Ascorbic acid (AA), also known as vitamin C, was initially identified as the factor preventing the scurvy disease, and became very popular for its antioxidant properties. It is an important ...co-substrate of a large class of enzymes, and regulates gene expression by interacting with important transcription factors. AA is important in all stressful conditions that are linked to inflammatory processes and involve immunity. It has been known for decades that the persistence of an inflammatory stimulus is responsible for the onset of many diseases. AA is essential to stimulate the immune system by increasing the strength and protection of the organism. Therefore, its immunostimulant, antinflammatory, antiviral and antibacterial roles are well known, we have summarized its main functions in different types of diseases related to the immune system and chronic inflammation. We can conclude that AA, due to its effects and diversity of regulated pathways, is suitable for use in various fields of medicine including immunology, toxicology, radiobiology and others. AA is not preferable to be used as an isolated mode of treatment, but it can be co-applied as an adjuvant to regulate immunity, gene expression and other important physiological processes. However, we propose that future studies will take into consideration the research of new combinations of antioxidant natural substances and drugs.
Diaporthe eres has been recently reported as the causal agent of hazelnut defects, with characteristic brown spots on the kernels surface and internal fruit discoloration. Knowledge regarding the ...ecology of this fungus is poor but, is critical to support a rationale and effective hazelnut crop protection strategy. Therefore, a study was performed to describe and model the effect of different abiotic factors such as temperature (T, 5-35°C, step 5°C) and water activity (aw 0.83-0.99, step 0.03) regimes on D. eres mycelial growth, pycnidial conidiomata development and asexual spore production during a 60-day incubation period. Alpha conidia germination was tested in the same T range and at different relative humidities (RH = 94, 97 and 100%) over 48 h incubation period. Fungal growth was observed from the first visual observation; regarding pycnidia and cirrhi, their development started after 8 and 19 days of incubation, respectively and increased over time. The optimum T for growth was 20-25°C and for pycnidia and cirrhi development was 30°C; aw ≥ 0.98 was optimal for the tested steps of the fungal cycle. The best condition for conidial germination of D. eres was at 25°C with RH = 100%. Quantitative data obtained were fitted using non- linear regression functions (Bete, logistic and polynomial), which provided a very good fit of the biological process (R2 = 0.793-0.987). These functions could be the basis for the development of a predictive model for the infection of D. eres of hazelnuts.
The volatilome of hazelnuts (
L.) encrypts information about phenotype expression as a function of cultivar/origin, post-harvest practices, and their impact on primary metabolome, storage conditions ...and shelf-life, spoilage, and quality deterioration. Moreover, within the bulk of detectable volatiles, just a few of them play a key role in defining distinctive aroma (i.e., aroma blueprint) and conferring characteristic hedonic profile. In particular, in raw hazelnuts, key-odorants as defined by
are: 2,3-diethyl-5-methylpyrazine (
and
); 2-acetyl-1,4,5,6-tetrahydropyridine (
); 2-acetyl-1-pyrroline (
); 2-acetyl-3,4,5,6-tetrahydropyridine (
); 3-(methylthio)-propanal (
); 3-(methylthio)propionaldehyde (
); 3,7-dimethylocta-1,6-dien-3-ol/linalool (citrus, floral); 3-methyl-4-heptanone (
); and 5-methyl-(E)-2-hepten-4-one (
). Dry-roasting on hazelnut kernels triggers the formation of additional potent odorants, likely contributing to the pleasant aroma of roasted nuts. Whiting the newly formed aromas, 2,3-pentanedione (
); 2-propionyl-1-pyrroline (
); 3-methylbutanal; (
); 4-hydroxy-2,5-dimethyl-3(2H)-furanone (
); dimethyl trisulfide (
) are worthy to be mentioned. The review focuses on high-quality hazelnuts adopted as premium primary material by the confectionery industry. Information on primary and secondary/specialized metabolites distribution introduces more specialized sections focused on volatilome chemical dimensions and their correlation to cultivar/origin, post-harvest practices and storage, and spoilage phenomena. Sensory-driven studies, based on
principles, provide insights on the aroma blueprint of raw and roasted hazelnuts while robust correlations between non-volatile precursors and key-aroma compounds pose solid foundations to the conceptualization of
.
