Browse publications by year: 2017

  1. Management of malodour fungating wound with nanocrystalline silver coated dressing
    Steffi W, Zaliana B, Amreen A, Nasirudin N
    Med J Malaysia, 2017 10;72(5):316-317.
    PMID: 29197891 MyJurnal
    Chronic exudative malodorous fungating wound of four years at the right arm due to diffuse large B cell lymphoma managed with silver dressings. In two months of application with nanocrystalline silver coated dressings, there was significant improvement in wound.
    MeSH terms: Aged; Bandages*; Chronic Disease; Female; Humans; Wounds and Injuries/drug therapy*; Wounds and Injuries/etiology; Lymphoma, B-Cell/complications; Outcome Assessment (Health Care); Silver Compounds/therapeutic use*; Nanoparticles*
  2. Relapse of B-cell acute lymphoblastic leukaemia presenting as right aural polyp with facial and mandibular nerves palsy
    Shiun Chuen C, Md Daud MK, Che Jalil NA, Hazmi H
    Med J Malaysia, 2017 10;72(5):318-320.
    PMID: 29197892 MyJurnal
    A patient presenting with an ear polyp is a common finding in otorhinolaryngology practice. The common causes include chronic otitis media and cholesteatoma. We report an adult female patient with a history of acute leukaemia presenting with chronic otitis media symptoms and right ear polyp. She was subsequently diagnosed as relapse of B-cell acute lymphoblastic leukaemia based on histopathological examination. The presentation may be similar to an inflammatory pathology of the middle ear, making it misleading.
    MeSH terms: Adult; B-Lymphocytes*; Diagnosis, Differential; Ear Neoplasms/diagnosis; Ear, Middle/physiopathology; Facial Paralysis/physiopathology*; Female; Humans; Mandible/physiopathology*; Mandibular Nerve/physiopathology*; Neoplasm Recurrence, Local/diagnosis*; Otitis Media/physiopathology; Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis*
  3. Management of concurrent thoracic and abdominal aortic aneurysms
    Saw ST, Feona SJ, Leong BDK
    Med J Malaysia, 2017 10;72(5):321-323.
    PMID: 29197893 MyJurnal
    Concurrent thoracic and abdominal aortic aneurysm is uncommon. It remains a formidable surgical challenge to vascular surgeons, as decision to treat in staged or simultaneous setting still debatable. We present, here, a case of a 62-year-old-man with asymptomatic concurrent thoracic and abdominal aortic aneurysms, which was successfully treated with two-stage hybrid endovascular repair. The aim of this case report is to discuss the treatment options available, possible associated complications and measures to prevent them.
    MeSH terms: Female; Humans; Middle Aged; Comorbidity*; Treatment Outcome; Endovascular Procedures
  4. Diagnostic challenge of Burkitt's lymphoma at early age
    Nor Fauziah MH, Faizah MZ, Loh CK
    Med J Malaysia, 2017 10;72(5):324-326.
    PMID: 29197894
    A four-year-old Ibanese boy presented with subacute abdominal distension for two months duration. Ultrasound and computed tomography (CT) scan showed solid liver masses as well as bowel and intraperitoneal lesions. Initial diagnosis of intraperitoneal inflammatory process as in tuberculosis with non-liquefied liver abscess with differential diagnosis of neoplastic process was made. Liver biopsy and peritoneal fluid analysis revealed Burkitt's lymphoma (BL). We aim to highlight the diagnostic challenge of BL in this young age group emphasizing on the ultrasound and CT features of intraabdominal BL. We would also want to stress the importance of early diagnosis of BL as it is known to be the most aggressive tumour within 24 hours yet to have good survival if early diagnosis was made.
    MeSH terms: Child, Preschool; Diagnosis, Differential; Humans; Male; Tomography, X-Ray Computed*; Outcome Assessment (Health Care); Diagnostic Techniques and Procedures
  5. A New Zealand platform to enable genetic investigation of adverse drug reactions
    Maggo SD, Chua EW, Chin P, Cree S, Pearson J, Doogue M, et al.
    N Z Med J, 2017 Dec 01;130(1466):62-69.
