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Fulltext Impaired of a non-DNA dependent methylation status decides the fat decision of bone marrow-derived C3H10T1/2 stem cell

Ali F, Ranneh Y, Ismail A, Vaes B

Springerplus, 2013;2:590.
PMID: 24294542 DOI: 10.1186/2193-1801-2-590

A decrease in the lineage commitment of multipotent Mesenchymal stem cells (MSC) to the bone forming osteoblast lineage and an increase in the commitment to the fat forming adipocyte lineage is more common in bone marrow of elderly persons. A link between methylation status and MSC differentiation remains unclear. Therefore, we hypothesize that hypomethylation may decide the fate decisions of MSC. In the current study, murine bone marrow derived-C3H10T1/2 stem cell was used to examine the role of methylation mechanism on the differentiation potential of stem cells into osteoblasts or adipocytes. C3H10T1/2 cells were treated with Periodate oxidized adenosine (Adox), an inhibitor of S-adenosylhomocysteine-dependent hydrolase (SAHH), which in turn block the non-DNA methylation pathway. The effect of hypomethylation on C3H10T1/2 stem cell differentiation was determined by measuring the alkaline phosphates activity and the degree of mineralization as well as Oil-red O staining and lipid content. The ratio of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) was determined as a metabolic indicator of cellular methylation potential. It was clearly observed that hypomethylation significantly (P
Fulltext The inhibitory activity of cocoa phenolic extract against pro-inflammatory mediators secretion induced by lipopolysaccharide in RAW 264.7 cells

Ranneh Y, Ali F, Al-Qubaisi M, Esa NM, Ismail A

Springerplus, 2016;5:547.
PMID: 27190746 DOI: 10.1186/s40064-016-2138-0

Cocoa is a rich source of polyphenols that has been traditionally used as the treatment of several types of inflammation related disease. The response to inflammation comprises the consecutive release of mediators and the enlistment of circulating leukocytes, such as macrophages. Currently, Cocoa-derived polyphenolics have shown anti-inflammatory effects in vivo, but the therapeutic benefits in vitro remain unclear. Therefore, in this study, the effect of cocoa polyphenolic extract (CPE) on RAW 264.7 macrophage cells sensitized by lipopolysaccharide as in vitro inflammatory model was investigated. The anti-inflammatory activity of CPE was assessed by measuring its ability to inhibit the pro-inflammatory enzyme 5-lipoxygenase (5-LOX) and the pro-inflammatory mediators prostaglandin E2 (PGE2), reactive oxygen species (ROS), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α). The results show that CPE significantly inhibits 5-LOX activity (p
Fulltext Identification of phenolic compounds in polyphenols-rich extract of Malaysian cocoa powder using the HPLC-UV-ESI-MS/MS and probing their antioxidant properties

Ali F, Ranneh Y, Ismail A, Esa NM

J Food Sci Technol, 2015 Apr;52(4):2103-11.
PMID: 25829590 DOI: 10.1007/s13197-013-1187-4

The antioxidant components of cocoa powder, which is rich in polyphenols, were isolated using column chromatography and high performance liquid chromatography. Polyphenolic compounds were then characterized by high-performance liquid chromatography/Ultraviolet and electronspray ionization-tandem mass spectrometry (HPLC-UV-/ESI-MS-MS). As a result, five phenolic compounds were detected. In this study we also investigated scavenging or the total antioxidant capacity (%) of cocoa polyphenol (CP) fractionated from cocoa powder extract. 114.0 mg/g of gallic acid -equivalent phenolics and 94.3 mg/g catechin- equivalent flavonoids were quantified in this extract. Their free radical-scavenging activity was assessed by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay, β-carotene bleaching test, and xanthine oxidase inhibitory activity (OX). Total antioxidant capacity (TAC) was further assessed against the myoglobin-induced oxidation of 6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid (ABTS) and expressed as Trolox equivalent. A high correlation between TAC and phenolic contents indicated that phenolic compounds from cocoa were a major contributor of antioxidant activity (0.967 ≤ r ≤ 1.00). CP extract had significantly (P
Role of fish oil in human health and possible mechanism to reduce the inflammation

Ellulu MS, Khaza'ai H, Abed Y, Rahmat A, Ismail P, Ranneh Y

Inflammopharmacology, 2015 Jun;23(2-3):79-89.
PMID: 25676565 DOI: 10.1007/s10787-015-0228-1

