributes to carfilzomib resistance. The mechanism of Nrf2 activation involved enhanced translation of Nrf2 as well as its positive regulator, the autophagy receptor sequestosome 1 (SQSTM1)/p62. The eukaryotic translation initiatio

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… FAO was determined by XF Cell Mito Stress Test using the XF Palmitate-BSA FAO substrate in the absence or presence of etomoxir (Eto), an inhibitor of carnitine palmitoyltransferase-1, the rate limiting enzyme in FAO. … Treatment with etomoxir, an inhibitor of carnitine palmitoyltransferase-1 (the rate limiting enzyme in FAO), sensitizes LP-1/Cfz cells (left graph) and KMS-11/Cfz cells (right graph) to carfilzomib. …