long term administration of low doses of mycotoxins in poultry 1 residues of ochratoxin a in broilers and laying hens

Abstract The occurrence and amount of residues of ochratoxin A (OA) in poultry tissues and organs were investigated in a trial aimed at measuring the effects of contamination approaching the patterns more frequently found in natural situations (i.e., small doses of OA in the diet for long periods). Hubbard male broilers and laying hens were treated with an OA-contaminated feed (50 ppb) from the 14th day of age onward. Both groups were further divided into subgroups, some of which underwent continual treatment (64 and 169 days, respectively) and others that were withdrawn from administration (maximum 28 and 82 days, respectively). Determination of residues was performed by high performance liquid chromatography. Residues in liver were higher in broilers (up to 11.0 ppb) than in hens (1.5 ppb), whereas the reverse occurred in kidney (up to .8 and 5.8 ppb, respectively). Residues (.8 ppb) were also in hen thigh muscle but not in breast muscle. Residues of OA in poultry appear to be of possible public health concern. Suggestions for monitoring are given

H3 histamine receptor-mediated activation of protein kinase calpha inhibits the growth of cholangiocarcinoma in vitro and in vivo

Histamine regulates functions via four receptors (HRH1, HRH2, HRH3, and HRH4). The D-myo-inositol 1,4,5-trisphosphate (IP(3))/Ca(2+)/protein kinase C (PKC)/mitogen-activated protein kinase pathway regulates cholangiocarcinoma growth. We evaluated the role of HRH3 in the regulation of cholangiocarcinoma growth. Expression of HRH3 in intrahepatic and extrahepatic cell lines, normal cholangiocytes, and human tissue arrays was measured. In Mz-ChA-1 cells stimulated with (R)-(alpha)-(-)-methylhistamine dihydrobromide (RAMH), we measured (a) cell growth, (b) IP(3) and cyclic AMP levels, and (c) phosphorylation of PKC and mitogen-activated protein kinase isoforms. Localization of PKC alpha was visualized by immunofluorescence in cell smears and immunoblotting for PKC alpha in cytosol and membrane fractions. Following knockdown of PKC alpha, Mz-ChA-1 cells were stimulated with RAMH before evaluating cell growth and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation. In vivo experiments were done in BALB/c nude mice. Mice were treated with saline or RAMH for 44 days and tumor volume was measured. Tumors were excised and evaluated for proliferation, apoptosis, and expression of PKC alpha, vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF receptor 2, and VEGF receptor 3. HRH3 expression was found in all cells. RAMH inhibited the growth of cholangiocarcinoma cells. RAMH increased IP(3) levels and PKC alpha phosphorylation and decreased ERK1/2 phosphorylation. RAMH induced a shift in the localization of PKC alpha expression from the cytosolic domain into the membrane region of Mz-ChA-1 cells. Silencing of PKC alpha prevented RAMH inhibition of Mz-ChA-1 cell growth and ablated RAMH effects on ERK1/2 phosphorylation. In vivo, RAMH decreased tumor growth and expression of VEGF and its receptors; PKC alpha expression was increased. RAMH inhibits cholangiocarcinoma growth by PKC alpha-dependent ERK1/2 dephosphorylation. Modulation of PKC alpha by histamine receptors may be important in regulating cholangiocarcinoma growth. (Mol Cancer Res 2009;7(10):1704-13

Quasi-simultaneous INTEGRAL, SWIFT, and NuSTAR Observations of the New X-Ray Clocked Burster 1RXS J180408.9-342058

We report the quasi-simultaneous INTEGRAL, SWIFT, and NuSTAR observations showing spectral state transitions in the neutron star low-mass X-ray binary 1RXS J180408.9−342058 during its 2015 outburst. We present results of the analysis of high-quality broad energy band (0.8–200 keV) data in three different spectral states: high/soft, low/very-hard, and transitional state. The broadband spectra can be described in general as the sum of thermal Comptonization and reflection due to illumination of an optically thick accretion disk. During the high/soft state, blackbody emission is generated from the accretion disk and the surface of the neutron star. This emission, measured at a temperature of kT_(bb) ~ 1.2 keV, is then Comptonized by a thick corona with an electron temperature of ~2.5 keV. For the transitional and low/very-hard state, the spectra are successfully explained with emission from a double Comptonizing corona. The first component is described by thermal Comptonization of seed disk/neutron star photons (kT_(bb) ~ 1.2 keV) by a cold corona cloud with kT_e ~ 8–10 keV, while the second one originates from lower temperature blackbody photons (kT_(bb) ≤ 0.1 keV) Comptonized by a hot corona (kT_e ~ 35 keV). Finally, from NuSTAR observations, there is evidence that the source is a new clocked burster. The average time between two successive X-ray bursts corresponds to ~7.9 and ~4.0 ks when the persistent emission decreases by a factor of ~2, moving from a very hard to transitional state. The accretion rate (~4 x 10⁻⁹ M⊙ yr ⁻¹) and the decay time of the X-ray bursts longer than ~30 s suggest that the thermonuclear emission is due to mixed H/He burning triggered by thermally unstable He ignition