The roles of Omega-3 FAs are inflammation antagonists, while Omega-6 FAs are precursors for inflammation. The plant form of Omega-3 FAs is the short-chain α-linolenic acid, and the marine forms are the long-chain fatty acids: docosahexaenoic acid and eicosapentaenoic acid. Omega-3 FAs have unlimited usages, and they are considered as omnipotent since they may benefit heart health, improve brain function, reduce cancer risks and improve people's moods. Omega-3 FAs also have several important biological effects on a range of cellular functions that may decrease the onset of heart diseases and reduce mortality among patients with coronary heart disease, possibly by stabilizing the heart's rhythm and by reducing blood clotting. Some review studies have described the beneficial roles of Omega-3 FAs in cardiovascular diseases (CVDs), cancer, diabetes, and other conditions, including inflammation. Studies of the effect of Omega-3 FAs gathered from studies in diseased and healthy population. CVDs including atherosclerosis, coronary heart diseases, hypertension, and metabolic syndrome were the major fields of investigation. In studies of obesity, as the central obesity increased, the level of adipocyte synthesis of pro-inflammatory cytokines like tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were increased and the level of anti-inflammatory adiponectin was decreased indicating a state of inflammation. The level of C reactive protein (CRP) synthesized from hepatocyte is increased by the influence of IL-6. CRP can be considered as a marker of systemic inflammation associated with increased risks of CVDs. In molecular studies, Omega-3 FAs have direct effects on reducing the inflammatory state by reducing IL-6, TNF-α, CRP and many other factors. While the appropriate dosage along with the administrative duration is not known, the scientific evidence-based recommendations for daily intake are not modified.
Induction of Chronic Subclinical Systemic Inflammation in Sprague-Dawley Rats Stimulated by Intermittent Bolus Injection of Lipopolysaccharide

Ranneh Y, Akim AM, Hamid HA, Khazaai H, Mokhtarrudin N, Fadel A, et al.

Arch Immunol Ther Exp (Warsz), 2019 Dec;67(6):385-400.
PMID: 31278602 DOI: 10.1007/s00005-019-00553-6

Chronic subclinical systemic inflammation has a key role in stimulating several chronic conditions associated with cardiovascular diseases, cancer, rheumatoid arthritis, diabetes, and neurodegenerative diseases. Hence, developing in vivo models of chronic subclinical systemic inflammation are essential to the study of the pathophysiology and to measure the immunomodulatory agents involved. Male Sprague-Dawley rats were subjected to intraperitoneal, intermittent injection with saline, or lipopolysaccharide (LPS) (0.5, 1, 2 mg/kg) thrice a week for 30 days. Hematological, biochemical, and inflammatory mediators were measured at different timepoints and at the end of the study. The hearts, lungs, kidneys, and livers were harvested for histological evaluation. Significant elevation in peripheral blood leukocyte includes neutrophils, monocytes, and lymphocytes, as well as the neutrophils-to-lymphocyte ratio. The pro-inflammatory mediator levels [C-reactive protein, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8] along with the biochemical profile (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, creatinine, and urea) were increased significantly (P
Fulltext Stingless bee honey protects against lipopolysaccharide induced-chronic subclinical systemic inflammation and oxidative stress by modulating Nrf2, NF-κB and p38 MAPK

