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Platelets are blood cells that are primarily produced by the shedding of megakaryocytes in the bone marrow. Platelets participate in a variety of physiological and pathological processes in vivo, including hemostasis, thrombosis, immune-inflammation, tumor progression, and metastasis. Platelets have been widely used for targeted drug delivery therapies for treating various inflammatory and tumor-related diseases. Compared to other drug-loaded treatments, drug-loaded platelets have better targeting, superior biocompatibility, and lower immunogenicity. Drug-loaded platelet therapies include platelet membrane coating, platelet engineering, and biomimetic platelets. Recent studies have indicated that platelet extracellular vesicles (PEVs) may have more advantages compared with traditional drugloaded platelets. PEVs are the most abundant vesicles in the blood and exhibit many of the functional characteristics of platelets. Notably, PEVs have excellent biological efficacy, which facilitates the therapeutic benefits of targeted drug delivery. This article provides a summary of platelet and PEVs biology and discusses their relationships with diseases. In addition, we describe the preparation, drug-loaded methods, and specific advantages of platelets and PEVs targeted drug delivery therapies for treating inflammation and tumors. We summarize the hot spots analysis of scientific articles on PEVs and provide a research trend, which aims to give a unique insight into the development of PEVs research focus. [ABSTRACT FROM AUTHOR]

Objective: This study aimed at examining the alterations in metabolomic profiles caused by treatment of H. pylori infection, and the associations between key plasma metabolites and the risk of gastric lesion progression during follow-up after treatment. Methods: An intervention trial was performed in 183 participants, 117 of whom were H. pylori positive participants receiving treatment for H. pylori infection. H. pylori positive participants were prospectively followed for 182 to 1,289 days. Untargeted metabolomics assays were conducted on plasma samples collected at baseline, 6 months after treatment, and during continued follow-up. Results: We identified 59 metabolites with differential posttreatment changes between participants with successful and failed H. pylori eradication, 17 metabolites significantly distinguished participants with successful vs. failed eradication. Two metabolites [PC(18:1(11Z)/14:1(9Z)) and (2S)-6-amino-2-formamidohexanamide] showed posttreatment changes positively associated with successful H. pylori eradication, and were inversely associated with the risk of gastric lesion progression among participants with successful eradication. In contrast, 9-decenoic acid showed posttreatment changes inversely associated with successful eradication: its level was positively associated with the risk of gastric lesion progression among participants with successful eradication. Although the identified metabolites showed a temporary but significant decline after treatment, the trend generally reversed during continued follow-up, and pretreatment levels were restored. Conclusions: Treatment of H. pylori infection significantly altered plasma metabolic profiles in the short term, and key metabolites were capable of distinguishing participants with successful vs. failed eradication, but might not substantially affect metabolic regulation in the long term. Several plasma metabolites were differentially associated with the risk of gastric lesion progression among participants with successful or failed eradication. [ABSTRACT FROM AUTHOR]

Objective: Upper gastrointestinal (UGI) cancers, predominantly gastric cancer (GC) and esophageal cancer (EC), are malignant tumor types with high morbidity and mortality rates. Accumulating studies have focused on metabolomic profiling of UGI cancers in recent years. In this systematic review, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with GC and EC. Methods: A systematic search of three databases (Embase, PubMed, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of GC and EC was conducted. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included articles. Results: A total of 52 original studies were included for review. A number of metabolites were differentially distributed between GC and EC cases and non-cases, including those involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and protein and lipid metabolism. Lactic acid, glucose, citrate, and fumaric acid were among the most frequently reported metabolites of cellular respiration while glutamine, glutamate, and valine were among the most commonly reported amino acids. The lipid metabolites identified previously included saturated and unsaturated free fatty acids, aldehydes, and ketones. However, the key findings across studies to date have been inconsistent, potentially due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. Conclusions: Studies on metabolomics have thus far provided insights into etiological factors and biomarkers for UGI cancers, supporting the potential of applying metabolomic profiling in cancer prevention and management efforts. [ABSTRACT FROM AUTHOR]

