Two Benthic Diatoms, Nanofrustulum shiloi and Striatella unipunctata, Encapsulated in Alginate Beads, Influence the Reproductive Efficiency of Paracentrotus lividus by Modulating the Gene Expression

Physiological effects of algal metabolites is a key step for the isolation of interesting bioactive compounds. Invertebrate grazers may be fed on live diatoms or dried, pelletized, and added to compound feeds. Any method may reveal some shortcomings, due to the leaking of wound-activated compounds in the water prior to ingestion. For this reason, encapsulation may represent an important step of bioassay-guided fractionation, because it may assure timely preservation of the active compounds. Here we test the effects of the inclusion in alginate (biocompatible and non-toxic delivery system) matrices to produce beads containing two benthic diatoms for sea urchin Paracentrotus lividus feeding. In particular, we compared the effects of a diatom whose influence on P. lividus was known (Nanofrustulum shiloi) and those of a diatom suspected to be harmful to marine invertebrates, because it is often present in blooms (Striatella unipunctata). Dried N. shiloi and S. unipunctata were offered for one month after encapsulation in alginate hydrogel beads and the larvae produced by sea urchins were checked for viability and malformations. The results indicated that N. shiloi, already known for its toxigenic effects on sea urchin larvae, fully conserved its activity after inclusion in alginate beads. On the whole, benthic diatoms affected the embryogenesis of P. lividus, altering the expression of several genes involved in stress response, development, skeletogenesis and detoxification processes. Interactomic analysis suggested that both diatoms activated a similar stress response pathway, through the up-regulation of hsp60, hsp70, NF-kappa B, 14-3-3 epsilon and MDR1 genes. This research also demonstrates that the inclusion in alginate beads may represent a feasible technique to isolate diatom-derived bioactive compounds

Evaluation of prognostic preoperative factors in patients undergoing surgery for spinal metastases: Results in a consecutive series of 81 cases

Background: Surgical treatment of spinal metastases should be tailored to provide pain control, neurological deficit improvement, and vertebral stability with low operative morbidity and mortality. The aim of this study was to analyze the predictive value of some preoperative factors on overall survival in patients undergoing surgery for spinal metastases. Methods: We retrospectively analyzed a consecutive series of 81 patients who underwent surgery for spinal metastases from 2015 and 2021 in the Clinic of Neurosurgery of Ancona (Italy). Data regarding patients’ baseline characteristics, preoperative Karnofsky Performance Status Score (KPS), and Frankel classification grading system, histology of primary tumor, Tokuhashi revised and Tomita scores, Spine Instability Neoplastic Score, and Epidural Spinal Cord Compression Classification were collected. We also evaluated the interval time between the diagnosis of the primary tumor and the onset of spinal metastasis, the type of surgery, the administration of adjuvant therapy, postoperative pain and Frankel grade, and complications after surgery. The relationship between patients’ overall survival and predictive preoperative factors was analyzed by the Kaplan–Meier method. For the univariate and multivariate analysis, the log-rank test and Cox regression model were used. P ≤ 0.05 was considered as statistically significant. Results: After surgery, the median survival time was 13 months. In our series, the histology of the primary tumor (P < 0.001), the Tomita (P < 0.001) and the Tokuhashi revised scores (P < 0.001), the preoperative KPS (P < 0.001), the adjuvant therapy (P < 0.001), the postoperative Frankel grade (P < 0.001), and the postoperative pain improvement (P < 0.001) were significantly related to overall survival in the univariate analysis. In the multivariate analysis, the Tomita (P < 0.001), Tokuhashi revised scores (P < 0.001), and the adjuvant therapy were confirmed as independent prognostic factors. Conclusion: These data suggest that patients with limited extension of primitive tumor and responsive to the adjuvant therapy are the best candidates for surgery with better outcome

BEYOND WAIST CIRCUMFERENCE IN AN ADULT MALE POPULATION OF SOUTHERN ITALY: IS THERE ANY ROLE FOR SUBSCAPULAR SKINFOLD THICKNESS IN THE RELATIONSHIP BETWEEN INSULIN-LIKE GROWTH FACTOR-1 SYSTEM AND METABOLIC PARAMETERS ?

ABSTRACT Background: Apart from waist circumference, other adiposity measures, such as subscapular skin fold (SST), arouse growing interest due to their relationship to metabolic complications and cardiovascular risk. The Insulin-like Growth Factor (IGF)-1 system is deregulated in obese subjects in proportion to their degree of visceral adiposity. Aim : To examine the association among IGF-1, IGF-Binding Protein (BP)1 and 3 levels and different measures of adiposity in a sample of adult male population in Southern Italy. Materials and Methods: A complete database for this analysis was available for 229 (age range 50–82 years) participating at 2002-2004 Olivetti Heart Study follow-up. Results: After adjustment for age, IGF-1 was inversely associated with BMI and waist circumference (p<0.05). IGFBP1 was inversely associated with BMI, waist circumference, SST, Homeostasis Model Assessment (HOMA) index, Fat Mass (FM). HOMA index, age and SST significantly predicted the IGFBP1 plasma levels, with 24% of IGFPB-1 variability explained at a linear regression analysis. Conclusions: IGFBP1 inversely correlated to adiposity and HOMA index. Among adiposity indexes, SST was the best predictor of IGFPB-1 levels. The evaluation of some components of the IGFs system, and simple measures of body adiposity, such as SST, may represent a further tool to better evidence phenotype profiles associated to the pathogenetic mechanism of cardiovascular risk factor clustering in male adults

Squamous cell carcinoma of the lower lip: FAS/FASL expression, lymphocyte subtypes and outcome.

