Browse publications by year: 2018

  1. Kamaludin H, Mahdin H, Abawajy JH
    PLoS One, 2018;13(3):e0193951.
    PMID: 29565982 DOI: 10.1371/journal.pone.0193951
    Although Radio Frequency Identification (RFID) is poised to displace barcodes, security vulnerabilities pose serious challenges for global adoption of the RFID technology. Specifically, RFID tags are prone to basic cloning and counterfeiting security attacks. A successful cloning of the RFID tags in many commercial applications can lead to many serious problems such as financial losses, brand damage, safety and health of the public. With many industries such as pharmaceutical and businesses deploying RFID technology with a variety of products, it is important to tackle RFID tag cloning problem and improve the resistance of the RFID systems. To this end, we propose an approach for detecting cloned RFID tags in RFID systems with high detection accuracy and minimal overhead thus overcoming practical challenges in existing approaches. The proposed approach is based on consistency of dual hash collisions and modified count-min sketch vector. We evaluated the proposed approach through extensive experiments and compared it with existing baseline approaches in terms of execution time and detection accuracy under varying RFID tag cloning ratio. The results of the experiments show that the proposed approach outperforms the baseline approaches in cloned RFID tag detection accuracy.
    MeSH terms: Automatic Data Processing/methods; Confidentiality; Humans; Computer Security; Radio Frequency Identification Device/methods*
  2. Jabbarzadeh Kaboli P, Ismail P, Ling KH
    PLoS One, 2018;13(3):e0193941.
    PMID: 29565994 DOI: 10.1371/journal.pone.0193941
    RAF kinases are a family of enzymes in the MAP kinase pathway that contribute to the development of different types of cancer. BRAF is the most important member of RAF kinases. BRAF mutations have been detected in 7% of all cancers and 66% of melanomas; as such, the FDA has approved a few BRAF inhibitor drugs to date. However, BRAF can activate CRAF leading to resistance to BRAF inhibitors. Berberine (BBR) is an alkaloid that is widely distributed in different plant species. Several studies have been carried out on the anti-cancer effects of BBR but direct targets of BBR are unknown. In this study, interactions of BBR derivatives against BRAF and CRAF kinases were modeled and predicted using an in silico-based approach. To analyze and identify the residues important in BRAF docking, we modeled interactions of ATP, the universal substrate of BRAF, and found that Lys483 and Asp594 are the most important residues involved in both ATP and BBR binding [(The average score = -11.5 kcal/mol (ATP); Range of scores = -7.78 to -9.55 kcal/mol (BBR)]. In addition to these polar residues, Trp530 and Phe583 are also applicable to the molecular docking of BRAF. We also observed that Asp593 was excluded from the enzyme cavity, while Phe594 was included inside the cavity, making the enzyme inactive. Finally, three alternatives for BBR were identified with dual RAF inhibition effects [The best scores against BRAF = -11.62 kcal/mol (BBR-7), -10.64 kcal/mol (BBR-9), and -11.01 kcal/mol (BBR-10); the best scores against CRAF = -9.68 kcal/mol (BBR-7), -9.60 kcal/mol (BBR-9), and -9.20 kcal/mol (BBR-10)]. Direct effects of BBR derivatives against BRAF and CRAF kinases had not yet been reported previously, and, thus, for the first time, we report three cycloprotoberberines as lead compounds against RAF kinases.
    MeSH terms: Antineoplastic Agents/pharmacology*; Berberine/pharmacology*; Humans; Mutation/drug effects; Neoplasms/drug therapy*; Neoplasms/metabolism; Protein Binding/physiology*; Proto-Oncogene Proteins c-raf/antagonists & inhibitors; Protein Kinase Inhibitors/pharmacology; raf Kinases/antagonists & inhibitors*; Proto-Oncogene Proteins B-raf/antagonists & inhibitors; Molecular Docking Simulation
  3. Iberahim N, Sethupathi S, Bashir MJK
    Environ Sci Pollut Res Int, 2018 Sep;25(26):25702-25714.
    PMID: 28550632 DOI: 10.1007/s11356-017-9180-5
    In this study, palm oil mill sludge was used as a precursor to prepare biochar using conventional pyrolysis. Palm oil mill sludge biochar (POSB) was prepared at different preparation variables, i.e., heating temperature (300-800 °C), heating rate (10-20 °C/min) and holding time (60-120 min). The prepared biochars were tested for sulfur dioxide (SO2) adsorption in a fixed bed reactor using 300 ppm of SO2 gas at 300 ml/min (with N2 gas as balance). Response surface central composite experimental design was used to optimize the production of biochar versus SO2 removal. A quadratic model was developed in order to correlate the effect of variable parameters on the optimum adsorption capacity of SO2 gas. The experimental values and the predicted results of the model were found to show satisfactory agreement. The optimum conditions for biochar preparation to yield the best SO2 removal was found to be at 405 °C of heating temperature, 20 °C/min of heating rate and 88 min of holding time. At these conditions, the average yield of biochar and adsorption capacity for SO2 gas was reported as 54.25 g and 9.75 mg/g, respectively. The structure of biochar and their roles in SO2 adsorption were investigated by surface area, morphology images, infrared spectra, and proximate analysis, respectively. The characterization findings suggested that POSB adsorbs SO2 mainly by the functional groups.
    MeSH terms: Adsorption; Air Pollutants; Charcoal*; Heating; Sewage; Sulfur Dioxide/chemistry*; Temperature
  4. Hamid A, Ibrahim FW, Ming TH, Nasrom MN, Eusoff N, Husain K, et al.
    BMC Complement Altern Med, 2018 Mar 20;18(1):101.
    PMID: 29558939 DOI: 10.1186/s12906-018-2161-5
    BACKGROUND: Zingiber zerumbet (L.) Smith belongs to the Zingiberaceae family that is widely distributed throughout the tropics, particularly in Southeast Asia. It is locally known as 'Lempoyang' and traditionally used to treat fever, constipation and to relieve pain. It is also known to possess antioxidant and anti-inflammatory activities. Based on these antioxidant and anti-inflammatory activities, this study was conducted to investigate the effects of ethyl-acetate extract of Z. zerumbet rhizomes against ethanol-induced brain damage in male Wistar rats.

