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Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis.

BACKGROUND: Ceramide plays pathogenic roles in nonalcoholic fatty liver disease (NAFLD) via multiple mechanisms, and as such inhibition of ceramide de novo synthesis in the liver may be of therapeutically beneficial in patients with NAFLD. In this study, we aimed to explore whether inhibition of ceramide signaling by myriocin is beneficial in animal model of NAFLD via regulating autophagy. METHODS: Sprague Dawley rats were randomly divided into three groups: standard chow (n = 10), high-fat diet (HFD) (n = 10) or HFD combined with oral administration of myriocin (0.3 mg/kg on alternate days f

Mitochondrial biogenesis: pharmacological approaches.

Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and div … dition of antioxidant supplements to the diet (dietary supplementation with antioxidants) such as L-carnitine, coenzyme Q10,MitoQ10 and other mitochondria-targeted antioxidants,N-acetylcysteine (NAC), vitamin C, vitamin E vitamin K1, vitamin B, sodium pyruvate or -lipoic acid. As aforementioned, other diseases do not have exclusively a mitochondrial origin …

Mice fed fish oil diet and upregulation of brown adipose tissue thermogenic markers.

PURPOSE: Fish oil (FO) elicits diverse beneficial effects. Reduction in or prevention of body mass (BM) gain in animal models may be associated with modulation of brown adipose tissue (BAT). We aimed to evaluate the effects of different high-fat diets with FO on BAT metabolism and thermogenic markers. METHODS: C57BL/6 male mice (3-month-old) were fed different diets during 8 weeks: standard-chow diet (SC 10% fat), high-fat lard diet (HF-L 50% fat), high-fat lard plus FO diet (HF-L+FO 50% fat), and high-fat FO diet (HF-FO 50% fat). We evaluated BM and performed an oral glucose tolerance test.

[Mechanism of total flavonoids from Smilacis Glabrae Rhizoma against obesity-associated colorectal cancer via regulation of fatty acid oxidation].

This study aimed to investigate the mechanism of total flavonoids from Smilacis Glabrae Rhizoma(SGF) against obesity-associated colorectal c … ted significantly increased expression of FAO-related proteins cluster of differentiation 36(CD36), carnitine palmitoyltransferase 1(CPT1), and acyl-CoA dehydrogenase long chain(ACADL), as well as elevated adenosine triphosphate(ATP) content. The phosphorylation levels of upstream regulatory proteins AMPK and ACC were significantly increased, while the expr …

[Buzhong Yiqi Decoction induces ferroptosis of A549/DDP cells to reverse cisplatin resistance in non-small cell lung cancer via AMPK/ACC1 signaling pathway].

This study aimed to investigate the molecular mechanism by which Buzhong Yiqi Decoction(BZYQD), a representative TCM formula for invigoratin … of AMPK, phosphorylated AMPK(p-AMPK), ACC1, fatty acid synthase(FASN), ATP-citrate lyase(ACLY), and carnitine palmitoyltransferase 1A(CPT1A). Immunofluorescence was used to observe lipid droplet synthesis in cells of each group under the intervention of BZYQD+cisplatin and AMPK inhibitor. The CCK-8 assay was adopted to examine the effect of the inhibitor on …

Cachexia as Evidence of the Mechanisms of Resistance and Tolerance during the Evolution of Cancer Disease.

During its evolution, cancer induces changes in patients' energy metabolism that strongly affect the overall clinical state and are responsible for cancer-related cachexia syndrome. To better understand the mechanisms underlying cachexia and its metabolic derangements, research efforts should focus on the events that are driven by the immune system activation during the evolution of neoplastic disease and on the phenomena of "resistance" and "tolerance" typically involved in the human body response against stress, pathogens, or cancer. Indeed, in the case where resistance is not able to elimin

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… The metabolic role of l -carnitine as an anticachectic agent is likely related to its ability to modulate the carnitine/carnitine palmitoyl transferase system. … In experimental preclinical models, l -carnitine was shown to ameliorate cancer cachexia and increase muscle mass by increasing the activities of carnitine palmitoyl transferase I and II [ 143 , 144 ]. …

Hepatic FATP5 expression is associated with histological progression and loss of hepatic fat in NAFLD patients.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are characterized by the accumulation of excess hepatic fat. However, in the progression from NASH to cirrhosis, hepatic fat is often lost. Our aim was to elucidate the mechanism underlying hepatic fat loss during NASH progression. METHODS: Liver biopsies were performed at The University of Tokyo Hospital between November 2011 and March 2016 on 146 patients with NAFLD and 14 patients with cryptogenic cirrhosis who were not being treated with any diabetes or dyslipidemia drugs. Among them, 70 patients

Experimental Drugs for Chemotherapy- and Cancer-Related Anemia.