    PMID: 29197902
    A multitude of factors can affect drug response in individuals. It is now well established that variations in genes, especially those coding for drug metabolising enzymes, can alter the pharmacokinetic and/or pharmacodynamic profile of a drug, impacting on efficacy and often resulting in drug-induced toxicity. The UDRUGS study is an initiative from the Carney Centre for Pharmacogenomics to biobank DNA and store associated clinical data from patients who have suffered rare and/or serious adverse drug reactions (ADRs). The aim is to provide a genetic explanation of drug-induced ADRs using methods ranging from Sanger sequencing to whole exome and whole genome sequencing. Participants for the UDRUGS study are recruited from various sources, mainly via referral through clinicians working in Canterbury District Health Board, but also from district health boards across New Zealand. Participants have also self-referred to us from word-of-mouth communication between participants. We have recruited various ADRs across most drug classes. Where possible, we have conducted genetic analyses in single or a cohort of cases to identify known and novel genetic association(s) to offer an explanation to why the ADR occurred. Any genetic results relevant to the ADR are communicated back to the referring clinician and/or participant. In conclusion, we have developed a programme for studying the genetic basis of severe, rare or unusual ADR cases resulting from pharmacological treatment. Genomic analyses could eventually identify most genetic variants that predispose to ADRs, enabling a priori detection of such variants with high throughput DNA tests.
    MeSH terms: Humans; New Zealand; Surveys and Questionnaires; Cohort Studies; Genetic Association Studies/methods; Drug-Related Side Effects and Adverse Reactions/genetics*; Pharmacogenomic Testing/methods*
  6. Fulltext Structure-dependent optoelectronic properties of perylene, di-indenoperylene (DIP) isolated molecule and DIP molecular crystal
    Mohamad M, Ahmed R, Shaari A, Goumri-Said S
    Chem Cent J, 2017 Dec 02;11(1):125.
    PMID: 29198000 DOI: 10.1186/s13065-017-0352-7
    Theoretical simulations were designed by first principles approach of density functional theory to investigate the structural and optoelectronic properties of different structural classes of perylene; isolated perylene, diindeno[1,2,3-cd:1',2',3'-lm]perylene (DIP) molecule and DIP molecular crystal. The presence of molecular interactions in DIP crystal proved its structure-dependent behaviours. The herringbone molecular arrangement of DIP crystal has influenced the electronic properties by triggering the intermolecular interactions that reduced the energy gaps between HOMO and LUMO of the crystal. Strong hybridization resulting from dense charges population near zero Fermi energy has pushed valence band maxima in the density of states of all perylene structures to higher energies. Under small energy input, charges are transferred continuously as observed in the spectra of conductivity and dielectric. The existence of strong absorption intensities are consistent with the former works and supported by the obtained polarized reflectivity and loss spectra.
  7. Effects of simulated microgravity on gene expression and biological phenotypes of a single generation Caenorhabditis elegans cultured on 2 different media
    Tee LF, Neoh HM, Then SM, Murad NA, Asillam MF, Hashim MH, et al.
    Life Sci Space Res (Amst), 2017 Nov;15:11-17.
    PMID: 29198309 DOI: 10.1016/j.lssr.2017.06.002
    Studies of multigenerational Caenorhabditis elegans exposed to long-term spaceflight have revealed expression changes of genes involved in longevity, DNA repair, and locomotion. However, results from spaceflight experiments are difficult to reproduce as space missions are costly and opportunities are rather limited for researchers. In addition, multigenerational cultures of C. elegans used in previous studies contribute to mixture of gene expression profiles from both larvae and adult worms, which were recently reported to be different. Usage of different culture media during microgravity simulation experiments might also give rise to differences in the gene expression and biological phenotypes of the worms. In this study, we investigated the effects of simulated microgravity on the gene expression and biological phenotype profiles of a single generation of C. elegans worms cultured on 2 different culture media. A desktop Random Positioning Machine (RPM) was used to simulate microgravity on the worms for approximately 52 to 54 h. Gene expression profile was analysed using the Affymetrix GeneChip® C. elegans 1.0 ST Array. Only one gene (R01H2.2) was found to be downregulated in nematode growth medium (NGM)-cultured worms exposed to simulated microgravity. On the other hand, eight genes were differentially expressed for C. elegans Maintenance Medium (CeMM)-cultured worms in microgravity; six were upregulated, while two were downregulated. Five of the upregulated genes (C07E3.15, C34H3.21, C32D5.16, F35H8.9 and C34F11.17) encode non-coding RNAs. In terms of biological phenotype, we observed that microgravity-simulated worms experienced minimal changes in terms of lifespan, locomotion and reproductive capabilities in comparison with the ground controls. Taking it all together, simulated microgravity on a single generation of C. elegans did not confer major changes to their gene expression and biological phenotype. Nevertheless, exposure of the worms to microgravity lead to higher expression of non-coding RNA genes, which may play an epigenetic role in the worms during longer terms of microgravity exposure.
