Puerarin prevents cadmium-induced mitochondrial fission in AML-12 cells via Sirt1-dependent pathway.

Recent investigations have revealed that puerarin (PU) alleviates cadmium (Cd)-caused hepatic damage via inhibiting oxidative stress. Mitochondria are dynamic organelles and play a critical part in regulating the occurrence of oxidative stress, but the role of mitochondria in the protection of PU against hepatocellular damage caused by Cd exposure remains unknown. Thus, this study was aimed to clarify this issue using mouse hepatocyte AML-12 cell line. Transmission electron microscopy analysis firstly showed that PU prevents Cd-induced mitochondrial ultrastructure damage. Mitochondrial network image analysis by confocal microscopy revealed that PU exerts the protection against Cd-induced cytotoxicity via restoring mitochondrial network fragmentation. Also, mitochondrial dynamic protein expression profiles showed that enhanced fission protein levels and inhibited fusion protein levels in Cd-treated cells were significantly reversed by PU, suggesting the protective effect of PU against Cd-induced mitochondrial fission. Moreover, changes of intracellular ATP level and protein levels of key regulators involving in mitochondrial biogenesis indicated that Sirtuin-1(Sirt1) pathway may be involved in the protection of Cd-impaired mitochondrial function by PU. Next, Sirt1 protein levels in treated cells were effectively regulated by genetic knockdown or chemical agonist SRT1720. Accordingly, alleviation of Cd-induced mitochondrial fission assays and cell viability by PU was markedly regulated by SRT1720 or Sirt1 knockdown, suggesting the indispensable role of Sirt1 in this process. Collectively, these findings highlight that PU prevents Cd-induced mitochondrial fission to alleviate cytotoxicity via Sirt1-dependent pathway, which provide novel evidences to fully understand the hepatoprotective action of PU against heavy metal toxicity.

Puerarin attenuates cadmium-induced hepatic lipid metabolism disorder by inhibiting oxidative stress and inflammation in mice.

Cadmium (Cd) is a common environmental pollutant with known toxic effects on the liver. Puerarin (PU), a natural flavonoid, has been shown to exert protective effect in numerous pathological processes. However, whether PU affords protection in Cd-induced liver damage is still equivocal. Therefore, 40 mice were treated with Cd and/or PU by gavage for 9 weeks, then the serum and liver samples were collected to verify this issue. In this study, Cd exposure triggered hepatic lipid metabolism disorders and resultant liver damage as evidenced by Oil Red O staining and total cholesterol (TC) and triglyceride (TG) levels in serum and liver, aspartate transaminase (AST) and alanine transaminase (ALT) levels in serum, and histopathology, which were significantly improved by PU. Moreover, PU also normalized the expression of Cd-disturbed lipid metabolism-related proteins to improve lipid accumulation, contributing to the alleviation of liver injury. Moreover, Cd-decreased antioxidative indices superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) as well as glutathione (GSH) in hepatic tissues were significantly attenuated by PU administration, while Cd-elevated hepatic malondialdehyde (MDA) and reactive oxygen species (ROS) levels were markedly down-regulated by PU treatment, demonstrating the antioxidant effect of PU against Cd exposure. In addition, PU supplementation increased the anti-inflammatory potential, and normalized the levels of proinflammatory cytokines during Cd exposure. In conclusion, these observations demonstrate that PU treatment decreases oxidative stress and inflammation response, which may contribute to prevent Cd-induced lipid metabolism disorder and consequent liver damage.

TASP1 Promotes Proliferation and Migration in Gastric Cancer via EMT and AKT/P-AKT Pathway.