    METHOD: Twenty-four male Wistar rats were divided into four groups which consist of normal, 1.8 g/kg ethanol (40% v/v), 200 mg/kg Z. zerumbet extract plus ethanol and 400 mg/kg Z. zerumbet plus ethanol. The extract of Z. zerumbet was given once daily by oral gavage, 30 min prior to ethanol exposure via intraperitoneal route for 14 consecutive days. The rats were then sacrificed. Blood and brain homogenate were subjected to biochemical tests and part of the brain tissue was sectioned for histological analysis.

    RESULT: Treatment with ethyl-acetate Z. zerumbet extract at 200 mg/kg and 400 mg/kg significantly reduced the level of malondialdehyde (MDA) and protein carbonyl (p 

    MeSH terms: Ethanol/toxicity*; Animals; Antioxidants/analysis; Antioxidants/pharmacology*; Antioxidants/chemistry; Brain/cytology; Brain/drug effects*; Brain/pathology; Male; Plant Extracts/pharmacology*; Plant Extracts/chemistry; Rats, Wistar; Oxidative Stress/drug effects; Zingiberaceae/chemistry*; Rats
  5. Thekkeparambil Chandrabose S, Sriram S, Subramanian S, Cheng S, Ong WK, Rozen S, et al.
    Stem Cell Res Ther, 2018 03 20;9(1):68.
    PMID: 29559008 DOI: 10.1186/s13287-018-0796-2
    BACKGROUND: While a shift towards non-viral and animal component-free methods of generating induced pluripotent stem (iPS) cells is preferred for safer clinical applications, there is still a shortage of reliable cell sources and protocols for efficient reprogramming.

    METHODS: Here, we show a robust episomal and xeno-free reprogramming strategy for human iPS generation from dental pulp stem cells (DPSCs) which renders good efficiency (0.19%) over a short time frame (13-18 days).

    RESULTS: The robustness of DPSCs as starting cells for iPS induction is found due to their exceptional inherent stemness properties, developmental origin from neural crest cells, specification for tissue commitment, and differentiation capability. To investigate the epigenetic basis for the high reprogramming efficiency of DPSCs, we performed genome-wide DNA methylation analysis and found that the epigenetic signature of DPSCs associated with pluripotent, developmental, and ecto-mesenchymal genes is relatively close to that of iPS and embryonic stem (ES) cells. Among these genes, it is found that overexpression of PAX9 and knockdown of HERV-FRD improved the efficiencies of iPS generation.