    MeSH terms: Animals; Culture Media/chemistry*; Locomotion/drug effects; Longevity/drug effects; Phenotype; Reproduction/drug effects; Space Flight; Caenorhabditis elegans/genetics*; Caenorhabditis elegans/growth & development*; Caenorhabditis elegans/physiology; Weightlessness Simulation*; Animals, Genetically Modified; Transcriptome
  8. Antioxidative and Inhibitory Effects of the Fruiting Body of Black Lingzhi Mushroom, Amauroderma rugosum (Agaricomycetes), on LDL Oxidation and HMG-CoA Reductase Activity
    Seng CK, Abdullah N, Aminudin N
    Int J Med Mushrooms, 2017;19(9):797-807.
    PMID: 29199554 DOI: 10.1615/IntJMedMushrooms.2017024374
    Amauroderma rugosum fruiting bodies possess excellent cardiovascular benefits, including antioxidative, antihyperlipidemic, antihypertensive, antiinflammatory, anti-platelet aggregation, and antithrombotic effects. In this article, we describe our investigations of the in vitro antioxidant activity and in vitro antiatherosclerotic potential through inhibitory effects on low-density lipoprotein (LDL), LDL peroxidation, and 3-hydroxy3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalytic activity using various fruiting body extracts partitioned with an organic solvent. Among 5 extracts/fractions tested, the semipolar ethyl acetate (EA) fraction demonstrated good antioxidant capacity based on total phenolic content, 2,2-diphenyl-1-picrylhydrazyl free radical scavenging, ferrous ion-chelating ability, cupric ion-reducing antioxidant capacity, and lipid peroxidation assays. The EA fraction also showed the strongest inhibitory effect on Cu2+-induced LDL oxidation via thiobarbituric acid reactive substances formation and HMG-CoA reductase activity. Chemical analysis conjointly identified 10 phenolic compounds (4 benzoic acid derivatives, 3 flavonoids, 1 cinnamic acid, 1 hexahydroxydiphenic acid dilactone, and 1 xanthone derivative), some of which play pivotal roles in arresting the physiopathogenesis of atherosclerosis, thereby attenuating the risk of cardiovascular events occurring.
    MeSH terms: Anti-Inflammatory Agents/pharmacology; Hypolipidemic Agents/pharmacology; Antioxidants/pharmacology*; Hydroxymethylglutaryl CoA Reductases/drug effects; Lipoproteins, LDL/drug effects; Oxidation-Reduction/drug effects; Lipid Peroxidation/drug effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology*; Reishi/chemistry*; Fruiting Bodies, Fungal/chemistry*
  9. Isolation and Characterization of Lectin from the Artist's Conk Medicinal Mushroom, Ganoderma applanatum (Agaricomycetes), and Evaluation of Its Antiproliferative Activity in HT-29 Colon Cancer Cells
    Kumaran S, Pandurangan AK, Shenbhagaraman R, Esa NM
    Int J Med Mushrooms, 2017;19(8):675-684.
    PMID: 29199567 DOI: 10.1615/IntJMedMushrooms.2017021274
    The growth and lectin production of Ganoderma applanatum, a white rot fungus, was optimized in broth cultures. The fungus was found to have a higher growth rate and higher lectin activity when grown in a medium adjusted to pH 6.5 at 26°C under stationary conditions. Expression of lectin activity started in 5-day-old mycelial culture; maximum activity was expressed after the 15th day of incubation. Among the various carbon and nitrogen sources tested, the carbon source sucrose and the nitrogen source yeast extract support maximum growth and lectin production. Lectin from G. applanatum was purified by ammonium sulfate precipitation and ion exchange chromatography. The purified fraction revealed a single band with a molecular weight of 35.0 kDa. Moreover, carbohydrates such as mannitol, glucose, sucrose, maltose, mannose, galactose, sorbose, and fructose were found to inhibit the hemagglutinating activity of the lectin. The purified lectins from G. applanatum contain cytotoxic and proapoptotic activities against HT-29 colon adenocarcinoma cells.
    MeSH terms: Antineoplastic Agents/isolation & purification*; Antineoplastic Agents/pharmacology; Antineoplastic Agents/chemistry; Carbon/metabolism; Chromatography, Ion Exchange; Colonic Neoplasms; Drug Screening Assays, Antitumor; Hemagglutination Tests; Humans; Hydrogen-Ion Concentration; Nitrogen/metabolism; Temperature; Cell Aging; Ganoderma/chemistry*; Lectins/isolation & purification; Lectins/pharmacology*; Lectins/chemistry; Cell Line, Tumor; Cell Proliferation/drug effects*
  10. Antidiabetic Properties of the Tiger's Milk Medicinal Mushroom, Lignosus rhinocerotis (Agaricomycetes), in Streptozotocin-Induced Diabetic Rats
    Nyam KL, Chow CF, Tan CS, Ng ST
    Int J Med Mushrooms, 2017;19(7):607-617.
