Therapeutic potential of the phosphino Cu(I) complex (HydroCuP) in the treatment of solid tumors

[Cu(thp)4][PF6] (HydroCuP) is a phosphino copper(I) complex highly soluble and stable in physiological media that has been developed as a possible viable alternative to platinum-based drugs for anticancer therapy. HydroCuP potently inhibited the growth of human cancer cells derived from solid tumors by inducing endoplasmatic reticulum (ER) stress thus leading to cell death through paraptosis with a preferential efficacy against cancer rather than non-cancer cells. Aim of the present study was to assess the therapeutic potential of HydroCuP in vivo, in syngenic and xenograft murine models of solid tumors by triggering the Unfolded Protein Response (UPR) pathway. With respect to platinum drugs, HydroCuP induced a markedly higher reduction of tumor growth associated with minimal animal toxicity. In human colorectal cancer xenografts, chemotherapy with HydroCuP was extremely effective in both oxaliplatin-sensitive and resistant models. The favorable in vivo tolerability of HydroCuP was also correlated to an encouraging biodistribution profile. Additionally, no signs of drug-related neurotoxicity and nephrotoxicity were observed. Altogether, these results demonstrate that HydroCuP appears worth of further investigation to evaluate its therapeutic activity towards a broad spectrum of solid malignancies

La Mediterranea verso l’Agenda 2030

With this book, the Mediterranea University of Reggio Calabria raises the profile of some of the research undertaken in various Departments in relation to the Sustainable Development Goals (SDGs) of Agenda 2030. SDGs represent a strategy that requires shared global involvement for its implementation. They are to be implemented through the adoption of national and local initiatives. The SDGs can and should become effective tools for sustainable development though a localization process and an effective involvement of local stakeholders. University, an institution committed to training, research and outreaching activities, is called to play its part in such a difficult and complex challenge; constant integration with the territory and local communities – in the conscious need to be the promoter of a progressive, indispensable cultural change – will support sustainable development not as an impossible “utopia” but an unescapable necessity.La Mediterranea verso l’Agenda 2030L'Università Mediterranea di Reggio Calabria con questo volume dà visibilità ad alcune delle ricerche intraprese dalla comunità scientifica dei suoi Dipartimenti, in relazione agli Obiettivi di Sviluppo Sostenibile (SDGs) dell'Agenda 2030.Gli SDGs rappresentano una Strategia la cui attuazione richiede un condiviso coinvolgimento globale. Essi devono essere attuati attraverso l’adozione di strategie nazionali di sviluppo sostenibile, declinate in azioni regionali e locali.  Gli SDGs possono e devono diventare strumenti efficaci per lo sviluppo sostenibile, attraverso un processo di localizzazione e un efficace coinvolgimento degli stakeholder locali.In una sfida così difficile e complessa, l'Università, istituzione impegnata nella formazione, nella ricerca e nella terza missione, è chiamata a fare la sua parte; la sua costante integrazione con il territorio e con le comunità locali, nella consapevole necessità di essere promotrice di un progressivo, indispensabile cambiamento culturale, indurrà a far si che lo sviluppo sostenibile non sia più visto come una impossibile "utopia", ma sia avvertito come una inderogabile necessità. L'Università Mediterranea di Reggio Calabria con questo volume dà visibilità ad alcune delle ricerche intraprese dalla comunità scientifica dei suoi Dipartimenti, in relazione agli Obiettivi di Sviluppo Sostenibile (SDGs) dell'Agenda 2030. Gli SDGs rappresentano una Strategia la cui attuazione richiede un condiviso coinvolgimento globale. Essi devono essere attuati attraverso l’adozione di strategie nazionali di sviluppo sostenibile, declinate in azioni regionali e locali.  Gli SDGs possono e devono diventare strumenti efficaci per lo sviluppo sostenibile, attraverso un processo di localizzazione e un efficace coinvolgimento degli stakeholder locali.In una sfida così difficile e complessa, l'Università, istituzione impegnata nella formazione, nella ricerca e nella terza missione, è chiamata a fare la sua parte; la sua costante integrazione con il territorio e con le comunità locali, nella consapevole necessità di essere promotrice di un progressivo, indispensabile cambiamento culturale, indurrà a far si che lo sviluppo sostenibile non sia più visto come una impossibile "utopia", ma sia avvertito come una inderogabile necessità.The Mediterranea University towards Agenda 2030With this book, the Mediterranea University of Reggio Calabria raises the profile of some of the research undertaken in various Departments in relation to the Sustainable Development Goals (SDGs) of Agenda 2030. SDGs represent a strategy that requires shared global involvement for its implementation. They are to be implemented through the adoption of national and local initiatives. The SDGs can and should become effective tools for sustainable development though a localization process and an effective involvement of local stakeholders. University, an institution committed to training, research and outreaching activities, is called to play its part in such a difficult and complex challenge; constant integration with the territory and local communities – in the conscious need to be the promoter of a progressive, indispensable cultural change – will support sustainable development not as an impossible “utopia” but an unescapable necessity.

