CXCL12/SDF-1 from perisynaptic Schwann cells promotes regeneration of injured motor axonterminals

The neuromuscular junction has retained through evolution the capacity to regenerate after damage, but little is known on the inter-cellular signals involved in its functional recovery from trauma, autoimmune attacks, or neurotoxins. We report here that CXCL12, also abbreviated as stromal-derived factor-1 (SDF-1), is produced specifically by perisynaptic Schwann cells following motor axon terminal degeneration induced by -latrotoxin. CXCL12 acts via binding to the neuronal CXCR4 receptor. A CXCL12-neutralizing antibody or a specific CXCR4 inhibitor strongly delays recovery from motor neuron degeneration invivo. Recombinant CXCL12 invivo accelerates neurotransmission rescue upon damage and very effectively stimulates the axon growth of spinal cord motor neurons invitro. These findings indicate that the CXCL12-CXCR4 axis plays an important role in the regeneration of the neuromuscular junction after motor axon injury. The present results have important implications in the effort to find therapeutics and protocols to improve recovery of function after different forms of motor axon terminal damage

Mitochondrial enzyme GLUD2 plays a critical role in glioblastoma progression

Background: Glioblastoma (GBM) is the most frequent and malignant primary brain tumor in adults and despite the progress in surgical procedures and therapy options, the overall survival remains very poor. Glutamate and α-KG are fundamental elements necessary to support the growth and proliferation of GBM cells. Glutamate oxidative deamination, catalyzed by GLUD2, is the predominant pathway for the production of α-KG. Methods: GLUD2 emerged from the RNA-seq analysis of 13 GBM patients, performed in our laboratory and a microarray analysis of 77 high-grade gliomas available on the Geo database. Thereafter, we investigated GLUD2 relevance in cancer cell behavior by GLUD2 overexpression and silencing in two different human GBM cell lines. Finally, we overexpressed GLUD2 in-vivo by using zebrafish embryos and monitored the developing central nervous system. Findings: GLUD2 expression was found associated to the histopathological classification, prognosis and survival of GBM patients. Moreover, through in-vitro functional studies, we showed that differences in GLUD2 expression level affected cell proliferation, migration, invasion, colony formation abilities, cell cycle phases, mitochondrial function and ROS production. In support of these findings, we also demonstrated, with in-vivo studies, that GLUD2 overexpression affects glial cell proliferation without affecting neuronal development in zebrafish embryos. Interpretation: We concluded that GLUD2 overexpression inhibited GBM cell growth suggesting a novel potential drug target for control of GBM progression. The possibility to enhance GLUD2 activity in GBM could result in a blocked/reduced proliferation of GBM cells without affecting the survival of the surrounding neurons

Pathological features and molecular phenotype of mmtv like‐positive feline mammary carcinomas

In the last few years MMTV‐like nucleotide sequences were detected in some feline and canine mammary tumours. Due to the confirmed role of cats in the epidemiology of the MMTV‐like virus, the aim of this study was to investigate the main pathological features of positive feline mammary carcinomas (FMCs). Twenty‐four FMCs were collected at the University of Bologna, submitted to laser microdissection and analysed by nested fluorescence‐PCR using primer sets specific for MMTV env sequence. For immunohistochemistry, an antibody against MMTV protein 14 (p14) was used. MMTV‐like sequences were detected in three out of 24 FMCs (12.5%), one tubular carcinoma, one tubulopapillary carcinoma and one ductal carcinoma. All PCR‐positive tumours were also positive for p14. Multiple nucleotide alignment has shown similarity to MMTV ranging from 98% to 100%. All the 102 examined FMCs were submitted to immunohistochemistry for molecular pheno-typing. Of the nine MMTV‐like positive FMCs, six were basal‐like and three luminal‐like. Our results demonstrate MMTV‐like sequences and protein in FMCs of different geographic areas. Molecular phenotyping could contribute to understand the possible role of MMTV‐like virus in FMC tumor biology

ANKRd44 gene silencing: A putative role in trastuzumab resistance in HER2-like breast cancer

Trastuzumab is an effective therapeutic treatment for Her2-like breast cancer; despite this most of these tumors develop resistance to therapy due to specific gene mutations or alterations in gene expression. Understanding the mechanisms of resistance to Trastuzumab could be a useful tool in order to identify combinations of drugs that elude resistance and allow a better response for the treated patients. Twelve primary biopsies of Her2+/hormone receptor negative (ER-/PgR-) breast cancer patients were selected based on the specific response to neoadjuvant therapy with Trastuzumab and their whole exome was sequenced leading to the identification of 18 informative gene mutations that discriminate patients selectively based on response to treatment. Among these genes, we focused on the study of the ANKRD44 gene to understand its role in the mechanism of resistance to Trastuzumab. The ANKRD44 gene was silenced in Her2-like breast cancer cell line (BT474), obtaining a partially Trastuzumab-resistant breast cancer cell line that constitutively activates the NF-kb protein via the TAK1/AKT pathway. Following this activation an increase in the level of glycolysis in resistant cells is promoted, also confirmed by the up-regulation of the LDHB protein and by an increased TROP2 protein expression, found generally associated with aggressive tumors. These results allow us to consider the ANKRD44 gene as a potential gene involved in Trastuzumab resistance

