Displaying publications 1 - 20 of 54 in total

  1. Manaharan T, Palanisamy UD, Ming CH
    Molecules, 2012;17(5):5915-23.
    PMID: 22609782 DOI: 10.3390/molecules17055915
    Preliminary investigations on 14 plant extracts (obtained by ethanolic and aqueous extraction) identified those having high antioxidant and a significant total phenolic content. Antihyperglycemic, α-amylase and α-glucosidase inhibition activities were also observed. A correlation between the antihyperglycemic activity, total phenolic content and antioxidant (DPPH scavenging) activity was established. To further substantiate these findings, the possibility of tannins binding non-specifically to enzymes and thus contributing to the antihyperglycemic activity was also investigated. Our study clearly indicated that the antihyperglycemic activity observed in the plant extracts was indeed not due to non-specific tannin absorption.
  2. Manaharan T, Ming CH, Palanisamy UD
    Food Chem, 2013 Jan 15;136(2):354-63.
    PMID: 23122070 DOI: 10.1016/j.foodchem.2012.08.056
    The insulin-like and/or insulin-sensitising effects of Syzygium aqueum leaf extract and its six bioactive compounds; 4-hydroxybenzaldehyde, myricetin-3-O-rhamnoside, europetin-3-O-rhamnoside, phloretin, myrigalone-G and myrigalone-B were investigated in 3T3-L1 adipocytes. We observed that, S. aqueum leaf extract (0.04-5 μg/ml) and its six bioactive compounds (0.08-10 μM) at non-cytotoxic concentrations were effectively enhance adipogenesis, stimulate glucose uptake and increase adiponectin secretion in 3T3-L1 adipocytes. Clearly, the compounds myricetin-3-O-rhamnoside and europetin-3-O-rhamnoside showed insulin-like and insulin-sensitising effects on adipocytes from a concentration of 0.08 μM. These compounds were far better than rosiglitazone and the other isolated compounds in enhancing adipogenesis, stimulating 2-NBDG uptake and increasing adiponectin secretion at all the concentrations tested. These suggest the antidiabetic potential of S. aqueum leaf extract and its six bioactive compounds. However, further molecular interaction studies to explain the mechanisms of action are highly warranted.
  3. Ling LT, Palanisamy UD, Cheng HM
    Molecules, 2010 Nov;15(11):7884-92.
    PMID: 21060296 DOI: 10.3390/molecules15117884
    The antioxidant activity of several Malaysian plant extracts was analyzed simultaneously with their pro-oxidant capacity. This ratio represents an index (ProAntidex) of the net free radical scavenging ability of whole plant extracts. We observed that ethanolic extracts of Nephelium lappaceum peel, Fragaria x ananassa leaf, Lawsonia inermis leaf, Syzygium aqueum leaf and grape seed had a lower Pro-Antidex than the commercially available Emblica™ extract which is an antioxidant agent with very low pro-oxidant activity. Among the aqueous extracts, Lawsonia inermis leaf, Nephelium mutobile leaf and grape seed had lower pro-oxidant activity compared to the Emblica™ extract. Among these extracts, aqueous extract of Nephelium mutobile leaf had a very low index of 0.05 compared to 0.69 for Emblica™. Most of the extracts had a far lower ProAntidex compared to the Vitamin C. The index enables us to identify extracts with high net free radical scavenging activity potential. The ProAntidex is beneficial as a screening parameter to the food industries and healthcare.
  4. Moorthy M, Khoo JJ, Palanisamy UD
    Heliyon, 2019 Aug;5(8):e02333.
    PMID: 31508523 DOI: 10.1016/j.heliyon.2019.e02333
    Despite the lack of its toxicity evaluation, traditional herbal products are being widely used for various health indications. Geraniin, an ellagitannin, is a bioactive compound found in many traditional herbal medicines. In spite its numerous health benefits ranging from anti-inflammatory, anti-hyperglycaemic, hepatoprotective, anti-cancer and anti-microbial, no toxicity data on geraniin is available. The objective of this study is to evaluate the acute oral toxicity of geraniin and an enriched geraniin-extract of Nephelium lappaceum L rind. This study followed the guidelines of the OECD 423 acute oral toxicity test. Subsequent to a single oral administration of the test compounds, the rats were observed for 14 days for signs of toxicity and mortality. Following euthanasia, full blood count, biochemistry of blood and histopathology assessment of organs were carried out. All parameters analysed indicated insignificant difference compared to control. The LD50 cut-off values for both geraniin and geraniin-enriched extract was established to be 2000 mg/kg b. w., following a single oral dose. It was however observed that the hepatocytes of three geraniin-administered rats exhibited a 'foamy appearance'. As such, the no-observed-adverse-effect level of geraniin is below 2000 mg/kg, while that of geraniin-enriched extract is up to 2000 mg/kg. Further detailed toxicity studies are required to establish geraniin or its enriched extract from Nephelium lappaceum L rind safe for human consumption.