    CONCLUSION: In conclusion, our study provides underlying epigenetic mechanisms that establish a robust platform for efficient generation of iPS cells from DPSCs, facilitating industrial and clinical use of iPS technology for therapeutic needs.

    MeSH terms: Cellular Reprogramming Techniques/methods*; Animals; Cells, Cultured; Dental Pulp/cytology*; Humans; Plasmids/genetics*; Mice, SCID; Mice, Inbred NOD; Epigenesis, Genetic*; Mice; Mesenchymal Stromal Cells/cytology*; Mesenchymal Stromal Cells/metabolism; Primary Cell Culture/methods; Cellular Reprogramming*
  6. Chan EWC, Wong SK, Chan HT
    J Integr Med, 2018 05;16(3):147-152.
    PMID: 29559215 DOI: 10.1016/j.joim.2018.03.001
    This short review provides an update of the anticancer and anti-inflammatory properties of casticin from Vitex species. Casticin is a polymethylflavone with three rings, an orthocatechol moiety, a double bond, two hydroxyl groups and four methoxyl groups. Casticin has been isolated from various tissues of plants in the Vitex genus: fruits and leaves of V. trifolia, aerial parts and seeds of V. agnus-castus and leaves of V. negundo. Studies have reported the antiproliferative and apoptotic activities of casticin from Vitex species. The compound is effective against many cancer cell lines via different molecular mechanisms. Studies have also affirmed the anti-inflammatory properties of casticin, with several molecular mechanisms identified. Other pharmacological properties include anti-asthmatic, tracheospasmolytic, analgesic, antihyperprolactinemia, immunomodulatory, opioidergic, oestrogenic, anti-angiogenic, antiglioma, lung injury protection, rheumatoid arthritis amelioration and liver fibrosis attenuation activities. Clinical trials and commercial use of the casticin-rich fruit extract of V. agnus-castus among women with premenstrual syndrome were briefly discussed.
    MeSH terms: Analgesics; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Cell Line; Female; Flavonoids; Fruit; Humans; Liver Cirrhosis; Premenstrual Syndrome; Seeds; Anti-Asthmatic Agents; Vitex; Lung Injury
  7. Lee CM, Dhillon MK, Sulaiman MA
    Arthroplast Today, 2018 Mar;4(1):78-84.
    PMID: 29560400 DOI: 10.1016/j.artd.2017.06.007
    Background: The use of navigation for total knee arthroplasty (TKA) improves limb alignment in the coronal and sagittal planes. However, similar improvements in femoral and tibial component rotation have not yet been realized using currently available systems.

    Methods: We developed a modified navigated TKA technique in which femoral rotation was set using the resected tibial plane as the reference with the aim of achieving a rectangular flexion gap. Limb alignment was assessed in a cohort of 30 knees using the navigation system. Post-operative limb alignment was measured using long-leg standing radiographs. Computed tomography was used to determine post-operative component orientation.

    Results: Sagittal alignment data improved from a mean of 7.8° varus (pre-operative) to 0.0° (post-operative), assessed by intra-operative navigation. Post-operative hip-knee-ankle axis alignment was 0.9° valgus (mean; standard deviation [SD] 1.7°). Mean femoral component rotation was 0.5° internally rotated (SD 2.6°), relative to the surgical transepicondylar axis. Mean tibial component rotation was 0.9° externally rotated (SD 5.5°). No soft tissue releases were performed.

    Conclusions: These results confirm that the desired femoral rotation, set using a tibia-first approach with the resected tibial plane as the reference, can be achieved without compromising overall limb alignment. Femoral component rotation was within a narrow range, with a moderate improvement in achieving more consistent tibial component rotation compared with other techniques. This technique may prove to be useful for surgeons wishing to employ a tibia-first philosophy for TKA while maximizing the benefits associated with computer-assisted navigation.

