Proof of concept: could snake venoms be a potential source of bioactive compounds for control of mould growth and mycotoxin production

© 2020 The Authors. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.The objective was to screen 10 snake venoms for their efficacy to control growth and mycotoxin production by important mycotoxigenic fungi including Aspergillus flavus, Aspergillus westerdijkiae, Penicillium verrucosum, Fusarium graminearum and F. langsethiae. The Bioscreen C rapid assay system was used. The venoms from the Viperidae snake family delayed growth of some of the test fungi, especially F. graminearum and F. langsethiae and sometimes A. flavus. Some were also able to reduce mycotoxin production. The two most potent crude snake venoms (Naja nigricollis and N. siamensis; 41 and 43 fractions, respectively) were further fractionated and 83/84 of these fractions were able to reduce mycotoxin production by >90% in two of the mycotoxigenic fungi examined. This study suggests that there may be significant potential for the identification of novel fungistatic/fungicidal bioactive compounds as preservatives of raw and processed food commodities post-harvest from such snake venoms.Peer reviewedFinal Published versio

High mobilization of CD133+/CD34+ cells expressing HIF-1α and SDF-1α in septic abdominal surgical patients

Background: The control of endothelial progenitor cells (CD133+/CD34+ EPCs) migrating from bone marrow to peripheral blood is not completely understood. Emerging evidence suggests that stromal cell-derived factor-1α (SDF-1α) mediates egression of EPCs from bone marrow, while the hypoxia inducible factor (HIF) transcriptional system regulates SDF-1α expression. Our study aimed to investigate the time course of circulating CD133+/CD34+ EPCs and its correlation with the expression of HIF-1α protein and SDF-1α in postoperative laparoscopic abdominal septic patients. Methods: Postoperative patients were divided in control (C group) and septic group (S group) operated immediately after the diagnosis of sepsis/septic shock. Blood samples were collected at baseline (0), 1, 3 and 7 postoperative days for CD133+/CD34+ EPCs count expressing or not the HIF-1α and SDF-1α analysis. Results: Thirty-two patients in S group and 39 in C group were analyzed. In C group CD133+/CD34+ EPCs count remained stable throughout the study period, increasing on day 7 (173 [0-421] /μl vs baseline: P = 0.04; vs day 1: P = 0.002). In S group CD133+/CD34+ EPCs count levels were higher on day 3 (vs day 1: P = 0.006 and day 7: P = 0.026). HIF-1α expressing CD133+/CD34+ EPCs count decreased on day 1 as compared with the other days in C group (day 0 vs 1: P = 0.003, days 3 and 7 vs 1: P = 0.008), while it was 321 [0-1418] /μl on day 3 (vs day 1; P = 0.004), and 400 [0-587] /μl on day 7 in S group. SDF-1α levels were higher not only on baseline but also on postoperative day 1 in S vs C group (219 [124-337] pg/ml vs 35 [27-325] pg/ml, respectively; P = 0.01). Conclusion: Our results indicate that sepsis in abdominal laparoscopic patients might constitute an additional trigger of the EPCs mobilization as compared with non-septic surgical patients. A larger mobilization of CD133+/CD34+ EPCs, preceded by enhanced plasmatic SDF-1α, occurs in septic surgical patients regardless of HIF-1α expression therein. Trial registration: ClinicalTrials.gov no. NCT02589535. Registered 28 October 2015

Risk factors for diabetic foot ulcers: An Albanian retrospective study of inpatients with type 2 diabetes