  5. Moorthy M, Sundralingam U, Palanisamy UD
    Foods, 2021 Feb 02;10(2).
    PMID: 33540692 DOI: 10.3390/foods10020299
    Obesity is a disease growing at an alarming rate and numerous preclinical studies have proven the role of polyphenols in managing this disease. This systematic review explores the prebiotic effect of polyphenols in the management of obesity among animals fed on a high-fat diet. A literature search was carried out in PubMed, Scopus, CINAHL, Web of Science, and Embase databases following the PRISMA guidelines. Forty-four studies reported a significant reduction in obesity-related parameters. Most notably, 83% of the studies showed a decrease in either body weight/visceral adiposity/plasma triacylglyceride. Furthermore, 42 studies reported a significant improvement in gut microbiota (GM), significantly affecting the genera Akkermansia, Bacteroides, Blautia, Roseburia, Bifidobacteria, Lactobacillus, Alistipes, and Desulfovibrio. Polyphenols' anti-obesity, anti-hyperglycaemic, and anti-inflammatory properties were associated with their ability to modulate GM. This review supports the notion of polyphenols as effective prebiotics in ameliorating HFD-induced metabolic derangements in animal models.
  6. Nathan FM, Singh VA, Dhanoa A, Palanisamy UD
    BMC Cancer, 2011;11:382.
    PMID: 21871117 DOI: 10.1186/1471-2407-11-382
    Oxidative stress is characterised by an increased level of reactive oxygen species (ROS) that disrupts the intracellular reduction-oxidation (redox) balance and has been implicated in various diseases including cancer. Malignant tumors of connective tissue or sarcomas account for approximately 1% of all cancer diagnoses in adults and around 15% of paediatric malignancies per annum. There exists no information on the alterations of oxidant/antioxidant status of sarcoma patients in literature. This study was aimed to determine the levels of oxidative stress and antioxidant defence in patients with primary bone and soft tissue sarcoma and to investigate if there exists any significant differences in these levels between both the sarcomas.
  7. Elendran S, Wang LW, Prankerd R, Palanisamy UD
    Pharm Biol, 2015;53(12):1719-26.
    PMID: 25853977 DOI: 10.3109/13880209.2014.1003356
    Natural products play a vital role in the discovery of leads for novel pharmacologically active drugs. Geraniin (GE) was identified as the major compound in the rind of Nephelium lappaceum L. (Sapindaceae), while ellagic and gallic acids have been shown to be its main metabolites. GE and its metabolites possess a range of bioactive properties including being an anti-infective, anticarcinogenic, antihyperglycemic, and antihypertensive.
  8. Elendran S, Muniyandy S, Lee WW, Palanisamy UD
    Food Funct, 2019 Feb 20;10(2):602-615.
    PMID: 30566155 DOI: 10.1039/c8fo01927d
    Ellagitannins, found abundantly in berries, pomegranates, walnuts and almonds, have been increasingly investigated for their health benefits. Geraniin (GE), an ellagitannin, found predominantly in herbal plants, as well has been shown to exhibit a number of biological activities. Like many hydrolysable tannins, geraniin is water-soluble and readily undergoes hydrolysis in the presence of hot water, weak acids and weak bases to yield several metabolites including corilagin (CO), ellagic acid (EA) and gallic acid (GA). There are numerous studies on the pharmacological effectiveness of GE, CO and GA. However, the intestinal permeability of GE and CO has never been investigated before. Caco-2 cell transport assay was utilized to evaluate the in vitro permeability of GE and its metabolites. GE, CO and EA were found to have no apparent permeability (Papp) while GA displayed a Papp value of 31.3 ± 1.1 × 10-6 cm s-1. Mass balance studies showed a loss of geraniin and its metabolites during transport. Chemical stability studies in the transport buffers revealed that GE and CO were hydrolyzed in the HBSS buffers. Experiments using lysed cells revealed that GE and its metabolites were metabolized during transport. Absorption and desorption studies confirmed the accumulation of EA inside the cells. The above results indicate that the compounds have poor oral absorption. To consider these compounds or their natural extracts as oral nutraceutical candidates, formulation strategies are mandatory.
  9. Phang SCW, Palanisamy UD, Kadir KA
    J Integr Med, 2019 Mar;17(2):100-106.
    PMID: 30738774 DOI: 10.1016/j.joim.2019.01.008
    OBJECTIVE: A preliminary study showed that geraniin extracted from Nephelium lappaceum L. at 50 mg/kg caused reduction in blood glucose and insulin resistance. The present study serves to further investigate the effects of geraniin at increasing doses between 3.125 and 100 mg/kg in high-fat diet-treated rats.

