The CRE-Like Element Inside the 5′-Upstream Region of the Rat Sodium/Iodide Symporter Gene Interacts with Diverse Classes of b-Zip Molecules that Regulate Transcriptional Activities through Strong Synergy with Pax-8

AbstractWe previously demonstrated that transcription of the rat sodium/iodide symporter (NIS) gene is regulated by NUE, an upstream enhancer located between nucleotides −2264 and −2495 of the 5′-flanking region. To elucidate the mechanism of TSH/cAMP-mediated regulation of NIS gene expression, we have characterized the putative cAMP response element (CRE)/activator protein (AP)-1 site (termed NUC) that is closely located between the two Pax-8 (paired box domain transcription factor-8) binding sites within NUE. In two different approaches using either gel supershift analyses or dominant-negative inhibitors of b-Zip molecules, we have shown that NUC can be recognized by several members of the AP-1 and CREB family transcription factors that modulate the transcriptional activity of NUE. Using tethered dimers of b-Zip molecules, we have also demonstrated that specific homo- or heterodimers of AP-1 can synergistically stimulate NUE activity in concert with Pax-8. To demonstrate further that NUC is a bona fide CRE, we made an artificial promoter with the five-time tandem repeat of this sequence (5xNUC). In comparison to the canonical CRE (5xCRE), 5xNUC manifested greater transcriptional activity and broader response to cAMP signaling. Hence, we postulate that the significance of this evolutionally conserved CRE-like site may lie in its broader cell type specificity

Prevalence of obesity and obesity-associated muscle wasting in patients on peritoneal dialysis

Background and aims: A progressive decrease in muscle mass until full-blown sarcopenia may occur in patients on peritoneal dialysis (PD) and worsen their life quality and expectancy. Here we investigate the prevalence of obesity and obesity-associated muscle wasting in PD patients. Patients and methods: The study design was observational, cross sectional. Body composition was assessed with BIA and BIVA in 88 PD patients (53.4 ± 13.1 years; 67% male). Patients with obesity and/or with reduced muscle mass were identified using FMI and SM/BW cutoff values, respectively. Inflammatory status was assessed by measuring CRP and fibrinogen blood levels. Results: A total of 44.3% of the patients showed a reduced muscle mass (37.5% moderate and 6.8% severe). The prevalence of obesity was 6.1%, 81.8%, and 100% in patients with normal, moderately, and severely reduced muscle mass, respectively (p < 0.05). Of the total, 15.2% of the patients with normal muscle mass, 18.4% of those with moderately reduced muscle mass, and 66.7% of those with severely reduced muscle mass had diabetes. The prevalence of severe muscle mass loss was higher in those with diabetes than in those without diabetes (22.2% vs. 2.8%, p < 0.05). Patients with obesity-associated muscle wasting showed higher fibrinogen (613.9 ± 155.1 vs. 512.9 ± 159.5 mg/dL, p < 0.05) and CPR (1.4 ± 1.3 vs. 0.6 ± 0.8 mg/dL, p < 0.05) blood concentrations than those with normal body composition. Conclusion: Obesity and diabetes were strongly associated with muscle mass loss in our PD patients. It remains to be established whether prevention of obesity with nutritional interventions can halt the occurrence of muscle mass loss in patients on PD

Soft tissue regeneration using leukocyte-platelet rich fibrin after exeresis of hyperplastic gingival lesions: Two case reports

Introduction The Leukocyte-PRF (Leukocyte-Platelet Rich Fibrin) belongs to a second generation of platelet concentrates which doesn’t need a biochemical blood manipulation. It is used for tissue healing and regeneration in periodontal and oral-maxillofacial surgery. We report two cases of hyperplastic gingival lesions treated by exeresis and application of PRF membranes in order to improve and accelerate tissue healing. Case Presentation Two patients (one Caucasian female, 78-year-old, and one Caucasian male, 30-year-old) were treated for hyperplastic gingival lesions. They underwent to exeresis of lesions and application of PRF membranes. Tissue healing was clinically evaluated after one, three, seven, fourteen and thirty post-operative days. No recurrences were observed after two years of semiannual follow up. Conclusion We obtained rapid and good healing of soft tissues probably due to the elevated content of leukocytes, platelets and growth factors in the leukocyte-platelet rich fibrin. According to our results we suggest L-PRF employment for wounds covering after exeresis of oral neoformations such as hyperplastic gingival lesions

