Role of Ajwa Date Fruit Pulp and Seed in the Management of Diseases through In Vitro and In Silico Analysis

This study investigated the health-promoting activities of methanolic extracts of Ajwa date seed and fruit pulp extracts through in vitro studies. These studies confirmed potential antioxidant, anti-hemolytic, anti-proteolytic, and anti-bacterial activities associated with Ajwa dates. The EC50 values of fruit pulp and seed extracts in methanol were reported to be 1580.35 ± 0.37 and 1272.68 ± 0.27 µg/mL, respectively, in the DPPH test. The maximum percentage of hydrogen peroxide-reducing activity was 71.3 and 65.38% for both extracts at 600 µg/mL. Fruit pulp and seed extracts inhibited heat-induced BSA denaturation by 68.11 and 60.308%, heat-induced hemolysis by 63.84% and 58.10%, and hypersalinity-induced hemolysis by 61.71% and 57.27%, and showed the maximum anti-proteinase potential of 56.8 and 51.31% at 600 μg/mL, respectively. Seed and fruit pulp inhibited heat-induced egg albumin denaturation at the same concentration by 44.31 and 50.84%, respectively. Ajwa seed showed minimum browning intensity by 63.2%, percent aggregation index by 64.2%, and amyloid structure by 63.8% at 600 μg/mL. At 100 mg/mL, Ajwa seed extract exhibited good antibacterial activity. Molecular docking analysis showed that ten active constituents of Ajwa seeds bind with the critical antioxidant enzymes, catalase (1DGH) and superoxide dismutase (5YTU). The functional residues involved in such interactions include Arg72, Ala357, and Leu144 in 1DGH, and Gly37, Pro13, and Asp11 in 5YTU. Hence, Ajwa dates can be used to develop a suitable alternative therapy in various diseases, including diabetes and possibly COVID-19-associated complications.

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PATH-65. MOLECULAR SIGNATURE OF FAT1 RELATED MOLECULES IN GLIOMAS IN THE CONTEXT OF THE WHO 2016 CLASSIFICATION

Neuro-Oncology ◽

10.1093/neuonc/noz175.660 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi158-vi158

Author(s):

Kunzang Chosdol ◽

Manvi Arora ◽

Nargis Malik ◽

Prerana Jha ◽

Jyotsna Singh ◽

...

Keyword(s):

Molecular Markers ◽

In Silico Analysis ◽

Molecular Signature ◽

World Health ◽

Low Grade ◽

Who Grade ◽

Inflammatory Microenvironment ◽

Molecular Features

Abstract Glioblastoma (GBM, WHO grade-IV) being the most malignant and aggressive form of glioma remains a major clinical challenge, with an overall 5-year survival rate of only 9.8%. Till recently, glioma diagnosis and grading were solely dependent on the phenotypic and histological features. However, with the advancement in the understanding of the molecular biology of glioma several molecules have been identified. The importance of these molecular/genotypic features of the tumor became evident by the inclusion of these molecular features by World Health Organization (WHO) in 2016 in glioma sub-grouping. Our lab is focused on studying the role of FAT1 gene (human ortholog of Drosophila tumor suppressor gene, fat) in glioma biology and aggressiveness. We observed FAT1 gene to have an oncogenic role in glioma where it has been found to upregulate migration/invasion, inflammatory microenvironment of the tumors, HIF1α expression/activity in the tumor-cells under severe hypoxia and in regulating EMT/stemness properties of GBM-cells under hypoxia. Here, we have characterized the molecular relationship between FAT1 related molecules and known- molecular markers of glioma with the hope of identifying glioma subgroup with a molecular signature of clinical significance by (i) analyzing the expression correlation of FAT1 and FAT1 regulated pro-inflammatroy molecules like COX2, IL1b and IL6 with the known- molecular markers of glioma like p53, IDH1, MGMT, EGFR, TERT in low-grade (grade-II) and high-grade (grade-III/IV) gliomas (n=50) by real-time PCR, sequencing, immunohistochemistry and in-silico analysis of TCGA-GBM-data (ii) Analyzed the regulatory role of FAT1 on the above known markers by siRNA mediated knockdown of FAT1 in in-vitro cell-culture system and (iii) further analyzed the identified molecular signature for their correlation with the patients prognosis/survival in the follow up patients. We observed a novel molecular signature with significant correlation with patients’ clinical outcome. Therapeutic targetting of FAT1 may benefit patients with high FAT1 expressing tumors.

