Effect of Yin Yang protein 1 transcriptionally regulating acetyl-CoA carboxylase 1 on the cell migration and lipogenesis in ovarian cancer / 肿瘤研究与临床

Objective:To investigate the expression of acetyl-CoA carboxylase 1 (ACC1) in ovarian cancer tissues and cells, and the related mechanisms of the effect of ACC1 on cell migration and lipogenesis in ovarian cancer.Methods:Samples including 1 case of normal ovarian tissue, 1 case of ovarian cancer primary lesion tissue and 1 case of ovarian cancer omentum metastatic tissue diagnosed by pathology examination of patients undergoing surgery resection who admitted to Linyi Cancer Hospital between January 2019 and December 2021 were collected. Immunohistochemistry was used to detect the protein levels of ACC1 and Yin Yang protein 1 (YY1) of all tissues. The PROMO database was used to predict the possible binding sites of YY1 and ACC1 promoter region. Through the assembled viral vector, the HEY cells of human ovarian cancer with ACC1 or YY1 expression [the untreated cells were treated as the negative control (NC)], or knocked down ACC1 or YY1 (the interference sequence sh1, sh2, sh3 was transferred to the target gene, and the negative control sequence shNC was transferred to the interference sequence). Double luciferase reporter gene assay was used to verify the binding sites of YY1 and ACC1 promoter and the activity of transcriptional regulation. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to detect the mRNA and protein expression levels of ACC1 and YY1 in the treated HEY cells, respectively. Transwell assay was used to detect the migration ability of HEY cells. Oil red O staining and Nile red staining were used to detect the lipid droplets in HEY cells.Results:The immunohistochemical scores of ACC1 and YY1 were 0, 2, 8 scores and 0, 4, 6 scores, respectively in normal ovarian tissue, primary lesion of ovarian cancer, and omentum metastatic tissue. Transwell assay showed that the number of invasive HEY cells in ACC1 overexpression group was more than that in NC group [(87.7±7.4) vs. (52.2±4.2), t = 5.19, P = 0.003]. The number of invasive HEY cells in ACC1-sh1 group, and ACC1-sh2 group with the knockdown of ACC1 was less than that in shNC group [(21.2±1.5), (29.7±2.3) vs. (56.2±5.3); t value was 6.41, 3.77; P < 0.001, P < 0.005]. The number of lipid droplets in HEY cells in the ACC1 overexpression group was more than that in the control NC group [Oil red O staining: (301±25) vs. (215±21); Nile red staining: (287±15) vs. (207±10); all P < 0.05]; the number of lipid droplets in HEY cells in ACC1-sh1 and ACC1-sh2 group with the knockdown of ACC1 was less than that in ACC1-shNC group [Oil red O staining: (113±8), (119±12) vs. (195±18); Nile red staining: (82±8), (117±11) vs. (165±17); all P < 0.05]. The result of dual luciferase reporter assay showed that overexpression of YY1 promoted the luciferase activity of the wild type ACC1 promoter region report gene ( P = 0.003), while the luciferase activity of the report gene was inhibited compared with the wild type after the mutation of binding sites of YY1 in ACCI promoter region ( P = 0.008). Western blot results showed that the expression levels of YY1 and ACC1 protein in HEY cells with YY1 overexpression group were higher than those in NC group, which indicated a synergistic increasing trend of both YY1 and ACC1; the expression levels of YY1 and ACC1 protein in YY1-sh1 group, YY1-sh2 group and YY1-sh3 group with the knockdown of YY1 were lower than those in the control YY1-shNC group, which indicated a synergistic decreasing trend of both YY1 and ACC1. Conclusions:ACC1 and YY1 are highly expressed in ovarian cancer metastatic tissues and both show a positive correlation trend. The expression level of ACC1 in vitro has an impact on cell migration and lipogenesis in ovarian cancer via YY1 transcriptionally regulating ACC1.

