Maternal and Fetal Metabolites in Gestational Diabetes Mellitus: A Narrative Review.

Gestational diabetes mellitus (GDM) is a major public health issue of our century due to its increasing prevalence, affecting 5% to 20% of all pregnancies. The pathogenesis of GDM has not been completely elucidated to date. Increasing evidence suggests the association of environmental factors with genetic and epigenetic factors in the development of GDM. So far, several metabolomics studies have investigated metabolic disruptions associated with GDM. The aim of this review is to highlight the usefulness of maternal metabolites as diagnosis markers of GDM as well as the importance of both maternal and fetal metabolites as prognosis biomarkers for GDM and GDM's transition to type 2 diabetes mellitus T2DM.

Subtle Immunoreactivity Differences in the Fractal Patterns of Membrane E-Cadherin in Gastric Adenocarcinoma.

Gastric cancer continues to be a significant malignancy worldwide, accounting for approximately one million new cases in 2020. Scientists are focusing on the cancerous cells' plasma membrane (PM) as a potential therapeutic target in cancer because it functions as the cell's interface with its environment through a variety of mechanisms. The capacity of membrane shape and its structures to influence biological processes frequently occurs through the regulation of enzymes or preferential protein binding to membranes via membrane shape changes. We aimed here to assess the morphological irregularities of the cellular membranes in gastric adenocarcinoma tumors, and to find any putative differences from normal gastric mucosae epithelial cells. We analyzed the pattern of E-cadherin at the level of the cell membrane using the fractal dimension (FD) analysis on fluorescence immunohistochemistry samples labeled with E-cadherin in gastric well/moderate and solid gastric adenocarcinoma from patients without any associated chemotherapeutic treatment or radiotherapy. Images were binarized based on a fixed threshold of the E-cadherin fluorescence channel, and then the FD of the binarized image outlines has been calculated in order to assess the ruggedness of the cellular membranes. Overall assessment of the FD revealed that the subtle membrane variations were evident enough to deem a statistically significant difference and the complexity of the membrane roughness was clearly higher for adenocarcinoma cases. We intended to evaluate if separating adenocarcinoma cases as low grade (G1 and G2) and high grade (G3 and solid), FD analysis could still differentiate membrane patterns and check if the available clinical parameters like age, gender, tumor location, lymph ganglia involved might correlate with FD values for adenocarcinoma patients. Altogether, the morphological analysis of a simple marker for the cell membrane can identify and distinguish tumor cells. Although there was a limited correlation between this analysis and the main clinical and pathological indicators of the disease, it will be very useful in the future for automatic computer-assisted diagnosis on slides, as well as for evaluating cellular adhesion and inter-cellular trafficking in cancer cells.

Systemic and adipose tissue inflammation in NASH: correlations with histopathological aspects.

INTRODUCTION: Non-alcoholic steatohepatitis (NASH) is a progressive form of liver steatosis that involves a risk of progression towards fibrosis, cirrhosis, and end-stage liver disease. Low-grade inflammation is recognized to be involved in non-alcoholic fatty liver disease (NAFLD) pathogeny. Additionally, adipose tissue dysfunction plays an important role in the development of metabolic diseases. PATIENTS, MATERIALS AND METHODS: We conducted a study on 68 patients with liver steatosis confirmed through liver biopsy during the surgery. In all the patients, we recorded anthropometric parameters and we performed blood tests for systemic inflammation [high-sensitivity C-reactive protein (hs-CRP), fibrinogen] and serum adipokines related to adipose tissue inflammation (leptin, adiponectin). Additional to histopathological examination, we also performed the immunohistochemical study of inflammatory mononuclear cells. RESULTS: The 68 patients had a mean age of 56.57±4.94 years old, had a mean value of hs-CRP of 2.30±0.91 mg∕L, a mean value of leptin of 14.02±17.02 ng∕mL and a mean value of adiponectin of 7.54±0.38 mg∕L. In all the cases studied by liver biopsy, the steatosis exceeded 5% of hepatocytes, but the frequency of NASH was 26.47%. Cluster of differentiation (CD)45-positive, CD4-positive, and CD8-positive T-lymphocytes predominated in the studied cases. We obtained a statistically significant high association between definite NASH and the values of hs-CRP, serum adiponectin and leptin∕adiponectin ratio (p<0.0001). CONCLUSIONS: Systemic and adipose tissue inflammation was statistically significant associated with histological lesions of steatosis and NASH, suggesting that the determination of hs-CRP and serum adipokines in dynamics in patients with NAFLD is predictive for the progression of the disease.

Immunoexpression of Snail, Twist1 and Slug in clear cell renal cell carcinoma.

Clear cell renal cell carcinomas (ccRCC) represent about 80% of the malignant neoplasia with this localization. Snail, Twist1 and Slug are transcription factors and play a central role in the epithelial-mesenchymal transition (EMT), which is involved in the progression of renal cell carcinoma (RCC). In this study, we analyzed the immunoexpression of these transcription factors in 50 cases of ccRCC, in relation to histopathological aggressiveness parameters of the lesions. The results indicated the association of Snail and Twist1 expression with high Fuhrman grade, as well as the association of Slug expression with low Fuhrman grade. The immunoexpression of Snail and Twist1 was significantly superior for advanced stages and Slug was overexpressed in early stages of ccRCC. Our study supports the usefulness of the Snail, Twist1 and Slug expression for the appreciation of aggressiveness in ccRCC, the panel being attractive for targeted therapy.

Immunoexpression of E-cadherin, P-cadherin and fibronectin in gastric carcinomas.

One of the mechanisms involved in gastric carcinomas progression is represented by epithelial-mesenchymal transition (EMT), a complex process during which tumor cells acquire an invasive and migratory mesenchymal phenotype. In this study, we analyzed the immunoexpression of E-cadherin, P-cadherin and fibronectin in 50 gastric carcinomas, in relation with the tumoral type, differentiation grade and lesions stage. The reactions presented variable patterns related to lesions stage. Membrane and cytoplasmic reactions were present in 62% of cases for E-cadherin and in 56% of cases for P-cadherin, being present only cytoplasmic in 34% of cases for fibronectin. The immunoexpression for E-cadherin and P-cadherin was superior in tubular gastric carcinomas, of low grade and early stage, while fibronectin expression was superior in discohesive or mixed gastric carcinomas, of high grade and in advanced stages. Negative E-∕P-cadherin and positive fibronectin immunophenotype may be associated with aggressive gastric carcinomas and supports the EMT involvement in gastric carcinogenesis.

Vertebral bone metastasis in breast cancer: a case report.

BACKGROUND: We report here a case of a 66-year-old woman with a very aggressive form of breast carcinoma, having both liver and bone dissemination points. CASE DESCRIPTION: The patient was admitted for a rapid onset disk-herniation-like syndrome, but which on further investigation proved to be in fact a metastatic case of breast cancer. We found evidence of disseminations at least in the lumbar vertebral bodies and the liver. Pathological analysis of the available vertebral metastasis revealed a HER2+ molecular pattern, accordingly to the newly evolving molecular typing of breast cancers. Despite a rapid treatment instauration, the patient reacted poorly to taxanes and octeoclast inhibitors, and died after less than 11 months from admitting to the hospital. CONCLUSIONS: This is a rare case of an aggressive breast carcinoma identified initially after the vertebral metastases themselves that induced a non-specific symptomatology.