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Pomegranate as a natural source of phenolic antioxidants

Journal of Food Bioactives ◽

10.31665/jfb.2020.9214 ◽

2020 ◽

Vol 9 ◽

Author(s):

Fellipe Lopes De Oliveira ◽

Thaise Yanka Portes Arruda ◽

Renan Da Silva Lima ◽

Sabrina Neves Casarotti ◽

Maressa Caldeira Morzelle

Keyword(s):

Antioxidant Activity ◽

Chronic Diseases ◽

Biological Effects ◽

Meat Products ◽

Phenolic Antioxidants ◽

Antioxidant Compounds ◽

Health Promoting

Pomegranate, a recognized source of phenolic compounds, has been associated with health-promoting benefits, mostly due to its antioxidant activity. Ellagic and gallic acids, anthocyanins, and ellagitannins are the main phenolics in pomegranate, showing antioxidant activity. For this reason, pomegranate has been used in foods, such as meat products, as an attempt to retard lipid oxidation and increase shelf-life. In recent years, in vitro, in vivo, and human studies reported the antioxidant activity of pomegranate, especially its peels, with reduced incidence of chronic diseases (e.g., cardiovascular ailments, cancer, neurodegenerative disease, type 2 diabetes, chronic kidney disease). This review aims to present the main antioxidant compounds on pomegranate and their biological effects, the antioxidant activity of pomegranate-based foods, the application of pomegranate as a natural antioxidant food additive, the role of pomegranate in the prevention and management of chronic diseases, as well as the trends and prospects regarding the application of pomegranate in innovative food and health.

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The Two Faces of Ascorbate: Prooxidant Activity and Radio-Sensitisation

10.26686/wgtn.17014772.v1 ◽

2021 ◽

Author(s):

◽

Georgia Carson

Keyword(s):

Dna Damage ◽

Alternative Therapy ◽

High Dose ◽

Intravenous Injections ◽

Unique Nature ◽

Therapy Option ◽

The Brain

<p>Although not recommended by mainstream oncologists, intravenous injections of pharmacological ascorbate are currently an alternative therapy option for cancer patients. Research has not yet determined whether high-dose ascorbate interacts favourably with radiation therapy to increase DNA damage, and therefore cell death in cancer. Some studies suggest that ascorbate can act as a prooxidant and increase the cytotoxic effect of irradiation in vitro. Glioblastoma multiforme (GBM) is a primary brain astrocytoma that is highly therapy resistant, so patients would be advantaged if ascorbate radiosensitised their cancer. In this investigation, flow cytometry and single cell gel electrophoresis (comet tail assay) were used to measure three indicators of DNA damage in GBM cells in response to ascorbate and irradiation, and were contrasted with immunofluorescence-revealed DNA damage from an intracranial mouse model of GBM. The pro-oxidant, radiosensitisation role of ascorbate was confirmed, as measured by H2AX, 8OHdG, and DSBs in vitro. With all three of these markers of DNA damage, combinations of irradiation and ascorbate had increased damage compared with individual treatments. However preliminary in vivo evidence indicates that increased DNA damage did not occur in an animal model of GBM, and in fact ascorbate may protect from DNA damage in an in vivo context. These findings complement previous results from our lab, and serve to fill in gaps in knowledge specifically around the DNA damaging effects of ascorbate. The unique nature of the brain environment, as enclosed by the blood brain barrier, prevents translation of data from other non-brain cancer studies, as such, this investigation also contributes to the exploration of a much needed avenue of research. Considering the context of ascorbate treatment as a potentially harmful currently used adjuvant, it is imperative to confirm or disprove its efficacy in a clinically relevant environment.</p>

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Cardiac miRNAs were involved in the regulation of pathophysiological mechanisms underlying HF in pediatric patients after ventricular assist device implantation

European Heart Journal ◽

10.1093/eurheartj/ehab724.0941 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

R Ragusa ◽

A Di Molfetta ◽

S Del Turco ◽

G Basta ◽

M Rizzo ◽

...

