Using chitosan nanoparticles and N-acetyl thiazolidine 4-carboxylic acid for olive trees efficiency raising, improving fruits properties and oil quality

Abstract Recently exposure of olive trees to many stresses particularly oil varieties led to decline in the olive yield. The target of the study is to improve vegetative growth and increase olive fruits quality as well as the fruit oil % and oil quality by applying chitosan nanoparticles (CHNPs) and N-acetyl thiazolidine 4-carboxylic acid (N-ATCA) under the conditions of Egypt. The experiment was carried out in the seasons of 2021 and 2022 on Arbosana olive trees 8 years old and 4×6 m apart the trees sprayed three times on 15th Sept., 1st Oct. and 15th Oct. with (CHNPs at 500, 1000 and 1500 ppm), (N-ATCA at 50, 100 and 150 ppm) and a combination between them and evaluate the vegetative growth of trees, fruit physiochemical characteristics, and oil properties during both study seasons. The application of CHNPs and N-ATCA and a combination of them led to increasing leaf area, total chlorophyll and proline content also increment fruit weight, flesh weight, oil color and oil % moreover improving the quality of produced oil. The improvement in growth, fruit quality, oil % and oil quality, were associated with increasing concentrations of CHNPs, N-ATCA and a combination of them especially (CHNPs at 1500 ppm + N-ATCA at 100 ppm and CHNPs at 1500 ppm + N-ATCA at 150 ppm). Spraying (CHNPs at 1500 ppm + N-ATCA at 150 ppm) is recommended to improve the tree growth, fruit quality, oil % and quality of Arbosana olive

Different Continuous Training Intensities Improve Echocardiographic Parameters, Quality of Life, and Functional Capacity in Heart Failure Patients with Reduced Ejection Fraction.

BackgroundMultiple comorbidities and physiological changes play a role in a range of heart failure conditions and influence the most effective approach to exercise-based rehabilitation. This research aimed to examine and compare the outcomes of continuous training at three different intensities, focusing on left ventricular (LV) remodeling, functional capacity, and quality of life among patients with heart failure with reduced ejection fraction (HFrEF).MethodsIn this randomized control trial, a total of 60 male patients (average age: 54.33 ±2.35 years) with HFrEF were randomly allocated into three groups: 1) High-intensity continuous training group (HICT), 2) Moderate-intensity continuous training group (MICT), and 3) Low-intensity continuous training group (LICT). All the training was performed on a bicycle ergometer 3 times/week for 12 weeks. Echocardiographic parameters (left ventricular ejection fraction, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, N-terminal pro-B-type natriuretic peptide (NT-proBNP), quality of life (Minnesota Living with Heart Failure Questionnaire), and functional capacity (6-minute walking test) were assessed before and the end of the study.ResultsThe HICT group demonstrated the greatest improvements in all measured variables when compared to the other two groups (P ConclusionIt was determined that HICT appears to yield the most favorable outcomes in enhancing echocardiographic measures, NT-proBNP levels, quality of life, and functional capacity among HFrEF patients

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

In Vitro and In Silico Investigation of Polyacetylenes from <i>Launaea capitata</i> (Spreng.) Dandy as Potential COX-2, 5-LOX, and BchE Inhibitors

Diverse secondary metabolites are biosynthesized by plants via various enzymatic cascades. These have the capacity to interact with various human receptors, particularly enzymes implicated in the etiology of several diseases. The n-hexane fraction of the whole plant extract of the wild edible plant, Launaea capitata (Spreng.) Dandy was purified by column chromatography. Five polyacetylene derivatives were identified, including (3S,8E)-deca-8-en-4,6-diyne-1,3-diol (1A), (3S)-deca-4,6,8-triyne-1,3-diol (1B), (3S)-(6E,12E)-tetradecadiene-8,10-diyne-1,3-diol (2), bidensyneoside (3), and (3S)-(6E,12E)-tetradecadiene-8,10-diyne-1-ol-3-O-β-D-glucopyranoside (4). These compounds were investigated for their in vitro inhibitory activity against enzymes involved in neuroinflammatory disorders, including cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and butyrylcholinesterase (BchE) enzymes. All isolates recorded weak–moderate activities against COX-2. However, the polyacetylene glycoside (4) showed dual inhibition against BchE (IC50 14.77 ± 1.55 μM) and 5-LOX (IC50 34.59 ± 4.26 μM). Molecular docking experiments were conducted to explain these results, which showed that compound 4 exhibited greater binding affinity to 5-LOX (−8.132 kcal/mol) compared to the cocrystallized ligand (−6.218 kcal/mol). Similarly, 4 showed a good binding affinity to BchE (−7.305 kcal/mol), which was comparable to the cocrystallized ligand (−8.049 kcal/mol). Simultaneous docking was used to study the combinatorial affinity of the unresolved mixture 1A/1B to the active sites of the tested enzymes. Generally, the individual molecules showed lower docking scores against all the investigated targets compared to their combination, which was consistent with the in vitro results. This study demonstrated that the presence of a sugar moiety (in 3 and 4) resulted in dual inhibition of 5-LOX and BchE enzymes compared to their free polyacetylenes analogs. Thus, polyacetylene glycosides could be suggested as potential leads for developing new inhibitors against the enzymes involved in neuroinflammation