    PMID: 29199582 DOI: 10.1615/IntJMedMushrooms.2017021186
    Diabetes mellitus is a major cause of morbidity and mortality worldwide. Although scientific evidence supporting its therapeutic efficacy is lacking, the use of the tiger's milk mushroom (TGM; Lignosus rhinocerotis), which is native to tropical areas such as Malaysia, Indonesia, and the Philippines, has been found to contain a very large amount of potential antioxidants. In this study, rats were weighed and then intravenously injected with 35 mg/kg streptozotocin (STZ). Rats were left for 1 week before blood glucose concentrations were measured to determine the onset of diabetes before the next procedure was conducted. Rats with blood glucose exceeding 7.0 mmol/L were considered diabetic and were included in the experiment. All groups were fed their respective treatments twice daily for 2 months throughout the experiment. Antidiabetic and antioxidant properties of freeze-dried TGM powder, such as reduced glutathione (GSH), superoxide dismutase (SOD), lipid peroxidation (LPO), and catalase (CAT) activities, were investigated in liver samples. The biological compounds present in the freeze-dried TGM powder was found to exhibit antidiabetic properties by significantly reducing elevated blood glucose concentrations to a normal range (3.0-7.0 mmol/L) in Sprague-Dawley rats with streptozotocin-induced diabetes, and increasing the body weight of the rats. Freeze-dried TGM powder was also found to possess antioxidant activity by significantly increasing GSH, CAT, and SOD activities while reducing LPO (P < 0.05). THis study shows that freeze-dried TGM powder exhibits significant antidiabetic properties and may be a potential supplement in ameliorating diabetic complications.
    MeSH terms: Animals; Antioxidants/pharmacology; Biological Products/therapeutic use*; Blood Glucose/metabolism; Body Weight; Diabetes Mellitus, Experimental/drug therapy*; Freeze Drying; Hematologic Tests; Hypoglycemic Agents/therapeutic use*; Lipids/blood; Male; Rats, Sprague-Dawley; Polyporales*; Rats
  11. Nephrotoxicity in Rats Exposed to Paracetamol: The Protective Role of Moralbosteroid, a Steroidal Glycoside
    Gupta G, Chellappan DK, Kikuchi IS, Pinto TJA, Pabreja K, Agrawal M, et al.
    J Environ Pathol Toxicol Oncol, 2017;36(2):113-119.
    PMID: 29199592 DOI: 10.1615/JEnvironPatholToxicolOncol.2017019457
    Paracetamol (PCM) has an acceptable safety profile when used at prescribed doses. However, it is now understood that paracetamol can damage the kidneys when administered as an overdose. In addition, oxidative stress can play a major role in causing nephrotoxicity. This investigation studies the efficacy of moralbosteroid isolated from M. alba stem bark. Nephrotoxicity was induced with administration of paracetamol. Nephroprotection was studied using two doses of the extract. The experimental animals were divided into four groups (n = 6). Two groups served as positive and negative controls, respectively, and two received the test substances. All of the contents were orally administered. Significant reductions in nephrotoxicity and oxidative damages were observed in the treatment groups. There was a marked decrease in blood levels of urea, creatinine, and lipid peroxidation. Furthermore, it was found that glutathione levels in the blood increased dramatically after treatment. Histological findings confirmed the potent renoprotective potential of moralbosteroid. This was evidenced by the minimized intensity of nephritic cellular destruction. In animal studies, moralbosteroid exhibited dose-dependent activity, which is thought to be mediated through its antioxidant potential.
    MeSH terms: Acetaminophen/toxicity*; Animals; Dose-Response Relationship, Drug; Kidney/drug effects*; Plant Extracts/pharmacology; Plant Extracts/chemistry; Steroids/pharmacology*; Rats, Wistar; Analgesics, Non-Narcotic/toxicity*; Protective Agents/pharmacology*; Plant Bark/chemistry; Morus/chemistry*; Rats
  12. Notes on Amanita section Caesareae from Malaysia
    Tang LP, Lee SS, Zeng NK, Cai Q, Zhang P, Yang ZL
    Mycologia, 2017 12 04;109(4):557-567.
    PMID: 29200380 DOI: 10.1080/00275514.2017.1394789
    Some Amanita specimens collected from Malaysia are critically investigated by morphological examination and molecular analysis of two gene fragments, the nuc rDNA partial 28S (28S) gene and the internal transcriber spacer (ITS1-5.8S-ITS2 = ITS) regions. Six phylogenetic species of Amanita section Caesareae are recognized among the studied collections. One of them is described as new, A. malayensis. Four of the phylogenetic species correspond with existing morphology-based taxa: A. aporema, A. javanica, A. princeps, and A. similis. The remaining species is not described because of the paucity of material. Detailed descriptions and the distribution of these southeastern Asian species are provided, along with a key to the species of section Caesareae from Malaysia.