Ranneh Y, Akim AM, Hamid HA, Khazaai H, Fadel A, Mahmoud AM

Nutr Metab (Lond), 2019;16:15.
PMID: 30858869 DOI: 10.1186/s12986-019-0341-z

Background: Epidemiological and experimental studies have extensively indicated that chronic subclinical systemic inflammation (CSSI) and oxidative stress are risk factors for several chronic diseases, including cancer, arthritis, type 2 diabetes, and cardiovascular and neurodegenerative diseases. This study examined the protective effect of stingless bee honey (SBH) supplementation against lipopolysaccharide (LPS)-induced CSSI, pointing to the possible involvement of NF-κB, p38 MAPK and Nrf2 signaling.
Methods: CSSI was induced in male Sprague Dawley rats by intraperitoneal injection of LPS three times per week for 28 days, and SBH (4.6 and 9.3 g/kg/day) was supplemented for 30 days.
Results: LPS-induced rats showed significant leukocytosis, and elevated serum levels of CRP, TNF-α, IL-1β, IL-6, IL-8, MCP-1, malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), accompanied with diminished antioxidants. Treatment with SBH significantly ameliorated inflammatory markers, MDA and 8-OHdG, and enhanced antioxidants in LPS-induced rats. In addition, SBH decreased NF-κB p65 and p38 MAPK, and increased Nrf2 expression in the liver, kidney, heart and lung of LPS-induced rats. Furthermore, SBH prevented LPS-induced histological and functional alterations in the liver, kidney, heart and lung of rats.
Conclusion: SBH has a substantial protective role against LPS-induced CSSI in rats mediated via amelioration of inflammation, oxidative stress and NF-κB, p38 MAPK and Nrf2 signaling.
Acute Inflammation and Oxidative Stress Induced by Lipopolysaccharide and the Ameliorative Effect of Stingless Bee Honey

Ranneh Y, Mahmoud AM, Fadel A, Albujja M, Akim AM, Hamid HA, et al.

Comb Chem High Throughput Screen, 2021;24(6):744-757.
PMID: 32957878 DOI: 10.2174/1386207323999200918152111

BACKGROUND: Systemic acute inflammation is the hallmark of sepsis and is associated with multiple organ dysfunction.
OBJECTIVE: This study investigated the potential of Stingless Bee Honey (SBH) to suppress lipopolysaccharide (LPS)-induced systemic acute inflammation in rats and to reveal the probable mechanism of action.
METHODS: Rats received 4.6 and 9.2 g/kg SBH for 7 days followed by a single injection of LPS after which blood samples were taken 6h later.
RESULTS: LPS induced liver, kidney, heart, and lung injury, were manifested by increased serum transaminases, alkaline phosphatase, creatine kinase, creatinine, and urea, along with multiple histological alterations, particularly leukocyte infiltration. Pro-inflammatory cytokines were elevated in the serum, and NF-κB p65, p38 MAPK, and HMGB-1 were significantly increased in different tissues of LPS-challenged rats. SBH prevented tissue injury, ameliorated pro-inflammatory cytokines, and suppressed NF-κB p65, p38 MAPK, and HMGB-1 in rats that had received LPS. In addition, SBH diminished reactive oxygen species (ROS) production, lipid peroxidation, and oxidative DNA damage, and enhanced glutathione and Nrf2 in LPS-treated rats.
CONCLUSION: SBH prevents systemic acute inflammation by suppressing NF-κB, p38 MAPK, HMGB-1, oxidative stress, and tissue injury in rats. Thus, SBH may represent an effective anti-inflammatory nutraceutical, pending further mechanistic studies.
Fulltext The effect of extrusion screw-speed on the water extractability and molecular weight distribution of arabinoxylans from defatted rice bran

Fadel A, Plunkett A, Ashworth J, Mahmoud AM, Ranneh Y, El Mohtadi M, et al.

J Food Sci Technol, 2018 Mar;55(3):1201-1206.
PMID: 29487463 DOI: 10.1007/s13197-017-3010-0

Arabinoxylans (AXs) are major dietary fibre in cereals. Recently, AXs have attracted a great deal of attention because of their biological activities. These activities have been suggested to be related to the content of low molecular weight (Mw) AXs, in particular those with Mw below 32 kDa. Rice bran is a rich source of AXs. However, water extraction of AXs is difficult and often gives low yield. Extrusion processing has been used to increase the solubility of cereal dietary fibre. The aim of this research was to study the effect of extrusion screw-speeds (80 and 160) rpm on the extraction yield and Mw of water extractable AXs from rice bran. It was found that the extraction of AXs increased significantly with an increase in screw speed and was accompanied by a significant decrease in the Mw of AXs from extruded rice bran. The percentage of very low molecular weight AXs (0.79-1.58 kDa) significantly increased with increasing screw speed.
Fulltext A review of studies examining the association between genetic biomarkers (short tandem repeats and single-nucleotide polymorphisms) and risk of prostate cancer: the need for valid predictive biomarkers

Albujja MH, Vasudevan R, Alghamdi S, Pei CP, Bin Mohd Ghani KA, Ranneh Y, et al.

