Search

Background: Previous studies have indicated that enhancement of autophagy lysosome pathway may be beneficial for Parkinson's disease (PD), in which aberrant accumulation of aggregated/misfolded proteins and mitochondrial dysfunction are considered as crucial pathogenesis. Recently, a number of studies have suggested the neuroprotective effects of lithium in models of several neurodegenerative diseases including PD. However, the exact mechanisms underlying this neuroprotection remain unclear. In our study, rotenone-exposed SH-SY5Y cells were used as an in vitro parkinsonian model to assess the autophagy-enhancing effect of lithium and the underlying mechanisms were further investigated.Results: Similar to the common used autophagy enhancer rapamycin (Rap, 0.2 μM), lithium (LiCl, 10 mM) significantly recovered the shrinkage of SH-SY5Y cells, and alleviated rotenone-induced cell apoptosis, mitochondrial membrane potential reduction and reactive oxygen species accumulation. Furthermore, the protective effects induced by LiCl were partially blocked by the co-treatment of autophagy inhibitors such as 3-methyladenine (3-MA, 10 mM) or chloroquine (CHL, 10 μM). Moreover, 3-MA or Chl suppressed LiCl-induced autophagy in the immunoblot assay. In addition, the co-localization of LC3 and mitochondria and the preservation of mitochondrial function within LiCl-treated cells were observed, confirming that the damaged mitochondria were cleared through autophagy (mitophagy).Conclusions: These findings suggested that lithium exerted neuroprotection against rotenone-induced injuries partially through the autophagy pathway. Pharmacologically induction of autophagy by lithium may represent a novel therapeutic strategy as a disease-modifier in PD. [ABSTRACT FROM AUTHOR]

Background: In vitro and in vivo studies have suggested that osteopontin (OPN) is associated with many types of cancers. However, no studies have reported the incidence of OPN polymorphisms and the risk of gastric cancer. The aim of this study was to investigate the association between OPN polymorphisms and gastric cancer in a Chinese patient population.Methods: Three genetic variants in the OPN promoter were genotyped using direct sequencing in 200 gastric cancer patients and 200 gender- and age-matched cancer-free controls. The 4-year survival curve was calculated using the Kaplan-Meier method and compared using the log-rank test for each single nucleotide polymorphism (SNP) site. We measured the promoter activity of the -443 T → C polymorphism using a dual luciferase reporter assay. Result: For the variant at nt -443 (CC), there was a significant difference between the number of patients with stage IV and those with stage I gastric cancer (IA + IB; P = 0.014) and between those with stage IV and all other stages of gastric cancer (IA + IB + II + III; P = 0.02). For the variant at nt -443 (CT), there was a significant difference between the number of gastric cancer patients with stage IV and those with stage II (P = 0.013). The survival rates for patients with the C/C genotype were significantly lower than for patients with the other two genotypes (C/T, T/T). Moreover, significantly higher luciferase activities were observed in the pGL3-C construct compared to the pGL3-T construct. Conclusions: This study provides the first evidence that variation at nt -443 in the OPN promoter increases the potential for gastric cancer metastasis and subsequent death in the Chinese population. [ABSTRACT FROM AUTHOR]

Background: Previous studies have indicated that enhancement of autophagy lysosome pathway may be beneficial for Parkinson’s disease (PD), in which aberrant accumulation of aggregated/misfolded proteins and mitochondrial dysfunction are considered as crucial pathogenesis. Recently, a number of studies have suggested the neuroprotective effects of lithium in models of several neurodegenerative diseases including PD. However, the exact mechanisms underlying this neuroprotection remain unclear. In our study, rotenone-exposed SH-SY5Y cells were used as an in vitro parkinsonian model to assess the autophagy-enhancing effect of lithium and the underlying mechanisms were further investigated. Results: Similar to the common used autophagy enhancer rapamycin (Rap, 0.2 μM), lithium (LiCl, 10 mM) significantly recovered the shrinkage of SH-SY5Y cells, and alleviated rotenone-induced cell apoptosis, mitochondrial membrane potential reduction and reactive oxygen species accumulation. Furthermore, the protective effects induced by LiCl were partially blocked by the co-treatment of autophagy inhibitors such as 3-methyladenine (3-MA, 10 mM) or chloroquine (CHL, 10 μM). Moreover, 3-MA or Chl suppressed LiCl-induced autophagy in the immunoblot assay. In addition, the co-localization of LC3 and mitochondria and the preservation of mitochondrial function within LiCl-treated cells were observed, confirming that the damaged mitochondria were cleared through autophagy (mitophagy). Conclusions: These findings suggested that lithium exerted neuroprotection against rotenone-induced injuries partially through the autophagy pathway. Pharmacologically induction of autophagy by lithium may represent a novel therapeutic strategy as a disease-modifier in PD.

