Dry grasslands of Hippocrepido glaucae-Stipion austroitalicae in the Pollino Massif (Calabria, Italy)

Rocky pastures dominated by Stipa austroitalica in the south-east of Italy were classified within an endemic alliance, Hippocrepido glaucae-Stipion austroitalicae, originally assigned to a Balkan order (Scorzoneretalia villosae). Actually, the distribution area of S. austroitalica extends further westwards and large patches are found on the south-east side of the Pollino Massif. This study aims to describe and characterise the plant communities dominated by S. austroitalica in this area and analyse their floristic and chorological relationships with other associations of Hippocrepido-Stipion. Moreover, their syntaxonomy is discussed in the context of the Italian and south European dry grasslands biogeography. The grasslands were studied on the basis of 19 phytosociological relevés. A larger data set, including 185 relevés with S. austroitalica, was used to visualise the relationships among the associations through nonmetric multi-dimensional scaling ordination. The results allowed the description of a new association, Bupleuro gussonei-Stipetum austroitalicae, classifi ed within Hippocrepido-Stipion. As a consequence, the alliance synrange was extended up to the Pollino Massif. The Hip pocrepido-Stipion, together with Cytiso spinescentis-Bromion erecti, was arranged in Euphorbietalia myrsinitidis, an endemic order of the Italian peninsula. The proposed scheme upgrades the syntaxonomy and nomenclature of the dry grasslands vegetation of central and southern Italy

Nebivolol as a Potent TRPM8 Channel Blocker: A Drug-Screening Approach through Automated Patch Clamping and Ligand-Based Virtual Screening

Transient Receptor Potential Melastatin 8 (TRPM8) from the melastatin TRP channel subfamily is a non-selective Ca2+-permeable ion channel with multimodal gating which can be activated by low temperatures and cooling compounds, such as menthol and icilin. Different conditions such as neuropathic pain, cancer, overactive bladder syndrome, migraine, and chronic cough have been linked to the TRPM8 mode of action. Despite the several potent natural and synthetic inhibitors of TRPM8 that have been identified, none of them have been approved for clinical use. The aim of this study was to discover novel blocking TRPM8 agents using automated patch clamp electrophysiology combined with a ligand-based virtual screening based on the SwissSimilarity platform. Among the compounds we have tested, nebivolol and carvedilol exhibited the greatest inhibitory effect, with an IC50 of 0.97 ± 0.15 µM and 9.1 ± 0.6 µM, respectively. This study therefore provides possible candidates for future drug repurposing and suggests promising lead compounds for further optimization as inhibitors of the TRPM8 ion channel

Chasmophytic vegetation of the class Asplenietea trichomanis in south-eastern Italy

The southeast of Italy is characterized by the presence of some highly phytogeographically relevant taxa with a Balkan-Aegean distribution. Three of these taxa, Campanula versicolor, Carum multiflorum and Scrophularia lucida, characterize the chasmophytic vegetation in central-southern Apulia (Serre Salentine and Bassa Murgia). Chasmophytic vegetation has already been referred to the Onosmetalia frutescentis order and to its only alliance Campanulion versicoloris, which are syntaxa with mainly a south-western Balkan distribution. This paper reports a phytosociological study of chasmophytic vegetation throughout the entire distributional range of these three species in south-eastern Italy and describes two new associations: Piptathero holciformis-Campanuletum versicoloris and Iberido carnosae-Athamantetum siculi.We analyse their floristic relationships with other communities described for southern Italy, the Adriatic area and the southern Balkans. As distinct from reports in the literature, the results show that south-eastern Italian rupicolous communities, now grouped under the new alliance Caro multiflori-Aurinion megalocarpae, have higher floristic similarity with the order Asplenietalia glandulosi, where they have been placed. In other words, the presence of different species gravitating in the East discriminates the chasmophytic vegetation of south-eastern Italy within a central Mediterranean order, rather than justifying its assignment to Onosmetalia frutescentis, whose distributional area is limited to the Balkan Peninsula

Cancer stem-neuroendocrine cells in an atypical carcinoid case report.

Lung neuroendocrine cells tumor (NET) classification and diagnosis, particularly for typical and atypical carcinoids, are complicated by a variable natural history and nonspecific symptoms. Mechanisms for the development and progression of well-differentiated lung NETs are still unclear. An accurate and timely diagnosis can ensure the implementation of appropriate treatment and impact on prognosis. One of the main unclear point is the definition of these cells’ composition. In fact, it is known that carcinoids are mainly constituted by neuroendocrine cells. Aim of our report is to show for the first time the presence of a high percentage of cancer stem cells (CSCs) in an atypical carcinoid. The ALDEFLUOR assay was used to identify and sort ALDHhigh and ALDHlow human lung cancer cells following tissue digestion. SOX2 was additionally determined by immunohistochemistry. All specimens contained the 53.10% of ALDHhigh cells among all viable lung cancer cells, which indicates that more than half of the entire tumor cell population was composed by CSCs. As expected also in immunohistochemistry, about a half of the nuclei of the cells were positive for SOX2. We strongly support the hypothesis of the presence of cancer stem-neuroendocrine cells (CSCs-NETs) as subpopulation in these types of tumors

Correlating tumor-infiltrating lymphocytes and lung cancer stem cells: a cross-sectional study.

