Ion Channel Involvement in Tumor Drug Resistance

Over 90% of deaths in cancer patients are attributed to tumor drug resistance. Resistance to therapeutic agents can be due to an innate property of cancer cells or can be acquired during chemotherapy. In recent years, it has become increasingly clear that regulation of membrane ion channels is an important mechanism in the development of chemoresistance. Here, we review the contribution of ion channels in drug resistance of various types of cancers, evaluating their potential in clinical management. Several molecular mechanisms have been proposed, including evasion of apoptosis, cell cycle arrest, decreased drug accumulation in cancer cells, and activation of alternative escape pathways such as autophagy. Each of these mechanisms leads to a reduction of the therapeutic efficacy of administered drugs, causing more difficulty in cancer treatment. Thus, targeting ion channels might represent a good option for adjuvant therapies in order to counteract chemo-resistance development

Exploiting the photoactivity of bacterial reaction center to investigate liposome dynamics

Charge recombination kinetics of bacterial photosynthetic protein Reaction Center displays an exquisite sensitivity to the actual occupancy of ubiquinone-10 in its QB-binding site. Here, we have exploited such phenomenon for assessing the growth and the aggregation/fusion of phosphocholine vesicles embedding RC in their membrane, when treated with sodium oleate

Detection of honey bee viruses in larvae of Vespa orientalis

The Oriental hornet (Vespa orientalis) is native to the southeastern Mediterranean, north-eastern and eastern Africa, the Middle East, Central Asia and it is well established in southern Italy. However, recent reports in Liguria, Trieste and Tuscany show great expansion of its areal probably due to climate change or involuntary anthropic actions. Adults feed on carbohydrates collected from fruit and nectar while brood is fed by workers with animal proteins (grasshoppers, flies, yellowjackets and bees). The interaction between the two species could lead to possible spillover of pathogens in both directions. Previous studies have already reported the presence of honey bee pathogens (virus, fungi and bacteria), in Vespae and have underlined their role in disseminating pathogens which could represent a threat for honey bees. Aim of this study was to detect the presence in V.orientalis of six honey bee viruses, more precisely Acute Bee Paralysis Virus (ABPV), Black Queen Cell Virus (BQCV), Chronic Bee Paralysis Virus (CBPV), Deformed Wing Virus (DWV), Kashmir Bee Virus (KBV), Sac Brood Virus (SBV), and to investigate possible transmission route. 30 adults and 29 larvae of V.orientalis and 2 pools of 10 honey bees (Apis mellifera ligustica) each were collected from the managed nest and apiary located both at the Department of Agricultural, Food and Forest Sciences-University of Palermo, and sent to the Department of Veterinary Medicine and Animal Productions- University of Naples “Federico II”. Samples were observed by stereomicroscope to assess possible alterations which could be indicative of the action of viruses and then subjected to multiplex PCR to detect viruses. No morphological alterations were identified despite the biomolecular results showed 25/30 adults and 24/29 larvae were infected with at least one virus (DWV). Adult samples presented also ABPV (19/30), BQCV (13/30), SBV (1/30); while larvae presented SBV (10/29), ABPV (5/29), BQCV (5/29). No sample resulted positive for CBPV and only 1/30 adult resulted positive for KBV. Honey bees’ positivities reflected those of the hornets: 2/2 DWV, 2/2 SBV, 2/2 BQCV and 1/2 ABPV. The viruses detected in our study are the most prevalent in apiaries across Italy and the overlapping of positivities between hornets and honey bees collected in the same site suggests possible transmission of honey bee viruses through ingestion of infected honey bees

Exploring the neuroanatomical bases of psychotic features in bipolar disorder

Although bipolar disorder (BD) is traditionally conceptualised as one diagnostic entity, the heterogeneity of pathophysiological manifestations in BD suggests the need to classify the subtypes of the illness based on neural markers. Specifically, the presence of psychotic symptoms seems to be relevant for the clinical outcome and may have specific neuroanatomical bases. The main objective of the present review was to assess whether the distinction between psychotic BD (PBD) and non-psychotic BD (NPBD) can improve the identification of the neurobiological markers of this complex illness. To this end, we summarised the findings from the magnetic resonance imaging studies that explored the cerebral correlates of psychosis in BD in terms of grey matter volume (GMV). Overall, the results suggest the presence of peculiar GMV differences between PBD and NPBD. Specifically, psychosis in BD seems to be associated with cortical GMV deficits compared with both healthy controls and NPBD, mainly in the frontal region. Conversely, NPBD patients showed GMV deficits in selective regions of the basal ganglia when compared with the other groups. Taken together, this evidence confirms the importance to classify BD based on the psychotic dimension, which may have a specific neurobiological architecture that partially overlaps across multiple psychotic disorders

The association between the serotonin and dopamine neurotransmitters and personality traits

Evidence from previous studies has reported that complex traits, including psychiatric disorders, are moderately to highly heritable. Moreover, it has also been shown that specific personality traits may increase the risk to develop mental illnesses. Therefore the focus of the research shifted towards the identification of the biological mechanisms underpinning these traits by exploring the effects of a constellation of genetic polymorphisms in healthy subjects. Indeed, studying the effect of genetic variants in normal personality provides a unique means for identifying candidate genes which may increase the risk for psychiatric disorders. In this review, we discuss the impact of two of the most frequently studied genetic polymorphisms on personality in healthy subjects, the 5-HTT polymorphism of the serotonin transporter and the DRD2/DRD4 polymorphisms of the D2/D4 dopamine's receptors. The main aims are: (a) to highlight that the study of candidate genes provides a fruitful ground for the identification of the biological underpinnings of personality without, though, reaching a general consensus about the strength of this relationship; and (b) to outline that the research in personality genetics should be expanded to provide a clearer picture of the heritability of personality traits