Threonine aspartase 1 (TASP1) was reported to function in the development of cancer. However, the regulatory mechanism of TASP1 in gastric cancer (GC) remains unclear. In this study, we determined the expression of TASP1 in tissues of GC patients, GC cells by qRT-PCR, and western blot and assessed the relationship between TASP1 and GC cell proliferation and migration via CCK-8 and transwell assay. It was found that the expression of TASP1 in GC tissues or GC cell lines was significantly higher than that in normal adjacent tissues or normal cells. The proliferation and migration of GC cells were inhibited upon TASP1 knockdown. Mechanism investigation revealed that TASP1 promoted GC cell proliferation and migration through upregulating the p-AKT/AKT expression. TASP1 induced GC cell migration via the epithelial -mesenchymal transition (EMT) pathway. In conclusion, TASP1 promotes GC progression through the EMT and AKT/p-AKT pathway, and it may serve as a new potential biomarker and therapeutic target for GC.

Puerarin induces Nrf2 as a cytoprotective mechanism to prevent cadmium-induced autophagy inhibition and NLRP3 inflammasome activation in AML12 hepatic cells.

Liver is the main target organ of cadmium (Cd) toxicity and puerarin (PU) has been shown to prevent Cd-induced hepatic cell damage via its antioxidant activity. Nrf2 acts as a critical regulator of cellular defense against various oxidative insults, but its role in the protection of PU against Cd-induced hepatic damage has not yet been clarified. Hereby, this study was designed to investigate the underlying mechanism using mouse hepatocyte line AML-12. Data firstly showed that Cd-inhibited Nrf2 pathway was markedly restored by PU treatment, assessed by Nrf2 nuclear translocation, protein levels of Keap1 and Nrf2 downstream target genes. Accordingly, Cd-reduced protein levels of antioxidant enzymes were significantly up-regulated by PU. Next, Nrf2 silencing cellular model was established to further elucidate the role of Nrf2 in the protection of PU against Cd-induced hepatic damage. Attenuation of Cd-induced autophagy inhibition and autophagosome accumulation by PU was remarkably countered by Nrf2 silencing. Moreover, alleviation of Cd-induced NLRP3 inflammasome activation by PU was distinctly prevented by Nrf2 knockdown, assessed by protein levels of NLRP3 inflammosome complex and downstream IL-18 and IL-1ß production. Collectively, our data suggest that PU restores Cd-induced Nrf2 inhibition to prevent autophagy inhibition and NLRP3 inflammasome activation, providing novel insights into the protection of PU against Cd-induced hepatic cell damage.

Effect of family support on quality of postoperative life in patients with digestive cancer.

BACKGROUND: Digestive tumors are malignant tumors of epithelial origin with high rates of morbidity and mortality worldwide. At present, surgery is the main treatment for patients with digestive tumors. In this study, we conducted a survey of patients with digestive cancers to explore the influence of family support on postoperative quality of life, with the aim of providing a basis of reference for further improvement of the quality of life of such patients. METHODS: A total of 82 patients with digestive cancer who underwent surgery in Hospital of Chengdu University of Traditional Chinese Medicine between October, 2018 and April, 2019 were selected to take part. The self-made questionnaire, the European Cancer Research and Treatment Organization's Core Quality of Life Questionnaire for Cancer Patients, and the Family Support Scale were used to investigate the patients, and the collected data were statistically analyzed. RESULTS: The family support scores of the 82 enrolled patients ranged from 5 to 15 points, with an average score of (8.86±2.47) points; 60 cases (73.17%) scored ≥10 points and 12 cases (26.83%) scored <10 points. Patients who were married, aged under 30 years old, or employed as civil servants had higher family support scores than other patients (P<0.05). The scores for physical function, emotional function, and overall health status/quality of life in patients who had a high family support score were higher than those in patients who had a low family support score (P<0.05). According to the logistic regression model, Patients with higher age, getting married, with education level of bachelor degree or above, occupation as farmer and with other digestive tract tumor got higher family support score. (P<0.05). CONCLUSIONS: Good family support can effectively improve quality of postoperative life for patients with digestive cancer. Education, age, occupation and marriage are all independent factors that affect family support.