    MeSH terms: Amanita/classification*; Amanita/cytology; Amanita/genetics; DNA, Fungal/genetics; Malaysia; Phylogeny*; RNA, Ribosomal, 28S/genetics; Spores, Fungal; DNA, Ribosomal Spacer/genetics; Fruiting Bodies, Fungal
  13. Fulltext Gastroprotective and Ulcer Healing Effects of Camel Milk and Urine in HCl/EtOH, Non-steroidal Anti-inflammatory Drugs (Indomethacin), and Water-Restraint Stress-induced Ulcer in Rats
    Hu Z, Chang X, Pan Q, Gu K, Okechukwu PN
    Pharmacogn Mag, 2017 Oct-Dec;13(52):559-565.
    PMID: 29200713 DOI: 10.4103/pm.pm_135_17
    Background: Camel milk has been reportedly used to treat dropsy, jaundice, tuberculosis, and diabetes while camel urine is used to treat diarrhea and cancer. However, there is no scientific evidence on the antiulcer activity of camel milk and urine. Thus, the present is designed to investigate the gastroprotective and ulcer healing effect of camel milk and urine on experimentally induced gastric ulcer models in rats.

    Materials and Methods: The gastroprotective effect was investigated in HCl/EtOH, water-restraint stress (WRS) and non-steroidal anti-inflammatory drugs (indomethacin)-induced ulcer models while ulcer healing activity was investigated in indomethacin-induced ulcer model. Cimetidine (100 mg/kg) was used as a standard antiulcer drug.

    Results: Acute toxicity study done up to a dosage of 10 ml/kg of camel milk and urine showed no signs of toxicity and mortality among the rats, indicating the present dosage of 5 ml/kg is safe to be administered to the rats. In the HCl/EtOH model, oral administration of cimetidine (100 mg/kg), camel urine (5 ml/kg), and camel milk (5 ml/kg) significantly (P < 0.05) inhibited gastric lesions by 83.7, 60.5 and 100%, respectively. In the WRS-induced model, cimetidine, and camel urine showed an ulcer inhibition of 100% while camel milk showed an inhibition of 50%. Similarly, in the indomethacin-induced ulcer model, cimetidine, camel milk, and urine showed an ulcer inhibition of 100, 33.3, and 66.7%, respectively. In addition, camel milk and urine also showed a significant (P < 0.05) ulcer healing effect of 100% in indomethacin-induced ulcer model, with no ulcers observed as compared to that of cimetidine, which offers a healing effect of 60.5%.

    Conclusion: The antiulcer activity of camel milk and urine may be attributed to its cytoprotective mechanism and antioxidant properties.

    SUMMARY: Acute toxicity findings revealed the dosage of 10 ml/kg of camel milk and urine seems no toxic and indicating the dosage of 5 ml/kg is safe to be administered to the ratsOral administration of cimetidine (100 mg/kg), camel urine (5 ml/kg), and camel milk (5 ml/kg) significantly inhibited gastric lesions by 83.7, 60.5 and 100% in the HCl/EtOH experimental modelThe results of this investigation have proven that camel milk and urine showed strong ulcer healing effect in indomethacin-induced gastric damage. Abbreviations used: NSAIDs: Non-steroidal anti-inflammatory drugs, UI: Ulcer index, ANOVA: One-way analysis of variance, WRS: Water-restraint stress, ROS: Reactive oxygen species.
    MeSH terms: Administration, Oral; Analysis of Variance; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cimetidine; Diabetes Mellitus; Diarrhea; Edema; Indomethacin; Jaundice; Milk; Neoplasms; Nerve Tissue Proteins; Stomach Ulcer; Tuberculosis; Ulcer; RNA-Binding Proteins; Reactive Oxygen Species; Rats
  14. Fulltext Helichrysetin Induces DNA Damage that Triggers JNK-Mediated Apoptosis in Ca Ski Cells
    Fong HY, Abd Malek SN, Yee HS, Karsani SA
    Pharmacogn Mag, 2017 Oct-Dec;13(52):607-612.
    PMID: 29200721 DOI: 10.4103/pm.pm_53_17
    Background: Cervical cancer has become one of the most common cancers in women and currently available treatment options for cervical cancer are very limited. Naturally occurring chalcones and its derivatives have been studied extensively as a potential anticancer agent in different types of cancer and helichrysetin is naturally occurring chalcone that possess potent antiproliferative activity toward human cancer cells.

    Materials and Methods: Inhibitory activity of helichrysetin was evaluated at different concentrations. Ability of helichrysetin to induce apoptosis and its relation with c-Jun N-terminal kinase (JNK)-mediated mechanism of apoptosis was assessed using flow cytometry and Western blotting.