The Small Molecule BIBR1532 Exerts Potential Anti-cancer Activities in Preclinical Models of Feline Oral Squamous Cell Carcinoma Through Inhibition of Telomerase Activity and Down-Regulation of TERT

Expression of telomerase reverse transcriptase (TERT) and telomerase activity (TA) is a main feature of cancer, contributing to cell immortalization by causing telomeres dysfunction. BIBR1532 is a potent telomerase inhibitor that showed potential anti-tumor activities in several types of cancer, by triggering replicative senescence and apoptosis. In a previous work, we detected, for the first time, TERT expression and TA in preclinical models of feline oral squamous cell carcinoma (FOSCC); therefore, we aimed at extending our investigation by testing the effects of treatment with BIBR1532, in order to explore the role of telomerase in this tumor and foreshadow the possibility of it being considered as a future therapeutic target. In the present study, treatment of FOSCC cell lines SCCF1, SCCF2, and SCCF3 with BIBR1532 resulted in successful inhibition of TA, with subsequent cell growth stoppage and decrease in cell viability. Molecular data showed that up-regulation of cell cycle inhibitor p21, unbalancing of Bax/Bcl-2 ratio, and down-regulation of survival gene Survivin were mostly involved in the observed cellular events. Moreover, BIBR1532 diminished the expression of TERT and its transcriptional activator cMyc, resulting in the down-regulation of epidermal growth factor receptor (EGFR), phospho-ERK/ERK ratio, and matrix metalloproteinases (MMPs)-1/-2 and−9, likely as a consequence of an impairment of TERT extra-telomeric functions. Taken together, our data suggest that BIBR1532 exerts multiple anti-cancer activities in FOSCC by inhibiting telomerase pathway and interfering with signaling routes involved in cell proliferation, cell survival, and invasion, paving the way for future translational studies aimed at evaluating its possible employment in the treatment of this severe tumor of cats

The treatment of peri-implant diseases: A new approach using HYBENX® as a decontaminant for implant surface and oral tissues

Background: Peri-implantitis is a pathological condition characterized by an inflammatory process involving soft and hard tissues surrounding dental implants. The management of periimplant disease has several protocols, among which is the chemical method HYBENX®. The aim of this study is to demonstrate the efficacy of HYBENX® in the treatment of peri-implantitis and to compare HYBENX® with other chemical agents used in the surgical treatment of peri-implantitis. Methods: The present study included a population of ten subjects with severe peri-implantitis. The procedure used in the study involves the application of HYBENX® after open-flap debridement. Each patient has been followed for 12 months after a single application of the decontaminant agent. Clinical and radiographical parameters were recorded at baseline, 3 months, and 12 months after treatment completion. Results: At baseline, a mean pocket probing depth (PPD) of 7.3 - 0.5 mm and a mean clinical attachment level (CAL) of 8.8 - 0.8 mm was recorded. An average residual PPD of 4.2 - 0.5 mm and a mean CAL of 5.2 - 0.8 mm were observed after 1 year. Additionally, the average of bone gain was about 3.4 mm, with a mean marginal bone level (MBL) change from 5.8 mm (baseline) to 2.4 mm (12 months). In total, 90% of the treated implants reached the success rate after the 1-year follow-up. Only in one case out of ten treated implants was resolution of the disease not achieved. Conclusion: Clinical improvements highlight that the procedure of open-flap debridement (OFD) + HYBENX® may be considered an effective technique in the treatment of peri-implantitis. From the results obtained, it can be concluded that the use of HYBENX® in the surgical treatment of peri-implantitis is promising. Overall, this protocol demands further studies to better understand the role and potential benefits of HYBENX® in the treatment of peri-implantitis

Psychosomatic syndromes are associated with IL-6 pro-inflammatory cytokine in heart failure patients

Psychosomatic syndromes have emerged as an important source of comorbidity in cardiac patients and have been associated with increased risk for adverse outcomes in patients with heart failure (HF). Understanding of the mechanisms underlying this connection is limited, however immune activity represents a possible pathway. While there have been numerous studies connecting immune activity to psychosomatic psychopathology, there is a lack of research on patients with HF. We examined forty-one consecutive outpatients affected by HF. We assessed psychosomatic psychopathology using the Diagnostic Criteria for Psychosomatic Research (DCPR) and the Patient Health Questionnaire-15 (PHQ-15). The Psychosocial Index (PSI) was used for assessing stress and psychosocial dimensions. Depression was evaluated with Beck Depression Inventory-II (BDI-II). Circulating levels of proinflammatory cytokines IL-6 and TNF-alpha were ascertained. Univariate and multivariable regression models were used to test for associations between inflammatory cytokines and psychosomatic psychopathology (i.e., DCPR syndromes, PHQ-15) and psychological dimensions (i.e., BDI-II, PSI). A significant positive correlation was found between IL-6 levels and psychosomatic psychopathology even when controlling for any confounding variables (i.e., Body-mass index (BMI), New York Heart Association (NYHA) class, smoking habits, alcohol consumption, statin use, aspirin use, beta blockers use, age, and gender). In contrast, the associations between TNF-alpha levels were non-significant. These findings can contribute to research in support of a psychoneuroimmune connection between psychosomatic psychopathology and HF. Findings also suggest the possibility that elevated IL-6 levels are more relevant for the pathogenesis of psychosomatic syndromes than for depression in patients with HF

The PAMELA Storage and Control Unit

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