OBJECTIVE: The aim of this study was to assess the impact of glucose control, diabetes-related complications and cardiometabolic risk factors on the risk of diabetic foot ulcers (DFUs) and DFU complications in Albanian adult inpatients with T2D.PATIENTS AND METHODS: We conducted a retrospective case-control study on 482 Albanian adult inpatients with T2D. DFU was defined as a full-thickness skin lesion requiring >= 14 days for healing and was classified at the time of hospital admission. Demographic and biochemical parameters of the study participants, the presence of comorbidities and diabetes -related complications at the time of hospital admission were evaluated through a retrospective chart review.RESULTS: Mean age of study participants was 54.8 +/- 10.7 years. Participants (284 males and 198 females) were divided into two groups: DFU (cases; n=104) and non-DFU (controls; n=378). Multivariate analysis (performed by a logistic regression model) revealed that the most relevant independent variables associated with DFU were BMI [OR= 0.62; p=0.007], HDL-cholesterol [OR=0.00; p<0.0001], triglycerides [OR=7.48; p=0.0004], cigarette smoking [OR=26.46; p=0.005], duration of diabetes [OR=1.53; p<0.0001], fasting plasma glucose (FPG) [OR=1.06; p<0.0001], systolic blood pressure (SBP) [OR=1.13; p=0.0004] and insulin therapy alone [OR=0.11; p=0.02]. ROC curve analysis showed that FPG (AUC=0.83), glycated hemoglobin (HbA1c) (AUC=0.75), triglycerides (AUC=0.78) and HDL-cholesterol (AUC=0.82) were the most reliable biomarkers able to detect DFU. In the DFU group, the most relevant independent variables associated with previous minor lower-extremity amputations (LEAs) were represented by HbA1c [OR=1.47; p=0.03], age <55 years [OR=0.12; p=0.0 5] and female sex [OR=4.18; p=0.03]; whereas the most relevant independent variables associated with diabetic peripheral neuropathy (DPN) were HbA1c [OR=1.70; p=0.006], SBP [OR=1.08; p=0.05], BMI [OR=1.20; p=0.03] and lack of cigarette smoking [OR=0.07; p=0.01]. Correlation analysis (performed through the nonparametric Spearman's rank correlation test or through the parametric Pearson test, as appropriate) revealed a significant positive relationship between HbA1c and FPG (r=0.58; p<0.0001), ulcer surface area (r=0.50; p<0.0001), ulcer grade (r= 0.23; p=0.02), minor LEAs (r=0.20; p=0.04), DPN (r=0.41; p<0.0001), and metformin therapy alone (r=0.72; p<0.0001). There was a significant inverse correlation between HbA1c and insulin therapy alone (r=-0.31; p=0.01) and combined metformin and insulin therapy (r=-0.60; p<0.0001). Both DFU and non-DFU groups exhibited suboptimal mean LDL-cholesterol levels (>100 mg/dl) and mean HbA1c values >7.5%. Moreover, in DFU group HbA1c values were markedly elevated (>= 10%) particularly in patients with a grade 3 ulcer and an ulcer surface area >= 4 cm2, as well as in patients with history of minor LEAs and in patients affected by DPN.CONCLUSIONS: The present study suggested that longer duration of diabetes, cigarette smoking, lower HDL-cholesterol levels, poor glucose control, and elevated triglyceride and SBP values may all represent major risk factors for the development of DFU in Albanian patients with T2D. Thus, community interventions and health policies aimed to improve the management of diabetes and related cardiometabolic risk factors should be urgently implemented in Albania, in order to prevent DFUs and other diabetes complications in patients with T2D

Nucleation of dislocations and their dynamics in layered oxide cathode materials during battery charging

Defects and their interactions in crystalline solids often underpin material properties and functionality as they are decisive for stability, result in enhanced diffusion, and act as a reservoir of vacancies. Recently, lithium-rich layered oxides have emerged among the leading candidates for the next-generation energy storage cathode material, delivering 50 % excess capacity over commercially used compounds. Oxygen-redox reactions are believed to be responsible for the excess capacity, however, voltage fading has prevented commercialization of these new materials. Despite extensive research the understanding of the mechanisms underpinning oxygen-redox reactions and voltage fade remain incomplete. Here, using operando three-dimensional Bragg coherent diffractive imaging, we directly observe nucleation of a mobile dislocation network in nanoparticles of lithium-rich layered oxide material. Surprisingly, we find that dislocations form more readily in the lithium-rich layered oxide material as compared with a conventional layered oxide material, suggesting a link between the defects and the anomalously high capacity in lithium-rich layered oxides. The formation of a network of partial dislocations dramatically alters the local lithium environment and contributes to the voltage fade. Based on our findings we design and demonstrate a method to recover the original high voltage functionality. Our findings reveal that the voltage fade in lithium-rich layered oxides is reversible and call for new paradigms for improved design of oxygen-redox active materials