Fungi of the genus
have been reported as the main causative agent of hazelnut defects in the Caucasus area. This study aimed to define which fungal species are present in defective hazelnuts grown in ...Turkey and confirm the role of
spp. Seven hazelnut orchards were selected, with each one located in a different Turkish Province (Düzce, Giresun, Ordu, Samsun, Sakarya, Trabzon, and Zonguldak), and hazelnuts were collected at early and full ripening. Fungal isolation and identification were performed at the genus level based on morphological characteristics. Several genera were isolated, with
spp. being among the prevalent. This was the only genus with increasing incidence from early to full ripening, and incidence at full ripening was positively correlated both with internal (ρ = 0.86) and visible defects (ρ = 0.81), which confirmed its role as the key causative agent of hazelnut defects. The correlation of defect occurrence with rainfall, reported in previous study, was not confirmed, possibly due to the low defect incidence. A total of 86
monosporic strains isolated from Turkish hazelnut samples, together with 33 strains collected in the Caucasus region and 6 from Italy, were analyzed with a multi-locus phylogeny based on three genomic loci (ITS,
-α, and
). The results showed that
strains can be grouped into 7 distinct clades, with a majority of Turkish strains (95%) being placed into a single clade related with
. These samples were organized into several sub-clades, which indicates the existence of genetically diverse sub-populations.
The quality defects of hazelnut fruits comprise changes in morphology and taste, and their intensity mainly depends on seasonal environmental conditions. The strongest off-flavor of hazelnuts is ...known as rotten defect, whose candidate causal agents are a complex of fungal pathogens, with
as the dominant genus. Timely indications on the expected incidence of rotten defect would be essential for buyers to identify areas where hazelnut quality will be superior, other than being useful for farmers to have the timely indications of the risk of pathogens infection. Here, we propose a rotten defect forecasting model, and we apply it in the seven main hazelnut producing municipalities in Turkey. We modulate plant susceptibility to fungal infection according to simulated hazelnut phenology, and we reproduce the key components of the
spp. epidemiological cycle
a process-based simulation model. A model sensitivity analysis has been performed under contrasting weather conditions to select most relevant parameters for calibration, which relied on weekly phenological observations and the post-harvest analyses of rotten incidence in the period 2016-2019, conducted in 22 orchards. The rotten simulation model reproduced rotten incidence data in calibration and validation datasets with a mean absolute error below 1.8%. The dataset used for model validation (321 additional sampling locations) has been characterized by large variability of rotten incidence, in turn contributing to decrease the correlation between reference and simulated data (
= 0.4 and 0.21 in West and East Black Sea region, respectively). This denotes the key effect of other environmental and agronomic factors on rotten incidence, which are not yet taken into account by the predictive workflow and will be considered in further improvements. When applied in spatially distributed simulations, the model differentiated the rotten incidence across municipalities, and reproduced the interannual variability of rotten incidence. Our results confirmed that the rotten defect is strictly dependent on precipitation amount and timing, and that plant susceptibility is crucial to trigger fungal infections. Future steps will envisage the application of the rotten simulation model to other hazelnut producing regions, before being operationally used for in-season forecasting activities.
In recent years the use of natural dietary antioxidants to minimize the cytotoxicity and the damage induced in normal tissues by antitumor agents is gaining consideration. In literature, it is ...reported that vitamin C exhibits some degree of antineoplastic activity whereas Mitoxantrone (MTZ) is a synthetic anti-cancer drug with significant clinical effectiveness in the treatment of human malignancies but with severe side effects. Therefore, we have investigated the effect of vitamin C alone or combined with MTZ on MDA-MB231 and MCF7 human breast cancer cell lines to analyze their dose-effect on the tumor cellular growth, cellular death, cell cycle and cell signaling. Our results have evidenced that there is a dose-dependence on the inhibition of the breast carcinoma cell lines, MCF7 and MDA-MB231, treated with vitamin C and MTZ. Moreover, their combination induces: i) a cytotoxic effect by apoptotic death, ii) a mild G2/M elongation and iii) H2AX and mild PI3K activation. Hence, the formulation of vitamin C with MTZ induces a higher cytotoxicity level on tumor cells compared to a disjointed treatment. We have also found that the vitamin C enhances the MTZ effect allowing the utilization of lower chemotherapic concentrations in comparison to the single treatments.
It is well known that hepatocellular carcinoma (HCC) is an arginine auxotroph due to argininosuccinate synthetase I deficiency. This study's purpose was to evaluate the effects of pegylated arginine ...deiminase (ADI) in terms of toxicity, tumor response, alpha-fetoprotein (AFP) levels, and serum arginine levels.
Eighty patients were randomly assigned to receive either 80 IU/m(2) or 160 IU/m(2) of ADI weekly for up to 6 months. Adverse events, serum arginine, AFP levels, and antibody production against ADI were measured on a regular basis. In addition, disease response and time to progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) and survival rates were evaluated.