Anemia in cancer patients is a relevant condition complicating the course of the neoplastic disease. Overall, we distinguish the anemia which arises under chemotherapy as pure adverse event of the toxic effects of the drugs used, and the anemia induced by the tumour-associated inflammation, oxidative stress, and systemic metabolic changes, which can be worsened by the concomitant anticancer treatments. This more properly cancer-related anemia depends on several overlapping mechanism, including impaired erythropoiesis and functional iron deficiency, which make its treatment more difficult. Stan

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… Low carnitine levels are associated with fatigue in some cases, including in patients with cancer. 144 , 145 Thus, several trials have evaluated l -carnitine supplementation for the treatment of cancer-associated fatigue. … L-carnitine supplementation in patients with advanced cancer and carnitine deficiency: a double-blind, placebo-controlled study. J Pain Symptom Manage . 2009;37(4):622–631. doi: 10.1016/j.jpainsymman.2008.03.021 147. Morris MS, Jacques PF, Rosenberg IH, Selhub J. …

Long-term stabilization of metastatic melanoma with sodium dichloroacetate.

Sodium dichloroacetate (DCA) has been studied as a metabolic cancer therapy since 2007, based on a publication from Bonnet et al demonstrating that DCA can induce apoptosis (programmed cell death) in human breast, lung and brain cancer cells. Classically, the response of cancer to a medical therapy in human research is measured by Response Evaluation Criterial for Solid Tumours definitions, which define "response" by the degree of tumour reduction, or tumour disappearance on imaging, however disease stabilization is also a beneficial clinical outcome. It has been shown that DCA can function as

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… To minimize the occurrence of DCA side effects, 3 additional natural medications were prescribed: Oral acetyl L-carnitine 500 mg 3 times a day, oral benfotiamine 80 mg twice a day and oral R-alpha lipoic acid 150 mg 3 times a day. These supplements were taken daily (no cycle). … Finally the patient added oral DCA therapy to the natural anti-cancer therapy, with 3 concurrent neuroprotective medicines (lipoic acid, acetyl L-carnitine and benfotiamine) and no concurrent conventional cancer therapies. …

Characterization of Internal Validity Threats to Phase III Clinical Trials for Chemotherapy-Induced Peripheral Neuropathy Management: A Systematic Review.

ObjectiveThe recent American Society of Clinical Oncology (ASCO) Clinical Guidelines for chemotherapy-induced peripheral neuropathy (CIPN) management (48 Phase III trials reviewed) only recommend duloxetine. However, before concluding that a CIPN intervention is ineffective, scientists and clinicians should consider the risk of Type II error in Phase III studies. The purpose of this systematic review was to characterize internal threats to validity in Phase III CIPN management trials.MethodsThe PubMed, CINAHL, EMBASE®, and Scopus databases were searched for Phase III clinical trials testing in

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… No further testing was recommended for acetyl-L-carnitine (ALC), amifostine, calcium/magnesium, diethyldithio-carbamate (DDTC), glutathione, nimodipine, Org 2766, all-trans retinoic acid, rhuLIF, or Vitamin E.[ 5 ] While strong evidence demonstrates the inefficacy of some agents (e.g., calcium/magnesium … ( n =1) | The administration of acetyl-L-carnitine had no effect on CIPN severity in comparison to placebo 12 weeks following randomization. …

Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy.

