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Sexually transmitted infections (STIs) are a difficult health challenge for immunocompromised patients. Patients treated for several haematological malignancies have further compromised immune systems. Furthermore, many chemotherapies, alone or associated with haematopoietic stem-cell transplantation, make the body's natural barriers extremely fragile. STIs can negatively impact both patient morbidity and mortality. In this Series paper, we discuss Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis, human immunodeficiency virus, herpes simplex virus, human papilloma virus, and hepatitis B virus, as we found them to be associated with increased risks for haematological malignancy treatments, either by incidence or by severity. Protective measures and vaccines for patients with haematological malignancies are also discussed. Large, well conducted studies should be encouraged, with the aim to systematically analyse the impacts of STIs in patients with haematological malignancies, especially given the difficulties that antimicrobial resistance can confer to patient management.

High β‐glucan hull‐less barley (cv. Chifaa) was used in functional bread production. Its technological and nutritional properties were compared with the one produced from bread wheat flour. Increasing levels of whole barley flour supplementation resulted in consistent increases in the Farinograph water absorption due to the high hydration capacity of β‐glucan in barley flour. Increasing whole barley flour supplementation levels had significant deteriorative effects on all of the bread quality characteristics probably due to dilution of gluten proteins. On the contrary, the mineral, β‐glucan, and phenolic contents and antioxidant capacities of breads supplemented with Chifaa were significantly higher than those of the bread produced from bread wheat. The glycemic index (GI) of the bread supplemented with 60% barley flour (66.4) was medium while the GI of the 45% barley flour‐supplemented bread (70.1) was very close to the limit value of the medium GI. The lower GI of the barley flour‐supplemented breads might be attributed to their higher β‐glucan contents. The results indicated that 3 g of β‐glucan can be provided from barley flour‐supplemented bread (at 45% and 60%), which is the limit to bear health claim. The results of the present study indicated that high β‐glucan hull‐less barley can be used to produce functional breads with better nutritional properties. The findings of this study may provide insights that can contribute to the studies on functional foods.

Durum wheat is among the cereal crops with the highest susceptibility to Fusarium Head Blight (FHB), the most devastating wheat disease. Purple pericarp durum wheat genotypes, having anthocyanin-rich grains, are an unexplored group of accessions, which may provide valuable information about the role of flavonoids in wheat-Fusariuminteraction. In this study, a purple pericarp durum wheat accession (Purple durum) was challenged with Fusarium graminearuminfection, evaluating the different responses of physiological traits, in comparison with an FHB-resistant line (DBC-480) and a commercial FHB-susceptible cultivar (Svevo). Purple durum showed high susceptibility to FHB, but the infection did not affect the seed set, as for the resistant control. In Purple durum flag leaves, lower flavonoid content and higher temperature depression, compared to the resistant control, were detected. The infection affected the difference between the spike temperature and the flag leaf temperature in the resistant and the susceptible control in an opposite way, while the total phenolic content was always higher in the infected spikes. Instead, the total anthocyanin content (TAC) of the spikes was considerably lower in Purple durum subjected to the infection compared to the mock plants, while TAC increased in the infected resistant genotype, suggesting an involvement of anthocyanins in the resistance mechanism of DBC-480. Association among morphological spike traits and physiological traits are discussed. Our results corroborate the importance of phenylpropanoids in FHB-wheat interaction and point attention on anthocyanin metabolism, suggesting to further consider these metabolites, which are under-investigated for durum wheat resistance.

Although post-transplant cyclophosphamide (PT-Cy) is effective for graft-versus-host disease (GVHD) prophylaxis, it is associated with toxicities, which might be dose-dependent. We compared the outcomes with PT-Cy at 80 mg/kg to those with PT-Cy at 100 mg/kg in elderly patients undergoing haploidentical hematopoietic cell transplantation (HCT). Inclusion criteria included peripheral blood stem cells, hematological malignancy, and age>65 years (or age>60 years if cardiac event history). Thirty-eight patients received PT-Cy at 80 mg/kg and 55 100 mg/kg, divided in two doses. The cumulative incidences (CI) of acute grade II–IV, acute grade III–IV, and moderate/severe chronic GVHD were 32%, 16%, and 13% with PT-Cy at 80 mg/kg compared to 33%, 13%, and 16% with 100 mg/kg, respectively. In multivariable analysis, reducing PT-Cy dose had no significant impact on GVHD. Neutrophil and platelet engraftments were significantly improved, and CI of BK virus-associated hemorrhagic cystitis was reduced with 80 mg/kg of PT-Cy compared to 100 mg/kg. At 2 years, non-relapse mortality was 16% and 31%, progression-free survival 65% and 49%, overall survival 70% and 56%, and GVHD-free, relapse-free survival 52% and 36% with 80 mg/kg and 100 mg/kg, respectively. Reducing PT-Cy dose to 80 mg/kg is safe and associated with improved hematological recovery and lower CI of hemorrhagic cystitis in elderly patients undergoing haploidentical HCT.