po 246 nandrolone affects cell growth and differentiation in hepatoma cells

Introduction Hepatocellular carcinoma (HCC) represents the sixth leading cancer and the third most common cause of death from cancer. Many different aetiological factors are involved in the development of HCC, which may be modulated by both estrogens and androgens hormones during its initiation, progression and metastasis. The misuse of anabolic androgenic steroids (AAS) is associated with serious adverse effects to the liver, including cellular adenomas and adenocarcinomas, and is considered a factor risk of developing hepatic sex hormone related tumours. The purpose of this study was to investigate the role of Nandrolone, one of the most commonly used AAS, in regulating proliferation and differentiation of HCC. Material and methods Human HCC cell line HepG2 was treated with Nandrolone, a synthetic androgen ligand, for 48 hs and its viability and proliferation was assessed by MTS and cell cycle analysis, respectively. The expression of protein involved in cell cycle regulation and differentiation markers were analysed by western blot and real time PCR. Measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were performed using Seahorse XF96 extracellular flux analyzer. Respiratory chain complex activities were assayed spectrophotometrically. Stemness surface markers expression was detected by FACSCalibur flow cytometer. Results and discussions Nandrolone treatment caused cell growth inhibition associated to a downregulation of cyclin D1 and an upregulation of the cyclin-dependent kinase inhibitors p21Waf1/Cip1 leading to cell cycle arrest in the G2 phase. Moreover, a significant overall impairment of mitochondrial functions, resulting in a reduced OCR and impairment of OXPHOS complexes activities were also observed, thus suggesting a role in the control of the metabolic reprogramming. Finally, a significant increase of the stemness markers was detected following Nandrolone treatment, also confirmed in additional human stem cell types and in an in vivo mouse model. Conclusion Nandrolone shows a strong anti-proliferative effect in differentiated tumour cells, promoting cancer cells stemness through cellular metabolic reprogramming. These results could have important public health implications in order to improve the primary prevention such as revising altered lifestyles, like AAS abuse

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets

Encapsulation of Nanostructures in a Dielectric Matrix Providing Optical Enhancement in Ultrathin Solar Cells

The incorporation of nanostructures in optoelectronic devices for enhancing their optical performance is widely studied. However, several problems related to the processing complexity and the low performance of the nanostructures have hindered such actions in real-life devices. Herein, a novel way of introducing gold nanoparticles in a solar cell structure is proposed in which the nanostructures are encapsulated with a dielectric layer, shielding them from high temperatures and harsh growth processing conditions of the remaining device. Through optical simulations, an enhancement of the effective optical path length of approximately four times the nominal thickness of the absorber layer is verified with the new architecture. Furthermore, the proposed concept in a Cu(In,Ga)Se2 solar cell device is demonstrated, where the short-circuit current density is increased by 17.4%. The novel structure presented in this work is achieved by combining a bottom-up chemical approach of depositing the nanostructures with a top-down photolithographic process, which allows for an electrical contact.This work was funded in part by the Fundação para a Ciência e a Tecnologia (FCT) under Grants IF/00133/2015, PD/BD/142780/2018 and SFRH/BD/ 146776/2019. The authors also want to acknowledge the European Union’s Horizon 2020 Research and Innovation Programme through the ARCIGS-M project under Grant 720887, the Special Research Fund (BOF) of Hasselt University, the FCT through the project NovaCell (PTDC/CTM-CTM/28075/ 2017), and InovSolarCells (PTDC/FISMAC/29696/2017) co-funded by FCT and the ERDF through COMPETE2020. The authors also want to acknowledge Sandra Maya for the production of images used in this work.info:eu-repo/semantics/publishedVersio

Silencing cytokeratin 18 gene inhibits intracellular replication of Trypanosoma cruzi in HeLa cells but not binding and invasion of trypanosomes