Prostate Int, 2020 Dec;8(4):135-145.
PMID: 33425790 DOI: 10.1016/j.prnil.2019.11.003

Prostate cancer (PCa) is a challenging polygenic disease because the genes that cause PCa remain largely elusive and are affected by several causal factors. Consequently, research continuously strives to identify a genetic marker which could be used as an indicator to predict the most vulnerable (i.e., predisposed) segments of the population to the disease or for the gene which may be directly responsible for PCa. To enhance the genetic etiology of PCa, this research sought to discover the key studies conducted in this field using data from the main journal publication search engines, as it was hoped that this could shed light on the main research findings from these studies, which in turn could assist in determining these genes or markers. From the research highlighted, the studies primarily used two kinds of markers: short tandem repeats or single-nucleotide polymorphisms. These markers were found to be quite prevalent in all the chromosomes within the research carried out. It also became apparent that the studies differed in both quantity and quality, as well as being conducted in a variety of societies. Links were also determined between the degree and strength of the relationship between these markers and the occurrence of the disease. From the studies identified, most recommended a larger and more diverse survey for the parameters which had not been studied before, as well as an increase in the size of the community (i.e., the population) being studied. This is an indication that work in this field is far from complete, and thus, current research remains committed toward finding genetic markers that can be used clinically for the diagnosis and screening of patients with PCa.
Fulltext Induction of Apoptosis and Modulation of Caspase Activity on MCF-7 Human Breast Cancer Cells by Bioactive Fractionated Cocoa Leaf Extract

Ranneh Y, Abu Bakar MF, Md Akim A, Bin Baharum Z, S Ellulu M, Fadel A

Asian Pac J Cancer Prev, 2023 Jul 01;24(7):2473-2483.
PMID: 37505782 DOI: 10.31557/APJCP.2023.24.7.2473

BACKGROUND: The objective of this study was to investigate the potential anti-proliferative activities of a methanolic extract of cocoa leaves (CL) obtained through sequential partition and fractionation against MCF-7 breast cancer cells. Methods: The methanolic extract of CL was partitioned in three separated solvents (hexane, dichloromethane, and methanol). Hexane partition was the most potent against MCF-7 cells growth with the lowest IC50 value. Then, it was subjected to two fractionation procedures, resulting in the identification of the CL bioactive fraction (II-F7) with potent toxicity against MCF-7 cells.
RESULTS: Further investigation into CL bioactive fraction (II-F7) revealed significant dose-dependent growth inhibitory effects on MCF-7 cells, which were attributed to the induction of apoptosis, as evidenced by the presence of apoptotic bodies, fragmented DNA, and disruption of mitochondrial membrane potential. Additionally, treatment with CL bioactive fraction (II-F7) upregulated the expression of pro-apoptotic genes (DDIT3, GADD45G and HRK) and significantly increased the activities of caspase-8 and caspase-9.
CONCLUSION: Overall, this study suggests that bioactive fraction (II-F7) from CL extract has significant and selective cytotoxicity against MCF-7 cells through inducing apoptosis and has potential as a therapeutic agent for breast cancer treatment.
Fulltext Comments on "Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics"

Ranneh Y, Mahmoud AM, Fadel A, Abu Bakar MF, Md Akim A

Front Pharmacol, 2023;14:1228359.
PMID: 37663246 DOI: 10.3389/fphar.2023.1228359
Fulltext Anti-aging and antioxidant of four traditional malaysian plants using simplex centroid mixture design approach

Ranneh Y, Abu Bakar MF, Ismail NA, Kormin F, Mohamed M, Md Akim A, et al.

Saudi J Biol Sci, 2021 Dec;28(12):6711-6720.
PMID: 34866970 DOI: 10.1016/j.sjbs.2021.07.048