    Results: Helichrysetin inhibited Ca Ski cells at half maximal inhibitory concentration 30.62 ± 0.38 μM. This compound has the ability to induce DNA damage, mitochondrial membrane disruption, and loss of cell membrane integrity. We have shown that apoptosis was induced through the activation of JNK-mediated apoptosis by DNA damage in the cells then triggering p53-downstream apoptotic pathway with increased expression of pro-apoptotic proteins, Bax and caspase 3, and suppression of Bcl-2 anti-apoptotic protein. DNA damage in the cells also caused phosphorylation of protein ataxia-telangiectasia mutated, an activator of DNA damage response.

    Conclusion: We conclude that helichrysetin can inhibit Ca Ski cells through DNA damage-induced JNK-mediated apoptotic pathway highlighting the potential of this compound as anticancer agent for cervical cancer.

    SUMMARY: Helichrysetin induced DNA damage in Ca Ski cellsDNA damage caused JNK-mediated phosphorylation of p53 resulting in p53-mediated apoptosisHelichrysetin is a potential DNA damage inducing agent through JNK activation to kill human cervical carcinoma cells. Abbreviations used: ATM: Ataxia-telangiectasia mutated, DAPI: 4',6-diamidino-2-phenylindole, DMSO: Dimethyl sulfoxide, FITC: Fluorescein isothiocyanate, IC50: Half maximal inhibitory concentration, JC1-5,5',6,6'-Tetrachloro: 1',3,3'-tetraethylbenzimidazolylcarbocyanine, iodide, JNK: c-Jun N-terminal kinase, MMP: Mitochondrial membrane potential, PBS: Phosphate-buffered saline, SRB: Sulforhodamine B, TUNEL: Terminal deoxynucleotidyl transferase dUTP nick labeling.
  15. Fulltext Anticancer effect of dentatin and dentatin-hydroxypropyl-β-cyclodextrin complex on human colon cancer (HT-29) cell line
    Al-Abboodi AS, Rasedee A, Abdul AB, Taufiq-Yap YH, Alkaby WAA, Ghaji MS, et al.
    Drug Des Devel Ther, 2017;11:3309-3319.
    PMID: 29200826 DOI: 10.2147/DDDT.S147626
    Introduction: Dentatin (DEN) (5-methoxy-2, 2-dimethyl-10-(1, 1-dimethyl-2propenyl) dipyran-2-one), a natural compound present in the roots of Clausena excavata Burm f, possesses pro-apoptotic and antiproliferative effects in various cancer cells. Because of its hydrophobicity, it is believed that its complexation with hydroxy-β-cyclodextrin (HPβCD) will make it a potent inhibitor of cancer cell growth. In the current work, the molecular mechanisms of apoptosis induced by DEN and DEN-HPβCD complex were demonstrated in human colon HT-29 cancer cells.

    Materials and methods: After the human colon HT-29 cancer cells were treated with DEN and DEN-HPβCD complex, their effects on the expression of apoptotic-regulated gene markers in mitochondria-mediated apoptotic and death receptor pathways were detected by Western blot analysis and reverse transcription polymerase chain reaction. These markers included caspases-9, 3, and 8, cytochrome c, poly (ADP-ribose) polymerase, p53, p21, cyclin A as well as the Bcl-2 family of proteins.

    Results: At 3, 6, 12, and 24 µg/mL exposure, DEN and DEN-HPβCD complex significantly affected apoptosis in HT-29 cells through the down-regulation of Bcl-2 and cyclin A in turn, and up-regulation of Bax, p53, p21, cytochrome c at both protein and mRNA levels. DEN and DEN-HPβCD complex also decreased cleaved poly (ADP-ribose) polymerase and induced caspases-3, -8, and -9.

    Conclusion: Results of this study indicate that the apoptotic pathway caused by DEN and DEN-HPβCD complex are mediated by the regulation of caspases and Bcl-2 families in human colon HT-29 cancer cells. The results also suggest that DEN-HPβCD complex may have chemotherapeutic benefits for colon cancer patients.

    MeSH terms: Antineoplastic Agents/pharmacology*; Antineoplastic Agents/chemistry; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Heterocyclic Compounds, 3-Ring/pharmacology*; Heterocyclic Compounds, 3-Ring/chemistry; Humans; Structure-Activity Relationship; Tumor Cells, Cultured; Apoptosis/drug effects; HT29 Cells; Cell Proliferation/drug effects
  16. Fulltext Down-top nanofabrication of binary (CdO)x (ZnO)1-x nanoparticles and their antibacterial activity
    Al-Hada NM, Mohamed Kamari H, Abdullah CAC, Saion E, Shaari AH, Talib ZA, et al.