Background: Histoplasmosis is one of the invasive fungal infections and presents with symptoms mainly in the lungs. Disseminated histoplasmosis (DH) is rare and its lesions in the gastrointestinal tract are even uncommon. The concomitant involvement of the upper and lower gastrointestinal tract has never been described in the immunocompetent individuals.Case Presentation: A 44-year-old immunocompetent Chinese man presented with fever, hepatosplenomegaly, fungal esophagitis and protuberant lesions with central depression and erosion along the mucous membrane of the colon. The patient was diagnosed as disseminated histoplasmosis by gastrointestinal endoscopy.Conclusions: Histoplasmosis should be taken caution in patients with fever and hepatosplenomegaly. Actions should be taken to avoid its disseminated infection associated high mortality. [ABSTRACT FROM AUTHOR]

Background: Studies on the association between MDM2 SNP309 (T > G) and gastric cancer have reported conflicting results. Thus, the aim of this study was to investigate whether MDM2 SNP309 is associated with susceptibility and prognosis of gastric carcinoma in Chinese patients.Methods: Total of 574 gastric carcinoma cases and 574 age- and sex-matched healthy controls were included. MDM2 polymorphism was detected by PCR- RFLP and infection of Helicobacter pylori (H. pylori) by a validated serology test. The functionality of MDM2 SNP309, with or without H. pylori lipopolysaccharide (LPS), was examined by dual-luciferase assay. Kaplan-Meier survival curves were used to evaluate survival. Additional, a meta-analysis was conducted to verity the findings.Results: MDM2 SNP309G/G genotype was associated with an increased risk of gastric carcinoma when compared with T/T genotype or T carriers (both P < 0.01), and a joint effect between MDM2 SNP309G/G and H. pylori infection was observed to intensify gastric carcinoma risk. SNP309G/G was identified as an independent marker of poor overall survival of carcinoma. In vitro, the luciferase assay further showed an increased transcriptional activity of SNP309G allele compared with SNP309T allele, and the function of polymorphism T309G in MDM2 gene promoter was intensified by H. pylori LPS. Pooled results from the meta-analysis confirmed that SNP309G/G genotype had a significantly increased risk of gastric carcinoma compared with T/T genotype or T carriers, consistent with the case-control findings.Conclusions: MDM2 SNP309G allele is associated with an increased risk and poor prognosis of gastric carcinoma in Chinese patients. Additional, there is a joint effect of MDM2 SNP309G/G allele and H. pylori infection on gastric carcinoma development, which may attribute to H. pylori LPS. [ABSTRACT FROM AUTHOR]

Background: Genetic information for Toxoplasma gondii isolates from pigs in eastern, south, and southwestern regions of China has been reported previously. However, there are no data from pigs in the northeastern area of the country. To better understand the epidemiology of T. gondii, we determined the seroprevalence and genotypes of T. gondii from pigs slaughtered for human consumption in Liaoning province, northeastern China., Findings: Out of 2063 pigs examined, 233 (11.26%) were seropositive for T. gondii by the modified agglutination test (MAT), and viable parasites were isolated by bioassay in mice from 23 (9.87%) of the 233 seropositive pigs. Fifteen out of 23 isolates were genotyped using 10 PCR-restriction fragment length polymorphism (RFLP) genetic markers including SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico. One isolate was identified as ToxoDB genotype #3 (type II-variant), and one was genotype #1 or #3. The other 13 isolates were ToxoDB #9 (type Chinese 1)., Conclusions: To our knowledge, this is the first report of T. gondii isolation and genotyping from pigs in northeastern China. This study indicates that pigs are a potential source for transmission of T. gondii to humans, therefore poses a potential public health concern. The genotyping results revealed the presence of genotype Chinese 1 in northeastern China, enriching the scope of T. gondii genotypes distribution in eastern Asia.

Background: Increasing evidence showed that miRNAs serve as modulators of human cancer, either as oncogene or tumor suppressors. Cisplatin resistance is the most common cause of chemotherapy failure in gastric cancer (GC). However, the roles of miRNAs in cisplatin resistance of GC remain largely unknown. The aim of the study was to identify a novel miRNA/gene pathway that regulates the sensitivity of GC cells to cisplatin., Methods: In this study, we chose miR-223 by qRT-PCR analysis, the most significantly up-regulated miRNA in GC, to investigate its formation of DDP-resistant phenotype of GC cells and possible molecular mechanisms., Results: We found that miR-223 was most significantly up-regulated miRNA in DDP-resistant GC cells compared with parental GC cells. Besides, its expression was also significantly up-regulated in GC tissues. FBXW7 was identified as the direct and functional target gene of miR-223. Overexpression of FBXW7 could mimic the effect of miR-223 down-regulation and silencing of FBXW7 could partially reverse the effect of miR-223 down-regulation on DDP resistance of DDP-resistant GC cells. Besides, miR-223 and FBXW7 could affect the G1/S transition of cell cycle by altering some certain cell cycle regulators. Furthermore, miR-223 was found to be significantly up-regulated in H. pylori infected tissues and cells, suggesting that H. pylori infection may lead to GC development and DDP resistance., Conclusions: Our findings revealed the roles of miR-223/FBXW7 signaling in the DDP resistance of GC cells and targeting it will be a potential strategic approach for reversing the DDP resistance in human GC.