Keyword(s):

Cardiac Muscle ◽

Real Time ◽

Mirna Expression ◽

Real Time Pcr ◽

In Silico ◽

In Silico Analysis ◽

Adiponectin Receptors ◽

Silico Analysis

Abstract Background VAD use in heart failure (HF) children have undergone rapid progress in the last three decades through pump technological innovation and improvement of perioperative care. Studies in HF adults showed that VAD put native heart at rest and lead to molecular changes in cardiac muscle, including at microRNA (miRNA) level. However, little is known on changes induced by VAD implant in cardiac miRNA expression and their putative targets in HF children. Purpose The aims of this study were to evaluate: 1) modification of miRNA expression in cardiac muscle from HF children after VAD support; 2) the putative targets of selected miRNAs by in silico analysis; 2) the role of the identify miRNAs on putative targets by in vitro study. Methods Cardiac biopsies were collected from HF children at the moment of VAD implant [n=8; 20 (7.5–64.5) months, 2 males; 19 (15.75–32.25) LVEF%] and at the time of heart transplant after VAD support [n=5; 32 (5–204) months; 4 males; 13.5 (10–18) LVEF%]. Cardiac miRNA expression was evaluated by NGS. The potential miRNA targets were identified by bioinformatics analyses and their cardiac expression by real-time PCR was evaluated. HL-1 cell line was used for testing the regulatory role of selected miRNA on predicted targets by miRNA mimic transfection study. Results At NGS, 465 miRNA were found on average in each sample and the cardiac expression levels of miR19a-3p, miR-1246 and miR-199b-5p decreased in HF children after VAD support compared to pre-implant (Fig. 1A-B). In silico analysis showed that more than 5000 potential gene targets regulated by miR-19a-3p, miR-1246 and miR-199b-5p. Among them, adiponectin receptors (AdipoR1, AdipoR2, T-CAD) were identified as common targets for 3 miRNAs. Real-time PCR data showed that levels of all adiponectin receptors increased significantly whilst the expression of 3 miRNAs decreased after VAD support (Fig. 1C). Moreover, AdipoR2 and T-CAD were inversely related to miRNA levels (Fig. 1D). In vitro studies confirmed the regulatory role of miR-1246 and miR-199b-5p on AdipoR2 (Fig. 1E-F), whilst only miR-199b-5p reduced the expression of T-CAD (Fig. 1G). Finally, AdipoR1 expression levels are not modified compared to control by miRNAs mimic transfection (data not shown). Conclusion In HF children the use of VAD could modify the expression of several miRNAs potentially involved in the regulation of several pathophysiological mechanisms underlying HF. Specifically, the reductions of miR-1246, mir-19a-3p, miR-199b-5p were associated with an increase of the adiponectin receptors AdipoR2 and T-CAD mRNA, suggesting the existence of a miRNAs related fine tuning of the adiponectin system at cardiac tissue level by VAD implant, able to favour the protective effect of adiponectin in HF cardiac muscle. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): FP7-ICT-2009 Project, Grant Agreement 24863 Figure 1

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Vasorelaxant Effects Induced by Red Wine and Pomace Extracts of Magliocco Dolce cv.

Pharmaceuticals ◽

10.3390/ph13050087 ◽

2020 ◽

Vol 13 (5) ◽

pp. 87 ◽

Cited By ~ 2

Author(s):

Gabriele Carullo ◽

Amer Ahmed ◽

Fabio Fusi ◽

Fabio Sciubba ◽

Maria Enrica Di Cocco ◽

...

Keyword(s):

Red Wine ◽

Epidemiological Studies ◽

Dependent Manner ◽

Bioactive Constituents ◽

Acid Radical ◽

Rat Thoracic Aorta ◽

Health Promoting ◽

Vasorelaxant Activity ◽

Seed Extracts

Several epidemiological studies demonstrate that moderate (red) wine consumption may afford protection against cardiovascular diseases. Protection is ascribed to the biological activity of wine components, many of which, however, are discarded during winemaking. In vitro rat thoracic aorta rings contracted with phenylephrine or KCl were used to assess the vasorelaxant activity of extracts from wine pomaces (seeds and skins) of the Calabrian autochthonous grape variety Magliocco dolce (Arvino). NMR spectroscopy was used to ascertain their chemical composition. Data demonstrate that seed and skin, but not must, extracts are capable of relaxing vascular preparations in an endothelium-dependent manner, similarly to the red wine extract, due to the presence of comparable amounts of bioactive constituents. In rings pre-contracted with 20–30 mM KCl, only seed extracts showed a moderate relaxation. The most efficacious vasodilating extract (wine) showed a good antioxidant profile in both [(2,2-diphenyl-1-picrylhydrazyl)acid] radical (DPPH) and [2,2’-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid)] radical (ABTS) assays. In conclusion, winemaking from Magliocco dolce grape can provide potentially health-promoting by-products useful in cardiovascular disease management.