Background: The exact relationship between nucleosome positioning and methylation of CpG islands in human pathogenesis is unknown. Methodology/Principal Findings: In the present study, we characterized the nucleosome position within the p16 CpG island and established a seeding methylation-specific PCR (sMSP) assay based on bisulfite modification to enrich the p16 alleles containing methylated-CpG at the methylation ''seeding'' sites within its intron-1 in gastric carcinogenesis. The sMSP-positive rate in primary gastric carcinoma (GC) samples (36/40) was significantly higher than that observed in gastritis (19/ 45) or normal samples (7/13) (P<0.01). Extensive clone sequencing of these sMSP products showed that the density of methylated-CpGs in p16 CpG islands increased gradually along with the severity of pathological changes in gastric tissues. In gastritis lesions the methylation was frequently observed in the region corresponding to the exon-1 coding-nucleosome and the 5'UTR-nucleosome; the methylation was further extended to the region corresponding to the promoternucleosome in GC samples. Only few methylated-CpG sites were randomly detected within p16 CpG islands in normal tissues. The significantly inversed relationship between the p16 exon-1 methylation and its transcription was observed in GC samples. An exact p16 promoter-specific 83 bp-MSP assay confirms the result of sMSP (33/55 vs. 1/6, P<0.01). In addition, p16 methylation in chronic gastritis lesions significantly correlated with H. pylori infection; however, such correlation was not observed in GC specimens. Conclusions/Significance:It was determined that de novo methylation was initiated in the coding region of p16 exon-1 in gastritis, then progressed to its 59UTR, and ultimately to the proximal promoter in GCs. Nucleosomes may function as the basic extension/progression unit of de novo methylation of p16 CpG islands in vivo. [ABSTRACT FROM AUTHOR]

The effects of a 7.3-y supplementation with garlic and micronutrients and of anti-He/icobacter pylon treatment with amoxicillin (1 g twice dailyl and omeprazole (20 mg twice daily) on serum folate, vitamin 8-12, homocysteine, and glutathione concentrations were assessed in a rural Chinese population. A randomized, double-blind, placebo-controlled, factorial trial was conducted to compare the ability of 3 treatments to retard the development of precancerous gastric lesions in 3411 subjects. The treatments were: 11 anti-H. pylon treatment with amoxicillin and omeprazole; 2) 7.3-y supplementation with aged garlic and steam-distilled garlic oil; and 3) 7.3-y supplementation with vitamin C, vitamin E, and selenium. All 3 treatments were given in a 2~ factorial design to subjects seropositive for H. pyloriinfection; only the garlic supplement and vitamin and selenium supplement were given in a 22 factorial design to the other sublects. Thirty-four subjects were randomly selected from each of the 12 treatment strata. Sera were analyzed after 7.3 y to measure effects on folate, vitamin B-i 2, homocysteine, and glutathione concentrations. Regression analyses adjusted for age, gender, and smoking indicated an increase of 10.2% (95%Cl: 2.9-i 8.1%) in serum folate after garlic supplementation and an increase of 13.4% l95%Cl: 5.3-22.2%) in serum glutathione after vitamin and selenium supplementation. The vitamin and selenium supplement did not affect other analytes and the amoxicillin and omeprazole therapy did not affect any of the variables tested. In this rural Chinese population, 7.3 y of garlic supplementation increased the serum folate concentration and the vitamin and selenium supplement increased that of glutathione, but neither affected serum concentrations of vitamin 6-12 or homocysteine. J. Nutr. 139: 106-112, 2009. [ABSTRACT FROM AUTHOR]