For acute lymphoblastic leukemia (ALL) patients, total body irradiation (TBI)- based conditioning regimens are the first choice specially in young population. However, several studies have shown an equivalence in clinical outcomes with thiotepa-based conditioning regimen. We performed a retrospective study to evaluate the outcome of adult ALL patients who received allogeneic hematopoietic stem cell transplantation (allo-HCT) with a thiotepa-busulfan-fludarabine (TBF) myeloablative conditioning regimen with reduced toxicity. Fifty-five patients received a TBF regimen. The median age of the patients was 51 years (range, 17 to 72.4). Most patients had a diagnosis of B-ALL (93%) with 7% having T-ALL. Two - and 5-year overall survival was 73.2% and 64%, respectively. At 2 years, leukemia-free survival and GVHD-free, relapse-free survival were 59.5% and 57.6%, and at 5 years, 53.4% and 51.8%, respectively. The 5-year non-relapse mortality was 15%. The day 180 cumulative incidence (CI) of grade II–IV acute GVHD and grade III–IV acute GVHD were 38.2% and 5.5%, respectively. At 2 years, the CI of chronic GVHD and extensive chronic GVHD was 16.9% and 1.9%, respectively. Our study results do suggest that using TBF as the conditioning regimen in adult ALL patients is a promising option with acceptable toxicity.

Post-transplant cyclophosphamide (PT-Cy) is effective for graft-versus-host disease (GVHD) prophylaxis, but it may cause dose-dependent toxicities, particularly in frail patients. Therefore, we compared the outcomes with a reduced PT-Cy total dose (70 mg/kg) to those with the standard PT-Cy dose (100 mg/kg) in haploidentical hematopoietic cell transplantation (HCT) patients aged ≥ 65 years and those with cardiac comorbidities. All consecutive patients with a hematological malignancy receiving peripheral blood stem cells (PBSCs) after a thiotepa-based conditioning with low-dose antithymocyte globulin were included. Thirty-three patients received PT-Cy at 70 mg/kg and 25 at 100 mg/kg. PT-Cy dose reduction did not increase the risk of GVHD and was associated with faster neutrophil and platelet recovery, and lower cumulative incidences of bacteremia (38% versus 72%, p= 0.004) and cardiac complications (12% versus 44%, p= 0.028). At 2 years, GVHD-free, relapse-free survival (GRFS) was higher with the reduced dose compared to the standard dose (60% versus 33%, p= 0.04). In conclusion, reducing PT-Cy total dose to 70 mg/kg is a safe and valid approach for elderly patients and those with cardiac comorbidities underdoing haploidentical HCT with PBSCs and low-dose antithymocyte globulin. The reduced PT-Cy dose was associated with improved hematological count recovery, lower incidence of toxicities, and higher GRFS.

•Phenylpropanoids pathway is early triggered in resistant genotypes.•In Purple durum the early infection increase quercetin.•Chalcone synthase gene was late boosted in stressed pigmented genotype.•Transcription factor Ppm1is late promoted by infection.•Purple durum accumulate anthocyanins due to infection.

