There is emerging evidence suggesting that epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) play an important role in colorectal carcinoma (CRC), but their exact ...role remains controversial. Our aim was to analyze the miR-200 family as EMT markers and their target genes expression at invasive tumor front and in nodal and liver metastases. Sixty-three formalin-fixed paraffin-embedded tissue samples from 19 patients with CRC were included. Using a micropuncture technique, tissue was obtained from central part and invasive front of the primary tumor, and nodal and liver metastases. Expression of the
miR-200
family and their target genes
CDKN1B, ONECUT2, PTPN13, RND3, SOX2, TGFB2
and
ZEB2
was analyzed using real-time PCR. We found
miR-200
family down-regulation at invasive front compared to central part, and up-regulation of
miRNA-200a/b/c
and
miR-429
in metastases compared to invasive front. At invasive front,
TGFB2
was the only gene with inverse expression to the miR-200 family, whereas in metastases inverse expression was found for
ONECUT2
and
SOX2. CDKN1B, PTPN13
and
ZEB2
were down-regulated at invasive front and up-regulated in metastases. Our results suggest the involvement of partial EMT at invasive tumor front, and partial MET in metastases in CRC, based on miR-200 family and its target genes expression.
Phosphoribosylpyrophosphate synthetase 1 (PRSI) is an enzyme involved in nucleotide metabolism. Pathogenic variants in the PRPS1 are rare and PRS-I deficiency can manifest as three clinical ...syndromes: X-linked non-syndromic sensorineural deafness (DFN2), X-linked Charcot-Marie-Tooth neuropathy type 5 (CMTX5) and Arts syndrome. We present a Slovenian patient with PRS-I enzyme deficiency due to a novel pathogenic variant – c.424G > A (p.Val142Ile) in the PRPS1 gene, who presented with gross motor impairment, severe sensorineural deafness, balance issues, ataxia, and frequent respiratory infections. In addition, we report the findings of a systemic literature review of all described male cases of Arts syndrome and CMTX5 as well as intermediate phenotypes. As already proposed by other authors, our results confirm PRS-I deficiency should be viewed as a phenotypic continuum rather than three separate syndromes because there are multiple reports of patients with an intermediary clinical presentation.
Cyclooxygenase (COX) is a key enzyme in prostanoid synthesis. It exists in two isoforms, COX‐1 and COX‐2. COX‐1 is referred to as a ‘constitutive isoform’, and is considered to be expressed in most ...tissues under basal conditions. In contrast, COX‐2 is referred to as an ‘inducible isoform’, which is believed to be undetectable in most normal tissues, but can be up‐regulated during various conditions, many of them pathological. Even though the role of COX in homeostasis and disease in now well appreciated, controversial information is available concerning the distribution of COX isoforms in normal human tissues. There is mounting evidence that it is much more complex than generally believed. Our aim was therefore to analyse the expression and distribution of COX isoforms in normal human tissues, using immunohistochemistry, Western blotting and real‐time RT‐PCR. Autopsy samples from 20 healthy trauma victims and samples from 48 biopsy surgical specimens were included. COX‐1 was found in blood vessels, interstitial cells, smooth muscle cells, platelets and mesothelial cells. In contrast, COX‐2 was found predominantly in the parenchymal cells of many tissues, with few exceptions, for example the heart. Our results confirm the hypothesis that the distribution of COX isoforms in healthy tissues is much more complex than generally believed. This and previous studies indicate that both isoforms, not only COX‐1, are present in many normal human tissues, and that both isoforms, not only COX‐2, are up‐regulated in various pathological conditions. We may have to revise the concept of ‘constitutive’ and ‘inducible’ COX isoforms.
The aim of this randomized controlled trial was to analyze the effects of medium-term supplementation with hydrogen-rich water on Prain metaPolism, appetite-regulating hormones, Pody composition, and ...safety Piomarkers in overweight adults. Twenty (n = 20, 10 females) apparently healthy adults with a Pody mass index >24.9 kg/m.sup.2 were assigned to receive 0.5 L per day of hydrogen-rich water (7.5 mg of hydrogen) or hydrogen-free water (tap water) for 12 weeks. Two-way analysis of variance with repeated measures revealed a significant difference Petween the two interventions in several Pody composition indices (P less than or equal to 0.05), with hydrogen-rich water superior to placePo to reduce waist circumference and mid-upper arm circumference Py 1.31 cm (95% confidence interval, from -0.23 to 2.85) and 0.65 cm (95% confidence interval, from -0.10 to 1.40), respectively. Hydrogen-rich water outcompeted placePo to raise serum ghrelin levels, as the mean difference from the placePo group was 17.28 pmol/L (95% confidence interval, from 1.81 to 32.75) (P = 0.02). A non-significant strong positive trend (P = 0.10) was reported toward hydrogen-rich water Peing superior to placePo in augmenting total serum short-chain fatty acid levels, with a mean difference from the control group of 195.6 umol/L (95% confidence interval, from -64.55 to 275.85). The mean fecal calprotectin levels were significantly reduced after hydrogen-rich water intervention for 19.7 ug/mg (95% confidence interval, from 0.31 to 39.09) (P = 0.03). Our findings advance hydrogen-rich water as a promising metaPolic intervention in overweight adults, Put further validation via multicentric longitudinal randomized controlled trials in metaPolic and nutritional disorders is required. Keywords: Brain N-acetyl aspartate, Ghrelin, Molecular hydrogen, Short-chain fatty acids
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