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An overview on the interplay between nutraceuticals and gut microbiota

PeerJ ◽

10.7717/peerj.4465 ◽

2018 ◽

Vol 6 ◽

pp. e4465 ◽

Cited By ~ 11

Author(s):

Adrian Catinean ◽

Maria Adriana Neag ◽

Dana Maria Muntean ◽

Ioana Corina Bocsan ◽

Anca Dana Buzoianu

Keyword(s):

Health Status ◽

Side Effects ◽

Alternative Therapy ◽

Animal Experiments ◽

Health Benefits ◽

Health Benefit ◽

Synthetic Drugs

BackgroundNowadays, growing attention was being given to the alternative ways to prevent or treat diseases. Nutraceuticals are used increasingly for this purpose. Many of these are being used as alternative therapy. Classic therapy with synthetic drugs, although very effective, has many side effects. The term “nutraceuticals” refers to the link between the nutritional and pharmaceutical domains. Also, lately, many studies have been done to investigate the role of microbiota in maintaining health. There is the hypothesis that some of the health benefits of nutraceuticals are due to their ability to change the microbiota. The aim of this review was to emphasize the link between the most commonly used nutraceuticals, the microbiota and the health benefits.MethodsWe selected the articles in PubMed, published up to July 2017, that provided information about most used nutraceuticals, microbiota and health benefits. In this review, we incorporate evidence from various types of studies, including observational,in vitroandin vivo, clinical studies or animal experiments.ResultsThe results demonstrate that many nutraceuticals change the composition of microbiota and can interfere with health status of the patients.DiscussionThere is evidence which sustains the importance of nutraceuticals in people’s health through microbiota but further studies are needed to complete the assessment of nutraceuticals in health benefit as a consequence of microbiota’s changing.

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Efficacy of Polyphenols in the Management of Dyslipidemia: A Focus on Clinical Studies

Nutrients ◽

10.3390/nu13020672 ◽

2021 ◽

Vol 13 (2) ◽

pp. 672

Author(s):

Francis Feldman ◽

Mireille Koudoufio ◽

Yves Desjardins ◽

Schohraya Spahis ◽

Edgard Delvin ◽

...

Keyword(s):

Animal Studies ◽

Lipoprotein Metabolism ◽

Hdl Cholesterol ◽

Critical Examination ◽

Wide Range ◽

Significant Research ◽

Study Heterogeneity ◽

Health Promoting

Polyphenols (PLPs), phytochemicals found in a wide range of plant-based foods, have gained extensive attention in view of their antioxidant, anti-inflammatory, immunomodulatory and several additional beneficial activities. The health-promoting effects noted in animal models of various non-communicable diseases explain the growing interest in these molecules. In particular, in vitro and animal studies reported an attenuation of lipid disorders in response to PLPs. However, despite promising preclinical investigations, the effectiveness of PLPs in human dyslipidemia (DLP) is less clear and necessitates revision of available literature. Therefore, the present review analyzes the role of PLPs in managing clinical DLP, notably by dissecting their potential in ameliorating lipid/lipoprotein metabolism and alleviating hyperlipidemia, both postprandially and in long-term interventions. To this end, PubMed was used for article search. The search terms included polyphenols, lipids, triglycerides, cholesterol, LDL-cholesterol and /or HDL-cholesterol. The critical examination of the trials published to date illustrates certain benefits on blood lipids along with co-morbidities in participant’s health status. However, inconsistent results document significant research gaps, potentially owing to study heterogeneity and lack of rigor in establishing PLP bioavailability during supplementation. This underlines the need for further efforts in order to elucidate and support a potential role of PLPs in fighting DLP.

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"Identification of Mechanisms By Which Mesenchymal Stem/Stromal Cells Contribute to Acute Myeloid Leukemia"

Blood ◽

10.1182/blood-2019-122558 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5194-5194

Author(s):

Allolo Aldreiwish ◽

Gauri Muradia ◽

Remi Gagne ◽

Marc Beal ◽

Carole Yauk ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stromal Cells ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

In Silico Analysis ◽

Leukemic Cells ◽

Silico Analysis ◽

Acute Myeloid

Acute myeloid leukemia (AML) is a blood malignancy resulting in abnormal hematopoiesis that is reported to be associated with alterations in the bone marrow microenvironment (BME). Current treatments for this heterogeneous disease, which target the leukemic cells but not the BME, are largely unsuccessful for the majority of AML subtypes. By better understanding the mechanisms by which the BME contributes to leukemogenesis, it may be possible to introduce more effective treatments for AML. Mesenchymal stem cells (MSCs) are an essential component of the BME that have been shown to support normal hematopoiesis. Therefore, MSCs may have several roles in the alteration of the BME, leukemogenesis, and AML relapse and can provide an excellent model for studying the BME in vitro. While some studies have characterized AML-derived MSCs (AML-MSCs), their exact role in the disease remains unclear. Our RNAseq analysis of AML-MSCs (n=30), and healthy donor MSCs (HD-MSCs) (n=8) identified that, among 7655 genes, 21 genes were significantly differentially expressed in AML-MSCs. Through in silico analysis of this gene set, genes of interest were identified as having the potential to directly alter the BME and affect AML pathogenesis through BMP/TGF-β pathways. Current work is focusing on investigation of the effects of selected genes with biological relevance on MSCs intrinsic and extrinsic functional properties. This study will improve our understanding of the role of MSCs in AML BME and help in the discovery of new therapeutic targets. Disclosures No relevant conflicts of interest to declare.