Patients with high-risk lymphoma have a poor prognosis when treated with standard chemoimmunotherapy. This retrospective study included 23 high-risk lymphoma patients with a median age at diagnosis of 59 (range, 35–68) years. They received 2 cycles of R-COPADM and 2 cycles of CYVE, completed by ASCT for fit patients. With a median follow-up of 46 (range, 3–78) months, three (13%) patients in the cohort died. Nearly half of the patients had an ECOG performance status of 2 or 3. Most patients in the cohort (91%, n= 21) had Ann Arbor stage III-IV disease, and 88% (n= 20) had an IPI of 3 to 5. LDH levels were elevated in 83% (n= 19) of patients. Overall, 30% of patients were identified as having double-expressor lymphoma and 22% as having DHL, while two patients (9%) had THL. The origin of the lymphoma was GC B-cell-like in 15 patients (65%) and ABC-like in 8 patients (35%). Cumulative incidence of relapse at 46 months was 14% (95% CI, 5–37), while overall survival was 87% (95% CI, 64–95) and progression-free survival was 83% (95% CI, 60–93). These results showed the efficacy and an acceptable safety profile of the R-COPADM/CYVE/ASCT regimen in high-risk lymphoma, including patients with DHL.

Falsification of drugs, entailing the use of drug substances from unknown unapproved suppliers, is one of the main concerns for the quality of medicines. Therefore, traceability of active ingredients represents an effective tool to fight the illegal trade of medicinal products. In this view, the present pilot study explores the profile of carvedilol active ingredients and possible differences related to the origin. Sixteen samples were examined by near-infrared spectroscopy (NIR), proton nuclear magnetic resonance (1H-NMR spectrometry) and liquid chromatography mass spectrometry (LC-MS) Q-TOF and the data were analysed by principal component analysis (PCA), cluster analysis and PLSDA discriminant analysis. The results evidenced that the combined information from the three techniques gave good classification of the samples neatly distinguishing the APIs from European countries from the APIs manufactured out of Europe. In particular, NIR spectroscopy provided effective separation between European and non-European manufacturers and 1H-NMR or LC-MS added specific information related to the separation. Concerning LC-MS Q-TOF, the analysis of multiple isobaric peaks proved to be highly predictive of the drug substance origin and emerged as a promising tool in the field of medicine traceability.

ABSTRACTHepatitis B virus (HBV) infection is one the most common in the world. Aim of this study is to perform a systematic review on the relationship between HBV vaccination and multiple sclerosis. Research was conducted on Pubmed, ISI Web of Science, and Scopus. Terms “hepatitis b vaccination”and “multiple sclerosis” were used. Meta-analysis and metaregression were performed. 414 papers were found. Seven articles were selected. For the reported crude risk estimates for MS no statistically significant association was observed with pooled OR 1,19 (95%CI: 0,96–1,49). For the adjusted ORs, the pooled odds ratio (OR) was 0, 965 (95%CI: 0,886– 1,051). Meta regression show that year of publication is negatively (β: −0,019; P < 0.001) and NOS score and publishing in Europe are positively associated with O.R. value. Funnel plot showed the presence of publication bias. Results showed that Hepatitis B vaccination is not associated with an increased risk of developing MS.

ABSTRACTIntroductionChemoprevention of cancer refers to the use of natural or synthetic compounds to abolish or perturb a variety of steps in tumor initiation, promotion, and progression. This can be realized through different mechanisms, including activation of free radical scavenging enzymes, control of chronic inflammation, and downregulation of specific signaling pathways.Areas coveredThe goal of this article is to critically review recent evidence on association between coffee and prevention of different types of cancer, with particular emphasis on the molecular mechanisms and the bioactive compounds involved in its anticancer activity.Expert opinionCoffee is a mixture of different compounds able to decrease the risk of many types of cancer. However, its potential anticancer activity is not completely understood. Hundreds of biologically active components such as caffeine, chlorogenic acid, diterpenes are contained in coffee. Further research is needed to fully elucidate the molecular mechanisms underlying the anticancer effects of coffee and fully understand the role of different confounding factors playing a role in its reported anticancer activity.

ABSTRACTCucurbita maximaDuch. is one of the most diversified Cucurbitaspecies worldwide. The objective of this study was to evaluate the genetic relationship between and within Tunisian and Italian Cucurbita maximagermplasm collections using morphological and molecular markers. The phenotypic parameters showed a large qualitative variability, primarily according to fruit-related traits, for both collections. The RAPD, ISSR and SRAP molecular marker systems used turned out to be effective in discriminating all the accessions. Among the Tunisian collection, the polymorphic information content (PIC) and genetic diversity (H) values were of 0.461 and 0.50 respectively, with a total of 96% of polymorphism detected. The Italian collection revealed a PIC and H values of 0.454 and 0.50 respectively and 90% of polymorphism. Population structure analysis reflected the geographical origin of the accessions and helped to classify the Tunisian collection into two populations and to group all the Italian accessions into one. The results suggest that the combination of morphological and molecular approaches is a highly reliable technique in studying and evaluating Cucurbita maximagermplasm which represents an important genetic resource to be preserved and used in breeding programs.