Update on the distribution of Aedes albopictus (Diptera: Culicidae) in Misiones, Argentina

The Asian tiger mosquito (Aedes albopictus, Diptera: Culicidae) has spread rapidly in the last 30 years from its native region in Southeast Asia. In Argentina, studies on its potential distribution suggest that this species could be found in temperate zones of the province of Buenos Aires. However, since its initial detection in 1998 Ae. albopictus is bounded to the subtropical province of Misiones. To evaluate the presence and abundance of Ae. albopictus in the Northeast of Argentina, we preliminarily evaluated the presence of this vector by analyzing its presence in tires of 20 cities belonging to the province of Misiones and four cities in Northern Corrientes, and then performed an evaluation of the vector in the towns where the vector was detected. Aedes albopictus was present only in two cities of Misiones: Eldorado and Colonia Aurora. Aedes aegypti and Ae. albopictus accounted for 86% of the individuals collected in the domiciles of both towns. In Colonia Aurora both species were in similar abundances suggesting a co-dominance. The present study extends the austral distribution of Ae. albopictus in Argentina to the city of Colonia Aurora where the highest abundance recorded in Argentina was detected. Nevertheless, the reasons of its bounded distribution in the region are not known

Digital detection of exosomes by interferometric imaging

Exosomes, which are membranous nanovesicles, are actively released by cells and have been attributed to roles in cell-cell communication, cancer metastasis, and early disease diagnostics. The small size (30–100 nm) along with low refractive index contrast of exosomes makes direct characterization and phenotypical classification very difficult. In this work we present a method based on Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) that allows multiplexed phenotyping and digital counting of various populations of individual exosomes (>50 nm) captured on a microarray-based solid phase chip. We demonstrate these characterization concepts using purified exosomes from a HEK 293 cell culture. As a demonstration of clinical utility, we characterize exosomes directly from human cerebrospinal fluid (hCSF). Our interferometric imaging method could capture, from a very small hCSF volume (20 uL), nanoparticles that have a size compatible with exosomes, using antibodies directed against tetraspanins. With this unprecedented capability, we foresee revolutionary implications in the clinical field with improvements in diagnosis and stratification of patients affected by different disorders.This work was supported by Regione Lombardia and Fondazione Cariplo through POR-FESR, project MINER (ID 46875467); Italian Ministry of Health, Ricerca Corrente. This work was partially supported by The Scientific and Technological Research Council of Turkey (grant #113E643). (Regione Lombardia; 46875467 - Fondazione Cariplo through POR-FESR, project MINER; Italian Ministry of Health, Ricerca Corrente; 113E643 - Scientific and Technological Research Council of Turkey)Published versio

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in diagnosis of pleural effusion of malignant origin

