The neuropeptide 26RFa is expressed in human prostate cancer and stimulates the neuroendocrine differentiation and the migration of androgeno-independent prostate cancer cells

AimAccumulating data suggest that neuropeptides produced by neuroendocrine cells play a crucial role in the progression and aggressiveness of hormone refractory prostate cancer (CaP). In this study, we have investigated the presence and function of the neuropeptide 26RFa in CaP.MethodsWe have localised and quantified tumour cells containing 26RFa and its receptor, GPR103, in CaP sections of various grades. In vitro experiments were performed to investigate the effects of 26RFa on the migration, proliferation and neuroendocrine differentiation of the androgeno-independent (AI) prostate cancer cell line DU145.Results26RFa and GPR103 are present in carcinomatous foci exhibiting a neuroendocrine differentiation, and the number of 26RFa and GPR103-immunoreactive cancer cells increases with the grade of CaP. 26RFa stimulated the migration of native or transdifferentiated AI DU145 cells, but had no effect on their proliferation. Furthermore, 26RFa induced the neuroendocrine differentiation of DU145 cells as assessed by the occurrence of neurite-like extensions and the increase of the expression of the neuroendocrine marker chromogranin A.ConclusionThe present data indicate that 26RFa may participate to the development of CaP at the AI state by promoting the neuroendocrine differentiation and the migration of cancer cells via autocrine/paracrine mechanisms.     

IFNGR2 genetic polymorphism associated with sex-specific paranoid schizophrenia risk

Background: Considering current scientific evidence about the significant role of chronic low grade inflammation in the physiopathology of schizophrenia, it has been hypothesized that changes in pro-inflammatory cytokines such as interferon gamma may have a significant role in the predisposition to schizophrenia.

Aim: This study focuses on identifying whether the functional polymorphism of interferon gamma receptor 2 (IFNGR2) is a risk factor for the development of schizophrenia.

Methods: This study was conducted by the RFLP-PCR on a Tunisian population composed of 225 patients with different sub-types of schizophrenia and 166 controls.

Results: The IFNGR2 (Q64R) polymorphism analysis showed higher frequencies of minor homozygous genotype (RR) and allele (R) in all patients compared to controls (21.8% vs 10.2%; p?=?.006, OR?=?2.54) and (44% vs 34.9%; p?=?.01; OR?=?1.46), respectively. This correlation was confirmed only for males. This study also noted a significant increase of the mutated homozygous (RR) genotype and (R) allele frequencies of IFNGR2 in paranoid schizophrenics compared to controls (31.4% vs 10.2%; p?=?.001; OR?=?3.34 and 47.2% vs 34.9%; p?=?.009; OR?=?1.66, respectively). This increase remains significant after using binary logistic regression to eliminate confounding factors such as age and sex. Additionally, carriers of RR genotype have significant lower scores on the Scale of Assessment of Positive (SAPS) and negative (SANS) symptoms comparatively to the carrier of the QQ?+?QR genotypes, suggesting that the R recessive allele carriers could have milder symptoms.

Conclusion: The IFNGR2Q64R polymorphism is correlated with male sex and paranoid schizophrenia. It is suggested that a chronic neuroinflammation may predispose to the paranoid schizophrenia development in men.     

Three‐dimensional distribution of tyrosine hydroxylase,vasopressin and oxytocin neurones in the transparent postnatal mouse brain