    Int J Nanomedicine, 2017;12:8309-8323.
    PMID: 29200844 DOI: 10.2147/IJN.S150405
    In the present study, binary oxide (cadmium oxide [CdO])x (zinc oxide [ZnO])1-x nanoparticles (NPs) at different concentrations of precursor in calcination temperature were prepared using thermal treatment technique. Cadmium and zinc nitrates (source of cadmium and zinc) with polyvinylpyrrolidone (capping agent) have been used to prepare (CdO)x (ZnO)1-x NPs samples. The sample was characterized by X-ray diffraction (XRD), scanning electron microscopy, energy-dispersive X-ray (EDX), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy. XRD patterns analysis revealed that NPs were formed after calcination, which showed a cubic and hexagonal crystalline structure of (CdO)x (ZnO)1-x NPs. The phase analysis using EDX spectroscopy and FTIR spectroscopy confirmed the presence of Cd and Zn as the original compounds of prepared (CdO)x (ZnO)1-x NP samples. The average particle size of the samples increased from 14 to 33 nm as the concentration of precursor increased from x=0.20 to x=0.80, as observed by TEM results. The surface composition and valance state of the prepared product NPs were determined by X-ray photoelectron spectroscopy (XPS) analyses. Diffuse UV-visible reflectance spectra were used to determine the optical band gap through the Kubelka-Munk equation; the energy band gap was found to decrease for CdO from 2.92 to 2.82 eV and for ZnO from 3.22 to 3.11 eV with increasing x value. Additionally, photoluminescence (PL) spectra revealed that the intensity in PL increased with an increase in particle size. In addition, the antibacterial activity of binary oxide NP was carried out in vitro against Escherichia coli ATCC 25922 Gram (-ve), Salmonella choleraesuis ATCC 10708, and Bacillus subtilis UPMC 1175 Gram (+ve). This study indicated that the zone of inhibition of 21 mm has good antibacterial activity toward the Gram-positive B. subtilis UPMC 1175.
    MeSH terms: Anti-Bacterial Agents/pharmacology*; Anti-Bacterial Agents/chemistry; Bacillus subtilis/drug effects; Drug Evaluation, Preclinical/methods; Escherichia coli/drug effects; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Oxides/pharmacology; Oxides/chemistry*; Particle Size; Salmonella/drug effects; X-Ray Diffraction; Zinc Oxide/pharmacology; Zinc Oxide/chemistry*; Spectroscopy, Fourier Transform Infrared; Cadmium Compounds/pharmacology; Cadmium Compounds/chemistry*; Microscopy, Electron, Transmission; Nanoparticles/chemistry*; Photoelectron Spectroscopy
  17. Fulltext Ulcer Prevention Effect Of 3,4,5-Tihydroxy-N0-[(2-Methyl-1H-Indol-3yl)Methylidene]Benzohydrazide In HCl/Ethanol-Induced Gastric Mucosal Damage In Rats
    Tayeby F, Salman AAA, Kamran S, Khaing SL, Salehen NB, Mohan GMAD
    Int J Med Sci, 2017;14(13):1317-1326.
    PMID: 29200945 DOI: 10.7150/ijms.20984
    The newly synthesized, 3,4,5-Trihydroxy-N 0-[(2-methyl-1H-indol-3-yl)-methylidene] benzohydrazide (TIBH), is an indole and gallic acid derivative. The aim of this research investigation was to evaluate the acute toxicity and the ulcer prevention potential of TIBH in HCl/Ethanol-induced gastric ulcer rat model. Six groups of rats were orally received 5ml/kg of vehicle (1 % Carboxy methyl cellulose) for the normal and ulcer control groups each, Omeprazole (20mg/kg) for positive control, 50 mg/kg, 100 mg/kg and 200 mg/kg of TIBH for experimental groups, respectively. After one hour, instead of rats in the normal group which received 5ml/kg of 1% CMC, other groups received 5ml/kg of HCl/Ethanol. All rats were sacrificed after one additional hour. Gastric juice, gastric mucosa, morphologies of gastric ulcers and protein expressions of both control and treatment groups were evaluated. TIBH showed a ulcer prevention potential by increase of the mucus secretion, decrease of the gastric acidity, up-regulation of HSP70 protein, down-regulation of Bax protein, decrease of the lipid peroxidation and the increase of the Superoxide dismutase (SOD) activity in gastric tissue homogenate. Acute toxicity assay exposed valuable information on the safety of this compound. TIBH had a dose dependent ulcer prevention potential against HCl/Ethanol-triggered gastric ulcer.