Squamous cell carcinoma (SCC) of the lip is a relatively common malignancy of the head and neck region. Tumour thickness, grading and perineural invasion are significant prognostic indicators. However, there is still the need of new reliable biological markers able to predict the prognosis of the single cases with an unfavourable biological behaviour unpredictable by the classic clinical-pathological parameters. 32 cases of (SCC) of the lower lip were analysed for their clinicopathologic features, and immunohistochemical expression of Fas/FasL in neoplastic cells and in inflammatory infiltrate. Moreover the density and phenotype of tumour-infiltrating lymphocytes (TIL) were analysed. The results were related with the follow-up of the patients ranging from 2 to 6 years. The cases with over-expression of Fas/FasL in neoplastic cells and Fas+ in T cells preferentially showed a more aggressive clinical behaviour (p<0.01). Moreover we found an alteration of the normal expression of CD4 and CD8 lymphocyte types in ten cases. This data suggest that the Fas/FasL pathway is involved in the close relation between neoplastic cells and T cells and so in the biological behaviour of these tumours

Exposure of E. coli to DNA-methylating agents impairs biofilm formation and invasion of eukaryotic cells via down regulation of the N-acetylneuraminate lyase NanA

DNA methylation damage can be induced by endogenous and exogenous chemical agents, which has led every living organism to develop suitable response strategies. We investigated protein expression profiles of Escherichia coli upon exposure to the alkylating agent methyl-methane sulfonate (MMS) by differential proteomics. Quantitative proteomic data showed a massive downregulation of enzymes belonging to the glycolytic pathway and fatty acids degradation, strongly suggesting a decrease of energy production. A strong reduction in the expression of the N-acetylneuraminate lyases (NanA) involved in the sialic acid metabolism was also observed. Using a null NanA mutant and DANA, a substrate analog acting as competitive inhibitor, we demonstrated that down regulation of NanA affects biofilm formation and adhesion properties of E. coli MV1161. Exposure to alkylating agents also decreased biofilm formation and bacterial adhesion to Caco-2 eukaryotic cell line by the adherent invasive E. coli (AIEC) strain LF82. Our data showed that methylation stress impairs E. coli adhesion properties and suggest a possible role of NanA in biofilm formation and bacteria host interactions

Intracellular Sphingosine-1-Phosphate Receptor 3 Contributes to Lung Tumor Cell Proliferation.

Background/Aims: The pleiotropic lipid mediator sphingosine-1-phosphate (S1P) exerts a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Epidemiological studies proved high levels of circulating S1P in non-small cell lung cancer (NSCLC) patients. Studies in literature suggest that high levels of S1P support carcinogenesis but the exact mechanism is still elusive. The aim of this study was to understand the mechanism/s underlying S1P-mediated lung tumor cell proliferation. Methods: We used human samples of NSCLC, a mouse model of first-hand smoking and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. Results: We found that the expression of S1PR3 was also into the nucleus of lung cells in vitro, data that were confirmed in lung tissues of NSCLC patients, smoking and tumor bearing BaP-exposed mice. The intranuclear, but not the membrane, localization of S1PR3 was associated to S1P-mediated proliferation of lung adenocarcinoma cells. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after Toll Like Receptor (TLR) 9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. Conclusion: These results prove that the nuclear S1PR3/SPHK II axis is involved in lung tumor cell proliferation, highlighting a novel molecular mechanism which could provide differential therapeutic approaches especially in non-responsive lung cancer patients

Evolution in endoscopic endonasal approach for the management of hypothalamic–pituitary region metastasis: A single-institution experience