Background: Lung cancer stem cells (LCSCs) are endowed with high aldehyde dehydrogenase (ALDH) expression and play roles in tumor proliferation, metastasis, and drug resistance. Their elusive nature may allow them to escape the immune response by tumor-infiltrating lymphocytes (TILs), which can positively affect the outcome in non-small cell lung cancer (NSCLC) patients. Despite independent investigations on both LCSCs and TILs, the relationship between the two has been very marginally considered. We analyzed whether these two cell types may be related as a prerequisite for novel diagnostic and therapeutic approaches. Methods: In this cross-sectional study, NSCLC human surgical specimens from 12 patients were tested by ALDEFLUOR assay to identify ALDHhigh cells. Fluorescence-activated cell sorting (FACS) analyses for CD3+, CD4+, and CD8+ TILs were performed in combination with immunohistochemistry evaluation. Results: Statistically positive correlations were found between ALDH+ and CD8+, and between ALDH+ and CD3+ cells populations; no correlation was found between ALDH+ and CD4+ cells. The expression of CD3+ and CD8+ by cells accounted for 40.1% and 58.7%, respectively, of the variability of ALDH+ cell expression by an R-squared index, which highlights the strong correlation between TILs and LCSCs. Immunohistochemistry revealed 6–25% positive cells. Conclusions: We report a correlation between cytotoxic TILs and LCSCs, which may contribute to the future development of targeted therapies focusing on the different roles of lymphocytes against lung cancer

Cancer stem cells and their microenvironment.

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Overall survival in patients with lung adenocarcinoma harboring "niche" mutations: an observational study

Objective: In addition to the most common somatic lung cancer mutations (i. e., KRAS and EGFR mutations), other genes may harbor mutations that could be relevant for lung cancer. We defined BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET mutations as “niche” mutations and analyzed. The aim of this retrospective cohort study was to assess the differences in the overall survival (OS) of patients with lung adenocarcinoma harboring niche somatic mutations. Results: Data were gathered for 252 patients. Mutations were observed in all genes studied, except c-MET, DDR2, MAP2K1, and RET. The multivariable analysis showed that 1) niche mutations had a higher mortality than EGFR mutations (HR = 2.3; 95% CI = 1.2–4.4; p = 0.009); 2) KRAS mutations had a higher mortality than EGFR mutations (HR = 2.5; 95% CI = 1.4–4.5; p = 0.003); 3) niche mutations presented a similar mortality to KRAS mutations (HR = 0.9; 95% CI = 0.6–1.5; p = 0.797). Methods: Three cohorts of mutations were selected from patients with lung adenocarcinoma and their OS was compared. Mutations that were searched for, were 1) BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET; 2) K-RAS; and 3) EGFR. Differences in OS between these three cohorts were assessed by means of a multivariable Cox model that adjusted for age, sex, smoking habits, clinical stages, and treatments. Conclusions: Niche mutations exhibited an increased risk of death when compared with EGFR mutations and a similar risk of death when compared with KRAS mutations

Cancer stem cells and macrophages: molecular connections and future perspectives against cancer.

Cancer stem cells (CSCs) have been considered the key drivers of cancer initiation and progression due to their unlimited self-renewal capacity and their ability to induce tumor formation. Macrophages, particularly tumor-associated macrophages (TAMs), establish a tumor microenvironment to protect and induce CSCs development and dissemination. Many studies in the past decade have been performed to understand the molecular mediators of CSCs and TAMs, and several studies have elucidated the complex crosstalk that occurs between these two cell types. The aim of this review is to define the complex crosstalk between these two cell types and to highlight potential future anti-cancer strategies

Expression of ALDH and SOX-2 in Pulmonary Sclerosing Pnemocytoma (PSP) of the Lung: Is There a Meaning Behind?

Background: Pulmonary sclerosing pneumocytoma (PSP) is a rare benign pulmonary tumor that derives from primitive respiratory epithelium of the pulmonary alveolus. The etiology and pathogenesis are still unclear. Histopathological diagnosis focuses on cells that are positive for TTF1, EMA, cytokeratin-7, and CAM 5.2. The aim of our study is to highlight the elevated expression of ALDH and the presence of SOX-2 in pulmonary sclerosing pneumocytoma. Methods: We report five cases of pulmonary sclerosing pneumocytoma undergone surgery at our Division of Thoracic Surgery, during a period between 1994 and 2011. ALDH and SOX-2 markers were also tested for positivity in all the patients. Results: Patients showed elevated expression of ALDH during immunohistochemistry and mild expression of SOX-2, although in two cases in which SOX-2 was highly expressed. Among these two patients, one presented with lymph node recurrence while the other had no recurrence with a PET-positive nodule. In particular, the patient who had developed recurrence had an ALDH score of 4 and a SOX-2 score of 3, whereas the patient with the PET-positive nodule showed an ALDH score of 4 with a mild SOX-2expression of score 1. Conclusions: This is the first attempt demonstrating the elevated expression of ALDH in this disease. SOX-2 expression was noted in both the patient who developed recurrence and the patient with a PET-positive nodule. We believe that further investigation may be highly useful to better characterize these two markers as well as understandtheir function