Aging is a naturally biological process with adverse effects. The continuous accumulation of reactive oxygen species (ROS) trigger cellular and tissue damage by activating several aging enzymes. The antioxidant properties of traditional medicinal plants used by Jakun aborigine's community are a promising approach to alleviate aging process and prevent Alzheimer. The aim of the current investigation was to optimize a novel anti-aging formulation from traditional plants (Cnestis palala stem, Urceola micrantha stem, Marantodes pumilum stem and Microporus xanthopus fruiting bodies) using simplex centroid mixture design (SCMD). After selecting the optimal formulations based on desirability function of antioxidant activity (DPPḢ, ABTS ˙ + and FRAP), they were further examined against the activity of aging-related-enzymes (collagenase, tyrosinase, acetyl- and butyrylcholinesterase). The single extracts of C. palala, U. micrantha and the binary mixture of C. palala and U. micrantha were the optimal formulations with high antioxidant activities. Single extract of U. micrantha showed the highest inhibition towards matrix metalloproteinase-1 (49.44 ± 4.11 %), while C. palala water extract showed highest inhibitions towards tyrosinase (14.06 ± 0.31%), acetylcholinesterase (32.92 ± 2.13%) and butyrylcholinesterase (34.89 ± 2.84%) enzymes. The single extracts of C. palala and U. micrantha displayed better activity as compared to the binary mixture formulation. In conclusion, these findings could be a baseline for further exploration of novel anti-aging agents from natural resources.
Fulltext Identification of Potential Genes for Benign Prostatic Hyperplasia and Prostate Cancer Susceptibility in Four X-chromosome Regions with High Frequency of Microvariant Alleles

Albujja MH, Messaudi SA, Vasudevan R, Al Ghamdi S, Chong PP, Ghani KA, et al.

Asian Pac J Cancer Prev, 2020 08 01;21(8):2271-2280.
PMID: 32856855 DOI: 10.31557/APJCP.2020.21.8.2271

BACKGROUND: The X-chromosome has been suggested to play a role in prostate cancer (PrCa) since epidemiological studies have provided evidence for an X-linked mode of inheritance for PrCa based on the higher relative risk among men who report an affected brother(s) as compared to those reporting an affected father. The aim of this study was to examine the potential association between the forensic STR markers located at four regions Xp22.31, Xq11.2-12, Xq26.2, and Xq28 and the risk of BPH and PrCa to confirm the impact of ChrX in the PrCa incidence. This may be helpful in the incorporation of STRs genetic variation in the early detection of men population at risk of developing PrCa.
METHODS: DNA samples from 92 patients and 156 healthy controls collected from two medical centers in Riyadh, Saudi Arabia were analyzed for four regions located at X-chromosome using the Investigator® Argus X-12 QS Kit.
RESULTS: The results demonstrated that microvariant alleles of (DXS7132, DXS10146, HPRTB, DXS10134, and DXS10135) are overrepresented in the BPH group (p < 0.00001). Allele 28 of DXS10135 and allele 15 of DXS7423 could have a protective effect, OR 0.229 (95%CI, 0.066-0.79); and OR 0.439 (95%CI, 0.208-0.925). On the other hand, patients carrying allele 23 of DXS10079 and allele 26 of DXS10148 presented an increased risk to PrCa OR 4.714 (95%CI, 3.604-6.166).
CONCLUSION: The results are in concordance with the involvement of the X chromosome in PrCa and BPH development. STR allele studies may add further information from the definition of a genetic profile of PrCa resistance or susceptibility. As TBL1, AR, LDOC1, and RPL10 genes are located at regions Xp22.31, Xq11.2-12, Xq26.2, and Xq28, respectively, these genes could play an essential role in PrCa or BPH.
Fulltext Honey and its nutritional and anti-inflammatory value

Ranneh Y, Akim AM, Hamid HA, Khazaai H, Fadel A, Zakaria ZA, et al.

BMC Complement Med Ther, 2021 Jan 14;21(1):30.
PMID: 33441127 DOI: 10.1186/s12906-020-03170-5

Inflammation is the main key role in developing chronic diseases including cancer, cardiovascular diseases, diabetes, arthritis, and neurodegenerative diseases which possess a huge challenge for treatment. With massively compelling evidence of the role played by nutritional modulation in preventing inflammation-related diseases, there is a growing interest into the search for natural functional foods with therapeutic and preventive actions. Honey, a nutritional healthy product, is produced mainly by two types of bees: honeybee and stingless bee. Since both types of honey possess distinctive phenolic and flavonoid compounds, there is recently an intensive interest in their biological and clinical actions against inflammation-mediated chronic diseases. This review shed the light specifically on the bioavailability and bioaccessibility of honey polyphenols and highlight their roles in targeting inflammatory pathways in gastrointestinal tract disorders, edema, cancer, metabolic and cardiovascular diseases and gut microbiota.

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