Linking migraine to gut dysbiosis and chronic non-communicable diseases

In the world, migraine is one of the most common causes of disability in adults. To date, there is no a single cause for this disorder, but rather a set of physio-pathogenic triggers in combination with a genetic predisposition. Among the factors related to migraine onset, a crucial role seems to be played by gut dysbiosis. In fact, it has been demonstrated how the intestine is able to modulate the central nervous system activities, through the gut-brain axis, and how gut dysbiosis can influence neurological pathologies, including migraine attacks. In this context, in addition to conventional pharmacological treatments for migraine, attention has been paid to an adjuvant therapeutic strategy based on different nutritional approaches and lifestyle changes able to positively modulate the gut microbiota composition. In fact, the restoration of the balance between the different gut bacterial species, the reconstruction of the gut barrier integrity, and the control of the release of gut-derived inflammatory neuropeptides, obtained through specific nutritional patterns and lifestyle changes, represent a possible beneficial additive therapy for many migraine subtypes. Herein, this review explores the bi-directional correlation between migraine and the main chronic non-communicable diseases, such as diabetes mellitus, arterial hypertension, obesity, cancer, and chronic kidney diseases, whose link is represented by gut dysbiosis

Characterization of Strombolian events by using independent component analysis

We apply Independent Component Analysis (ICA) to seismic signals recorded at Stromboli volcano. Firstly, we show how ICA works considering synthetic signals, which are generated by dynamical systems. We prove that Strombolian signals, both tremor and explosions, in the high frequency band (>0.5 Hz), are similar in time domain. This seems to give some insights to the organ pipe model generation for the source of these events. Moreover, we are able to recognize in the tremor signals a low frequency component (<0.5 Hz), with a well defined peak corresponding to 30s

Systemic treatment of malignant gastrointestinal neuroectodermal tumour after childhood neuroblastoma: chemotherapy in malignant gastrointestinal neuroectodermal tumour

Malignant gastrointestinal neuroectodermal tumour is an extremely rare neoplasm that arises in the wall of the small bowel, stomach or large bowel in youngaged and middle-aged adults. Histologically, it is generally characterized by monomorphic cells with clear cytoplasma, S-100 protein expression, and EWSR1 gene translocation. To the best of our knowledge, we describe for the first time, the case of a young woman with a diagnosis of metastatic gastrointestinal neuroectodermal tumour arising from ileum, who had a childhood adrenal neuroblastoma with liver, bone and lymph nodes metastasis, treated with four cycles of chemotherapy with the schedule CADO-CVP (CADO: cyclophosphamide 300 mg/m2/day on days 1–5, vincristine 1,5 mg/m2/ day on days 1 and 5, and doxorubicin 60 mg/m2/day on day 5; CVP: cisplatin 40 mg/m2/day on days 1–5 and etoposide 100 mg/m2/day on days 1–5) followed by right adrenal, kidney, lymph nodes and liver lesion resection, conditioning chemotherapy (melphalan-carmustineteniposide), stem cells autologous transplantation and consecutively radiotherapy on the spine (T9 to L3) for a total of 30 Gy. For the second diagnosis of gastrointestinal neuroectodermal tumour with liver metastasis, she underwent ileal tumour resection and platinum-anthracycline based chemotherapy with initial shrinkage of liver metastasis. Unfortunately, despite the initial response and the following delivered therapies, she died for rapid progressive disease. Taking into account the late effects of past therapeutic modalities, a long-term surveillance of young child treated for neuroblastoma, is required to appreciate their overall risks of second malignancies

Statistical and agent-based modelling of the transmissibility of different SARS-CoV-2 variants in England and impact of different interventions

The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and the agent-based model Covasim, in June 2021, to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50-80% more transmissible than B.1.177 and Delta to be 65-90% more transmissible than Alpha. Using these estimates in Covasim (calibrated 1 September 2020 to 20 June 2021), in June 2021, we found that due to the high transmissibility of Delta, resurgence in infections driven by the Delta variant would not be prevented, but would be strongly reduced by delaying the relaxation of restrictions by one month and with continued vaccination. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'