  8. Cheng WY, Liu MT
    Heliyon, 2018 Feb;4(2):e00518.
    PMID: 29560442 DOI: 10.1016/j.heliyon.2018.e00518
    Sixteen mumps virus (MuV) sequences collected in Taiwan between 2006 and 2016 were characterized as genotype F (n = 1), G (n = 7), H (n = 4), J (n = 2), and K (n = 2). Mumps genotype F strain was imported from China in 2008 which was in accordance with the epidemic genotype in China. The Philippines was indicated as export country of three genotype H strains in 2007-2010 and Vietnam as export country of one genotype K strain in 2016 that matched with genotypes described in previous reports. Four strains of genotype G were imported from Japan, Thailand, Malaysia and Myanmar individually indicated that genotype G spreads widely in Asia as well as in the global. In this study, mumps strains of genotype G was first reported in relation to import from Malaysia and Myanmar. Furthermore, Indonesia was referred to export MuV of genotype J in 2007 for the first time. Molecular genotyping benefits the differentiation of circulating mumps viruses and can be used to investigate the transmission pathways. The dynamic genotypes of imported cases revealed the epidemic genotypes in nearby countries.
  9. Yakop F, Abd Ghafar SA, Yong YK, Saiful Yazan L, Mohamad Hanafiah R, Lim V, et al.
    Artif Cells Nanomed Biotechnol, 2018;46(sup2):131-139.
    PMID: 29561182 DOI: 10.1080/21691401.2018.1452750
    PURPOSE: The purpose of this study was to investigate apoptotic activity of silver nanoparticle Clinacanthus nutans (AgNps-CN) towards HSC-4 cell lines (oral squamous cell carcinoma cell lines).

    METHODS: Methods involved were MTT assay (cytotoxic activity), morphological cells analysis, flow cytometry and cell cycle analysis and western blot.

    RESULTS: MTT assay revealed IC50 concentration was 1.61 µg/mL, 3T3-L1 cell lines were used to determine whether AgNps-CN is cytotoxic to normal cells. At the highest concentration (3 µg/mL), no cytotoxic activity has been observed. Flow cytometry assay revealed AgNps-CN caused apoptosis effects towards HSC-4 cell lines with significant changes were observed at G1 phase when compared with untreated cells. Morphological cells analysis revealed that most of the cells exhibit apoptosis characteristics rather than necrosis. Protein study revealed that ratio of Bax/Bcl-2 increased mainly due to down-regulation of Bcl-2 expression.

    CONCLUSION: AgNps-CN have shown potential in inhibiting HSC-4 cell lines. IC50 was low compared to few studies involving biosynthesized of silver nanoparticles. Apoptosis effects were shown towards HSC-4 cell lines by the increased in Bax/Bcl-2 protein ratio. Further study such as PCR or in vivo studies are required.

    MeSH terms: Animals; Antineoplastic Agents/pharmacology; Antineoplastic Agents/chemistry; Carcinoma, Squamous Cell/pathology*; Cell Survival/drug effects; Humans; Mouth Neoplasms/pathology*; Plant Extracts/chemistry; Silver/pharmacology*; Silver/chemistry; 3T3 Cells; Apoptosis/drug effects*; Plant Leaves/chemistry*; Acanthaceae/chemistry*; Nanotechnology; Cell Line, Tumor; Cell Proliferation/drug effects; Mice; Metal Nanoparticles/chemistry*; Cell Cycle Checkpoints/drug effects
  10. Bukhsh A, Nawaz MS, Ahmed HS, Khan TM
    Medicine (Baltimore), 2018 Mar;97(12):e9847.
    PMID: 29561461 DOI: 10.1097/MD.0000000000009847
    BACKGROUND: Diabetes self-care activities, like, healthy diet, regular exercise, self-monitoring of blood glucose, and rational use of medicines are considered to play a vital role in establishing euglycemia. Health literacy among type 2 diabetes mellitus (T2DM) patients in Pakistan is very low, which is the most likely cause for poor clinical outcomes. This study is designed to investigate the impact of pharmacist-led educational intervention on glycemic control, self-care activities and disease knowledge among T2DM patients in Pakistan.

    METHODS: In this randomized controlled trail, effectiveness of a 6-month pharmacist-led educational intervention will be examined on glycemic control, diabetes self-care activities and disease knowledge of 80 adult T2DM patients (age >30 years) with poorly controlled T2DM (HbA1c> 7%), after randomizing them into intervention and control groups, at diabetes care clinic of Capital Hospital Islamabad, Pakistan.