We report results of a thiotepa-based conditioning in haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-CY) and antithymocyte globulin (ATG), for unmanipulated peripheral blood stem cell (PBSC) transplants, in 80 patients with hematological malignancies. Patients in complete remission (CR) received a thiotepa–busulfan–fludarabine (TBF) regimen, while patients with relapsed/refractory (R/R) malignancies received a sequential regimen consisting of thiotepa–etoposide–cyclophosphamide (TEC) and reduced-intensity conditioning (RIC). The median age was 52 (range, 17–72) years, 44% patients had R/R disease at transplant, and the median follow-up was 417 (range, 180–1595) days. The median days to neutrophil engraftment was 17 (range, 12–34). The cumulative incidences (CI) of acute graft-versus-host disease (GVHD) grade III to IV, severe chronic GVHD, nonrelapse mortality (NRM), and relapse were 16%, 16%, 26, and 26%, respectively. The 2-year overall survival (OS) and disease-free survival (DFS) were 53% and 47%, respectively. There were no significant differences between the patients in CR and R/R patients in terms of engraftment, GVHD, NRM, relapse, OS, or DFS. We conclude that thiotepa-based regimen with PT-CY can be modified with PBSC and ATG, still providing low toxicity, protection against GVHD, and low relapse incidence. Particularly encouraging are the results with the modification to sequential regimen in R/R patients.

•GBS analysis identified variants in response to water-related genes•Drought increased oxidative stress and reduced stomata density in sensitive cv Iride•Biostimulants allow to mitigate drought stress in sensitive DW cultivars

Durum wheat is mainly used for the production of pasta, but a significant amount is also used for bread and other products worldwide. However, leavened bread made from durum wheat flour or as blends results in bread with lower loaf volume compared to bread made from hexaploid wheat probably due to poor dough strength and/or extensibility. Durum wheat lacks the glutenin subunits important in bread making, in particular the Glu‐D1subunit 5 + 10. Efforts are being made by researchers to introduce high molecular weight glutenin subunits (HMW‐GS), specifically 1, 2*, 17 + 18, 2 + 12, and 5 + 10 and combinations into durum wheat to improve baking quality. Typically, this work has not evaluated pasta‐making quality and dual purpose durum wheat is desirable. This work reports the effects of the addition of HMW‐GS 2 + 12 and 5 + 10 in various durum wheat backgrounds on dough‐ and pasta‐making quality. Durum wheats, Svevo, Svevo partial waxy (null 4A, null 7A, low amylose ~14%), and Lira biotypes 42/45 differing in their LMW‐GS as type 1, weak dough, and type 2, strong dough, respectively, were compared with lines having the Glu‐D1subunit pair 2 + 12 or 5 + 10. For Svevo, the Glu‐B17 + 8 subunits were removed. The absence of 7 + 8 in Svevo reduced the over strong dough strengthening effect, especially from 5 + 10 but also 2 + 12 found previously when 7 + 8 is present. The weak gluten Lira42 genotype benefited from the improved dough strength from 2 + 12/5 + 10, and both Lira biotypes showed much larger effects on dough strength from the Glu‐D1pairs than with Svevo, a better quality variety. The impacts on pasta were variable depending on the genotype. For Lira42, the presence of 2 + 12 lowered stickiness and cooking loss while stickiness was only reduced in Lira45 with 5 + 10. For Svevo (without 7 + 8), there was little to no impact on pasta quality from the presence of either 2 + 12 or 5 + 10. The very low amylose Svevo (SvLA) pasta quality was improved greatly by 5 + 10 improving firmness and reducing stickiness and cooking loss although still softer than Svevo. Manipulation of the glutenin composition of durum wheat by introduction of Glu‐D1subunits 2 + 12 or 5 + 10 in various durum backgrounds had different effects. Generally, dough strength was improved more so in the weaker dough strength genotypes with these subunits and removing Glu‐B17 + 8 from Svevo provided a more balanced dough strength. Pasta firmness in Svevo and Lira with these subunits was not affected, and there were minimal changes in other pasta properties except an improvement in pasta stickiness in Lira. In the variable amylose Svevo genotypes, the 5 + 10 subunit pair improved pasta firmness of the overly soft low amylose waxy pasta and reduced stickiness. Manipulation of the glutenin subunit composition of durum wheat by introduction of Glu‐D1subunits affected dough properties, improving dough strength in genotypes with weak gluten. This study found minor impacts on pasta quality allowing the flexibility to develop durum with a better balance of glutenin subunits more suited to bread making without adversely affecting pasta‐making quality and acceptability.