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Preparation and characterization of Pomegranate for Cough Treatment

International Journal for Research in Applied Science and Engineering Technology ◽

10.22214/ijraset.2021.39591 ◽

2021 ◽

Vol 9 (12) ◽

pp. 2227-2233

Author(s):

Mr. Chate Mahesh Madhukar

Keyword(s):

Health Management ◽

Neuroprotective Effect ◽

Health Benefits ◽

In Vivo Studies ◽

Promoting Effect ◽

Health Promoting ◽

Anti Oxidant

Abstract: Pomegranates fruits have innumerable health benefits and its implication in diseases cure have been widely recognized since ancient time. Moreover, pomegranate fruits, seeds and peels are intensively used in traditional medicine as a natural therapy. It contains numerous valuable ingredients such as flavonoids, ellagitannin, punicalagin, ellagic acid, vitamins and minerals. The principal constituents including punicalagins and ellagitannin are responsible for immeasurable health benefits due to its strong antioxidant activity. Additionally, constituents of pomegranate show health promoting effect through the modulation of physiological and biochemical pathways. Recent evidences suggested that pomegranates fruits, peels and seeds illustrate therapeutics implications in health management via inhibition of free radical effect and modulation of enzymes activity linked with diseases development and progression. In this review, we summarize the therapeutic role of pomegranate fruits, seeds and peels in the health managements based on in vitro and in vivo studies. Keywords: Pomegranates, Anti-oxidant, Anti-inflammatory effect, Heptoprotective effect, Neuroprotective effect and antimicrobial effects.

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Effects of different extracts of three Annona species on egg-hatching processes of Haemonchus contortus

Journal of Helminthology ◽

10.1017/s0022149x19000397 ◽

2019 ◽

Vol 94 ◽

Cited By ~ 1

Author(s):

G.S. Castañeda-Ramírez ◽

J.F.J. Torres-Acosta ◽

P. Mendoza-de-Gives ◽

J. Tun-Garrido ◽

J.A. Rosado-Aguilar ◽

...

Keyword(s):

Haemonchus Contortus ◽

Methanolic Extract ◽

Ovicidal Activity ◽

Leaf Extracts ◽

Egg Hatching ◽

Egg Hatch ◽

Methanolic Extracts ◽

Morula Stage

Abstract This study assessed the in vitro anthelmintic (AH) activity of methanol and acetone:water leaf extracts from Annona squamosa, A. muricata and A. reticulata against Haemonchus contortus eggs. The egg hatch test was used to determine the effective concentrations required to inhibit 50% of eggs hatching (EC50). The role of polyphenols on AH activity was measured through bioassays with and without polyvinylpolypyrrolidone (PVPP). Methanolic extracts mainly caused the death of eggs at the morula stage (ovicidal activity). Meanwhile, acetone:water extracts caused egg-hatching failure of developed larvae (larvae failing eclosion (LFE) activity). The lowest EC50 values against H. contortus eggs were observed for the methanolic extracts from A. reticulata and A. muricata (274.2 and 382.9 µg/ml, respectively). From the six extracts evaluated, the methanolic extracts of A. muricata, A. reticulata and A. squamosa showed the highest ovicidal activity, resulting in 98.9%, 92.8% and 95.1% egg mortality, respectively. When the methanolic extract of A. squamosa was incubated with PVPP, its AH activity increased. Similarly, when acetone:water extracts of A. muriata and A. reticulata were incubated with PVPP, their LFE activity increased. Alkaloids were only evident in methanolic extracts, irrespective of PVPP incubation. The presence of acetogenins was not observed. In conclusion, methanolic extracts obtained from leaves of A. muricata, A. reticulata and A. squamosa showed ovicidal activity affecting the morula of H. contortus eggs, with minor LFE activity. Meanwhile, acetone:water extracts showed mostly LFE activity, with a lower proportion of ovicidal activity.

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