Abdominal CT: a radiologist-driven adjustment of the dose of iodinated contrast agent approaches a calculation per lean body weight

BACKGROUND: The contrast agent (CA) dose for abdominal computed tomography (CT) is typically based on patient total body weight (TBW), ignoring adipose tissue distribution. We report on our experience of dosing according to the lean body weight (LBW). METHODS: After Ethics Committee approval, we retrospectively screened 219 consecutive patients, 18 being excluded for not matching the inclusion criteria. Thus, 201 were analysed (106 males), all undergoing a contrast-enhanced abdominal CT with iopamidol (370 mgI/mL) or iomeprol (400 mgI/mL). LBW was estimated using validated formulas. Liver contrast-enhancement (CEL) was measured. Data were reported as mean\u2009\ub1\u2009standard deviation. Pearson correlation coefficient, ANOVA, and the Levene test were used. RESULTS: Mean age was 66\u2009\ub1\u200913 years, TBW 72\u2009\ub1\u200915 kg, LBW 53\u2009\ub1\u200911 kg, and LBW/TBW ratio 74\u2009\ub1\u20098%; body mass index was 26\u2009\ub1\u20095 kg/m2, with 9 underweight patients (4%), 82 normal weight (41%), 76 overweight (38%), and 34 obese (17%). The administered CA dose was 0.46\u2009\ub1\u20090.06 gI/kg of TBW, corresponding to 0.63\u2009\ub1\u20090.09 gI/kg of LBW. A negative correlation was found between TBW and CA dose (r\u2009=\u2009-0.683, p\u2009<\u20090.001). CEL (Hounsfield units) was 51\u2009\ub1\u200918 in underweight patients, 44\u2009\ub1\u20098 in normal weight, 42\u2009\ub1\u20099 in overweight, and 40\u2009\ub1\u20096 in obese, with a significant difference for both mean (p\u2009=\u20090.004) and variance (p\u2009<\u20090.001). A low but significant positive correlation was found between CEL and CA dose in gI per TBW (r\u2009=\u20090.371, p\u2009<\u20090.001) or per LBW (r\u2009=\u20090.333, p\u2009<\u20090.001). CONCLUSIONS: The injected CA dose was highly variable, with obese patients receiving a lower dose than underweight patients, as a radiologist-driven 'compensation effect'. Diagnostic abdomen CT examinations may be obtained using 0.63 gI/kg of LBW

Rifiuti spiaggiati: problema ambientale e di sanità pubblica

L’accumulo sulle spiagge di materiale naturale o antropico raramente è stato esplorato da una prospettiva “One Health”, che ne consideri l’impatto ambientale e sanitario. In questo lavoro, il modello concettuale Determinanti - Pressioni - Stato - Impatti - Risposte (DPSIR) è stato adattato al problema dei rifiuti spiaggiati, ed applicato ad un comune costiero italiano (Nord Toscana) a forte vocazione turistica

New insights in the expression of stromal caveolin 1 in breast cancer spread to axillary lymph nodes

Recent evidence suggests that a loss of expression of caveolin in the stromal compartment (sCav-1) of human invasive breast carcinoma (IBC) may be a predictor of disease recurrence, metastasis and poor outcome. At present, there is little knowledge regarding the expression of sCav-1 at the metastatic sites. We therefore studied sCav-1 expression in IBCs and in their axillary lymph nodes to seek a correlation with cancer metastasis. 189 consecutive invasive IBCs (53 with axillary lymph node metastases and 136 without) were studied by immunohistochemistry, using a rabbit polyclonal anti-Cav-1 antibody. In IBCs sCav-1 was evaluated in fibroblasts scattered in the tumor stroma whereas in lymph nodes sCav-1 was assessed in fibroblast-like stromal cells. For the first time, we observed a statistically significant progressive loss of sCav-1 from normal/reactive axillary lymph nodes of tumors limited to the breast to metastatic axillary lymph nodes, through normal/reactive axillary lymph nodes of tumors with axillary metastatic spread. These data indicate that Cav-1 expressed by the stromal compartment of lymph nodes, somehow, may possibly contribute to metastatic spread in IBC

Detriti spiaggiati come possibile veicolo di virus: contaminazione e sopravvivenza

Le spiagge sono interessate dall’accumulo di biomassa e rifiuti antropici. Ciò comporta non solo un impatto ambientale ed economico ma anche effetti sulla salute derivanti dall’esposizione a microorganismi potenzialmente patogeni. La contaminazione microbica delle spiagge è stata studiata principalmente considerando funghi e batteri, mentre esistono pochi dati sui virus. Nel presente lavoro, gli aspetti legati al rischio virale per la salute sono stati affrontati valutando la presenza di virus nel materiale spiaggiato e nella sabbia sottostante e la loro sopravvivenza nella sabbia e nell’acqua di mare