The emerging role of ferroptosis in liver cancers

: Liver cancer represents a global health challenge with worldwide growth. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Indeed, approximately 90% of HCC cases have a low survival rate. Moreover, cholangiocarcinoma (CC) is another malignant solid tumor originating from cholangiocytes, the epithelial cells of the biliary system. It is the second-most common primary liver tumor, with an increasing course in morbidity and mortality. Tumor cells always show high metabolic levels, antioxidant modifications, and an increased iron uptake to maintain unlimited growth. In recent years, alterations in iron metabolism have been shown to play an important role in the pathogenesis of HCC. Several findings show that a diet rich in iron can enhance HCC risk. Hence, elevated iron concentration inside the cell may promote the development of HCC. Growing evidence sustains that activating ferroptosis may potentially block the proliferation of HCC cells. Even in CC, it has been shown that ferroptosis plays a crucial role in the treatment of tumors. Several data confirmed the inhibitory effect in cell growth of photodynamic therapy (PDT) that can induce reactive oxygen species (ROS) in CC, leading to an increase in malondialdehyde (MDA) and a decrease in intracellular glutathione (GSH). MDA and GSH depletion/modulation are crucial in inducing ferroptosis, suggesting that PDT may have the potential to induce this kind of cell death through these ways. A selective induction of programmed cell death in cancer cells is one of the main treatments for malignant tumors; thus, ferroptosis may represent a novel therapeutic strategy against HCC and CC

Viral hepatitis and iron dysregulation: molecular pathways and the role of lactoferrin

The liver is a frontline immune site specifically designed to check and detect potential pathogens from the bloodstream to maintain a general state of immune hyporesponsiveness. One of the main functions of the liver is the regulation of iron homeostasis. The liver detects changes in systemic iron requirements and can regulate its concentration. Pathological states lead to the dysregulation of iron homeostasis which, in turn, can promote infectious and inflammatory processes. In this context, hepatic viruses deviate hepatocytes' iron metabolism in order to better replicate. Indeed, some viruses are able to alter the expression of iron-related proteins or exploit host receptors to enter inside host cells. Lactoferrin (Lf), a multifunctional iron-binding glycoprotein belonging to the innate immunity, is endowed with potent antiviral activity, mainly related to its ability to block viral entry into host cells by interacting with viral and/or cell surface receptors. Moreover, Lf can act as an iron scavenger by both direct iron-chelation or the modulation of the main iron-related proteins. In this review, the complex interplay between viral hepatitis, iron homeostasis, and inflammation as well as the role of Lf are outlined

Distinct EpCAM-Positive stem cell niches are engaged in chronic and neoplastic liver diseases

In normal human livers, EpCAMpos cells are mostly restricted in two distinct niches, which are (i) the bile ductules and (ii) the mucous glands present inside the wall of large intrahepatic bile ducts (the so-called peribiliary glands). These EpCAMpos cell niches have been proven to harbor stem/progenitor cells with great importance in liver and biliary tree regeneration and in the pathophysiology of human diseases. The EpCAMpos progenitor cells within bile ductules are engaged in driving regenerative processes in chronic diseases affecting hepatocytes or interlobular bile ducts. The EpCAMpos population within peribiliary glands is activated when regenerative needs are finalized to repair large intra- or extra-hepatic bile ducts affected by chronic pathologies, including primary sclerosing cholangitis and ischemia-induced cholangiopathies after orthotopic liver transplantation. Finally, the presence of distinct EpCAMpos cell populations may explain the histological and molecular heterogeneity characterizing cholangiocarcinoma, based on the concept of multiple candidate cells of origin. This review aimed to describe the precise anatomical distribution of EpCAMpos populations within the liver and the biliary tree and to discuss their contribution in the pathophysiology of human liver diseases, as well as their potential role in regenerative medicine of the liver

Chronic MPTP in Mice Damage-specific Neuronal Phenotypes within Dorsal Laminae of the Spinal Cord

The neurotoxin 1-methyl, 4-phenyl, 1, 2, 3, 6-tetrahydropiridine (MPTP) is widely used to produce experimental parkinsonism. Such a disease is characterized by neuronal damage in multiple regions beyond the nigrostriatal pathway including the spinal cord. The neurotoxin MPTP damages spinal motor neurons. So far, in Parkinson’s disease (PD) patients alpha-synuclein aggregates are described in the dorsal horn of the spinal cord. Nonetheless, no experimental investigation was carried out to document whether MPTP affects the sensory compartment of the spinal cord. Thus, in the present study, we investigated whether chronic exposure to small doses of MPTP (5 mg/kg/X2, daily, for 21 days) produces any pathological effect within dorsal spinal cord. This mild neurotoxic protocol produces a damage only to nigrostriatal dopamine (DA) axon terminals with no decrease in DA nigral neurons assessed by quantitative stereology. In these experimental conditions we documented a decrease in enkephalin-, calretinin-, calbindin D28K-, and parvalbumin-positive neurons within lamina I and II and the outer lamina III. Met-Enkephalin and substance P positive fibers are reduced in laminae I and II of chronically MPTP-treated mice. In contrast, as reported in PD patients, alpha-synuclein is markedly increased within spared neurons and fibers of lamina I and II after MPTP exposure. This is the first evidence that experimental parkinsonism produces the loss of specific neurons of the dorsal spinal cord, which are likely to be involved in sensory transmission and in pain modulation providing an experimental correlate for sensory and pain alterations in PD

