Distinct microbiota dysbiosis in patients with non-erosive reflux disease and esophageal adenocarcinoma

Non-erosive reflux disease (NERD) and esophageal adenocarcinoma (EAC) are often regarded as bookends in the gastroesophageal reflux disease spectrum. However, there is limited clinical evidence to support this disease paradigm while the underlying mechanisms of disease progression remain unclear. In this study, we used 16S rRNA sequencing and mass-spectrometer-based proteomics to characterize the esophageal microbiota and host mucosa proteome, respectively. A total of 70 participants from four patient groups (NERD, reflux esophagitis, Barrett’s esophagus, and EAC) and a control group were analyzed. Our results showed a unique NERD microbiota composition, distinct to control and other groups. We speculate that an increase in sulfate-reducing Proteobacteria and Bacteroidetes along with hydrogen producer Dorea are associated with a mechanistic role in visceral hypersensitivity. We also observed a distinct EAC microbiota consisting of a high abundance of lactic acid-producing bacteria (Staphylococcus, Lactobacillus, Bifidobacterium, and Streptococcus), which may contribute towards carcinogenesis through dysregulated lactate metabolism. This study suggests the close relationship between esophageal mucosal microbiota and the appearance of pathologies of this organ

Identification of subgroup-specific miRNA patterns by epigenetic profiling of sporadic and Lynch syndrome-associated colorectal and endometrial carcinoma

Abstract Background Altered expression of microRNAs (miRNAs) commonly accompanies colorectal (CRC) and endometrial carcinoma (EC) development, but the underlying mechanisms and clinicopathological correlations remain to be clarified. We focused on epigenetic mechanisms and aimed to explore if DNA methylation patterns in tumors depend on DNA mismatch repair (MMR) status, sporadic vs. Lynch-associated disease, and geographic origin (Finland vs. Australia). Treatment of cancer cell lines with demethylating agents revealed 109 significantly upregulated miRNAs. Seven met our stringent criteria for possible methylation-sensitive miRNAs and were used to screen patient specimens (205 CRCs and 36 ECs) by methylation-specific multiplex ligation-dependent probe amplification. Results Three miRNAs (129-2, 345, and 132) with low methylation levels in normal tissue and frequent hypermethylation in tumors were of particular interest. Hypermethylation of miR-345 and miR-132 associated with MMR deficiency in CRC regardless of geographic origin, and hypermethylation of miR-132 distinguished sporadic MMR-deficient CRC from Lynch-CRC. Finally, hypermethylation of miRNAs stratified 49 endometrial hyperplasias into low-methylator (simple hyperplasia) and high-methylator groups (complex hyperplasia with or without atypia) and suggested that miR-129-2 methylation in particular could serve as a marker of progression in early endometrial tumorigenesis. Conclusions Our study identifies miR-345 and miR-132 as novel differentially methylated miRNAs in CRC, thereby facilitating sub-classification of CRC and links miR-129-2 methylation to early endometrial tumorigenesis

The Tumor Suppressor Gene, RASSF1A, Is Essential for Protection against Inflammation -Induced Injury

10.1371/journal.pone.0075483PLoS ONE810-POLN

Physiologic specialization within Sphacelotheca reiliana (Kühn) Clint. on Sorghum and the Biology of its Chlamydospores in the Soil

Corresponding to the title, the present study was concerned with two aspects. In the first of these, two chlamydosporous sori from corn were collected from California and Washington and 18 chlamydosporous sori from sorghum were collected from California, New Mexico, Texas, and India. Chlamydosporous cultures or paired monosporidial cultures from these were hypodermically injected as desired into seedlings of one or more of four sweet corn varieties and 57 sorghum varieties. Chlamydosporous cultures from the two corn sources yielded head smut on three sweet corn varieties and not on any of 14 sorghum varieties. Cultures from 14 of 18 sorghum sources yielded head smut on Sugar Drip sorghum and on North Star sweet corn, while cultures from the remaining four yielded head smut only on Sugar Drip sorghum. The 18 sorghum head smut cultures were differentiated on a set of five sorghum varieties, and comprised four races according to sources; (1) California, (2) Poona 1 and Coimbatore 2, (3) Poona 2 and (4) Texas, New Mexico and Coimbatore 1. The difference between the sorghum and the corn head smut fungi accordingly was considered to be varietal, rather than racial as supposed by Reed. The sorghum and the corn head smut fungi were readily hybridized. In the second part of the study, chlamydospores germinated in soil by forming long multicellular hyphae, the lower cells of which were empty while the apical cells filled with vacuolated or nonvacuolated protoplasm. The absence of sporodial formation may account for the low number of races found in this pathogen and for the apparent natural stability of the sorghum and corn head smut fungi as separate units. Chlamydospore abundance in soil affected the per cent incidence of head-smutted sorghum plants. Within limits the per cent incidence of head-smutted sorghum plants was linearly related to the logarithm of the number of chlamydospores in soil. The threshold number of viable spores necessary for infection being estimated at about 800 per gram of soil. The abundance of infectious chlamydospores in soil declined rapidly after 7 days to sub-threshold levels at a temperature of near-freezing, regardless of soil moisture. The decline at 10°, 20° and 30°C, and at soil moistures near the wilting point, 20%, 40% and 100% of field capacity was less rapid and in most instances did not reach the threshold limit within 30 days. In supplementary studies sorghum seeds carrying 52,631 or 404,578 chlamydospores per seed failed to yield smutted plants. A dominant form of resistance to head smut was contributed by FC 811 Faterita to a sorghum hybrid. Sorghum head smut is a widely distributed disease of sorghum reported from Africa, Argentina, Brazil, China, India, Italy, Japan, Middle Easer New South Wales, Soviet Union and Unites States. It is the result of infection of seedlings by germinating seed or soil-borne chlamydospores of the fungus Sphacelotheca reiliana (Kuhn) Clint., which fungus completely destroys the inflorescence of the growing plant, replacing it with its own body of mycelium and chlamydospores. Corn is also attacked by the fungus and sustains the disease

Long-term management of patients taking proton pump inhibitors

Proton pump inhibitors have changed the management of acid-related upper gastrointestinal disorders. Other effective strategies for reducing upper gastrointestinal morbidity include lifestyle modification, Helicobacter pylori eradication for patients with present or past peptic ulcer disease and infection, and less potent therapy for mild dyspepsia and gastro-oesophageal reflux. Proton pump inhibitors have a definite role in the prevention of recurrence of oesophageal strictures. They can also be used to prevent the ulcerative complications of non-steroidal anti-inflammatory drugs in patients at high risk. In Barrett's oesophagus the efficacy of proton pump inhibitors in preventing disease progression and the development of adenocarcinoma is unclear