Effect of milk on sebaceous gland spots and the IGF-1/SREBP-1/ACC-1 signaling pathway in golden hamsters / 中华皮肤科杂志

Objective:To investigate the effect of milk on sebum secretion in golden hamsters, and to explore its possible mechanism of action.Methods:Eighteen golden hamsters were randomly and equally divided into 3 groups: blank control group receiving no intervention, whole-milk group gavaged with whole milk, and skimmed-milk group gavaged with skimmed milk. The gavage feeding was performed at a dose of 2.5 ml twice a day for 4 consecutive weeks. The maximum transverse diameter and maximum longitudinal diameter of bilateral sebaceous gland spots were measured on days 0, 7, 14, 21 and 28 after the start of intervention, and the area of sebaceous gland spots was calculated; at 24 hours after the last gavage, bilateral sebaceous gland spot tissues were resected, and subjected to immunohistochemical study to determine the expression of insulin-like growth factor-1 (IGF-1) /sterol regulatory element-binding protein-1 (SREBP-1) /acetyl-coenzyme A carboxylase (ACC-1) signaling pathway in sebaceous gland spots. Statistical analysis was carried out by using repeated measures analysis of variance, one-way analysis of variance for independent groups, Kruskal-Wallis H test, and least significant difference- t test for multiple comparisons. Results:Repeated measures analysis of variance showed that there was no significant difference in the area of sebaceous gland spots of golden hamsters among the 3 groups ( F= 0.96, P= 0.417) . The IGF-1 expression was significantly higher in the skimmed-milk group (0.39 ± 0.03) than in the blank control group (0.35 ± 0.03, t= 2.62, P= 0.021) and whole-milk group (0.33 ± 0.02, t= 3.82, P= 0.002) ; compared with the blank control group (0.36 ± 0.02) , the skimmed-milk group showed significantly increased SREBP-1 expression (0.42 ± 0.04, t= 2.64, P= 0.021) ; the ACC-1 expression was significantly higher in the skimmed-milk group (0.40 ± 0.03) and whole-milk group (0.40 ± 0.05) than in the blank control group (0.34 ± 0.03; t= 2.39, 2.47, P= 0.031, 0.026, respectively) . Conclusion:Milk may promote sebum secretion in golden hamsters through the IGF-1/SREBP-1/ACC-1 signaling pathway.

Research on the mechanism of hypoxia promoting the migration of lung adenocarcinoma A549 cells / 中国应用生理学杂志

Objective: To investigate the mechanism that hypoxia promotes the migration of lung adenocarcinoma A549 cells. Methods: A549 cells were cultured and cells that knockdown of acetyl-CoA carboxylase 1 (ACC1) were obtained by transfection with lentivirus, and cells that knockdown of sterol regulatory element-binding proteins-1 (SREBP-1) were obtained by treated with si-RNA. A549 cells were treated with hypoxia combined with hypoxia inducible factor-1α (HIF-1α) inhibitor PX-478 (25 μmol); Hypoxia combined with linoleic acid (LA) (20 μmol) treated A549 cells with ACC1 knockdown, and A549 cells with SREBP-1 knockdown were treated by hypoxia. Transwell migration assay was used to detect cell migration. Western blot was conducted to detect HIF-1α, ACC1 and epithelial mesenchymal transition (EMT) related proteins, Vimentin, E-Cadherin and SREBP-1; Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was performed to detect the changes of ACC1 and SREBP-1 mRNA in A549 cells after hypoxia and HIF-1α inhibitor PX-478 (25 μmol) treatment. Each experiment was repeated three times. Results: Compared with the normoxic control group, hypoxia promoted the migration of A549 cells (P＜0.01), and up-regulated the expressions of ACC1, HIF-1α (all P＜0.01) and SREBP-1 (P＜0.05). PX-478 (25 μmol) inhibited the migration of A549 cells induced by hypoxia and down-regulated the expression of SREBP-1 (all P＜0.05). ACC1 mRNA and SREBP-1 mRNA levels were increased after hypoxia treatment of A549 cells (all P＜0.05). The levels of ACC1 mRNA and SREBP-1 mRNA were decreased after A549 cells treated with hypoxia combined with PX-478 (25 μmol) for 24 h (P＜0.05, P＜0.01). Knockdown of SREBP-1 in A549 cells was obtained by transfection with si-RNA. Transwell migration assay showed the number of cell migration in si-SREBP-1 group was less than that in normoxia control group (P＜0.01). The si-SREBP-1 group and the si-NC group were treated with hypoxia. Compared with the control group, the number of cell migration in the si-SREBP-1 group was decreased (P＜0.01), however, the difference was not statistically significant compared with the normoxia si-SREBP-1 group (P＞0.05). Western blot showed that the expression of ACC1 in the si-SREBP-1 group was lower than that in the control group (P＜0.01). Compared with the control group, the expression of ACC1 was decreased after si-SREBP-1 group treated with hypoxia (P＜0.01). Knockdown of ACC1 inhibited the migration of A549 cells (P＜0.05). After knockdown of ACC1, the migration number of A549 cells under normoxia and 5% O2 conditions had no significant difference (P＞0.05). Application of LA under hypoxia condition rescued ACC1-knockdown induced inhibitory effect on hypoxia-promoted A549 cell migration (P＜0.05). Conclusion: Hypoxia promotes migration of lung adenocarcinoma A549 cells by regulating fatty acid metabolism through HIF-1α/SREBP-1/ACC1 pathway.

Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies to treat HCC, such as targeted tyrosine kinase inhibitors, immune based therapies and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation and progression is driven by reprogramming of metabolism, in particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal of new nomenclature for non-alcoholic fatty liver disease (NAFLD), indicates growing appreciation of metabolism in the pathogenesis of liver disease, including HCC, thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment. In this review, we introduce directions by highlighting the metabolic targets in glucose, fatty acid, amino acid and glutamine metabolism, which are suitable for HCC pharmaceutical intervention. We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment. Furthermore, opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.

Cytochrome P450 endoplasmic reticulum-associated degradation (ERAD): therapeutic and pathophysiological implications

The hepatic endoplasmic reticulum (ER)-anchored cytochromes P450 (P450s) are mixed-function oxidases engaged in the biotransformation of physiologically relevant endobiotics as well as of myriad xenobiotics of therapeutic and environmental relevance. P450 ER-content and hence function is regulated by their coordinated hemoprotein syntheses and proteolytic turnover. Such P450 proteolytic turnover occurs through a process known as ER-associated degradation (ERAD) that involves ubiquitin-dependent proteasomal degradation (UPD) and/or autophagic-lysosomal degradation (ALD). Herein, on the basis of available literature reports and our own recent findings of as well as experimental studies, we discuss the therapeutic and pathophysiological implications of altered P450 ERAD and its plausible clinical relevance. We specifically (i) describe the P450 ERAD-machinery and how it may be repurposed for the generation of antigenic P450 peptides involved in P450 autoantibody pathogenesis in drug-induced acute hypersensitivity reactions and liver injury, or viral hepatitis; (ii) discuss the relevance of accelerated or disrupted P450-ERAD to the pharmacological and/or toxicological effects of clinically relevant P450 drug substrates; and (iii) detail the pathophysiological consequences of disrupted P450 ERAD, contributing to non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) under certain synergistic cellular conditions.

Adipose tissue is less responsive to food restriction anti-inflammatory effects than liver, muscle, and brain in mice

High caloric intake promotes chronic inflammation, insulin resistance, and chronic diseases such as type-2 diabetes, which may be prevented by food restriction (FR). The effect of FR on expression of pro-inflammatory and anti-inflammatory genes in adipose tissue, liver, muscle, and brain was compared. Male Swiss mice were submitted to FR (FR group) or had free access to food (control group) during 56 days. The liver, gastrocnemius muscle, brain, and epididymal white adipose tissue (WAT) were collected for analysis of gene expressions. FR attenuated inflammation in the liver, brain, and gastrocnemius muscle but did not markedly change inflammatory gene expression in epididymal WAT. We concluded that adipose tissue was less responsive to FR in terms of gene expression of pro-inflammatory and anti-inflammatory genes.

Research progress in acetyl-CoA carboxylase inhibitors / 中国药科大学学报

@#Non-alcoholic fatty liver disease(NAFLD)is characterized by excessive fat deposition in hepatocytes, fat accumulates mainly in the form of triglycerides, triglycerides derive from esterification of glycerol and free fatty acids; and the synthesis of fatty acid is abnormally active in tumor cells, which is significantly higher than that of normal cells, providing necessary lipid substrates for the formation of biofilms, the production of signaling molecules and energy during the proliferation and development of tumor cells. Acetyl-CoA carboxylase(ACC)is the limiting-rate enzyme of de novo lipogenesis. And it is also an enzyme that catalyzes the first step of the fatty acid synthesis pathway; its catalyzed product, malonyl-CoA, also inhibits the oxidation of fatty acids. ACC inhibition can reduce fatty acid synthesis and promote fatty acid oxidation, which reduce the amount of fatty acids in the body. Hence, attenuating fat accumulation could improve NAFLD, and reduction of fatty acid content inhibits development of tumor tissues because lipid substrates could not satisfy the requirement of cancer cells. Therefore, ACC inhibitors have potential to be the novel drugs that can treat NAFLD and cancer. The recent research progress on ACC inhibitors is reviewed in this paper.