Background: Autotaxin (ATX) possesses lysophospholipase D (lyso PLD) activity, which converts lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA). The ATX-LPA signaling axis has been implicated in angiogenesis, chronic inflammation and tumor progression. Osteopontin (OPN) is an important chemokine involved in the survival, proliferation, migration, invasion and metastasis of gastric cancer cells. The focus of the present study was to investigate the relationship between the ATX-LPA axis and OPN., Results: In comparison with non-treated cells, we found that the ATX-LPA axis up-regulated OPN expression by 1.92-fold in protein levels and 1.3-fold in mRNA levels. The ATX-LPA axis activates LPA2, Akt, ERK and ELK-1 and also protects SGC7901 cells from apoptosis induced by Taxol treatment., Conclusions: This study provides the first evidence that expression of OPN induced by ATX-LPA axis is mediated by the activation of Akt and MAPK/ERK pathways through the LPA2 receptor. In addition, OPN is required for the protective effects of ATX-LPA against Taxol-induced apoptosis and ATX-LPA-induced migration of SGC7901 cells.

Background: Human cervical cancer oncoprotein 1 (HCCR-1), reported as a negative regulator of p53, is over-expressed in a variety of human cancers. However, it is yet unknown whether HCCR-1 plays any role in pancreatic cancer development. The aim of this study was to investigate the effect of epidermal growth factor on the expression of HCCR in pancreatic cancer cells, and to explore if PI3K/Akt/mTOR signaling pathway mediated this expression., Methods: A polyclonal antibody against HCCR protein was raised by immunizing Balb/c mice with the purified recombinant protein pMBPc-HCCR. Tissue samples were constructed on a tissue chip, and the expression of HCCR was investigated by immunohistochemistry assay and Western blotting. Pancreatic cell line, PANC-1 cells were stably transfected with plasmids containing sense-HCCR-1 fragment and HCCR siRNA fragment. MTT and transwell assay were used to investigate the proliferation and invasion of stable tansfectants. The specific inhibitor of PI3K and mTOR was used to see if PI3K/mTOR signal transduction was involved in the induction of HCCR gene expression. A Luciferase assay was used to see if Akt can enhance the HCCR promoter activity., Results: HCCR was up-regulated in pancreatic tumor tissues (mean Allred score 4.51+/-1.549 vs. 2.87+/-2.193, P<0.01), especially with high expression in poorly differentiated pancreatic cancer. The growth of cells decreased in HCCR-1 siRNA transfected cells compared with vector transfectants. The number of invasion cells was significantly lower in HCCR-1 siRNA transfected cells (24.4+/-9.9) than that in vector transfectants (49.1+/-15.4). Treatment of PANC-1 cells with epidermal growth factor increased HCCR protein level in a dose- and time-dependent manner. However, application of LY294002 and rapamycin caused a dramatic reduction of epidermal growth factor-induced HCCR expression. Over-expression of exogenous constitutively active Akt increased the HCCR promoter activity; in contrast, dominant negative Akt decreased the promoter activity., Conclusions: EGF-induced HCCR-1 over-expression is mediated by PI3K/AKT/mTOR signaling which plays a pivotal role in pancreatic tumor progression, suggesting that HCCR-1 could be a potential target for cancer therapeutics.

Objective: The objective of this survey was to study the association between Helicobacter pylori infection and the severity of coronary atherosclerosis., Methods: The study population consisted of 961 consecutive patients (711 males and 250 females) who underwent coronary angiography for suspected or known coronary atherosclerosis. The patients' body mass index, blood pressure, the blood lipid, blood glucose, leukocyte count (10(9)/L), neutrophil count (10(9)/L), and Helicobacter pylori-specific IgG antibodies were performed. Coronary angiograms were scored according to vessel score and Gensini's score., Results: A significant association between H. pylori infection and coronary atherosclerosis as well as its severity was not find in this cross section study (p = 0.858). And, the level distribution of vessel score (p = 0.906) and Gensini's score (p = 0.905) were similar in the seropositivity group and seronegativity group of Helicobacter pylori infection. However, the level of fasting high-density lipoprotein cholesterol (mmol/L) (p = 0.013) was significantly lower in the seropositivity group than that in the seronegativity group of Helicobacter pylori infection., Conclusions: In conclusion, in the present study, a significantly correlation between Helicobacter pylori seropositivity and angiographically evaluated severity of atherosclerosis was not find. And, the present study showed a good correlation between Helicobacter pylori infection and decreased HDL cholesterol. However, the exact mechanisms need further study.