Helicobacter pyloriinfection is a major cause of peptic ulcer disease and gastric cancer. This study postulated that cranberry juice would be effective in the suppression ofH. pyloriin an endemically infected population at high risk for gastric cancer.A prospective, randomized, double-blind, placebo-controlled trial was conducted in Linqu County of Shandong Province, China, where 189 adults aged 48.9 ± 11.2 years (mean± SD) withH. pyloriinfection were randomly divided into two groups: cranberry juice (n = 97) and placebo (n = 92). Participants were assigned to orally receive two 250-ml juice boxes of cranberry juice or matching placebo beverage daily for 90 days. The degree ofH. pyloriinfection was determined using the13C-urea breath test before randomization at 35 and 90 days of intervention to assess the efficacy of cranberry juice in alleviating infection.A total of 189 subjects with positive13C-urea breath test results prior to randomization completed the study. At day 35 of intervention, 14 of the 97 (14.43%) from the the cranberry juice treatment group and 5 of the 92 (5.44%) of the placebo recipients had negative13C-urea breath test results. After 90 days, the study concluded that 14 of the 97 subjects in the cranberry juice treatment group versus 5 of the 92 in the placebo group yielded negative test results. Eleven individuals from the cranberry juice treatment group and only two from the placebo group were negative at 35 and 90 days of experiment. These results are significant (p < .05).Regular consumption of cranberry juice can suppressH. pyloriinfection in endemically afflicted populations. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection and the cytokine-mediated inflammatory responses play important roles in gastric cancer pathogenesis. This case control study was conducted to assess the association between genetic polymorphisms in interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor a (TNFa), which are involved in H.pylori infection, and risk of gastric cancer. Genotypes were determined by PCR-based denaturing high-performance liquid chromatography analysis and direct DNA sequencing in 250 incident cases with gastric cancer and 300 controls recruited in Northern China. Serum levels of anti-H.pylori IgG and IgA were measured by enzyme-linked immunosorbent assay to indicate H.pylori infection. We found that the risk of gastric cancer was significantly elevated in subjects with the IL-8-251 AA [adjusted odds ratio (OR) 2.02; 95% confidence interval (CI) 1.273.21] or IL-10-1082 G (OR 2.02; 95% CI 1.243.29) or TNFa-308 AG (OR 1.81; 95% CI 1.043.14) genotype. An elevated risk of gastric cancer was observed in subjects with H.pylori infection and the IL-8-251 AA genotype (OR 2.54; 95% CI 1.384.72) or IL-10-1082 G carriers (OR 2.62; 95% CI 1.424.93). An increased OR was also suggested for IL-1B-31 and TNFa-238, but confidence intervals included the null value. There was no evidence of increased risk for any of the other polymorphisms evaluated. These findings suggest that genetic polymorphisms in IL-8, IL-10 and TNFa may play important roles in developing gastric cancer in the Chinese population. [ABSTRACT FROM AUTHOR]

Background: Mutation of Wnt signal antagonists Apc or Axin activates β-catenin signaling in many cancers including the majority of human colorectal adenocarcinomas. The phenotype of apc or axin mutation in the fruit fly Drosophila melanogaster is strikingly similar to that caused by mutation in the segment-polarity gene, naked cuticle (nkd). Nkd inhibits Wnt signaling by binding to the Dishevelled (Dsh/Dvl) family of scaffold proteins that link Wnt receptor activation to bcatenin accumulation and TCF-dependent transcription, but human NKD genes have yet to be directly implicated in cancer. Methodology/Principal Findings: We identify for the first time mutations in NKD1 - one of two human nkd homologs - in a subset of DNA mismatch repair-deficient colorectal tumors that are not known to harbor mutations in other Wnt-pathway genes. The mutant Nkd1 proteins are defective at inhibiting Wnt signaling; in addition, the mutant Nkd1 proteins stabilize bcatenin and promote cell proliferation, in part due to a reduced ability of each mutant Nkd1 protein to bind and destabilize Dvl proteins. Conclusions/Significance: Our data raise the hypothesis that specific NKD1 mutations promote Wnt-dependent tumorigenesis in a subset of DNA mismatch-repair-deficient colorectal adenocarcinomas and possibly other Wnt-signal driven human cancers. [ABSTRACT FROM AUTHOR]