    RESULTS: The primary outcome is change in patients' HbA1c, whereas, changes in self-care activities and patients' disease knowledge are the secondary outcomes. After baseline assessment of their self-care activities and disease knowledge by using validated Urdu versions of Diabetes Self-management Questionnaire (DSMQ) and Diabetes Knowledge Questionnaire (DKQ), respectively, interventional group patients will be supplemented with a face-to-face pharmacist-led educational intervention, whereas, the control group will receive usual care. Intervention arm patients will be educated successively at their first follow-up visit (12th week) and telephonically after every 4 weeks. All assessments will be made at baseline and end of trail for both intervention and control groups. Multivariate general linear model will be applied to analyze the effects of the intervention.

    CONCLUSION: Glycemic control in T2DM patients requires optimum self-care activities. This study is an attempt to improve self-care behaviors among poorly controlled T2DM patients who are at higher risk of diabetes-associated late complications.
    MeSH terms: Diabetes Mellitus, Type 2/blood; Diabetes Mellitus, Type 2/psychology; Diabetes Mellitus, Type 2/therapy*; Hemoglobin A, Glycosylated/metabolism*; Humans; Health Knowledge, Attitudes, Practice*; Patient Education as Topic*; Pharmacists*; Self Care*; Time Factors; Patient Selection
  11. Miya Shaik M, Tamargo IA, Abubakar MB, Kamal MA, Greig NH, Gan SH
    Genes (Basel), 2018 Mar 21;9(4).
    PMID: 29561798 DOI: 10.3390/genes9040174
    MicroRNAs (miRNAs) are short, endogenous, non-coding RNAs that post-transcriptionally regulate gene expression by base pairing with mRNA targets. Altered miRNA expression profiles have been observed in several diseases, including neurodegeneration. Multiple studies have reported altered expressions of miRNAs in the brains of individuals with Alzheimer's disease (AD) as compared to those of healthy elderly adults. Some of the miRNAs found to be dysregulated in AD have been reported to correlate with neuropathological changes, including plaque and tangle accumulation, as well as altered expressions of species that are known to be involved in AD pathology. To examine the potentially pathogenic functions of several dysregulated miRNAs in AD, we review the current literature with a focus on the activities of ten miRNAs in biological pathways involved in AD pathogenesis. Comprehensive understandings of the expression profiles and activities of these miRNAs will illuminate their roles as potential therapeutic targets in AD brain and may lead to the discovery of breakthrough treatment strategies for AD.
    MeSH terms: Neuropathology; Aged; Alzheimer Disease; Brain; Humans; RNA, Messenger; Gene Expression; Base Pairing; MicroRNAs; Plaque, Amyloid
  12. Kamada T, Kang MC, Phan CS, Zanil II, Jeon YJ, Vairappan CS
    Mar Drugs, 2018 Mar 21;16(4).
    PMID: 29561805 DOI: 10.3390/md16040099
    Soft corals are known to be prolific producers of a wide spectrum of biologically active cembranoids. One new cembranoid, sinularolide F (2), along with three known compounds, cembranolide (1), (E,E,E)-6,10,14-trimethyl-3-methylene-cis-3α,4,5,8,9,12,13,15α-octahydrocyclo tetradeca[β]furan-2(3H)-one (3), and denticulatolide (4), were isolated from the Bornean soft coral Sinularia sp. Compounds 2 and 4 showed potential anti-inflammatory activities against lipopolysaccharide-stimulated RAW 264.7 with IC50 values less than 6.25 µg/mL and anticancer activity against HL60 cell lines. The compounds' mechanisms of action were investigated via the Western blot evaluation of their protein markers. These activities could be attributed to the presence of tertiary methyl at C-8 and the compounds' 3D configurations.
    MeSH terms: RAW 264.7 Cells; Animals; Anti-Inflammatory Agents/metabolism; Anti-Inflammatory Agents/pharmacology*; Anti-Inflammatory Agents/chemistry; Diterpenes/pharmacology; Diterpenes/chemistry; Molecular Structure; Anthozoa/metabolism; Anthozoa/chemistry*; Mice
  13. Winterbourn CC, Cheah FC
    N Engl J Med, 2018 03 15;378(11):1067-8.
    PMID: 29542310 DOI: 10.1056/NEJMc1801271
    Comment on: Luzzatto L, Arese P. Favism and Glucose-6-Phosphate Dehydrogenase Deficiency.
    N Engl J Med. 2018 Jan 4;378(1):60-71. Review. PubMed PMID: 29298156.