Penile cancer: prognostic and predictive factors in clinical decision-making

: Penile cancer (PC) is a typical tumor of non-industrialized countries. The incidence is 20-30 times higher in Africa and South America, considering the elevated prevalence of sexually transmitted diseases. Histologically, PC includes squamous cell carcinoma (SCPC), the most frequent, and nonsquamous carcinoma (NSCPC). Early diagnosis is the goal, whereas later diagnosis relates to poor functional outcomes and worse prognosis. The 5-year survival rate is 85% for patients with histologically regional negative lymph nodes, compared to 29%-40% for those with histologically regional positive lymph nodes. To date no new drugs are approved, and there are few new data about molecular mechanisms underlying tumorigenesis. The SCPC remains a rare tumor and the current therapeutic algorithm is based principally on retrospective analysis and less on prospective trials. In this review article, biomarkers of prognosis and efficacy of current treatments are summarized with a focus on those that have the potential to affect treatment decision-making in SCPC

1H-NMR metabolomics reveals the Glabrescione B exacerbation of glycolytic metabolism beside the cell growth inhibitory effect in glioma

BACKGROUND: Glioma is the most common and primary brain tumors in adults. Despite the available multimodal therapies, glioma patients appear to have a poor prognosis. The Hedgehog (Hh) signaling is involved in tumorigenesis and emerged as a promising target for brain tumors. Glabrescione B (GlaB) has been recently identified as the first direct inhibitor of Gli1, the downstream effector of the pathway. METHODS: We established the overexpression of Gli1 in murine glioma cells (GL261) and GlaB effect on cell viability. We used 1H-nuclear magnetic resonance (NMR) metabolomic approach to obtain informative metabolic snapshots of GL261 cells acquired at different time points during GlaB treatment. The activation of AMP activated protein Kinase (AMPK) induced by GlaB was established by western blot. After the orthotopic GL261 cells injection in the right striatum of C57BL6 mice and the intranasal (IN) GlaB/mPEG5kDa-Cholane treatment, the tumor growth was evaluated. The High Performance Liquid Chromatography (HPLC) combined with Mass Spectrometry (MS) was used to quantify GlaB in brain extracts of treated mice. RESULTS: We found that GlaB affected the growth of murine glioma cells both in vitro and in vivo animal model. Using an untargeted 1H-NMR metabolomic approach, we found that GlaB stimulated the glycolytic metabolism in glioma, increasing lactate production. The high glycolytic rate could in part support the cytotoxic effects of GlaB, since the simultaneous blockade of lactate efflux with \u3b1-cyano-4-hydroxycinnamic acid (ACCA) affected glioma cell growth. According to the metabolomic data, we found that GlaB increased the phosphorylation of AMPK, a cellular energy sensor involved in the anabolic-to-catabolic transition. CONCLUSIONS: Our results indicate that GlaB inhibits glioma cell growth and exacerbates Warburg effect, increasing lactate production. In addition, the simultaneous blockade of Gli1 and lactate efflux amplifies the anti-tumor effect in vivo, providing new potential therapeutic strategy for this brain tumor

Tyrosol may prevent obesity by inhibiting adipogenesis in 3T3-L1 preadipocytes

Tyrosol (TR), a major polyphenol found in extra virgin olive oil (EVOO), exerts several antioxidant effects. However, only scarce evidences are present regarding its activity on adipocytes and obesity. This study evaluated the role of TR in adipogenesis. Murine 3T3-L1 preadipocytes were incubated with TR (300 and 500 μM), and TR administration inhibited adipogenesis by downregulation of several adipogenic factors (leptin and aP2) and transcription factors (C/EBPα, PPARγ, SREBP1c, and Glut4) and by modulation of the histone deacetylase sirtuin 1. After complete differentiation, adipocytes treated with 300 and 500 μM TR showed a reduction of 20% and 30% in lipid droplets, respectively. Intracellular triglycerides were significantly reduced after TR treatment (p &lt; 0.05). Mature adipocytes treated with TR at 300 and 500 μM showed a marked decrease in the inflammatory state and oxidative stress as shown by the modulation of specific biomarkers (TNF, IL6, ROS, and SOD2). TR treatment also acted on the early stage of differentiation by reducing cell proliferation (~40%) and inducing cell cycle arrest during Mitotic Expansion Clonal (first 48 h of differentiation), as shown by the increase in both S1 phase and p21 protein expression. We also showed that TR induced lipolysis by activating the AMPK-ATGL-HSL pathway. In conclusion, we provided evidence that TR reduces 3T3-L1 differentiation through downregulation of adipogenic proteins, inflammation, and oxidative stress. Moreover, TR may trigger adipose tissue browning throughout the induction of the AMPK-ATGL-UCP1 pathway and, subsequently, may have promise as a potential therapeutic agent for the treatment and prevention of obesity