“Full factorial design of experiments dataset for parallel-connected lithium-ion cells imbalanced performance investigation”

This paper shares an experimental dataset of lithium-ion battery parallel-connected modules. The campaign, conducted at the Stanford Energy Control Laboratory, employs a comprehensive full factorial Design of Experiment methodology on ladder-configured parallel strings. A total of 54 test conditions were investigated under various operating temperatures, cell-to-cell interconnection resistance, cell chemistry, and aging levels. The module-level testing procedure involved Constant Current Constant Voltage (CC-CV) charging and Constant Current (CC) discharge. Beyond monitoring total module current and voltage, Hall sensors and thermocouples were employed to measure the signals from each individual cell to quantify both current and temperature distribution within each tested module configuration. Additionally, the dataset contains cell characterization data for every cell (i.e. NCA Samsung INR21700-50E and NMC LG-Chem INR21700-M50T) used in the module-level experiments. This dataset provides valuable resources for developing battery physics-based, empirical, and data-driven models at single cell and module level. Ultimately, it contributes to advance our understanding of how cell-to-cell heterogeneity propagates within the module and how that affects the overall system performance

Different iron-handling in inflamed small and large cholangiocytes and in small and large-duct type intrahepatic cholangiocarcinoma

Cholangiocarcinoma (CCA) represents the second most common primary hepatic malignancy and originates from the neoplastic transformation of the biliary cells. The intrahepatic subtype includes two morpho-molecular forms: large-duct type intrahepatic CCA (iCCA) and small-duct type iCCA. Iron is fundamental for the cellular processes, contributing in tumor development and progression. The aim of this study was to evaluate iron uptake, storage, and efflux proteins in both lipopolysaccharide-inflamed small and large cholangiocytes as well as in different iCCA subtypes. Our results show that, despite an increase in interleukin-6 production by both small and large cholangiocytes, ferroportin (Fpn) was decreased only in small cholangiocytes, whereas transferrin receptor-1 (TfR1) and ferritin (Ftn) did not show any change. Differently from in vitro models, Fpn expression was increased in malignant cholangiocytes of small-duct type iCCA in comparison to large-duct type iCCA and peritumoral tissues. TfR1, Ftn and hepcidin were enhanced, even if at different extent, in both malignant cholangiocytes in comparison to the surrounding samples. Lactoferrin was higher in large-duct type iCCA in respect to small-duct type iCCA and peritumoral tissues. These findings show a different iron handling by inflamed small and large cholangiocytes, and small and large-duct type iCCA. The difference in iron homeostasis by the iCCA subtypes may have implications for the tumor management

Integrated Geomatic Techniques for Georeferencing and Reconstructing the Position of Underground Archaeological Sites: The Case Study of the Augustus Sundial (Rome)

A large part of the archaeological remains still to be discovered and excavated are not in remote and depopulated areas of the earth but are often beneath urban centres that have buried them with centuries of debris and later constructions. Excavating in these contexts is much more complex than digging in rural or sparsely inhabited areas because of the constraints imposed by existing buildings and infrastructure. It should also be considered that within an urbanised area, any archaeological remains are concentrated in the subsoil of the historic centre, which is, therefore, often surmounted by buildings that are more recent than the remains but historical as well, and thus, of considerable value and vulnerability. For this reason, an archaeological excavation in an urban area must be preceded by a real feasibility study, where the potential risks for the structures above are minimised and accurately quantified. In many situations, as in the case under study, the discovery of a small segment of a structure is the only clue to reconstruct the development of the remaining part still to be excavated, which may stretch tens or hundreds of metres away from the measurable part. As a consequence, an error of a few centimetres in the survey of the excavated part can lead to errors of metres in estimating the positions of the far parts still to be excavated, and this, in many cases, as in the one under study, must absolutely be avoided. In practice, high-precision geomatic surveys, in support of the archaeological and historical interpretation of the observable structures, will help to establish the exact locations to possibly continue the excavations, helping the accurate planning of the excavation itself. Here, we have shown how the various techniques, compared to each other, have made it possible to reconstruct the location of a short stretch (less than 7 metres) of the Emperor Augustus' Sundial, the only currently visible evidence of a scientific instrument of imposing dimensions (tens of metres in length and height) that served to define some of the characteristics of the calendar that we still use today. The portion of the sundial currently observable, according to the most reliable hypotheses, is located approximately at one end of a structure and extends for several tens of metres. The accurate positioning of the observable parts in a geodetic reference system will enable to identify with certainty the possible areas in which excavation may continue and will also allow to accurately reconstruct the principle of operation of the sundial through an approach that could be defined as "reverse engineering" of the scientific instrument itself. The aim of this work is to study and thus define the combination and integration of existing geomatic techniques for this specific field of applicatio