IntroductionEndonasal endoscopic surgery has changed the treatment perspectives for different lesions of the hypothalamic–pituitary region. The metastases of the hypothalamic–pituitary region represent 0.4% of all intracranial metastatic tumors and account for only 1.8% of surgically managed pituitary lesions. The aim of tshis study is to describe a single-center institutional experience with 13 cases of hypothalamic–pituitary metastasis focused on presurgical workup, the evolution of the surgical technique, and postsurgical management according to our protocols, showing effects on progression-free and overall survival rates for this relatively uncommon location.Material and MethodsWe retrospectively reviewed the whole series of patients that received the endoscopic endonasal approach at the Division of Neurosurgery at the University of Naples “Federico II” undergoing surgery from January 1997 to December 2021. We identified 13 cases whose pathology reports revealed a metastatic lesion. Statistical analysis was performed to determine the Kaplan–Meier survival function and assess for log-rank differences in survival based on gender, surgical treatment, and postoperative therapy (p-value &lt; 0.02*).ResultsThe pathology report disclosed lung adenocarcinoma (six cases, 46%), breast adenocarcinoma (two cases, 15.4%), clear cell renal carcinoma (one case, 7%), melanoma (one case, 7%), colorectal adenocarcinoma (one case, 7%), uterine cervix carcinoma (one case, 7%), and follicular thyroid carcinoma (one case, 7%). A standard endoscopic endonasal approach was performed in 10 patients (76.9%), while an extended endonasal procedure was performed in only three cases (23%). Biopsy was the surgical choice in five patients with infiltrative and invasive lesions and a poor performance status (38%), while in the cases where neurovascular decompression was necessary, a subtotal resection was achieved in five patients (38%) and partial resection in three patients (23%). Recovery of visual field defect was observed in six of seven patients with visual loss (85.7%), improvement of oculomotor nerve palsy occurred in four of seven patients with this defect (57.1%), while the impairment of oculomotor palsy was observed in three patients (42.9%). Visual function was stable in the other patients. The median progression-free survival and overall survival were 14 and 18 months, respectively. There were statistically significant differences in PFS and OS in patients who underwent adjuvant radiotherapy (p=0.019 is referred to OS and p=0.017 to PFS, respectively; p-value = 0.02).ConclusionsThe endoscopic endonasal approach is a viable approach for the management of hypothalamic–pituitary metastases as this surgery provides an adequate opportunity to obtain tissue sample and neurovascular decompression, both being crucial for continuing the integrated adjuvant therapy protocols

AIM2 Inflammasome Activation Leads to IL-1α and TGF-β Release From Exacerbated Chronic Obstructive Pulmonary Disease-Derived Peripheral Blood Mononuclear Cells

Chronic obstructive pulmonary disease (COPD) is now the fourth-leading cause of death worldwide and its prevalence is increasing. The progressive decline of lung function and airway remodelling are a consequence of chronic inflammatory responses. It was recently postulated the involvement of the inflammasome in COPD, although the underlying mechanism/s still need to be elucidated. Therefore, we isolated peripheral blood mononuclear cells (PBMCs) from exacerbated/unstable COPD patients. The stimulation of PBMCs with an AIM2 inflammasome activator, Poly dA:dT, led to IL-1α, but not IL-1β, release. The release of this cytokine was caspase-1- and caspase-4-dependent and correlated to higher levels of 8-OH-dG in COPD compared to non-smoker and smoker-derived PBMCs. Interestingly, AIM2-depedent IL-1α release was responsible for higher TGF-β levels, crucial mediator during pro-fibrotic processes associated to COPD progression. In conclusion, our data highlight the involvement of AIM2/caspase-1/caspase-4 in IL-1α-induced TGF-β release in unstable COPD-derived PBMCs, opening new therapeutic perspectives for unstable COPD patients

Studio dell’espressione dell’Homeobox gene CDX2 nella metaplasia intestinale e nelle lesioni neoplastiche e preneoplastiche dello stomaco e correlazioni clinico-patologiche con l’infezione da Helicobacter Pilory

BACKGROUND: Gastric carcinoma can be divided into the intestinal and diffuse type, or the differentiated and indifferentiated type, on the basis of its tendency to gland formation. Intestinal metaplasia (IM), where intestinal-type carcinoma is thought to develop, is classified into incomplete and complete types. The latter, which resembles small-intestinal absorptive epithelium, has been considered a precancerous lesion, and its development is strongly associated with Helicobacter Pilory (HP) infection. The molecular mechanism underlying the onset of IM remain elusive. AIMS: To evaluate the evolution of the IM, and to study by immunohistochemistry the expression of the homeobox gene CDX2 in IM before and after the pharmacological treatment for the Helicobacter Pilory eradication, and in 10 cases of gastric carcinoma of intestinal type with associated precancerous lesions. MATERIALS AND METHODS: Formalin-fixed and paraffin embedded tissue from gastric biopsy of 30 patients with complete IM, and 10 cases of gastric carcinoma (pT2bN1Mx) of intestinal type were enrolled. HP infection was assessed by modified Giemsa staining and CDX2 expression by immunohistochemical staining. For each cases of IM we studied two biopsies (before and after HP treatment). 11 cases of gastric biopsy specimens from normal controls were used as control. RESULTS: CDX2 was expressed in a nuclear pattern in all cases of IM before and after the pharmacological treatment for HP. All but one gastric carcinoma were negative for CDX2, in one case we found a quickly CDX2 cytoplasmatic expression. CONCLUSION: Our data confirm that CDX2 represent a transcription factor which is involved in the different aspects of gastric pathogenesis. It may be of special importance in inflammatory condition resulting in the development of intestinal metaplasia. However, CDX2 expression is reduced in gastric carcinomas as compared with IM. On the other hand, it is associated with tumor progression in the subgroup of intestinal carcinoma. Our results, in according with the data reported in literature to date, indicate that CDX2 expression in gastric cancer tissues can be a novel prognostic marker for patient survival