    METHODS: Geraniin (95% purity) was extracted and purified from rambutan rind. Two groups of male Sprague-Dawley rats were fed with 60% high-fat diet and standard rat chow, respectively, for 12 weeks. High-fat diet-treated rats were then administered geraniin at different doses. Body weight, blood pressure and blood glucose readings were measured. At the end of treatment, blood was collected for analysis of glycated haemoglobin A1c (HbA1c), insulin, advanced glycation end-product (AGE) levels, renin, aldosterone and electrolytes.

    RESULTS: Within the first week of treatment, even the lowest dose of geraniin caused a significant reduction in blood pressure, which was comparable to control diet-treated rats. There were no changes in serum electrolytes, renin or aldosterone. Similarly, there was a significant reduction in serum insulin, insulin resistance and AGE levels at the lowest dose. However, there was no significant decrease in fasting blood glucose or HbA1c. The effects of decreasing insulin, insulin resistance and AGEs were observed only at the lower doses, unlike the results observed for blood pressure reduction.

    CONCLUSION: Geraniin at lower doses improved blood pressure and other metabolic parameters. Secondary metabolites of geraniin, associated with antihypertensive activity, are relatively different to those involved in inhibiting AGE formation and increasing insulin sensitivity. The secondary metabolites of geraniin may be individually responsible for the bioactivities demonstrated.

  10. Chong EY, Palanisamy UD, Jacob SA
    Patient Prefer Adherence, 2019;13:195-207.
    PMID: 30774315 DOI: 10.2147/PPA.S182516
    Purpose: This study prepares the groundwork on the potential design and development of a mobile health (mHealth) app that will be able to bridge the communication gap between pharmacists and patients who are Deaf and Hard of Hearing (DHoH).

    Patients and methods: A focus group discussion was conducted with 12 community pharmacists. Participants were recruited using snowball sampling. Audio-recordings were transcribed verbatim, and analyzed using a thematic approach.

    Results: Three themes were apparent: 1) suggestions for app design and content, 2) perceived benefits of the app, and 3) potential challenges related to the app. Participants believed the app would be able to facilitate and improve communication, and hence relationship, between pharmacists and the DHoH. Potential challenges of the app were highlighted, such as the need for manpower to manage the app, and its cost to this group of economically disadvantaged people. There were also concerns about privacy and security.

    Conclusions: This study allowed community pharmacists, one of the end-users of the app, to provide feedback on the contents and design of the app, which would allow them to provide pharmaceutical care services to patients who are DHoH, and better serve them. Potential benefits and challenges of the app were also identified. Undoubtedly, through the mHealth app, community pharmacists will be better equipped to serve and communicate with the DHoH, and this will hopefully translate to improved health outcomes in these patients.

  11. Jacob SA, Chong EY, Goh SL, Palanisamy UD
    Mhealth, 2021;7:29.
    PMID: 33898598 DOI: 10.21037/mhealth.2020.01.04
    Background: Deaf and hard-of-hearing (DHH) patients have trouble communicating with community pharmacists and accessing the healthcare system. This study explored the views on a proposed mobile health (mHealth) app in terms of design and features, that will be able to bridge the communication gap between community pharmacists and DHH patients.