    MeSH terms: Favism*; Glucosephosphate Dehydrogenase Deficiency*
  14. Samsuddin NAC, Khan MF, Maulud KNA, Hamid AH, Munna FT, Rahim MAA, et al.
    Sci Total Environ, 2018 Jul 15;630:1502-1514.
    PMID: 29554768 DOI: 10.1016/j.scitotenv.2018.02.289
    Southeast Asian haze is a semi-natural phenomenon that chokes the region each year during the dry monsoon season. Smoke-haze episodes caused by the vegetation and peat fires in Indonesia severely affected large parts of Malaysia during the 2015 El Niño phenomenon. This study aimed to evaluate the factors that influenced the concentrations of aerosol and trace gases during the 2015 haze and non-haze period on a semi-urban site in the southern part of Malaysian peninsula that facing Sumatra (Muar, Site A), and on an urban site near to Kuala Lumpur, influenced by the city centre (Cheras, Site B). Local land use data and the cluster of air mass weighted backward trajectory were used to identify the potential factors from local sources and the transboundary region, respectively. The annual median concentrations of PM10 for semi-urban and urban sites were 45.0μg/m3 and 47.0μg/m3, respectively for the study period (Jan-Dec 2015) from the hourly observation dataset. The highest PM10 concentrations during the haze were 358μg/m3 and 415μg/m3 for the two sites, respectively, representing absolutely unhealthy air. However, the trace gases were within the safe threshold. The average concentrations of PM10 and carbon monoxide were two fold higher during the haze than the non-haze episodes on both sites. Nitrogen dioxide was more influenced by haze compared with sulphur dioxide and ozone. The results of the land use change suggest that the local factor can also partially affect the air pollution on the urban area (Site B) but more visible in 2015. The results of the backward trajectory and the wildfire radiative power showed that the smoke-haze episodes that affected Malaysia in 2015 were mainly initiated in the Indonesian Sumatra and Kalimantan regions. This study provides a very useful information towards the impacted region during El Niño haze episode.
    MeSH terms: Aerosols; Air Pollution; Carbon Monoxide; Fires; Indonesia; Malaysia; Nitrogen Dioxide; Ozone; Seasons; Smoke; Soil; Sulfur Dioxide; Urbanization; El Nino-Southern Oscillation
  15. Ali Khan MS, Ahmed N, Misbah, Arifuddin M, Zakaria ZA, Al-Sanea MM, et al.
    Food Chem Toxicol, 2018 May;115:523-531.
    PMID: 29555329 DOI: 10.1016/j.fct.2018.03.021
    In view of the report on anti-nociceptive activity of Leathery Murdah, Terminalia coriacea {Roxb.} Wight & Arn. (Combretaceae) leaves, the present study was conducted to isolate the active constituents and identify the underlying mechanisms. The methanolic extract of T. coriacea leaves (TCLME) at doses 125, 250 and 500 mg/kg orally, was subjected to various in-vivo assays in acetic acid induced writhing and formalin induced paw-licking tests with aspirin (100 mg/kg) and morphine (5 mg/kg) as reference drugs. Three flavonoids, rutin, robinin and gossypetin 3-glucuronide 8-glucoside were isolated and characterized from TCLME for the first time. The extract showed significant (p 
    MeSH terms: Methanol/chemistry*; Analgesics/pharmacology*; Animals; Dose-Response Relationship, Drug; Flavonoids/pharmacology*; Glyburide/pharmacology; Male; Plant Extracts/pharmacology*; Plant Extracts/chemistry; Plant Leaves/chemistry*; Opioid Peptides/metabolism; Terminalia/chemistry*; Mice; KATP Channels/antagonists & inhibitors; Pain Management/methods
  16. Charoenpitakchai M, Wiwatwarayos K, Jaisupa N, Rusmili MRA, Mangmool S, Hodgson WC, et al.
    PMID: 29556251 DOI: 10.1186/s40409-018-0146-y
    Background: Envenoming by kraits (genusBungarus) is a medically significant issue in South Asia and Southeast Asia. Malayan krait (Bungarus candidus) venom is known to contain highly potent neurotoxins. In recent years, there have been reports on the non-neurotoxic activities of krait venom that include myotoxicity and nephrotoxicity. However, research on such non-neurotoxicity activities of Malayan krait venom is extremely limited. Thus, the aim of the present study was to determine the myotoxic, cytotoxic and nephrotoxic activities ofB. candidusvenoms from northeastern (BC-NE) and southern (BC-S) Thailand in experimentally envenomed rats.