Oral dichloroacetate sodium (DCA) has been investigated as a novel metabolic therapy for various cancers since 2007, based on data from Bonnet et al that DCA can trigger apoptosis of human lung, breast and brain cancer cells. Response to therapy in human studies is measured by standard RECIST definitions, which define "response" by the degree of tumour reduction, or tumour disappearance on imaging. However, Blackburn et al have demonstrated that DCA can also act as a cytostatic agent in vitro and in vivo, without causing apoptosis (programmed cell death). A case is presented in which oral DCA

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… The oral DCA regimen that was developed included three natural medications acetyl L-carnitine[ 29 - 31 ], R-alpha lipoic acid[ 32 - 34 ] and benfotiamine[ 35 - 37 ], for the primary purpose of neuropathy prevention. … Natural therapies that were combined with DCA (acetyl L-carnitine, alpha lipoic acid and benfotiamine) assisted the patient with reduction of side effects, but are not known to function as cancer therapies. …

Lipid metabolism analysis for peripheral blood in patients with alcohol-induced and steroid-induced osteonecrosis of the femoral head.

OBJECTIVES: Osteonecrosis of the femoral head (ONFH), also known as vascular necrosis of the femoral head, is combined with lipid metabolism … nents was greater than 0.9, including 1D-myo-Inositol 1,2-cyclic phosphate, L-pyroglutamic acid, DL-carnitine, 8-amino-7-oxononanoic acid, Clobetasol, and presqualene diphosphate. In the AONFH group, there were 9 differential lipid metabolites related to the disease stages, including LPG 18:1, serotonin, PC (22:4e/23:0), PC (19:2/18:5), hypoxanthin, PE (18: …

Severe hyperammonemia from intense skeletal muscle activity: A rare case report and literature review.

RATIONALE: Adult hyperammonemia is most often the result of hepatic dysfunction. Hyperammonemia in the setting of normal hepatic function is a much less common phenomenon and has usually been associated with medications and certain disease states. Here, we present an unusual case of severe hyperammonemia caused physiologically by intense muscle activity in a patient lacking any evidence of liver disease. PATIENT CONCERNS: A 36-year-old woman was brought to the emergency department for a suicide attempt after being found covered in Lysol and Clorox germicidal bleach. She was noted to be in a s

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… Total parenteral nutrition (TPN) administration may elevate serum ammonia levels by exacerbating carnitine deficiency, particularly in cirrhotics who may already be carnitine deficient. [ 32 ] Carnitine is an essential factor in long-chain fatty acid metabolism, as it is involved in translocation of … Plasma carnitine levels in patients receiving home parenteral nutrition. Am J Clin Nutr 1986;43:85–91. [33] Buono MJ, Clancy TR, Cook JR. Blood lactate and ammonium ion accumulation during graded exercise in humans. J Appl Physiol 1984;57:135–9. [34] Lester L, Braude DA, Niles C, et al. …

Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN).

Chemotherapy induced peripheral neuropathy (CIPN) is a type of neuropathic pain that is a major dose-limiting side-effect of potentially curative cancer chemotherapy treatment regimens that develops in a "stocking and glove" distribution. When pain is severe, a change to less effective chemotherapy agents may be required, or patients may choose to discontinue treatment. Medications used to alleviate CIPN often lack efficacy and/or have unacceptable side-effects. Hence the unmet medical need for novel analgesics for relief of this painful condition has driven establishment of rodent models of C

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… The latter is an acetylated derivative of the natural amino acid, L-carnitine, that has an essential role in the transport of long-chain free fatty acids into mitochondria (Zheng et al., 2011 , 2012 ). … Chemotherapy-induced allodinia: neuroprotective effect of acetyl-L-carnitine . In Vivo 19 , 631 – 637 15875786 Giannoccaro M. P. Donadio V. Gomis Perez C. Borsini W. Di Stasi V. Liguori R. ( 2011 ). …

Complete failure of insulin-transmitted signaling, but not obesity-induced insulin resistance, impairs respiratory chain function in muscle.

The role of mitochondrial dysfunction in the development of insulin resistance and type 2 diabetes remains controversial. In order to specifically define the relationship between insulin receptor (InsR) signaling, insulin resistance, hyperglycemia, hyperlipidemia and mitochondrial function, we analyzed mitochondrial performance of insulin-sensitive, slow-oxidative muscle in four different mouse models. In obese but normoglycemic ob/ob mice as well as in obese but diabetic mice under high-fat diet, mitochondrial performance remained unchanged even though intramyocellular diacylglycerols (DAGs),

Effect of the Shensong Yangxin Capsule on Energy Metabolism in Angiotensin II-Induced Cardiac Hypertrophy.