Mechanism of Prunellae Spica Extracts on Lipid Metabolism in ZDF Rats Based on AMPK/ACC Signalling Pathway / 中国实验方剂学杂志

Objective: To observe the effect of Prunellae Spica extracts (PS) on the lipid metabolism in Zuker Diabetes Fatty (ZDF) rats based on AMP-activated protein kinase/acetyl CoA carboxylase (AMPK/ACC) signaling pathway.Method: The 32 male ZDF (fa/fa) type 2 diabetic rats were randomly divided into model group,metformin group (180 mg·kg-1·d-1),and low and high-dose PS groups (12.25,24.5 mg·kg-1·d-1),with 8 in each group.8 male Zuker Lean (ZL) rats were selected as normal group.Body weight and fasting blood glucose were monitored at the 0th,4th and 8th weeks after administration.After 8 weeks,abdominal aorta blood was collected,serum was frozen at-20℃ by centrifugation,liver tissue was frozen at-80℃,fixed with 4% paraformaldehyde and embedded in paraffin.Serum triglyceride (TG),cholesterol (CHO),low density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA) levels were measured by radioimmunoassay.Fat droplets in hepatocytes were measured by oil red O staining.Gene expressions of AMP-activated protein kinase-alpha 2(AMPKα2),Acetyl CoA carboxylase (ACC) in liver were detected by real-time polymerase chain reaction (Real-time PCR).Protein expressions of p-AMPKα were observed by immuno-histochemical (IHC) method.Result: Compared with the normal group,the T2DM model group showed significant increases in serum levels of TG,CHO,LDL-C,FFA and lipid droplets in hepatocytes.AMPKα2 mRNA expression was decreased,while ACC1 and ACC2 mRNA expressions were increased significantly.p-AMPKα protein expression in liver was decreased significantly (PPα2,down-regulation in mRNA expressions of ACC1 and ACC2,and up-regulation in protein expression of p-AMPKα(PPConclusion:PS can effectively improve liver lipid metabolism in ZDF rats.Its mechanism may be related to the regulation of AMPK/ACC signaling pathway in liver.

Matrine attenuates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity maintaining AMPK/UCP2 pathway

Oxidative stress and cardiomyocyte apoptosis are involved in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity. Matrine is well-known for its powerful anti-oxidant and anti-apoptotic capacities. Our present study aimed to investigate the effect of matrine on DOX-induced cardiotoxicity and try to unearth the underlying mechanisms. Mice were exposed with DOX to generate DOX-induced cardiotoxicity or normal saline as control. H9C2 cells were used to verify the effect of matrine . DOX injection triggered increased generation of reactive oxygen species (ROS) and excessive cardiomyocyte apoptosis, which were significantly mitigated by matrine. Mechanistically, we found that matrine ameliorated DOX-induced uncoupling protein 2 (UCP2) downregulation, and UCP2 inhibition by genipin could blunt the protective effect of matrine on DOX-induced oxidative stress and cardiomyocyte apoptosis. Besides, 5'-AMP-activated protein kinase 2 () deficiency inhibited matrine-mediated UCP2 preservation and abolished the beneficial effect of matrine in mice. Besides, we observed that matrine incubation alleviated DOX-induced H9C2 cells apoptosis and oxidative stress level activating AMPK/UCP2, which were blunted by either AMPK or UCP2 inhibition with genetic or pharmacological methods. Matrine attenuated oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity maintaining AMPK/UCP2 pathway, and it might be a promising therapeutic agent for the treatment of DOX-induced cardiotoxicity.