    Methods: A community-based participatory research method was utilized. Two focus group discussions (FGDs) were conducted in Malaysian sign language (BIM) with a total of 10 DHH individuals. Respondents were recruited using purposive sampling. Video-recordings were transcribed and analyzed using a thematic approach.

    Results: Two themes emerged: (I) challenges and scepticism of the healthcare system; and (II) features of the mHealth app. Respondents expressed fears and concerns about accessing healthcare services, and stressed on the need for sign language interpreters. There were also concerns about data privacy and security. With regard to app features, the majority preferred videos instead of text to convey information about their disease and medication, due to their lower literacy levels.

    Conclusions: For an mHealth app to be effective, app designers must ensure the app is individualised according to the cultural and linguistic diversity of the target audience. Pharmacists should also educate patients on the potential benefits of the app in terms of assisting patients with their medicine-taking.

  12. Sundralingam U, Chakravarthi S, Radhakrishnan AK, Muniyandy S, Palanisamy UD
    Pharmaceutics, 2020 Aug 25;12(9).
    PMID: 32854385 DOI: 10.3390/pharmaceutics12090807
    Oral tamoxifen used in the prevention and treatment of ductal carcinoma in situ (DCIS) (estrogen-positive) patients has limited acceptance, due to its adverse side effects. The efficacy of tamoxifen is related to its major metabolite, 4-hydroxytamoxifen. Local transdermal therapy of 4-hydroxytamoxifen to the breast might avert the toxicity of oral tamoxifen, while maintaining efficacy. We aim to study the skin irritancy, as well as to evaluate the efficacy of the developed transfersome formulations, with/without emu oil, using a syngeneic mouse model of breast cancer. We also quantified tamoxifen/4-hydroxytamoxifen concentrations in blood plasma and performed histopathology. The skin irritancy test showed that the pure emu oil and transfersome formulations with or without the emu oil did not cause skin irritancy in the animals studied. A sensitive and specific LC-MS/MS method for the quantification of tamoxifen and 4-hydroxytamoxifen was developed and validated. Studies on tumor volume and necrosis (histopathology) using the breast cancer mouse model showed that the 4-OHT transfersomal formulations, with and without emu oil, showed comparable efficacy with that of orally administered tamoxifen. However, the transfersomal formulations, with and without emu oil, resulted in significantly lower (10.24 ± 0.07 and 32.45 ± 0.48 ng/mL, respectively) plasma concentrations of 4-hydroxytamoxifen, compared to the oral tamoxifen (TAMX) group (634.42 ± 7.54 ng/mL). This study demonstrated the potential use of emu oil in a local transdermal formulation for the treatment of breast cancer and its reduced adverse effects.
  13. Perera A, Ton SH, Moorthy M, Palanisamy UD
    Int J Food Sci Nutr, 2020 Dec;71(8):940-953.
    PMID: 32319838 DOI: 10.1080/09637486.2020.1754348
    In this study, the insulin-like and insulin sensitising effects of the ellagitannins geraniin, corilagin, ellagic acid, gallic acid and Nephelium lappaceum rind extract in 3T3-L1 adipocytes was investigated. It was observed that non-toxic concentrations of geraniin and its metabolites (0.2-20 μM) and N. lappaceum extract (0.2-20 μg/mL) exhibited insulin-like properties in the absence of insulin and insulin-sensitising properties in the presence of insulin particularly with regards to glucose uptake in 3T3-L1 adipocytes. The compounds were further able to promote adipocyte differentiation and may be involved in the inhibition of lipolysis in 3T3-L1 adipocytes in the presence of insulin. However further study into the molecular mechanisms of action of these compounds need to be carried out to better understand the potential of these compounds/extracts to act as therapeutic agents for hyperglycaemia associated with diabetes mellitus and obesity.
  14. Arumugam B, Palanisamy UD, Chua KH, Kuppusamy UR
    Mol. Vis., 2019;25:47-59.
    PMID: 30820141
    Purpose: Oxidative stress is implicated in the etiology of diabetes and its debilitating complications, such as diabetic retinopathy (DR). Various flavonoids have been reported to be useful in reducing DR progression. Myricetin derivatives (F2) isolated from leaf extract of Syzygium malaccense have the potential to serve as functional food as reported previously. The present study was performed with the aim of determining the antioxidant potential and protective effect of myricetin derivatives (F2) isolated from leaf extract of S. malaccense against glucose oxidase (GO)-induced hydrogen peroxide (H2O2) production that causes oxidative stress in ARPE-19 (RPE) cells.