Durum wheat is used to make leavened bread; however, durum bread has inferior loaf volume, structure, and texture compared to bread made from common wheat. One approach to overcome this is to transfer key storage protein genes present at the Glu‐D1locus from bread wheat into durum. Durum wheat Svevo missing Glu‐B1subunits 7 + 8 and Lira biotypes with low molecular weight glutenin subunits types 1 and 2 were evaluated for their breadmaking potential with and without high molecular weight glutenin subunits 2 + 12 or 5 + 10. Bread made from blends of durum and a commercial baker's flour (10%, 25%, 50% w/w) assessed over two seasons in 10 different genotypes showed that as more durum was included in the mixture, loaf volume and texture score declined. Incorporation of the 2 + 12 subunit pair in the genotypes Lira42 and Lira45 improved bread quality but not in Svevo, whereas including 5 + 10 improved bread quality of Lira42 had no effect on Lira45 but reduced quality of Svevo. Low amylose Svevo had similar loaf quality to Svevo while adding 5 + 10 had minimal impact except at 50% with a small improvement in loaf quality. Bread stored up to 7 days became firmer partly due to increased starch retrogradation, and loaves were similar to bread made from baker's flour. Low amylose Svevo kept the loaf fresher but only up to 3 days of storage. Subunit pair 5 + 10 made the loaf firmer after 7 days compared to control. Addition of the 2 + 12 or 5 + 10 benefited the weaker type gluten as found in Lira 42 (LMW‐1, HMW 20) but not with stronger dough in Svevo even in the absence of HMW 7 + 8. It appears that while Glu‐D1subunits are critical for good breadmaking in hexaploid wheat, they appear to have limited value in improving loaf volume and structure in durum bread. Some improvements in bread quality can be obtained by introducing genes coding for Glu‐D1subunits 2 + 12 and 5 + 10 in durum wheat depending on the genotype, especially weak dough types, and the results presented comprise the first report of such effect.

The hypoglycemic effect of different forms of camel milk, i.e., pasteurized (CM), powdered (PcM) and evaporated (EcM) in a rat model of chemically-induced diabetes was studied. Diabetes was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg b.w.). Diabetic rats were supplemented with CM (ad lib), PcM (18.4 g/kg b.w.) and EcM (12.2 g/kg b.w.) for a period of 21 days. EcM feeding was found to normalize serum glucose, triglycerides, LDL-cholesterol, serum creatinine, bilirubin, uric acid and liver enzymes levels. On the other hand, CM and PcM feeding did not reduce the levels of serum glucose, lipids, and kidney and liver function markers to their normal values. Accordingly, histopathological examinations also showed visible signs of pancreatic β-cells repair with mild cellular atrophy in EcM fed diabetic rats. The data suggested that low temperature processed milk-concentrate consumption may represent a complimentary approach to maintaining normal serum glucose levels and securing optimal renal and hepatic function with diabetes.

ABSTRACTIntroduction: Basil (Ocimum basilicum L., OB) is a plant world widely used as a spice and a typical ingredient of the healthy Mediterranean diet. In traditional medicine, OB is indicated for many maladies and conditions; OB-containing nutritional supplements are increasingly sold. Conversely, safety concerns have been raised about the promutagens and procarcinogens alkenylbenzenes contained in OB.Areas covered: A critical review of the current status of OB as a nutraceutical, the pharmacology of its bioactive components, the rationale for its indications, and its safety.Expert opinion: Due to the polyphenolic and flavonoidic content, OB can be considered as an important ingredient in healthy diets; OB preparations may be effective as chemopreventive agents or adjunctive therapy in the treatment of different clinical conditions.From a toxicological perspective, since the tumorigenic potential of alkenylbenzenes is counteracted by other OB constituents such as nevadensin, it can be concluded that OB consumption in food and preparations is safe. The only concern relates to OB essential oils: in this case, a concentration limit for alkenylbenzenes should be precautionary defined, and the use of plant chemotypes with no or low levels of these alkylbenzenes for the preparation of essential oils should be made compulsory.