<p>Abstract</p> <p>Background</p> <p>As an obligatory intracellular parasite, <it>Trypanosoma cruzi</it>, the etiological agent of Chagas' disease, must invade and multiply within mammalian cells. Cytokeratin 18 (CK18) is among the host molecules that have been suggested as a mediator of important events during <it>T. cruzi</it>-host cell interaction. Based on that possibility, we addressed whether RNA interference (RNAi)-mediated down regulation of the CK18 gene could interfere with the parasite life cycle <it>in vitro</it>. HeLa cells transiently transfected with CK18-RNAi had negligible levels of CK18 transcripts, and significantly reduced levels of CK18 protein expression as determined by immunoblotting or immunofluorescence.</p> <p>Results</p> <p>CK18 negative or positive HeLa cells were invaded equally as well by trypomastigotes of different <it>T. cruzi </it>strains. Also, in CK18 negative or positive cells, parasites recruited host cells lysosomes and escaped from the parasitophorous vacuole equally as well. After that, the growth of amastigotes of the Y or CL-Brener strains, was drastically arrested in CK18 RNAi-treated cells. After 48 hours, the number of amastigotes was several times lower in CK18 RNAi-treated cells when compared to control cells. Simultaneous staining of parasites and CK18 showed that in HeLa cells infected with the Y strain both co-localize. Although the amastigote surface protein-2 contains the domain VTVXNVFLYNR previously described to bind to CK18, in several attempts, we failed to detect binding of a recombinant protein to CK-18.</p> <p>Conclusion</p> <p>The study demonstrates that silencing CK18 by transient RNAi, inhibits intracellular multiplication of the Y and CL strain of <it>T. cruzi </it>in HeLa cells, but not trypanosome binding and invasion.</p

Stakeholders, collaboration, food, and wine: The case of Jumilla’s Gastronomic Days

An emerging literature on gastronomic events highlights the growing interest among academics, event organisers and development agencies in identifying potential or actual outcomes from gastronomic events. Partly in response to such interest, this study seeks to contribute to the literature on events management, studying the contribution of various stakeholders involved in the ‘Gastronomic Days’ of Jumilla, Spain. Semi-structured, face-to-face, in-depth interviews were conducted with the managers and owners of four participating businesses to the event. The data collection was complemented through on-site visits, observations, and interviews with eight other local businesses. The findings underline the significance of collaboration among these participants to grow and sustain the event, as well as voluntary efforts by event ‘stakeholders.’ Importantly, a common objective was identified in the form of enhancing the image of the local products, and overall that of the region, to ‘convert’ residents, and also outside consumers and tourists to Jumilla’s products. These findings have significant implications for Jumilla’s community. In particular, the importance and efforts of a region’s food stakeholders in contributing to adding value and improving the local food culture emerge as useful aspects, with potential benefits for local food growers, hospitality and tourism sectors, and residents

Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling following infection

<p>Abstract</p> <p>Background</p> <p>Gut homeostasis is central to whole organism health, and its disruption is associated with a broad range of pathologies. Following damage, complex physiological events are required in the gut to maintain proper homeostasis. Previously, we demonstrated that ingestion of a nonlethal pathogen, <it>Erwinia carotovora carotovora 15</it>, induces a massive increase in stem cell proliferation in the gut of <it>Drosophila</it>. However, the precise cellular events that occur following infection have not been quantitatively described, nor do we understand the interaction between multiple pathways that have been implicated in epithelium renewal.</p> <p>Results</p> <p>To understand the process of infection and epithelium renewal in more detail, we performed a quantitative analysis of several cellular and morphological characteristics of the gut. We observed that the gut of adult <it>Drosophila </it>undergoes a dynamic remodeling in response to bacterial infection. This remodeling coordinates the synthesis of new enterocytes, their proper morphogenesis and the elimination of damaged cells through delamination and anoikis. We demonstrate that one signaling pathway, the epidermal growth factor receptor (EGFR) pathway, is key to controlling each of these steps through distinct functions in intestinal stem cells and enterocytes. The EGFR pathway is activated by the EGF ligands, Spitz, Keren and Vein, the latter being induced in the surrounding visceral muscles in part under the control of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Additionally, the EGFR pathway synergizes with the JAK/STAT pathway in stem cells to promote their proliferation. Finally, we show that the EGFR pathway contributes to gut morphogenesis through its activity in enterocytes and is required to properly coordinate the delamination and anoikis of damaged cells. This function of the EGFR pathway in enterocytes is key to maintaining homeostasis, as flies lacking EGFR are highly susceptible to infection.</p> <p>Conclusions</p> <p>This study demonstrates that restoration of normal gut morphology following bacterial infection is a more complex phenomenon than previously described. Maintenance of gut homeostasis requires the coordination of stem cell proliferation and differentiation, with the incorporation and morphogenesis of new cells and the expulsion of damaged enterocytes. We show that one signaling pathway, the EGFR pathway, is central to all these stages, and its activation at multiple steps could synchronize the complex cellular events leading to gut repair and homeostasis.</p