Research progress of acetyl-CoA carboxylase in cancer metabolism / 国际肿瘤学杂志

Abnormal fatty acid metabolism is one of the unique metabolic ways in which malignant cells maintain their growth needs and plays a crucial role in tumor progression.Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme in fatty acid synthesis and oxidative metabolism.More and more researches confirm that ACC is highly expressed in many tumors,and is closely related to tumor progression and prognosis of patients,which makes ACC as a potential marker for clinical diagnosis and prognosis.Tumor cell fatty acid synthesis can be blocked and fatty acid β oxidation can be stimulated by inhibiting the activity of ACC,resulting in serious lipid consumption of tumor,and then inhibit tumor growth and proliferation.Investigating the effect and molecular mechanisms of ACC in the genesis and development of tumors can provide a new insight into cancer targeted molecular therapy.

Effects of Exendin-4 on expressions of lipid metabolism related genes in HepG2 cells with insulin resistance / 吉林大学学报(医学版)

Objective:To investigate the effects of Exendin-4 (Ex-4) on the expressions of lipid metabolism related genes in the human liver cancer HepG2 cells with insulin resistance (IR),and to elucidate the effect of Ex-4in improvement of IR.Methods:The HepG2 cells in logarithmic growth phase were induced into IR model with high concentration of insulin,then divided into control group (HepG2 cells),IR group (HepG2 cells were treated with insulin,HepG2-IR cells),and Ex-4 group (HepG2-IR cells were treated with Ex-4).Glucose oxidase (GOD-POD)kit was used to detect the consumption of glucose.The cell morphology and intracellular lipid drip formation were observed by Oil red O staining.The triglyceride (TG) level in cells was detected by kit;qRT-PCR was used to detect the mRNA expression levels of acetyl-CoA carboxylase (ACC),fatty acid synthase (FAS),sterol regulatory element-binding protein-1c (SREBP-1c) and apolipoprotein B100 (apoB100).Results:Compared with control group (HepG2 cells),the glucose consumption in the HepG2-IR cells in IR group was significantly decreased (P＜0.01).Compared with IR group,the glucose consumption in the HepG2-IR cells in Ex-4 group was increased (P＜0.05).The Oil O red staining results showed that compared with control group,the fat percentage in the HepG2-IR cells in IR group was increased (P＜0.05);compared with IR group,the fat percentage in Ex-4 group was decreased (P＜0.05).Compared with control group,the level of TG in the cells in IR group was significantly increased (P＜0.01);compared with IR group,the level of TG in the cells in Ex-4 group was significantly decreased (P＜0.05).The qT-PCR results showed that compared with control group,the expression levels of ACC FAS and SREBP-1cmRNA in the cells in IR group were increased (P＜0.01),and the expression level of apoB100 mRNA was decreased (P＜0.05);compared with IR group,the expression levels of ACC,FAS and SREBP-1c mRNA in the cells in Ex-4 group were decreased (P＜0.05),and the expression level of apoB100 mRNA was increased (P＜0.01).Conclusion:Ex-4 can regulate the expressions of lipid metabolism related genes in the HepG2 cells and improve IR.

Effect of Huangqi San on AMPK/ACC/CPT1 pathway in hyperlipidemia rats / 中国中药杂志

To investigate the mechanism of the treatment of hyperlipidemia rats induced by Huangqi San. The 40 male SD rats were randomly divided into normal group, model group, Huangqi San low and high dose group (1, 2 g·kg⁻¹), and positive lipitor group (2 mg·kg⁻¹). The normal group feeds on base feed, and other groups feed on high-fat feed. After 8 weeks, the hyperlipidemia model was successful. After intervention by drugs for 13 weeks, fasting blood glucose, total cholesterol, triglycerides and LDL cholesterol content of all rats were measured. The pathological changes of liver and skeletal muscle of rats were observed in rats. Real-time PCR and Western blot were used to detect the mRNA and protein expression levels of AMPK signaling pathway in the liver and skeletal muscles (AMPK, ACC, CPT1A, SREBP2, HMGCR). The degree of FPG, TC, TG and LDL-C were the highest in the model group, and the liver and skeletal muscle pathology were the most obvious. After intervention by Huangqi San and lipitor, a significant reduction in the blood sugar blood fat, liver, and skeletal muscle injury has improved significantly, except SREBF2 and HMGCR mRNA and protein expression of this enzyme is reduced, other AMPK pathway related mRNA and protein expression increased significantly. Huangqi San effect is superior to lipitor. Huangqi San may improve hyperlipidemia by regulating the AMPK signaling pathway, increasing the oxidation of fatty acids and inhibiting cholesterol synthesis.