The amylose-amylopectin ratio influences starch properties. A higher amylose content is associated with slower starch digestion thus reducing the postprandial plasma glucose response and improving the overall postprandial metabolism. So far, limited evidence is available on the metabolic effect of wheat-based foods rich in amylose. This randomised controlled study investigated the acute metabolic effects of amylose-rich wheat-based rusks in overweight subjects focusing on potential mechanisms. Ten overweight subjects consumed in random order two test meals differing only in the carbohydrate source: rusks prepared with amylose-rich wheat flour (ARR) or conventional wheat flour (control). Blood samples were taken at fasting and over 4 h after the meal. Satiety and intestinal fermentation were evaluated by VAS and H2-breath test, respectively. ARR reduced plasma glucose response during the first two hours after the meal and the desire to eat, and increased breath hydrogen concentration at 4 h (p< 0.05 for all). Moreover, according to computational models, the ARR slightly reduced intestinal glucose absorption in the first hour after the meal and increased the overall postprandial insulin sensitivity. Rusks made with amylose-rich flour could be useful for improving postprandial glucose metabolism and reduce the desire to eat, thus possibly contributing to the prevention and treatment of overweight/obesity, impaired glucose tolerance or diabetes.

BackgroundSwallowing difficulties are arising in an increasing number of patients, especially in elderly people. When deglutition ability is completely compromised, enteral administration of a drug via feeding tubes is used. Licensed pharmacists have to compound the original solid forms to enable this drug therapy.ObjectivesTo evaluate the possibility of compounding original commercial tablets to produce a liquid formulation suitable for administering via a feeding tube.MethodsTwo liquid formulations containing potassium canrenoate 5 mg/mL were prepared: a standard solution obtained by solubilising raw material and an extemporaneous preparation obtained by dissolving film-coated 100 mg tablets. Spectrophotometric determinations (UV range) of the drug established chemical stability of the analyte up to 60 days. Samples were tested for microbial growth. Gravimetric quantifications of liquid formulations were used to check any weight loss during the different steps before enteral administration.ResultsUV data confirmed the chemical stability of potassium canrenoate up to 60 days. Samples showed no microbial growth. A higher weight loss was recorded in extemporaneous preparations than in the standard solution (10.7% vs 7.6%) according to the gravimetric quantification.ConclusionIt is possible to compound the original tablets into a liquid formulation suitable for administration via a feeding tube.

ABSTRACTIntroduction: Nuclear factor (erythroid-derived-2)-like 2 is one of the most efficient cytoprotective rheostats against exogenous or endogenous oxidative insults. At present, the modulation of the Nrf2 pathway represents an interesting and highly explored strategy in the oncological area.Area covered: In this review, we present and discuss the different modulation of the Nrf2 pathway by some natural compounds with a well demonstrated anticancer activity, and critically analyze the challenges associated with the development of an Nrf2-based anticancer strategy.Expert opinion: Many natural compounds with a well-defined anticancer activity are able to modulate this pathway. Both Nrf2 inducers and inhibitors can be useful as anticancer strategy. However, since Nrf2 modulates many networks potentially involved in the detoxification process of anticancer drugs, its activation in cancer cells could lead to chemoresistance. The switch between a beneficial or detrimental role of Nrf2 in cancer cells essentially depends on the tight control of its activity, the specific conditions of tumor microenvironment, and cell type. In line with the paucity of clear data related to the mechanisms underpinning the role of Nrf2 in cancer development and chemoresistance, discovery and development of Nrf2-based strategies is one of the most critical and challenging assignments for fighting cancers.

