Intrapartum foetal heart rate decelerations are physiological adaptations to hypoxia: a critical appraisal of the recent evidence

Electronic intrapartum foetal monitoring (also known as cardiotocography, CTG) is the standard technique to assess the foetal well-being during labour. In the last decade, several researchers have provided useful information regarding the pathophysiology of foetal heart rate (FHR) decelerations, the main CTG feature to cause interpretation disagreement; recent evidence summarized in this paper set new grounds to reconceptualize the “classical” aetiology of intrapartum foetal hypoxia and FHR decelerations. Each deceleration is generated from hypoxia, and it is the dynamic pattern of these decelerations that gives information about the status of metabolic and cardiac adaption mechanism of the foetus. The relationship to uterine contractions or the morphology of deceleration should no longer be used to discriminate a reassuring or non-reassuring CTG trace

LonP1 Differently Modulates Mitochondrial Function and Bioenergetics of Primary Versus Metastatic Colon Cancer Cells

Mitochondrial Lon protease (LonP1) is a multi-function enzyme that regulates mitochondrial functions in several human malignancies, including colorectal cancer (CRC). The mechanism(s) by which LonP1 contributes to colorectal carcinogenesis is not fully understood. We found that silencing LonP1 leads to severe mitochondrial impairment and apoptosis in colon cancer cells. Here, we investigate the role of LonP1 in mitochondrial functions, metabolism, and epithelial-mesenchymal transition (EMT) in colon tumor cells and in metastasis. LonP1 was almost absent in normal mucosa, gradually increased from aberrant crypt foci to adenoma, and was most abundant in CRC. Moreover, LonP1 was preferentially upregulated in colorectal samples with mutated p53 or nuclear \u3b2-catenin, and its overexpression led to increased levels of \u3b2-catenin and decreased levels of E-cadherin, key proteins in EMT, in vitro. LonP1 upregulation also induced opposite changes in oxidative phosphorylation, glycolysis, and pentose pathway in SW480 primary colon tumor cells when compared to SW620 metastatic colon cancer cells. In conclusion, basal LonP1 expression is essential for normal mitochondrial function, and increased LonP1 levels in SW480 and SW620 cells induce a metabolic shift toward glycolysis, leading to EMT

Physical mechanical consolidation and protection of Miocenic limestone used on Mediterranean historical monuments: the case study of Pietra Cantone (southern Sardinia, Italy)

The present work aims to study the consolidating and protective chemical treatments of the Pietra Cantone, a Miocenic (lower Tortonian) limestone widely used in important monuments and historical buildings of Cagliari (southern Sardinia, Italy). Similar limestones of the same geological period have also been used in several important monuments of Mediterranean area, i.e., Malta and Gozo Islands, Matera (central Basilicata, Italy), Lecce (southern Puglia, Italy) and Balearic Islands (Spain). The Pietra Cantone limestone shows problems of chemical–physical decay, due to their petrophysical and compositional char- acteristics: high porosity (on average 28–36 vol%), low cemented muddy-carbonate matrix, presence of phyllosil- icates and sindepositional sea salts (\3%). So, after placed in the monument, this stone is easily alterable by weath- ering chemical processes (e.g., carbonate dissolution and sulfation) and also by cyclic mechanisms of crystalliza- tion/solubilization of salts and hydration/dehydration of hygroscopic phases of the clay component. To define the mineralogical-petrographic features (composition, texture) of limestone, the clay and salt crystalline phases, the optical microscope in polarized light and diffraction anal- ysis were used. To define the petrophysical characteristics (i.e., shape and size distribution of porosity, surface area(SBET), matrix microstructures, rock composition) and interactions of chemical treatments with rock, SEM–EDS analysis and N2 porosimetry with BET and BJH methods were used. To evaluate the efficacy of Na/K-silicates, ethyl silicate consolidants and protective nano-molecular silane monomer water repellent, the mechanical strengths (uni- axial compressive strength, point load and flexural resis- tance), water/helium open porosity, water absorption and vapour permeability data determined before and after the chemical treatments of the Pietra Cantone samples from monument were compared

In vitro digested milk proteins: Evaluation of angiotensin-1-converting enzyme inhibitory and antioxidant activities, peptidomic profile, and mucin gene expression in HT29-MTX cells

Over the past decades, several studies investigated the health-promoting functions of milk peptides. However, to date many hurdles still exist regarding the widespread use of milk-derived bioactive peptides, as they may be degraded during gastrointestinal digestion. Thus, the aim of our study was to in vitro digest intact whey protein isolate (WPI) and casein proteins (CNP), mimicking in vivo digestion, to investigate their bioactive effects and to identify the potential peptides involved. Whey protein isolate and CNP were digested using a pepsin-pancreatin protocol and ultra-filtered (3-kDa cutoff membrane). A permeate (3 kDa) were obtained. Soy protein was included as a control (CTR). Angiotensin-1-converting enzyme inhibitory (ACE1-I) and antioxidant activity (AOX) were assessed and compared with those observed in undigested proteins and CTR. Furthermore, the permeate was characterized by nano-liquid chromatography electrospray ionization tandem mass spectrometry (LC-nano ESI MS/MS) using a shotgun peptidomic approach, and retentate was further digested with trypsin and analyzed by MS using a shotgun proteomic approach to identify potentially bioactive peptides. Further, the effects of WPI, CNP, and CTR retentate on cell metabolic activity and on mucus production (MUC5AC and MUC2 gene expression) were assessed in intestinal goblet HT29-MTX-E12 cells. Results showed that WPI permeate induced a significant ACE1-I inhibitory effect [49.2 ± 0.64% (SEM)] compared with undigested WPI, CNP permeate, and retentate or CTR permeate (10.40 ± 1.07%). A significant increase in AOX (1.58 ± 0.04 and 1.61 ± 0.02 µmol of trolox AOX equivalents per mg of protein, respectively) upon digestion was found in WPI. Potentially bioactive peptides associated with ACE1-I and antihypertensive effects were identified in WPI permeate and CNP retentate. At specific concentrations, WPI, CNP, and CTR retentate were able to stimulate metabolic activity in HT29-MTX-E12 cells. Expression of MUC5AC was increased by CNP retentate and unaltered by WPI retentate; MUC2 expression was significantly increased by 0.33 mg/g of CNP and reduced by 1.33 mg/g of CNP. Our results confirm that milk proteins may be rich sources of bioactive compounds, with the greatest beneficial potential of CNP at the intestinal goblet cell level

In vitro effects of lactoferrin on intestinal and mammary epithelial cell lines

Lactoferrin is an iron binding glycoprotein endowed with multiple functions, including non-specific immune defence against pathogens, immunomodulatory activity and regulation of cell growth. The gastrointestinal tract of the newborn and the mammary gland are targets of the biological action of lactoferrin. This work aimed at examining the effects of human and bovine lactoferrin on cell growth using intestinal and mammary epithelial cell lines and at evaluating the protective effect of bovine lactoferrin against cytotoxic damage induced by bacterial lipopolysaccharides in a bovine mammary epithelial cell line. It was shown that lactoferrin could be involved in regulating the growth of both intestinal and mammary epithelial cells depending on its concentrations, cell culture conditions and cell line used. The presence of lactoferrin binding sites on the cell surface was also discussed. Moreover, the data obtained suggested that bovine lactoferrin could contribute to counteract the effect of bacterial endotoxins