BACKGROUND: Shensong Yangxin Capsule (SSYX), traditional Chinese medicine, has been used to treat arrhythmias, angina, cardiac remodeling, c … ey factor - adenosine monophosphate-activated protein kinase (AMPK), fatty acids oxidation factor - carnitine palmitoyltransferase-1 (CPT-1), and glucose oxidation factor - glucose transporter- 4 (GLUT-4) were measured by PCR and Western blotting analysis. RESULTS: With the increase in the concentration of SSYX (from 0.25 to 1.0 μg/ml), an increased mitoch …

The Effect of Docosahexaenoic Acid and α-Lipoic Acid as Prevention of Bortezomib-Related Neurotoxicity in Patients With Multiple Myeloma.

Background and Aims: In cancer patients, a common complication during chemotherapy is chemotherapy-induced peripheral neuropathy (CIPN). For this reason, we decided to conduct a phase II prospective study on 33 patients with multiple myeloma at first diagnosis, to evaluate whether a nutraceutical compound given for 6 months during bortezomib (BTZ) treatment succeeded in preventing the onset of neurotoxicity. Methods: Neurological evaluation, electroneurography, and functional and quality of life (QoL) scales were performed at baseline and after 6 months. We administered a tablet containing doc

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… Differently in the study of Callender et al, 28 the addition of acetyl-carnitine for prophylactic purposes leads to a minor appearance of grade 3 CIPN in the treated group compared with the control group. … BMC Cancer . 2012 ; 12 : 355 . 22894640 10.1186/1471-2407-12-355 PMC3459710 71 Bianchi G Vitali G Caraceni A , et al Symptomatic and neurophysiological responses of paclitaxel- or cisplatin induced neuropathy to oral acetyl-L-carnitine . …

Research progress on the anti-cancer mechanisms of edible salty-flavored Chinese materia medica.

Edible salty-flavored Chinese materia medica (ESCM) refers to a category of traditional Chinese medicine (TCM) that also serve as food, characterized by their salty flavor. According to the TCM theory, ESCM can soften and disperse knots, thus potentially offering benefits for cancer prevention and treatment. With cancer remaining a major global health challenge, its primary prevention strategies, especially through dietary modification, are crucial. ESCM have recently garnered substantial attention, due to their remarkable clinical efficacy and low side-effect profile. Researches on ESCM demon

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… , Tea polyphenols, L-carnitine, Magnesium stearate | G20141178 Hongyangshen Brand Lotus Leaf Zelda Cassia Seed Extract Tablets | Cassiae Semen extract, Nelumbinis Folium extract, Alismatis Rhizoma extract, Oolong tea extract | G20150208 St. … Cassia Seed Capsules | Cassiae Semen, Gynostemma pentaphyllum Makino, L-Carnitine-L-Tartrate, Nelumbinis Folium, Microcrystalline cellulose, Magnesium stearate | G20240313 Runxintang Carnitine Cassia Seed Tablets | Cassiae Semen extract, L-Carnitine-L-Tartrate, Alismatis Rhizoma extract, Nelumbinis …

Prevention of Bortezomib-Related Peripheral Neuropathy With Docosahexaenoic Acid and α-Lipoic Acid in Patients With Multiple Myeloma: Preliminary Data.

BACKGROUND AND AIMS: Peripheral neuropathy is a common complication of chemotherapy that can induce marked disability that negatively affects the quality of life in patients with multiple myeloma (MM). The aim of this study was to prevent the onset or the worsening of peripheral neuropathy in MM patients treated with bortezomib (BTZ), using a new nutritional neuroprotective compound. We report preliminary results of 18 out of 33 patients who completed the study. METHODS: We administered a tablet of Neuronorm to patients, containing docosahexaenoic acid 400 mg, α-lipoic acid 600 mg, vitamin C

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… In contrast, in the study of Callender et al 28 the addition of acetyl-carnitine for prophylactic purposes leads to a lesser appearance of grade 3 CIPN in the treated group compared with the control group. … BMC Cancer . 2012 ; 12 : 355 . 22894640 10.1186/1471-2407-12-355 PMC3459710 66 Bianchi G Vitali G Caraceni A et al Symptomatic and neurophysiological responses of paclitaxel- or cisplatin-induced neuropathy to oral acetyl-L-carnitine . …