Objective: In this research, fatty acid profile and polyphenolic content of an ethanolic extract of walnut from Juglans regia L. collected in Central Italy, were characterized. The potential antioxidant and anti-inflammatory effects of the extract were investigated in the human keratinocytes cell line. Methods: Fatty acid profile was determined by gas chromatography/mass spectrometry analysis, total phenolic content by Folin-Ciocalteu method and aluminum chloride colorimetric method was used for determination of total flavonoids. Kertatinocytes were exposed to t-butyl hydroperoxide or Tumor Necrosis Factor alfa in the absence or presence of extract. Reduced glutathione was determined by Sedlak method; lipid peroxidation was assessed by measuring thiobarbituric acid reactive substances. t-butyl hydroperoxide and Tumor Necrosis Factor alfa-induced intracellular reactive oxygen species were monitored by fluorescent probes. The expression of some genes related to the inflammatory process (IL-6, IL-8, ikB, and ICAM) were analysed by Real-time PCR. Results: JRE contains a favourable fatty acid profile with low saturated fats (19%) and high-unsaturated fats (81%) with a prevalence of the omega-6 linoleic acid (48%). Also a significant amount of polyphenols was found (5,0052 mg gallic acid equivalent/gdw). Antioxidant and anti-inflammatory properties of JRE were observed on analysed cellular model. JRE antioxidants counteracted ROS production, GSH depletion and lipid peroxidation as well downregulated the expression of some genes related to the inflammatory process. Moreover, polyunsaturated fatty acids exhibited anti-inflammatory properties. Conclusion: The obtained results uphold walnut as dietary adjunct in health promotion and drive towards its development in drug therapy against chronic inflammatory disorders, including inflammatory skin diseases.

Resistance to IFN-I–induced antineoplastic effects has been reported in many tumors and arises, in part, from epigenetic silencing of IFN-stimulated genes by DNA methylation. We hypothesized that restoration of IFN-stimulated genes by co-administration of the demethylating drug 5-aza-2′-deoxycitidine (decitabine [DAC]) may enhance the susceptibility to IFN-I–mediated antitumoral effects in melanoma. We show that combined administration of IFN-I and DAC significantly inhibits the growth of murine and human melanoma cells, both in vitro and in vivo. Compared with controls, DAC/IFN-I–treated melanoma cells exhibited reduced cell growth, augmented apoptosis, and diminished migration. Moreover, IFN-I and DAC synergized to suppress the growth of three-dimensional human melanoma spheroids, altering tumor architecture. These direct antitumor effects correlated with induction of the IFN-stimulated gene Mx1. In vivo, DAC/IFN-I significantly reduced melanoma growth via stimulation of adaptive immunity, promoting tumor-infiltrating CD8+T cells while inhibiting the homing of immunosuppressive CD11b+myeloid cells and regulatory T cells. Accordingly, exposure of human melanoma cells to DAC/IFN-I induced the recruitment of immune cells toward the tumor in a Matrigel (Corning Life Sciences, Kennebunkport, ME)-based microfluidic device. Our findings underscore a beneficial effect of DAC plus IFN-I combined treatment against melanoma through both direct and immune-mediated anti-tumor effects.

The high-molecular-weight glutenin subunits (HMW-GS) represent a major component of the endosperm storage protein in the grains of wheat and its related species. Their technological importance results from their ready formation of intermolecular disulfide bonds, which underlie much of the visco-elasticity displayed by gluten and hence the processing quality of the flour. Here, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that the Chinese wheat cultivar Xiaoyanmai 7 formed four distinct HMW-GS, two of which are likely the product of a known allele at the Glu-B1 locus, whereas the other two did not match any known HMW-GS. A combined analysis based on reversed-phase high-performance liquid chromatography (RP-HPLC), N-terminal sequencing and mass spectrometry confirmed that the two novel proteins were genuine HMW-GS. Inspection of the DNA sequences showed that one of the novel HMW-GS was encoded by an x-type and the other by a y-type secalin gene. A karyotypic analysis confirmed that six of the seven pairs of Xiaoyanmai 7’s D genome chromosomes (the exception was chromosome 2D) had been replaced by rye chromosomes. The y-type HMW secalin present in Xiaoyanmai 7 differed from the standard By and Dy HWM-GS by the presence of an additional cysteine residue in its C-terminal domain.