OBJECTIVES The aim of the present study was to evaluate the diagnostic accuracy of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in differentiating benign from malignant exudative pleural effusions. METHODS This is a unicentre observational study including 97 consecutive patients with exudative pleural effusions. Metalloproteinase-9, tissue inhibitor of metalloproteinase-1, lactate dehydrogenase, ferritin, carcinoembryonic antigen and carbohydrate antigen 15-3 were measured in pleural effusion and serum by enzyme-linked immunosorbent assay. The activity of metalloproteinase-9 was also evaluated by substrate zymography. The data were correlated with final diagnosis of pleural effusions to evaluate the diagnostic accuracy. RESULTS Of the 97 eligible patients, 6 were excluded. Of the 91 patients included in the study, 70 had malignant pleural effusions and 21 had benign pleural effusions. Both in sera and pleural effusions, matrix metalloproteinase-9 (P < 0.0001), tissue inhibitor of metalloproteinase-1 (P < 0.0001) and carcinoembryonic antigen (P < 0.0001) levels were higher in neoplastic patients than in benign group. Zymography analysis showed a most prominent band at a molecular weight of 92 kDa (metalloproteinase-9) whereas a less intense band was observed at 72 kDa (metalloproteinase-2). A significant correlation was found between metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels in pleural effusion (P < 0.0001; r = 0.8) and serum (P < 0.03; r = 0.2). Pleural effusion metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels showed higher value of sensitivity (97 and 91%, respectively) and specificity (90 and 95%, respectively) compared with other standard markers. Serum metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels showed similar results. Among 70 neoplastic patients, 29 had negative pleural cytology. Of these, 25 presented elevated levels of metalloproteinase-9 and tissue inhibitor of metalloproteinase-1, whereas 4 patients had elevated levels of one of the two markers. CONCLUSIONS Our results showed that metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 might be valuable markers in differentiating benign from malignant pleural effusions. Their levels are neither influenced by the histology and tumour origin nor by the presence of tumour cells in pleural effusions. Thus, their use in clinical practice could help in the selection of patients needing more invasive procedures, such as thoracoscopic biopsy.OBJECTIVES The aim of the present study was to evaluate the diagnostic accuracy of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in differentiating benign from malignant exudative pleural effusions. METHODS This is a unicentre observational study including 97 consecutive patients with exudative pleural effusions. Metalloproteinase-9, tissue inhibitor of metalloproteinase-1, lactate dehydrogenase, ferritin, carcinoembryonic antigen and carbohydrate antigen 15-3 were measured in pleural effusion and serum by enzyme-linked immunosorbent assay. The activity of metalloproteinase-9 was also evaluated by substrate zymography. The data were correlated with final diagnosis of pleural effusions to evaluate the diagnostic accuracy. RESULTS Of the 97 eligible patients, 6 were excluded. Of the 91 patients included in the study, 70 had malignant pleural effusions and 21 had benign pleural effusions. Both in sera and pleural effusions, matrix metalloproteinase-9 (P < 0.0001), tissue inhibitor of metalloproteinase-1 (P < 0.0001) and carcinoembryonic antigen (P < 0.0001) levels were higher in neoplastic patients than in benign group. Zymography analysis showed a most prominent band at a molecular weight of 92 kDa (metalloproteinase-9) whereas a less intense band was observed at 72 kDa (metalloproteinase-2). A significant correlation was found between metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels in pleural effusion (P < 0.0001; r = 0.8) and serum (P < 0.03; r = 0.2). Pleural effusion metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels showed higher value of sensitivity (97 and 91%, respectively) and specificity (90 and 95%, respectively) compared with other standard markers. Serum metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels showed similar results. Among 70 neoplastic patients, 29 had negative pleural cytology. Of these, 25 presented elevated levels of metalloproteinase-9 and tissue inhibitor of metalloproteinase-1, whereas 4 patients had elevated levels of one of the two markers. CONCLUSIONS Our results showed that metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 might be valuable markers in differentiating benign from malignant pleural effusions. Their levels are neither influenced by the histology and tumour origin nor by the presence of tumour cells in pleural effusions. Thus, their use in clinical practice could help in the selection of patients needing more invasive procedures, such as thoracoscopic biopsy

Exploring the Gut Microbiome Alteration of the European Hare (Lepus europaeus) after Short-Term Diet Modifications

This study aimed to characterise the gut microbiome composition of European hares (Lepus europaeus) and its potential changes after a short-term diet modification. The high sensitivity of European hare to habitat changes makes this species a good model to analyse possible alterations in gut microbiome after the introduction of additional nourishment into the diet. In total, 20 pairs were chosen for the experiments; 10 pairs formed the control group and were fed with standard fodder. The other 10 pairs represented the experimental group, whose diet was integrated with apples and carrots. The DNA from fresh faecal pellets collected after 4 days from the start of the experiment was extracted and the V3-V4 hypervariable regions were amplified and sequenced using the Illumina MiSeq® platform. The obtained amplicon sequence variants were classified into 735 bacterial genera belonging to 285 families and 36 phyla. The control and the experimental groups appeared to have a homogenous dispersion for the two taxonomic levels analysed with the most abundant phyla represented by Bacteroidetes and Firmicutes. No difference between control and experimental samples was detected, suggesting that the short-term variation in food availability did not alter the hares’ gut microbiome. Further research is needed to estimate significant time threshold

Harmonic technology versus neodymium-doped yttrium aluminium garnet laser and electrocautery for lung metastasectomy: An experimental study