Over the years, advances in immunohistochemistry techniques have been a critical step in detecting and mapping neuromodulatory substances in the central nervous system. The better quality and specificity of primary antibodies, new staining procedures and the spectacular development of imaging technologies have allowed such progress. Very recently, new methods permitting tissue transparency have been successfully used on brain tissues. In the present study, we combined whole‐mount immunostaining for tyrosine hydroxylase (TH), oxytocin (OXT) and arginine vasopressin (AVP), with the iDISCO+ clearing method, light‐sheet microscopy and semi‐automated counting of three‐dimensionally‐labelled neurones to obtain a (3D) distribution of these neuronal populations in a 5‐day postnatal (P5) mouse brain. Segmentation procedure and 3D reconstruction allowed us, with high resolution, to map TH staining of the various catecholaminergic cell groups and their ascending and descending fibre pathways. We show that TH pathways are present in the whole P5 mouse brain, similar to that observed in the adult rat brain. We also provide new information on the postnatal distribution of OXT and AVP immunoreactive cells in the mouse hypothalamus, and show that, compared to AVP neurones, OXT neurones in the supraoptic (SON) and paraventricular (PVN) nuclei are not yet mature in the early postnatal period. 3D semi‐automatic quantitative analysis of the PVN reveals that OXT cell bodies are more numerous than AVP neurones, although their immunoreactive soma have a volume half smaller. More AVP nerve fibres compared to OXT were observed in the PVN and the retrochiasmatic area. In conclusion, the results of the present study demonstrate the utility and the potency of imaging large brain tissues with clearing procedures coupled to novel 3D imaging technologies to study, localise and quantify neurotransmitter substances involved in brain and neuroendocrine functions.     

A potential role for the secretogranin II‐derived peptide EM66 in the hypothalamic regulation of feeding behaviour

EM66 is a conserved 66‐amino acid peptide derived from secretogranin II (SgII), a member of the granin protein family. EM66 is widely distributed in secretory granules of endocrine and neuroendocrine cells, as well as in hypothalamic neurones. Although EM66 is abundant in the hypothalamus, its physiological function remains to be determined. The present study aimed to investigate a possible involvement of EM66 in the hypothalamic regulation of feeding behaviour. We show that i.c.v. administration of EM66 induces a drastic dose‐dependent inhibition of food intake in mice deprived of food for 18 hours, which is associated with an increase of hypothalamic pro‐opiomelanocortin (POMC) and melanocortin‐3 receptor mRNA levels and c‐Fos immunoreactivity in the POMC neurones of the arcuate nucleus. By contrast, i.c.v. injection of EM66 does not alter the hypothalamic expression of neuropeptide Y (NPY), or that of its Y1 and Y5 receptors. A 3‐month high‐fat diet (HFD) leads to an important decrease of POMC and SgII mRNA levels in the hypothalamus, whereas NPY gene expression is not affected. Finally, we show that a 48 hours of fasting in HFD mice decreases the expression of POMC and SgII mRNA, which is not observed in mice fed a standard chow. Taken together, the present findings support the view that EM66 is a novel anorexigenic neuropeptide regulating hypothalamic feeding behaviour, at least in part, by activating the POMC neurones of the arcuate nucleus.     

A Clinical and Echocardiographic Score to Identify Pulmonary Hypertension Due to HFpEF

Background

Heart failure with preserved ejection fraction (HFpEF) is a frequent cause of pulmonary hypertension (PH) that is not easy to differentiate from precapillary PH. We aimed to determine whether the characteristic features of the patients may help differentiate between HFpEF and precapillary PH.

A prospective study of one‐carbon metabolism biomarkers and cancer of the head and neck and esophagus

Experimental and epidemiological data suggest that factors of one‐carbon metabolism are important in the pathogenesis of several cancers, but prospective data on head and neck cancer (HNC) and esophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants from 10 countries who donated a blood sample. The current study included 516 cancer cases of the head and neck and esophagus and 516 individually matched controls. Plasma levels of vitamins B2, B6, B9 (folate), B12, and methionine and homocysteine were measured in pre‐diagnostic plasma samples and analyzed in relation to HNC and esophagus cancer risk, as well as post‐diagnosis all‐cause mortality. After controlling for risk factors, study participants with higher levels of homocysteine had elevated risk of HNC, the odds ratio (OR) in conditional analysis when comparing the top and bottom quartiles of homocysteine [OR_{Q4vs. Q1}] being 2.13 (95% confidence interval [95% CI] 1.13–4.00, p for trend 0.009). A slight decrease in HNC risk was also seen among subjects with higher levels of folate (OR_{Q4vs. Q1} 0.63, 95% CI 0.35–1.16, p for trend 0.02). Subgroup analyses by anatomical sub‐site indicated particularly strong associations with circulating homocysteine for oral cavity and gum cancer (p for trend 8 × 10^?4), as well as for oropharynx cancer (p for trend 0.008). Plasma concentrations of the other investigated biomarkers did not display any clear association with risk or survival. In conclusion, study participants with elevated circulating levels of homocysteine had increased risk of developing squamous cell carcinoma of the head and neck.     