    Methods: Rats were administered Malayan krait (BC-NE or BC-S) venom (50 μg/kg, i.m.) or 0.9% NaCl solution (50 μL, i.m.) into the right hind limb. The animals were sacrificed 3, 6 and 24 h after venom administration. The right gastrocnemius muscle and both kidneys were collected for histopathological analysis. Blood samples were also taken for determination of creatine kinase (CK) and lactate dehydrogenase (LDH) levels. The human embryonic kidney cell line (HEK-293) was used in a cell proliferation assay to determine cytotoxic activity.

    Results: Administration of BC-NE or BC-S venom (50 μg/kg, i.m.) caused time-dependent myotoxicity, characterized by an elevation of CK and LDH levels. Histopathological examination of skeletal muscle displayed marked muscle necrosis and myofiber disintegration 24 h following venom administration. Both Malayan krait venoms also induced extensive renal tubular injury with glomerular and interstitial congestion in rats. BC-NE and BC-S venoms (100-0.2 μg/mL) caused concentration-dependent cytotoxicity on the HEK-293 cell line. However, BC-NE venom (IC50 = 8 ± 1 μg/mL; at 24 h incubation;n = 4) was found to be significantly more cytotoxic than BC-S venom (IC50 = 15 ± 2 μg/mL; at 24 h incubation;n = 4). In addition, the PLA2activity of BC-NE venom was significantly higher than that of BC-S venom.

    Conclusions: This study found that Malayan krait venoms from both populations possess myotoxic, cytotoxic and nephrotoxic activities. These findings may aid in clinical diagnosis and treatment of envenomed patients in the future.

  17. Hashim NHF, Mahadi NM, Illias RM, Feroz SR, Abu Bakar FD, Murad AMA
    Extremophiles, 2018 Jul;22(4):607-616.
    PMID: 29556723 DOI: 10.1007/s00792-018-1021-z
    Dienelactone hydrolase, an α/β hydrolase enzyme, catalyzes the hydrolysis of dienelactone to maleylacetate, an intermediate for the Krebs cycle. Genome sequencing of the psychrophilic yeast, Glaciozyma antarctica predicted a putative open reading frame (ORF) for dienelactone hydrolase (GaDlh) with 52% sequence similarity to that from Coniophora puteana. Phylogenetic tree analysis showed that GaDlh is closely related to other reported dienelactone hydrolases, and distantly related to other α/β hydrolases. Structural prediction using MODELLER 9.14 showed that GaDlh has the same α/β hydrolase fold as other dienelactone hydrolases and esterase/lipase enzymes, with a catalytic triad consisting of Cys-His-Asp and a G-x-C-x-G-G motif. Based on the predicted structure, GaDlh exhibits several characteristics of cold-adapted proteins such as glycine clustering in the binding pocket, reduced protein core hydrophobicity, and the absence of proline residues in loops. The putative ORF was amplified, cloned, and overexpressed in an Escherichia coli expression system. The recombinant protein was overexpressed as soluble proteins and was purified via Ni-NTA affinity chromatography. Biochemical characterization of GaDlh revealed that it has an optimal temperature at 10 °C and that it retained almost 90% of its residual activity when incubated for 90 min at 10 °C. The optimal pH was at pH 8.0 and it was stable between pH 5-9 when incubated for 60 min (more than 50% residual activity). Its Km value was 256 μM and its catalytic efficiency was 81.7 s-1. To our knowledge, this is the first report describing a novel cold-active dienelactone hydrolase-like protein.
  18. Zamrus SNH, Akhtar MN, Yeap SK, Quah CK, Loh WS, Alitheen NB, et al.
    Chem Cent J, 2018 Mar 19;12(1):31.
    PMID: 29556774 DOI: 10.1186/s13065-018-0398-1
    BACKGROUND: Curcumin is one of the leading compound extracted from the dry powder of Curcuma longa (Zingiberaceae family), which possess several pharmacological properties. However, in vivo administration exhibited limited applications in cancer therapies.