We compared the efficacy of non-anatomical lung resections with that of three other techniques: monopolar electrocautery; neodymium-doped yttrium aluminium garnet laser and harmonic technology. We hypothesized that the thermal damage with harmonic technology could be reduced because of the lower temperatures generated by harmonic technology compared with that of other devices.OBJECTIVES We compared the efficacy of non-anatomical lung resections with that of three other techniques: monopolar electrocautery; neodymium-doped yttrium aluminium garnet laser and harmonic technology. We hypothesized that the thermal damage with harmonic technology could be reduced because of the lower temperatures generated by harmonic technology compared with that of other devices. METHODS Initial studies were performed in 13 isolated pig lungs for each group. A 1.5-cm capsule was inserted within the lung to mimic a tumour and a total of 25 non-anatomical resections were performed with each device. The damage of the resected lung surface and of the tumour border were evaluated according to the colour (ranging from 0 - pink colour to 4 - black colour), histological (ranging from Score 0 - no changes to Score 3 - presence of necrotic tissue) and radiological (ranging from Score 0 - isointense T2 signal at magnetic resonance imaging to Score 3 - hyperintense T2 signal) criteria. A total of seven non-anatomical resections with harmonic technology were also performed in two live pigs to assess if ex vivo results could be reproducible in live pigs with particular attention to haemostatic and air-tightness properties. RESULTS In the ex vivo lung, there was a statistical significant difference between depth of thermal damage (P < 0.0001) in electrocautery (1.3 [1.2-1.4]), laser (0.9 [0.6-0.9]) and harmonic (0.4 [0.3-0.5]) groups. Electrocautery had a higher depth of thermal damage compared with that of the laser (P = 0.01) and harmonic groups (P = 0.0005). The harmonic group had a less depth of thermal damage than that of the laser group (P = 0.01). Also, histological damages of tumour borders (P < 0.001) and resected lung surface (P < 0.001), radiological damage of tumour borders (P < 0.001) and resected lung surface (P < 0.001) and colour changes (P < 0.001) were statistically different between three study groups. Resections of in vivo pig lungs showed no bleeding; 2 of 7 cases of low air leaks were found; however, they ceased by sealing lung parenchyma with harmonic technology. CONCLUSIONS Our experimental data support the resections performed with the use of harmonic technology. The lack of severe tissue alterations could favour healing of parenchyma, assure air tightness and preserve functional lung parenchyma. However, randomized controlled studies are needed in an in vivo model to corroborate our findings

Possible biotic interactions that are affecting the presence of Aedes albopictus (Diptera: Culicidae) in Misiones, Argentina

In Argentina, despite local Aedes albopictus presents a certain degree of egg dormancy that would allow to be present at temperate latitudes its distribution is limited to two provinces with a subtropical climate: Misiones and Corrientes. Therefore, it is possible that other factors are limiting the expansion of this vector. To evaluate possible interactions that are affecting population and spread of this specie, we sampled artificial breeding site in Eldorado (urban environment) and Colonia Aurora (rural environment), Misiones province, in October 2015, April and November 2016 and April 2017.Para acceder a la videoconferencia completa, hacer clic en "Enlace externo".Sociedad Latinoamericana de Ecología de Vectore

Osteotomía de Evans sin injerto óseo en el pie plano estadio IIB del adulto

Objetivo: Evaluar los resultados radiográficos y funcionales al año de la cirugía, en una serie consecutiva de pacientes con diagnóstico de pie plano valgo estadio IIB, sometidos a una osteotomía de Evans sin injerto óseo. Materiales y Métodos: Se evaluó, en forma retrospectiva, a dos grupos de pacientes: grupo 1 (placa con espaciador, n = 12) y grupo 2 (celdas de PEEK, n = 14). La edad promedio era de 47 años (DE 18) en el grupo 1 y de 54 años (DE 12) en el grupo 2. Resultados: Se evaluó a 26 pacientes (28 pies operados); 20 (77%) eran mujeres. Las mediciones radiográficas: ángulo de inclinación del calcáneo, ángulo astrágalo-calcáneo (perfil), ángulo astrágalo-calcáneo (frente), cobertura astragalonavicular, altura de la columna medial, longitud de la columna externa, arrojaron diferencias estadísticamente significativas entre las determinaciones preoperatorias y al año de la cirugía. El puntaje promedio de la escala de la AOFAS al año fue de 96 (DE 4,70) en el grupo 1 y de 95 (DE 4,98) en el grupo 2. El puntaje en la escala analógica visual para dolor fue de 1,2 (DE 0,42) en el grupo 1 y 1,16 (DE 0,46) en el grupo 2. Conclusiones: De acuerdo con los resultados obtenidos, concluimos en que la osteotomía de Evans sin el uso de injerto óseo logra preservar las correcciones obtenidas en el mediano plazo utilizando placas con espaciador o celdas de PEEK