    Methods: Antioxidant properties were assessed through various radical (DPPH, ABTS, and nitric oxide) scavenging assays and determination of total phenolic content and ferric reducing antioxidant power level. ARPE-19 cells were preincubated with samples before the addition of GO (to generate H2O2). Cell viability, change in intracellular reactive oxygen species (ROS), H2O2 levels in cell culture supernatant, and gene expression were assessed.

    Results: F2 showed higher antioxidant levels than the extract when assessed for radical scavenging activities and ferric reducing antioxidant power. F2 protected the ARPE-19 cells against GO-H2O2-induced oxidative stress by reducing the production of H2O2 and intracellular reactive oxygen species. This was achieved by the activation of nuclear factor erythroid 2-related factor 2 (Nrf2/NFE2L2) and superoxide dismutase (SOD2), as well as downregulation of nitric oxide producer (NOS2) at the transcriptional level.

    Conclusions: The results showed that myricetin derivatives from S. malaccense have the capacity to exert considerable exogenous antioxidant activities and stimulate endogenous antioxidant activities. Therefore, these derivatives have excellent potential to be developed as therapeutic agents for managing DR.

  15. Sundralingam U, Khan TM, Elendran S, Muniyandy S, Palanisamy UD
    Pak J Pharm Sci, 2019 May;32(3):1121-1128.
    PMID: 31278729
    There has been a number of studies looking into an alternative mode of therapy for the treament of breast cancer via 4-hydroxytamoxifen (4-OHT) transdermal administration.This systematic review aims to compare the safety and efficacy of a transdermal 4-OHT local therapy and oral tamoxifen (oral-T) on the treatment of ductal carcinoma in situ breast cancer. Through a systematic search of health science databases, eligible trials were located and the end points assessed were Ki-67 labeling index, concentration of 4-OHT in breast adipose tissue (ng/g) and plasma (ng/ml). Revman 5.3 version was used to perfom the meta-analysis. Three trials were identified (n=103), while only two were included for meta analysis. The mean difference between the two studies included were 0.40 and -10.58. Overall the I2 value was 89.0%, (Tau2 =53.86) and the differences between the two trials were statistically significant p=0.002. The meta analysis of the randomized controlled trials showed that the use of local transdermal therapy of 4-OHT gel is more safer than oral-T. However, due to the limited number of studies, the potential use of 4-OHT topical transdermal therapy for the treatment of breast cancer could not be concluded for healthcare professionals.
  16. Sundralingam U, Muniyandy S, Radhakrishnan AK, Palanisamy UD
    J Liposome Res, 2021 Sep;31(3):217-229.
    PMID: 32648792 DOI: 10.1080/08982104.2020.1777155
    The anti-inflammatory property of ratite oils as well as its ability to act as a penetration enhancer makes it an ideal agent to be used in transdermal formulations. The present study aims to develop an effective transfersomal delivery of 4-hydroxytamoxifen (4-OHT), an anti-cancer drug, using ratite oil as a carrier agent for the treatment of breast cancer (BC). The 4-OHT transfersomes were prepared with and without ratite oils using soy phosphatidylcholine and three different edge activators (EAs) in five different molar ratios using the rotary evaporation-ultrasonication method. Optimal transfersome formulations were selected using physical-chemical characterization and ex vivo studies. Results from physical-chemical characterization of the developed formulations found sodium taurocholate to be the most suitable EA, which recorded highest entrapment efficiency of 95.1 ± 2.70% with 85:15, (w/w) and lowest vesicle size of 82.3 ± 0.02 nm with 75:25, (w/w) molar ratios. TEM and DSC studies showed that the vesicles were readily identified and present in a nearly perfect spherical shape. In addition, formulations with emu oil had better stability than formulations with ostrich oil. Physical stability studies at 4 °C showed that ratite oil transfersomes were stable up to 4 weeks, while transfersomes without ratite oils were stable for 8 weeks. Ex vivo permeability studies using porcine skin concluded that 4-OHT transfersomal formulations with (85:15, w/w) without emu oil have the potential to be used in transdermal delivery approach to enhance permeation of 4-OHT, which may be beneficial in the treatment of BC.
