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Background: The antitumorigenic effects of active ingredient of garlic, diallyl disulfide (DADS), has been extensively studied & found to retard the growth of neoplastic cells than any other allyl sulfur compounds of garlic. Earlier we have reported antitomorogenic properties of DADS, showing tumor regression by interfering with the liver glucose utilization, protein synthesis as well as lipid synthesis in tumor cells. Aim: To assess the effect of diallyl disulfide on liver nucleotide metabolism in experimentally induced hepatoma in mice. Materials & Methods: Swiss albino male mice were divided into four groups - normal, control, preventive and curative groups. Hepatoma was induced by intraperitoneal injection of Ehrlich ascites carcinoma (EAC) cells. DADS (100 mg/kg body weight/mouse/day) was orally fed to protective and curative group mice for a stipulated time period. Mice of all the groups were sacrificed, and liver tissue adenosine deaminase (ADA) activity and uric acid (UA) levels were measured. Results: The present study shows a significant decrease in ADA activity and UA levels in protective (p >0.001) and curative groups (p >0.01) as compared to control group. Conclusion: DADS has inhibitory effects on nucleotide metabolism by inhibiting the activities of ADA and xanthine oxidase enzymes, and by reducing the production of deoxy ribonucleotides, probably by involving in thiol-disulfide exchange reactions.
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@#The transcription factor c-Myc regulates the proliferation, differentiation, metabolism and other key processes of normal cells extensively.The unleashed MYC oncogene frequently produces abundant c-Myc protein, which directly regulates the gene expression of key metabolic enzymes, or tumor-related metabolic pathways by inhibiting microRNA, leading to abnormal metabolism characterized by heightened nutrients uptake, enhanced glycolysis and glutaminolysis, and elevated fatty acid and nucleotide synthesis.This paper briefly summarizes how c-Myc regulated metabolism on glycolysis, glutamine metabolism, tricarboxylic acid cycle, lipid metabolism and nucleotide synthesis in cancer cell,which provides some theoretical reference for the development of antitumor targets and drugs involving c-Myc.
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BACKGROUND An increasing amount of research has led to the positioning of nucleoside diphosphate kinases (NDPK/NDK) as key metabolic enzymes among all organisms. They contribute to the maintenance the intracellular di- and tri- phosphate nucleoside homeostasis, but they also are involved in widely diverse processes such as gene regulation, apoptosis, signal transduction and many other regulatory roles. OBJETIVE Examine in depth the NDPKs of trypanosomatid parasites responsible for devastating human diseases (e.g., Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp.) which deserve special attention. METHODS The earliest and latest advances in the topic were explored, focusing on trypanosomatid NDPK features, multifunctionality and suitability as molecular drug targets. FINDINGS Trypanosomatid NDPKs appear to play functions different from their host counterparts. Evidences indicate that they would perform key roles in the parasite metabolism such as nucleotide homeostasis, drug resistance, DNA damage responses and gene regulation, as well as host-parasite interactions, infection, virulence and immune evasion, placing them as attractive pharmacological targets. MAIN CONCLUSIONS NDPKs are very interesting multifunctional enzymes. In the present review, the potential of trypanosomatid NDPKs was highlighted, raising awareness of their value not only with respect to parasite biology but also as molecular targets.
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Objective: The classical formula of Dingxiang Shiditang can be used for hiccup and vomit which caused by many reasons,its molecular mechanism of this formula was investigated.Method: Based on the integrated pharmacology platform of traditional Chinese medicine,the potential molecular mechanism of Dingxiang Shiditang was revealed from the dimensions of multi-components and multi-targets.Result: There were 89 compounds related to hiccup and vomit of Dingxiang Shiditang,and there was 1 common target[cannabinoid receptor 1(CNR1)].On the one hand,CNR1 could inhibit the occurrence of hiccup and vomit by inhibiting the release of γ-aminobutyric acid(GABA),dopamine,5-hydroxytryptamine(5-HT);on the other hand,CNR1 could inhibit gastrointestinal motility and delay gastric emptying,and it was speculated that CNR1 may play a role in regulating gastrointestinal motility through brain-gut axis.Meanwhile,the mechanism of Dingxiang Shiditang may be related to nucleotide metabolism and nervous system.Conclusion: Dingxiang Shiditang may regulate gastrointestinal motility by affecting the release of neurotransmitters,mitochondrial energy metabolism,and achieve its effect on hiccup and vomit based on the joint intervention of multiple targets and multiple pathways.
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Objective: To explore the intervention of baicalein on D-galactose-induced aging rats by 1H-NMR metabonomics methods. Methods: The aging model was induced by sc injection of D-galactose (150 mg/kg) in rats, and the effects of baicalein (50, 100, and 200 mg/kg) on autonomic activities of aging rats were investigated. After 10 weeks, the serum of rats was collected for 1H-NMR detection, and the anti-aging effects of baicalein were explored using multivariate statistical analysis. Results: Baicalein significantly improved the locomotor activities of aging rats. Compared with control group, the levels of alanine, acetic acid, pyruvic acid, tyrosine, and N-acetyl glycoproteins in rat serum of model group increased, while the levels of glutamine, dimethyl glycine, glycine, threonine, creatinine, and histidine decreased. These 11 potential biomarkers could be reversely regulated after treatment with baicalein. Conclusion: Baicalein exerts anti-aging effects likely through regulation of amino acid metabolism, nucleotide metabolism, and glucose metabolism.