Four patients were excluded from the survival analysis because they developed exclusion criteria after randomization, but before first treatment. The number of patients in the two cohorts were similar (n = 37 in the low-dose cohort, n = 39 in the high-dose cohort). Mean (+/-SE) survival for all subjects was 15.8 months (474 days +/- 39 days) from time of diagnosis of unresectable disease. Arginine levels remained below baseline for 50 days while antibodies against ADI reached a plateau at approximately the same time. There were no deaths attributed to ADI treatment. Only two patients were withdrawn for immunogenic-related adverse events. Grade 2, 3, or 4 toxicities were recorded in 92, 19, and 0 patients, respectively.
Pegylated ADI is a promising drug that capitalizes on a significant enzymatic deficiency in HCC. It is safe, well tolerated, and may benefit patients with unresectable HCC.
Production of hazelnuts is affected by defects, the incidence of which is year-dependent but also economically damaging. The objectives of the present study were to quantify the incidence of ...different fungal genera in hazelnuts, and define the causal agent/agents of nut defects. A 4-year study (2013 to 2016) was carried out in the Caucasus region, in an orchard planted in 2008 with hazelnut cv. Anakliuri. Hazelnuts were sampled at early and full ripening stages, observed for defects, and then associated fungi were isolated. Nuts with necrotic spots and internal browning were commonly found, and some collected in 2016 were completely rotted, wet and almost black. Alternaria, Aspergillus, Cladosporium, Colletotrichum, Diaporthe, Fusarium, Penicillium, Pestalotiopsis and Phoma spp. were regularly isolated from diseased and symptomless nuts. Diaporthe spp. was the dominant genus, with increasing incidence from early to full ripening, and were more isolated from defected compared to healthy kernels and in the years with the greatest incidence of defects. Rainfall was associated with the incidence of nut defects. The role of Diaporthe as a key cause hazelnut defects was confirmed by pathogenicity tests. Three isolates from the Diaporthe population were identified as D. eres on the basis of EF, ACT, TUB and ITS loci. This supports the crucial role of climate during the crop-growing season for the development of defects in hazelnuts caused by Diaporthe.
The CXCR4/CXCL12 axis plays a role in cancer metastases, stem cell mobilization and chemosensitization. Proof of concept for efficient CXCR4 inhibition has been demonstrated in stem cell mobilization ...prior to autologous transplantation in hematological malignancies. Nevertheless CXCR4 inhibitors suitable for prolonged use as required for anticancer therapy are not available. To develop new CXCR4 antagonists a rational, ligand-based approach was taken, distinct from the more commonly used development strategy. A three amino acid motif (Ar-Ar-X) in CXCL12, also found in the reverse orientation (X-Ar-Ar) in the vMIP-II inhibitory chemokine formed the core of nineteen cyclic peptides evaluated for inhibition of CXCR4-dependent migration, binding, P-ERK1/2-induction and calcium efflux. Peptides R, S and I were chosen for evaluation in in vivo models of lung metastases (B16-CXCR4 and KTM2 murine osteosarcoma cells) and growth of a renal cells xenograft. Peptides R, S, and T significantly reduced the association of the 12G5-CXCR4 antibody to the receptor and inhibited CXCL12-induced calcium efflux. The four peptides efficiently inhibited CXCL12-dependent migration at concentrations as low as 10 nM and delayed CXCL12-mediated wound healing in PES43 human melanoma cells. Intraperitoneal treatment with peptides R, I or S drastically reduced the number of B16-CXCR4-derived lung metastases in C57/BL mice. KTM2 osteosarcoma lung metastases were also reduced in Balb/C mice following CXCR4 inhibition. All three peptides significantly inhibited subcutaneous growth of SN12C-EGFP renal cancer cells. A novel class of CXCR4 inhibitory peptides was discovered. Three peptides, R, I and S inhibited lung metastases and primary tumor growth and will be evaluated as anticancer agents.
In this work, we characterized conjugated linolenic acids (e.g., punicic acid) as the major components of the hydrophilic fraction (80% aqueous methanol extract) from pomegranate (Punica granatum L.) ...seed oil (PSO) and evaluated their anti-inflammatory potential on some human colon (HT29 and HCT116), liver (HepG2 and Huh7), breast (MCF-7 and MDA-MB-231) and prostate (DU145) cancer lines. Our results demonstrated that punicic acid and its congeners induce a significant decrease of cell viability for two breast cell lines with a related increase of the cell cycle G0/G1 phase respect to untreated cells. Moreover, the evaluation of a great panel of cytokines expressed by MCF-7 and MDA-MB-231 cells showed that the levels of VEGF and nine pro-inflammatory cytokines (IL-2, IL-6, IL-12, IL-17, IP-10, MIP-1α, MIP-1β, MCP-1 and TNF-α) decreased in a dose dependent way with increasing amounts of the hydrophilic extracts of PSO, supporting the evidence of an anti-inflammatory effect. Taken together, the data herein suggest a potential synergistic cytotoxic, anti-inflammatory and anti-oxidant role of the polar compounds from PSO.
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