Effects of Power and Laser Speed on the Mechanical Properties of AlSi7Mg0.6 Manufactured by Laser Powder Bed Fusion

The AlSi7Mg0.6 alloy, with its good tolerance against strain, is used in laser powder bed fusion (LPBF) to produce parts with complex geometries for aerospace engineering. Production of parts with good mechanical strength requires, however, the optimization of laser parameters. This study thus evaluated the influence of scanning speed, laser power, and strategy on several mechanical properties (tensile/resilience/hardness) to identify an optimal processing region. Results have shown the profound influence of laser power and scanning speed on mechanical properties, with a limited influence from the laser strategy. Tensile strength values ranging from 122 to 394 MPa were obtained, while Young’s Modulus varied from 17 to 29 GPa, and the elongation at break ranged from 2.1 to 9.8%. Surface plots of each property against laser power and speed revealed a region of higher mechanical properties. This region is found when using 50 µm thick layers for energy densities between 25 and 35 J/mm³. Operating at higher values of energy density yielded sub-optimal properties, while a lower energy density resulted in poor performances. Results have shown that any optimization strategy must not only account for the volumic energy density value, but also for laser power itself when thick layers are used for fabrication. This was shown through parts exhibiting reduced mechanical performances that were produced within the optimal energy density range, but at low laser power. By combining mid-speed and power within the optimal region, parts with good microstructure and limited defects such as balling, keyhole pores, and hot cracking will be produced. Heat-treating AlSi7Mg0.6 parts to T6 temper negatively affected mechanical performances. Adapted tempering conditions are thus required if improvements are sought through tempering.     

Protective Effect of Pistacia lentiscus Oil Against Bleomycin-Induced Lung Fibrosis and Oxidative Stress in Rat

We aimed in the present study to investigate the protective effect of Pistacia lentiscus oil against bleomycin-induced lung fibrosis as well as the involvement of oxidative stress in such protection. In this respect, adult male Wistar rats were used and divided into three groups of twenty each: control (NaCl, 0.9%), bleomycin, and bleomycin (4 mg/kg b.w.) + P. lentiscus oil (3 g/kg, b.w.). Animals were pretreated for 30 days before the induction of fibrosis by bleomycin and 1 wk after the induction of fibrosis. The oil principal compounds detected by gas chromatography analysis are: Linoleic and palmitic acids (70.6 and 24.7%, respectively). Our data demonstrated that P. lentiscus oil protected against bleomycin-induced fibrosis as evidenced by TGFβ immunostaining increase in lungs fibrocytes as well as inflammatory infiltrate. We also showed that acute bleomycin-induced fibrosis was accompanied by an oxidative stress in lung tissue as assessed by an increase of lipid peroxidation as well as antioxidant enzyme activities depletion such as superoxide dismutase (SOD) and catalase (CAT). More importantly, P. lentiscus oil treatment reversed all bleomycin-induced oxidative stress parameters disturbances. In conclusion, we suggest that P. lentiscus oil had potent protective effects against bleomycin-induced fibrosis due in part to its antioxidant properties.     

Difficulty in diagnosing acute appendicitis in the presence of acute portal vein thrombosis: the role of CT scan. Report of 2 cases

Acute appendicitis can cause of portal vein thrombosis. Diagnosis of appendicitis can be difficult because its symptoms may be masked by those of acute portal vein thrombosis. We report 2 cases of appendicitis associated with acute portal vein thrombosis whose diagnosis was delayed by several months. The delayed diagnosis of acute appendicitis in the presence of acute portal vein thrombosis can be avoided by using spiral-computed tomography and careful investigation of signs of appendicitis.