Creatine (Cr) - along with the Cr kinase (CK) system - plays a fundamental role in muscle biochemistry and physiology not limited to its ergogenic role. Indeed, Cr has been shown to exert pleiotropic effects, which promote protein accretion, muscle-specific protein synthesis, growth in cultured myogenic cells and favour the myogenic process either in normal or stressing conditions. This review focuses on the effects of Cr supplementation on cellular and mitochondrial biochemistry and function in the course of skeletal muscle differentiation, either in normal or oxidatively stressing conditions, and on the ensuing nutraceutical/therapeutic perspectives.

Gender-related differences in sex hormones might have a key role in the development of atherosclerosis though direct vascular effects of sex hormones are not yet well understood. Thus, the main purpose of this study was to compare the effects of sex hormones on inflammatory response in Human Umbilical Vein Endothelial Cells (HUVECs) obtained from both male and female donors. We analyzed the expression of receptors and enzymes relevant to the action of androgens (AR, 5α-reductase 1 and 5α-reductase 2) and estrogens (ERα, ERβ, and aromatase) in male and female HUVECs. Furthermore, we analyzed the effect of testosterone (T), 17β-estradiol (E2), dihydrotestosterone (DHT), and several androgenic-anabolic steroids (AAS) on VCAM-1, ICAM-1, and E-selectin gene expression and on adhesion of U937 cells to TNF-α-stimulated male and female HUVECs. Our results reveal that in HUVECs, regardless of gender, the components involved in the androgen action pathway are predominant as compared to those of estrogen action pathway. In both HUVEC genders, the inflammatory effect of TNF-α was amplified by co-administration of T or DHT and several AAS frequently used in doping, while E2had no effect. This is the first study analyzing, under identical culture conditions, the key components of sex hormone response in male and female HUVECs and the possible role of sex hormones in regulating the endothelial inflammatory response. The data obtained in our experimental system showed a pro-inflammatory effect of androgens, while conclusively excluding any protective effect for all the tested hormones.

Eleven candidate reference genes were evaluated in stem tissues of two melon (Cucumis meloL) genotypes infected with Fusarium oxysporumf.sp. melonis(FOM) race 1, to investigate the most stable internal control gene to use in gene expression study in melon under biotic stress. The candidate reference genes, utilized in the qRT-PCR, were selected among the most common reference genes reported in melon literature as well as on melon sequences found in available databases. The expression stability of the reference genes selected, was tested by using the geNorm and NormFinder statistical algorithms. Irrespective of the plant response to FOM infection, there was substantial agreement in gene ranks of both software. The ribosomal protein L2gene had the high transcript stability while the elongation factor, cyclophilin7and 18S rRNAwere the least stable. The best three reference genes, ribosomal protein L2, actin*and cyclophilinwere used to normalize the expression data of the glutathione S-transferasein the resistant and susceptible plants. Differences in the expression data emerged for both genotypes and were more evident in the resistant one. The ribosomal protein L2showed similar normalized expression values in both genotypes and thus it could be indicated as unique internal control for gene expression analysis in melon under FOM infection. This work represents the first in-depth study on reference genes validation in melon under biotic stress condition. The identification of such genes would improve the accuracy and reliability of gene expression studies and speed up candidate disease resistant gene analysis in melon.

A durum wheat TILLING (targeting induced local lesions in genomes) population of 2601M3 families was developed from cv. Svevo using ethyl methanesulfonate as a chemical mutagen. The entire M3 population was field-grown for phenotypic evaluations. Despite the polyploid nature of the wheat genome, a preliminarily phenotypic screening showed a high frequency of morphological alterations (~22%); specific phenotyping for seed morphology was undertaken. Furthermore, a reverse-genetics experiment was performed on DNA collected from M2 leaves for the homoeologous genes SBEIIa-A and SBEIIa-B involved in starch metabolism. One non-sense mutation for both genes was identified; specific crosses are planned in order to pyramid the two mutations.

In this paper, the authors perform a bioinformatics homology search analysis of miRNAs in human, mouse, and rat. The pipeline defined uses previously existing tools (Blast and miRDeep2) that are based on homology. This was successfully used to identify novel miRNAs in humans, mouse, and rat. This work was motivated by the finding and experimental validation of mir-155 in the alternate rat genome (Celera), which is missing in the reference assembly and was previously unknown. This miRNA is encoded in a long noncoding RNA (Bic) and had been already discovered in humans and mice but not in rats. The discovery of “hidden” miRNAs opens new perspectives for finding many more nonconserved miRNAs, as well as novel long noncoding RNAs.