Effects of Exendin-4 on expressions of lipid metabolism related genes in HepG2 cells with insulin resistance / 吉林大学学报(医学版)

Objective: To investigate the effects of Exendin-4 (Ex-4) on the expressions of lipid metabolism related genes in the human liver cancer HepG2 cells with insulin resistance (IR), and to elucidate the effect of Ex-4 in improvement of IR. Methods: The HepG2 cells in logarithmic growth phase were induced into IR model with high concentration of insulin, then divided into control group (HepG2 cells), IR group (HepG2 cells were treated with insulin, HepG2-IR cells), and Ex-4 group (HepG2-IR cells were treated with Ex-4). Glucose oxidase (GOD-POD) kit was used to detect the consumption of glucose. The cell morphology and intracellular lipid drip formation were observed by Oil red O staining. The triglyceride (TG) level in cells was detected by kit; qRT-PCR was used to detect the mRNA expression levels of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), sterol regulatory element-binding protein-1c (SREBP-lc) and apolipoprotein B100 (apoBlOO). Results: Compared with control group (HepG2 cells), the glucose consumption in the HepG2-IR cells in IR group was significantly decreased (P<0. 01). Compared with IR group, the glucose consumption in the HepG2-IR cells in Ex-4 group was increased (P<0. 05). The Oil O red staining results showed that compared with control group, the fat percentage in the HepG2-IR cells in IR group was increased (P<0. 05); compared with IR group, the fat percentage in Ex-4 group was decreased (P< 0.05). Compared with control group, the level of TG in the cells in IR group was significantly increased (P< 0. 01); compared with IR group, the level of TG in the cells in Ex-4 group was significantly decreased (P<0. 05). The qT-PCR results showed that compared with control group, the expression levels of ACC FAS and SREBP-lc mRNA in the cells in IR group were increased (P<0. 01), and the expression level of apoBlOO mRNA was decreased (P<0. 05); compared with IR group, the expression levels of ACC, FAS and SREBP-lc mRNA in the cells in Ex-4 group were decreased (P<0. 05), and the expression level of apoBlOO mRNA was increased (P< 0.01). Conclusion: Ex-4 can regulate the expressions of lipid metabolism related genes in the HepG2 cells and improve IR.

Clinical Characteristics of Patients after Aryloxyphenoxy Propionate Herbicide Ingestion

PURPOSE: No studies have been conducted to investigate the acute toxicity of aryloxyphenoxypropionate herbicides in humans following ingestion. Therefore, this study was conducted to investigate the clinical characteristics of aryloxyphenoxypropionate herbicide poisoning and provide guidance for physicians treating patients who have ingested these types of herbicides. METHODS: A retrospective observational case series was conducted using ten patients with history of aryloxyphenoxy propionate herbicide. Data were collected for clinical manifestation, management and final outcome. RESULTS: The most common symptoms were gastrointestinal irritation and an altered mental state (Glasgow Coma Scale<15). An elevated lactate level was a common laboratory abnormality, and prolonged QTc interval was commonly observed. These clinical features normalized within one day of supportive treatment. CONCLUSION: The acute toxicity of aryloxyphenoxypropionate herbicides in humans is manageable with supportive treatment. However, physicians should take into account depressed consciousness, the possibility of arrhythmia, and an elevated lactate level when planning their treatment strategy.

Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids

The classical functions of bile acids include acting as detergents to facilitate the digestion and absorption of nutrients in the gut. In addition, bile acids also act as signaling molecules to regulate glucose homeostasis, lipid metabolism and energy expenditure. The signaling potential of bile acids in compartments such as the systemic circulation is regulated in part by an efficient enterohepatic circulation that functions to conserve and channel the pool of bile acids within the intestinal and hepatobiliary compartments. Changes in hepatobiliary and intestinal bile acid transport can alter the composition, size, and distribution of the bile acid pool. These alterations in turn can have significant effects on bile acid signaling and their downstream metabolic targets. This review discusses recent advances in our understanding of the inter-relationship between the enterohepatic cycling of bile acids and the metabolic consequences of signaling via bile acid-activated receptors, such as farnesoid X nuclear receptor (FXR) and the G-protein-coupled bile acid receptor (TGR5).

