A novel synthetic peptide from a tomato defensin exhibits antibacterial activities against Helicobacter pylori

Defensins are a class of cysteine-rich proteins, which exert broad spectrum antimicrobial activity. In this work, we used a bioinformatic approach to identify putative defensins in the tomato genome. Fifteen proteins had a mature peptide that includes the well-conserved tetradisulfide array. We selected a representative member of the tomato defensin family; we chemically synthesized its gamma-motif and tested its antimicrobial activity. Here, we demonstrate that the synthetic peptide exhibits potent antibacterial activity against Gram-positive bacteria, such as Staphylococcus aureus A170, Staphylococcus epidermidis, and Listeria monocytogenes, and Gram-negative bacteria, including Salmonella enterica serovar Paratyphi, Escherichia coli, and Helicobacter pylori. In addition, the synthetic peptide shows minimal (<5%) hemolytic activity and absence of cytotoxic effects against THP-1 cells. Finally, SolyC exerts an anti-inflammatory activity in vitro, as it downregulates the level of the proinflammatory cytokines TNF-alpha and IFN-gamma

Nutritional controlled preparation and administration of different tomato purées indicate increase of β-carotene and lycopene isoforms, and of antioxidant potential in human blood bioavailability: A pilot study

The isoforms of lycopene, carotenoids, and their derivatives including precursors of vitamin A are compounds relevant for preventing chronic degenerative diseases such as cardiovascular diseases and cancer. Tomatoes are a major source of these compounds. However, cooking and successive metabolic processes determine the bioavailability of tomatoes in human nutrition. To evaluate the effect of acute/chronic cooking procedures on the bioavailability of lycopene and carotene isoforms in human plasma, we measured the blood levels of these compounds and of the serum antioxidant potential in volunteers after a meal containing two different types of tomato sauce (rustic or strained). Using a randomized cross-over administration design, healthy volunteers were studied, and the above indicated compounds were determined by HPLC. The results indicate an increased bioavailability of the estimated compounds and of the serum antioxidant potential with both types of tomato purée and the subsequently derived sauces (the increase was greater with strained purée). This study sheds light on the content of nutrient precursors of vitamin A and other antioxidant compounds derived from tomatoes cooked with different strategies. Lastly, our study indicates that strained purée should be preferred over rustic purée

Pentacyclic triterpenes from Terminalia arjuna show multiple benefits on aged and dry skin

BACKGROUND Pentacyclic triterpenoids improve epidermal barrier function and induce collagen production. Here, their effects on cutaneous aging by means of objective instrumental measurements were elucidated. METHODS Reconstituted human epidermis, cultivated keratinocytes and fibroblasts were incubated with Terminalia arjuna triterpenes (T. arjuna bark extract), and mRNA and protein expression of various genes was determined using microarray analysis, qRT-PCR and ELISA techniques. Clinical efficacy of T. arjuna bark extract versus vehicle control cream was elucidated in 30 patients and transepidermal water loss (TEWL), skin hydration and elasticity were measured. Another 30 female patients in their postmenopausal phase were treated with a similar regime, and skin sebum content, cutaneous blood microcirculation and skin density/echogenicity were assessed. RESULTS Incubation with T. arjuna triterpenes increased FGF-2, TSP-1, TGF-\textgreekb and CTGF expression, and VEGF secretion in vitro. Elevated lactate dehydrogenase release upon sodium dodecyl sulphate challenge was reversed by the application of T. arjuna bark extract. T. arjuna bark extract decreased TEWL, improved skin moisturization, reduced scaliness and led to significantly improved skin elasticity. Also, increases in blood microflow and skin sebum content as well as improved skin thickness/echogenicity were noted on postmenopausal skin, resulting in visible reduction of sagging skin on the jowls as demonstrated by digital photography. CONCLUSION T. arjuna bark extract appears as an innovative active ingredient that exerts versatile antiaging properties in vitro and in vivo

The Salmonella effector SteD mediates MARCH8-1 dependent ubiquitination of MHC II molecules and inhibits T cell activation

The SPI-2 type III secretion system (T3SS) of intracellular Salmonella enterica translocates effector proteins into mammalian cells. Infection of antigen-presenting cells results in SPI-2 T3SS-dependent ubiquitination and reduction of surface-localized mature MHC class II (mMHCII). We identify the effector SteD as required and sufficient for this process. In Mel Juso cells, SteD localized to the Golgi network and vesicles containing the E3 ubiquitin ligase MARCH8 and mMHCII. SteD caused MARCH8-dependent ubiquitination and depletion of surface mMHCII. One of two transmembrane domains and the C-terminal cytoplasmic region of SteD mediated binding to MARCH8 and mMHCII, respectively. Infection of dendritic cells resulted in SteD-dependent depletion of surface MHCII, the co-stimulatory molecule B7.2, and suppression of T cell activation. SteD also accounted for suppression of T cell activation during Salmonella infection of mice. We propose that SteD is an adaptor, forcing inappropriate ubiquitination of mMHCII by MARCH8 and thereby suppressing T cell activation