  18. Fulltext Peptides as Therapeutic Agents for Dengue Virus
    Chew MF, Poh KS, Poh CL
    Int J Med Sci, 2017;14(13):1342-1359.
    PMID: 29200948 DOI: 10.7150/ijms.21875
    Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients.
    MeSH terms: Antiviral Agents/therapeutic use; Dengue/drug therapy*; Dengue/epidemiology; Dengue/virology; Dengue Virus/drug effects*; Dengue Virus/pathogenicity; Humans; Peptides/therapeutic use*; Dengue Vaccines/therapeutic use; Virus Internalization/drug effects; Peptidomimetics/therapeutic use*
  19. Fulltext Blockade of Eosinophil-Induced Bronchial Epithelial-Mesenchymal Transition with a Geranyl Acetophenone in a Coculture Model
    Lee YZ, Yap HM, Shaari K, Tham CL, Sulaiman MR, Israf DA
    Front Pharmacol, 2017;8:837.
    PMID: 29201006 DOI: 10.3389/fphar.2017.00837
    Epithelial-mesenchymal transition (EMT) is currently recognized as the main cellular event that contributes to airway remodeling. Eosinophils can induce EMT in airway epithelial cells via increased transforming growth factor (TGF)-β production. We assessed the effect of synthetic 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA) upon eosinophil-induced EMT in a cellular model. The human eosinophil cell line EoL-1 was used to induce EMT in BEAS-2B human bronchial epithelial cells. The induction of EMT was dose-dependently suppressed following tHGA treatment in which the epithelial morphology and E-cadherin expression were not altered. Protein and mRNA expression of vimentin, collagen I and fibronectin in eosinophil-induced epithelial cells were also significantly suppressed by tHGA treatment. Following pathway analysis, we showed that tHGA suppressed eosinophil-induced activator protein-1-mediated TGF-β production by targeting c-Jun N-terminal kinase and phosphoinositide 3-kinase signaling pathways. These findings corroborated previous findings on the ability of tHGA to inhibit experimental murine airway remodeling.
    MeSH terms: Acetophenones; Animals; Eosinophils; Fibronectins; Humans; Phloroglucinol; Vimentin; Antigens, CD; Cadherins; Transcription Factor AP-1; Phosphatidylinositol 3-Kinases; Mice; Airway Remodeling; Phosphatidylinositol 3-Kinase; Epithelial-Mesenchymal Transition
  20. Fulltext A Marine Actinomycete Rescues Caenorhabditis elegans from Pseudomonas aeruginosa Infection through Restitution of Lysozyme 7
    Fatin SN, Boon-Khai T, Shu-Chien AC, Khairuddean M, Al-Ashraf Abdullah A
    Front Microbiol, 2017;8:2267.
    PMID: 29201023 DOI: 10.3389/fmicb.2017.02267
    The resistance of Pseudomonas aeruginosa to conventional antimicrobial treatment is a major scourge in healthcare. Therefore, it is crucial that novel potent anti-infectives are discovered. The aim of the present study is to screen marine actinomycetes for chemical entities capable of overcoming P. aeruginosa infection through mechanisms involving anti-virulence or host immunity activities. A total of 18 actinomycetes isolates were sampled from marine sediment of Songsong Island, Kedah, Malaysia. Upon confirming that the methanolic crude extract of these isolates do not display direct bactericidal activities, they were tested for capacity to rescue Caenorhabditis elegans infected with P. aeruginosa strain PA14. A hexane partition of the extract from one isolate, designated as Streptomyces sp. CCB-PSK207, could promote the survival of PA14 infected worms by more than 60%. Partial 16S sequence analysis on this isolate showed identity of 99.79% with Streptomyces sundarbansensis. This partition did not impair feeding behavior of C. elegans worms. Tested on PA14, the partition also did not affect bacterial growth or its ability to colonize host gut. The production of biofilm, protease, and pyocyanin in PA14 were uninterrupted, although there was an increase in elastase production. In lys-7::GFP worms, this partition was shown to induce the expression of lysozyme 7, an important innate immunity defense molecule that was repressed during PA14 infection. GC-MS analysis of the bioactive fraction of Streptomyces sp. CCB-PSK207 revealed the presence of methyl esters of branched saturated fatty acids. In conclusion, this is the first report of a marine actinomycete producing metabolites capable of rescuing C. elegans from PA14 through a lys-7 mediated activity.
    MeSH terms: Actinomyces; Methanol; Animals; Esters; Fatty Acids; Hexanes; Gas Chromatography-Mass Spectrometry; Muramidase; Pancreatic Elastase; Pseudomonas aeruginosa; Pyocyanine; Streptomyces; Caenorhabditis elegans; Actinobacteria
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