Actions of natural products in regulating lipid metabolism through activating AMP-activated protein kinase: Research advances / 国际药学研究杂志

AMP-activated protein kinase (AMPK) is an energy sensor playing a key role in regulation of cellular metabolism. When activated by increased intracellular AMP/ATP ratio or by other factors, AMPK promotes the oxidation of fatty acid, increases energy production and improves glucose uptake and use. Meanwhile, it inhibits glycogen synthesis, gluconeogenesis and lipid synthesis, thus reducing energy consumption and keeping the balance of cell energy metabolism. There are many natural products with regulating lipid metabolism such as flavones, saponins, and alkaloids. Their mechanisms of regulating lipid metabolism are different. In recent years, many natural products with AMPK-activating activity have been identified. This paper reviews the research progress in the actions of natural products in regulating lipid metabolism through activation of AMPK.

Nutraceuticals as potential therapeutic agents for colon cancer: a review

Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

Effects of medicinal herb water extracts on expression of hepatic glucokinase, pyruvate dehydrogenase and acetyl-CoA carboxylase mRNA

We studied the anti-diabetic effects of medicinal herb water extracts on expression of hepatic glucokinase (GCK), pyruvate dehydrogenase (PDH), and acetyl-CoA carboxylase (ACC) mRNA. The medicinal herbs used for experiments were Cornus officinalis (CO), Paeonia suffruticosa Andrews (PSA), Discorea japonica Thunb. (DJ), Rehmannia glutinosa (RG), Lycium chinense (LC), and Pyrus pyrifolia (PP). For GCK mRNA expression, CO, RG, and LC water extracts exhibited a more effective activity than other extracts. Cells treated with RG and LC water extracts showed an increase in expression of PDH mRNA to 191% and 124%, respectively, compared to control. Expression of ACC mRNA was significantly higher in LC water extract. These data indicate that CO, RG, and LC water extracts stimulates expression of hepatic GCK, PDH, and ACC mRNA.

The effect of Ghrelin on activation of UCP3 and phosphorylation of ACC under the high fat environment in rat myoblast / 中国医师杂志

ObjectiveTo study the effect of Ghrelin on activation of UCP3 and phosphorylation of ACC under the high fat environment in rat myoblast,and to support the study on prevention of type 2 diabetes.MethodsThe rat myoblast were exposed to 0.3 mmol/L palmitic acid for 12 h,at the same time,10-11 mol/L,10-9 mol/L,10-7 mol/L Ghrelin were added.The expression of UCP3 mRNA was determined by RT-PCR.The protein levels of UCP3 and p-ACC were measured by western blotting.ResultsCompared with the control group,UCP3 mRNA and the protein levels of UCP3 and p-ACC were obviously decreased in 0.3 mmol/L PA group(UCP3 mRNA:P =0.000,UCP3 protein levels:P =0.000,p-ACC protein levels:P =0.003).Compared with the 0.3 mmol/L PA group,with the increasing concentration of Ghrelin,UCP3 mRNA and the protein levels of UCP3 and p-ACC were elevated.The effects of 10-7 mol/L Ghrelin were significant(UCP3 mRNA:P =0.017,UCP3 protein levels:P =0.000,p-ACC protein levels:P =0.007).ConclusionsGhrelin could enhance activation of UCP3 and phosphorylation of ACC under high fat environment in rat myoblast.

Acetyl-CoA carboxylase expression in the liver of quail with hyperuricemia and abdominal obesity / 中华内分泌代谢杂志

The quail model of hyperuricemia combined with abdominal obesity was induced by high purine diet.Body weight in model group showed no change.Serum uric acid level in model group was increased significantly on 7,14,21,and 28 d( P＜0.05 or P＜0.01 ).Abdominal fat index in model group increased significantly on 28d.On 7 d and 28 d,serum free fatty acid level was increased significantly.Acetyl-CoA carboxylase( ACC ) protein expression in the liver of model quail was increased as shown by ELISA and immunohistochemisty ( P＜0.05 or P＜0.01 ),suggesting that the alteration of ACC expression contributes to the pathogenesis of hyperuricemia combined with abdominal obesity.