  17. Manaharan T, Chakravarthi S, Radhakrishnan AK, Palanisamy UD
    Toxicol Rep, 2014;1:718-725.
    PMID: 28962285 DOI: 10.1016/j.toxrep.2014.09.006
    In this study, the acute and subchronic toxicity effect of the Syzygium aqueum leaf extract (SA) was evaluated. For the acute toxicity study, a single dose of 2000 mg/kg of the SA was given by oral-gavage to male Sprague-Dawley (SD) rats. The rats were observed for mortality and toxicity signs for 14 days. In the subchronic toxicity study the SA was administered orally at doses of 50, 100, and 200 mg/kg per day for 28 days to male SD rats. The animals were sacrificed at the end of the experiment. The parameters measured including food and water intake, body weight, absolute and relative organ weight, blood biochemical tests and histopathology observation. In both the acute and subchronic toxicity studies, SA did not show any visible signs of toxicity. There were also no significant differences between the control and SA treated rats in terms of their food and water intake, body weight, absolute and relative organ weight, biochemical parameters or gross and microscopic appearance of the organs. There were no acute or subchronic toxicity observed and our results indicate that this extract could be devoid of any toxic risk. This is the first in vivo study reported the safety and toxicity of SA.
  18. Phang SCW, Ahmad B, Abdul Kadir K, M Palanisamy UD
    Adv Nutr, 2023 Sep;14(5):1159-1169.
    PMID: 37321474 DOI: 10.1016/j.advnut.2023.06.006
    There are a large number of studies that have reported benefits of tocotrienol-rich fraction (TRF) in various populations with different health status. To date, no systematic reviews have examined randomized controlled trials (RCTs) on the effect of TRF supplementations specifically in patients with type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis aim to examine the changes in HbA1c (glycated hemoglobin), blood pressure, and serum Hs-CRP (C-reactive protein high sensitivity) levels at post-TRF supplementation. Online databases including PubMed, Scopus, OVID Medline, and Cochrane Central Register of Controlled Trials were searched from inception until March 2023 for RCTs supplementing TRF in patients with T2DM. A total of 10 studies were included in the meta-analysis to estimate the pooled effect size. The Cochrane Risk-of-Bias (RoB) Assessment Tool was utilized to evaluate the RoB in individual studies. The meta-analysis revealed that TRF supplementation at a dosage of 250-400 mg significantly decreased HbA1c (-0.23, 95% CI: -0.44, -0.02, P < 0.05, n = 754), particularly where the intervention duration is less than 6 mo (-0.47%, 95% CI: -0.90, -0.05, P < 0.05, n = 126) and where duration of diabetes is less than 10 y (-0.37, 95% CI: -0.68, -0.07, P < 0.05, n = 83). There was no significant reduction in systolic and diastolic blood pressure and serum Hs-CRP (P > 0.05). The present meta-analysis demonstrated that supplementing with TRF in patients with T2DM decreased HbA1c but does not decrease systolic and diastolic blood pressure and serum Hs-CRP.
  19. Palanisamy UD, Sivanathan M, Radhakrishnan AK, Haleagrahara N, Subramaniam T, Chiew GS
    Molecules, 2011 Jul 05;16(7):5709-19.
    PMID: 21730920 DOI: 10.3390/molecules16075709
    Ostrich oil has been used extensively in the cosmetic and pharmaceutical industries. However, rancidity causes undesirable chemical changes in flavour, colour, odour and nutritional value. Bleaching is an important process in refining ostrich oil. Bleaching refers to the removal of certain minor constituents (colour pigments, free fatty acid, peroxides, odour and non-fatty materials) from crude fats and oils to yield purified glycerides. There is a need to optimize the bleaching process of crude ostrich oil prior to its use for therapeutic purposes. The objective of our study was to establish an effective method to bleach ostrich oil using peroxide value as an indicator of refinement. In our study, we showed that natural earth clay was better than bentonite and acid-activated clay to bleach ostrich oil. It was also found that 1 hour incubation at a 150 °C was suitable to lower peroxide value by 90%. In addition, the nitrogen trap technique in the bleaching process was as effective as the continuous nitrogen flow technique and as such would be the recommended technique due to its cost effectiveness.
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