Selecting b-thalassemia patients for gene therapy: a decision-making algorithm

The Societ\ue0 Italiana Talassemie ed Emoglobinopatie (Italian Society of Thalassemias and Hemoglobinopathies, SITE) has developed this document based on multidisciplinary discussions of a panel of experts to provide guidance on the identification and selection of patients with transfusion-dependent beta-thalassemia (\u3b2-TDT) who could benefit from gene therapy. Currently, allogeneic transplantation of hematopoietic stem cells is the only curative and most widely used therapy treatment for \u3b2-TDT. However, recent trials of gene therapy have reported very promising results in terms of overall survival and thalassemia-free survival and are opening a new landscape of treatment. This algorithm for the selection of patients suitable for gene therapy and the supporting notes were formulated by consensus review after an evaluation of currently available scientific evidence using validated criteria. The evidence was interpreted with caution because clinical trial experience of gene therapy is currently limited, a conventional treatment is available for patients with \u3b2-TDT and the availability of gene therapy will, at least initially, be quite limited. Clinical experience of allogeneic transplantation in \u3b2-TDT, which began in 1981, immediately showed the importance of patient risk stratification in order to achieve the best results (see the Pesaro experience and their classification of patients according to risk). Published data in the literature and the recent analysis of clinical evidence by the European Registry of Hemoglobinopathies of a large number of patients (2011 and 2018 analyses) confirm that young patient age (&lt;14 years) and the availability of a human leukocyte antigen (HLA)-identical family donor are factors that offer the best outcome from allogeneic transplantation. Current knowledge of, and experience with, non-conventional treatments, such as allogeneic transplantation and gene therapy, are discussed in order to identify the best available treatment and indication for these patients according to their characteristics. At this point in time, when we can see the emergence of \u2018the age of gene therapy\u2019, it is essential to establish the optimal patient setting in which gene therapy can be applied, or better, to define the setting that represents the most suitable indication for gene therapy, identify the patients who should have clinical priority for access to the procedure, and set out requirements and recommendations for the identification of qualified treatment centers for gene therapy. When considering changes to the treatment of patients with \u3b2-TDT, including gene therapy, it is essential that a detailed consultation is held with the patient and their caregiver/family to discuss all possible risks and potential benefits from the treatment. Discussion of this aspect of care is outside of the scope of this document but remains an important element of patient care

The TES-based Cryogenic AntiCoincidence Detector (CryoAC) of ATHENA X-IFU: a large area silicon microcalorimeter for background particles detection

We are developing the Cryogenic AntiCoincidence detector (CryoAC) of the ATHENA X-IFU spectrometer. It is a TES-based particle detector aimed to reduce the background of the instrument. Here, we present the result obtained with the last CryoAC single-pixel prototype. It is based on a 1 cm2 silicon absorber sensed by a single 2mm x 1mm Ir/Au TES, featuring an on-chip heater for calibration and diagnostic purposes. We have illuminated the sample with 55Fe (6 keV line) and 241Am (60 keV line) radioactive sources, thus studying the detector response and the heater calibration accuracy at low energy. Furthermore, we have operated the sample in combination with a past-generation CryoAC prototype. Here, by analyzing the coincident detections between the two detectors, we have been able to characterize the background spectrum of the laboratory environment and disentangle the primary (i.e. cosmic muons) and secondaries (mostly secondary photons and electrons) signatures in the spectral shape.Comment: Accepted for publication in the Journal of Low Temperature Physics for LTD-20 special issu

Characterization of the inflammatory cell infiltrate and expression of costimulatory molecules in chronic echinococcus granulosus infection of the human liver

Background: The local immune responses to chronic echinococcal infections in various organs are largely unknown. Since the liver is the most frequently involved organ in such infections in human we aimed to characterize the inflammatory as well as immune cell infiltrate around hydatid cysts in the liver and compared to common inflammatory processes of the liver. Method: Surgical samples from the liver of 21 cystic echinococcosis (CE) patients were studied and the distribution of different types of inflammatory and immune cells were determined by immunohistochemistry. Furthermore, expression levels of costimulatory CTLA4, CD28, CD80 and CD86 molecules were measured at RNA level by PCR. Liver biopsy samples from patients with steatohepatitis (SH, n = 11) and chronic hepatitis (CH, n = 11) were used as non-inflammatory and chronic inflammatory controls, respectively. The composition and density of the inflammatory and immune cell infiltrates have been compared by using morphometry. Results: CD3+ T cells predominated the inflammatory infiltrate in all pathological processes, while in CE samples CD20+ B cells, in CH samples CD68+ macrophages were also frequent. Both myeloperoxidase (MPO) + leukocytes and CD68+ macrophages were found to be significantly decreased in CE as compared to either SH or CH samples. Concerning T cell subtypes, only CD8+ T cells were found to be significantly decreased in SH samples. CD1a + dendritic cells were almost completely missing from CE biopsies unlike in any other sample types. There were no differences detected in the mRNA expression of costimulatory molecules except decreased expression of CD28 in CE samples. Conclusion: In the hydatid lesions of the liver of chronic echinococcal infections T cell-mediated immunity seems to be impaired as compared to other types of chronic inflammatory processes, suggesting an immunosuppressive role for Echinococcus granulosus, which deserve further attentions

Plant Dynamic Metabolic Response to Bacteriophage Treatment After Xanthomonas campestris pv. campestris Infection

Periodic epidemics of black rot disease occur worldwide causing substantial yield losses. Xanthomonas campestris pv. campestris (Xcc) represents one of the most common bacteria able to cause the above disease in cruciferous plants such as broccoli, cabbage, cauliflower, and Arabidopsis thaliana. In agriculture, several strategies are being developed to contain the Xanthomonas infection. The use of bacteriophages could represent a valid and efficient approach to overcome this widespread phenomenon. Several studies have highlighted the potential usefulness of implementing phage therapy to control plant diseases as well as Xcc infection. In the present study, we characterized the effect of a lytic phage on the plant Brassica oleracea var. gongylodes infected with Xcc and, for the first time, the correlated plant metabolic response. The results highlighted the potential benefits of bacteriophages: reduction of bacterium proliferation, alteration of the biofilm structure and/or modulation of the plant metabolism and defense response