Puerarin prevents cadmium-induced hepatic cell damage by suppressing apoptosis and restoring autophagic flux.

Cadmium (Cd) is a common heavy metal contamination that is highly toxic to liver. Puerarin (PU), a potent free radical scavenger, has been shown to exert cytoprotective effect in numerous pathological processes. However, whether PU affords protection against Cd-induced hepatotoxicity remains unclear to be known. Here, we aimed to investigate the protective effect of PU on Cd-induced hepatotoxicity in an immortalized mouse hepatocyte line, AML-12. First, Cd-induced cytotoxicity in AML-12 cells was obviously ameliorated by PU treatment. Also, Cd-induced apoptotic cell death was markedly alleviated by PU treatment, evidenced by two methods. Simultaneously, Cd-elevated malondialdehyde and reactive oxygen species levels were significantly reduced by PU administration, demonstrating the antioxidant effect of PU against Cd exposure. Moreover, Cd-induced blockage of autophagic flux in AML-12 cells was obviously restored by PU treatment, evidenced by immunoblot analysis of autophagy marker proteins and tandem fluorescent-tagged LC3 method. Resultantly, Cd-induced autophagosome accumulation was significantly alleviated by PU treatment. In conclusion, these observations demonstrate that PU treatment alleviates Cd-induced hepatic cell damage by inhibiting apoptosis and restoring autophagy activity, which is intimately related with its antioxidant activity.

Alleviation of Lead-Induced Apoptosis by Puerarin via Inhibiting Mitochondrial Permeability Transition Pore Opening in Primary Cultures of Rat Proximal Tubular Cells.

Previous study has demonstrated that mitochondrial-dependent apoptotic pathway is involved in the nephroprotective effect of puerarin (PU) against lead-induced cytotoxicity in primary cultures of rat proximal tubular (rPT) cells. To further clarify how PU exerts its antiapoptotic effects, this study was designed to investigate the role of mitochondrial permeability transition (MPT) and subsequent apoptotic events in the process of PU against Pb-induced cytotoxicity in rPT cells. The results showed that Pb-mediated mitochondrial permeability transition pore (MPTP) opening together with mitochondrial cytochrome c release, activations of caspase-9 and caspase-3, and subsequent poly-ADP-ribose polymerase (PARP) cleavage can be effectively blocked by the addition of PU. Simultaneously, upregulation and downregulation of Bcl-2 and Bax with increased Bcl-2/Bax ratio due to PU administration further alleviated Pb-induced mitochondrial apoptosis. Moreover, PU can reverse Pb-induced ATP depletion by restoring mitochondrial fragmentation to affect ATP production and by regulating expression levels of ANT-1 and ANT-2 to improve ATP transport. In summary, PU produced a significant protection against Pb-induced mitochondrial apoptosis in rPT cells by inhibiting MPTP opening to ameliorate the mitochondrial dysfunction.

[Secular changes on the morphological development and nutrition status of Tibetan students from 1985 to 2005].

OBJECTIVE: To study the secular changes on both morphological development and nutritional status among Tibetan students, from 1985 to 2005. METHODS: Data from the Chinese national survey on students' physical fitness and health in 1985, 1995, 2000 and 2005 were used to analyze and find out the difference of the morphological development and nutrition status of Tibetan students aged 7 - 18 years in different years. RESULTS: From 1985 to 2005, the height and weight of Tibetan students had a growing trend. The height and weight of schoolboys and schoolgirls aged 7 - 18 years increased 3.94 cm, 5.08 kg, 2.25 cm, and 4.24 kg respectively, while the circumference decreased without significance. The prevalence rates of underweight and malnutrition in Tibetan students further went down along with the improvement of their nutritional status. However, the prevalence rates on both overweight and obesity increased continuously, affecting the health status of Tibetan students. CONCLUSION: From 1985 to 2005, the morphological development of Tibetan students had a growing trend and their nutrition status improved. However, the prevalence of overweight and obesity continuously increased.