MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma.

Despite progress in treatment strategies, only ~24% of pancreatic ductal adenocarcinoma (PDAC) patients survive >1 year. Our goal was to elucidate deregulated pathways modulated by microRNAs (miRNAs) in PDAC and Vater ampulla (AMP) cancers. Global miRNA expression was identified in 19 PDAC, 6 AMP and 25 paired, histologically normal pancreatic tissues using the GeneChip 4.0 miRNA arrays. Computational approaches were used for miRNA target prediction/identification of miRNA-regulated pathways. Target gene expression was validated in 178 pancreatic cancer and 4 pancreatic normal tissues from The Cancer Genome Atlas (TCGA). 20 miRNAs were significantly deregulated (FC≥2 and p<0.05) (15 down- and 5 up-regulated) in PDAC. miR-216 family (miR-216a-3p, miR-216a-5p, miR-216b-3p and miR-216b-5p) was consistently down-regulated in PDAC. miRNA-modulated pathways are associated with innate and adaptive immune system responses in PDAC. AMP cancers showed 8 down- and 1 up-regulated miRNAs (FDR p<0.05). Most enriched pathways (p<0.01) were RAS and Nerve Growth Factor signaling. PDAC and AMP display different global miRNA expression profiles and miRNA regulated networks/tumorigenesis pathways. The immune response was enriched in PDAC, suggesting the existence of immune checkpoint pathways more relevant to PDAC than AMP.

Different patterns between mechanical and electrical activities: an approach to investigate gastric motility in a model of long-term diabetic rats.

The relationship between time-courses of mechanical and electrical events in longstanding diabetes was investigated in rats. Magnetic markers and electrodes were surgically implanted in the gastric serosa of male rats. Simultaneous recordings were obtained by AC biosusceptometry, electromyography and electrogastrography one, three and six months after injections of saline (control) or alloxan (diabetic). Frequency and amplitude of contraction, abnormal rhythmic index and half-bandwidth were obtained (ANOVA P < 0.05). Antral hypomotility and gastric motility instability were observed in the signal waveform of diabetic rats at the three time points of study. The mean frequency (4.4 ± 0.4 cpm) was strictly similar, but the mechanical and electrical correlation was lowest for diabetics groups. Decreases in mechanical amplitude were observed for all diabetic groups compared with control; also the ranges of frequency were much wider in diabetes. The half-bandwidth increased since the first month in mechanical recordings and only after the third month in electrical. In diabetic animals, about 40% of gastric activity was abnormal (against 12% in control) and may reach 60% in the sixth month of mechanical recordings. The multi-instrumental approach showed a more substantial deterioration in mechanical activity and created an integrative view of gastric motility for longstanding diabetic model.

Exfoliative cytology of the oral mucosa in type II diabetic patients: morphology and cytomorphometry.

BACKGROUND: In recent years, important advances have occurred in the determination of diagnostic criteria for the disease diabetes mellitus and in new strategies for its treatment. The purpose of this research was to develop a new method for diabetes diagnosis by microscopic and cytomorphometric analyses of the oral epithelium. METHODS: The smears were obtained from three distinct oral sites: buccal mucosa (cheek), tongue dorsum, and floor of the mouth in 10 control individuals and 10 type II diabetic patients. The oral smears were stained with Papanicolaou EA-36 solution. The nuclear (NA) and cytoplasmic (CA) areas were evaluated from 50 integral cells predominant in each oral site by the use of the KS 300 image analysis system (Carl Zeiss, Germany), by which the cytoplasmic/nuclear ratio (C/N) was calculated. RESULTS: The results showed that: (i) the epithelial cells of the diabetic group exhibited figures of binucleation and occasional karyorrhexis in all layers; (ii) the NA was markedly higher (P < 0.05) in the diabetic group; (iii) the CA did not exhibit a statistically significant difference (P > 0.05) between these two groups; and (iv) the C/N mean was 37.4% lower in the type II diabetic group. CONCLUSIONS: These results associated with clinical observations suggest that diabetes mellitus can produce alterations in oral epithelial cells, detectable by microscopy and cytomorphometry, which can be used in the diagnosis of this disease.