    RESULTS: Twenty-four curcumin derivatives have synthesized, which comprises cyclohexanone 1-10, acetone 11-17 and cyclopentanone 18-24 series. All the curcuminoids were synthesized by the acid or base catalyzed Claisen Schmidt condenstion reactions, in which β-diketone moiety of curcumin was modified with mono-ketone. These curcuminoids 1-24 were screened against HeLa, K562, MCF-7 (an estrogen-dependent) and MDA-MB-231 (an estrogen-independent) cancer cell lines. Among them, acetone series 11-17 were found to be more selective and potential cytotoxic agents. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines. Among the cyclohexanone series, the compound 4 exhibited (IC50 = 11.04 ± 2.80, 6.50 ± 01.80, 8.70 ± 3.10 and 2.30 ± 1.60 µg/mL) potential cytotoxicity against four proposed cancer cell lines, respectively. All the curcucminoids were characterized with the detailed1H NMR, IR, UV-Vis, and mass spectroscopic techniques. The structure of compound 4 was confirmed by using the single X-ray crystallography. Additionally, we are going to report the first time spectral data of (2E,6E)-2,6-bis(2-methoxybenzylidene)cyclohexanone (1). Structure-activity relationships revealed that the mono-carbonyl with 2,5-dimethoxy substituted curcuminoids could be an essential for the future drugs against cancer diseases.

    CONCLUSIONS: Curcuminoids with diferuloyl(4-hydroxy-3-methoxycinnamoyl) moiety with mono carbonyl exhibiting potential cytotoxic properties. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines.

  19. Tan VP, Macdonald HM, Gabel L, McKay HA
    Arch Osteoporos, 2018 Mar 20;13(1):31.
    PMID: 29556801 DOI: 10.1007/s11657-018-0441-9
    Physical activity is essential for optimal bone strength accrual, but we know little about interactions between physical activity, sedentary time, and bone outcomes in older adolescents. Physical activity (by accelerometer and self-report) positively predicted bone strength and the distal and midshaft tibia in 15-year-old boys and girls. Lean body mass mediated the relationship between physical activity and bone strength in adolescents.

    PURPOSE: To examine the influence of physical activity (PA) and sedentary time on bone strength, structure, and density in older adolescents.

    METHODS: We used peripheral quantitative computed tomography to estimate bone strength at the distal tibia (8% site; bone strength index, BSI) and tibial midshaft (50% site; polar strength strain index, SSIp) in adolescent boys (n = 86; 15.3 ± 0.4 years) and girls (n = 106; 15.3 ± 0.4 years). Using accelerometers (GT1M, Actigraph), we measured moderate-to-vigorous PA (MVPAAccel), vigorous PA (VPAAccel), and sedentary time in addition to self-reported MVPA (MVPAPAQ-A) and impact PA (ImpactPAPAQ-A). We examined relations between PA and sedentary time and bone outcomes, adjusting for ethnicity, maturity, tibial length, and total body lean mass.

    RESULTS: At the distal tibia, MVPAAccel and VPAAccel positively predicted BSI (explained 6-7% of the variance, p 

    MeSH terms: Adolescent; Female; Humans; Male; Motor Activity; Time Factors; Tomography, X-Ray Computed/methods; Exercise*; Bone Density*; Sedentary Lifestyle*; Self Report; Accelerometry/methods
  20. Chan CYW, Chiu CK, Ler XY, Ng YH, Chian XH, Tan PH, et al.
    Spine (Phila Pa 1976), 2018 Oct 01;43(19):E1143-E1151.
    PMID: 29557927 DOI: 10.1097/BRS.0000000000002645
    STUDY DESIGN: Retrospective study.

    OBJECTIVE: To investigate the association between postoperative upper instrumented vertebrae (UIV) tilt angle with postoperative medial shoulder and neck imbalance.

    SUMMARY OF BACKGROUND DATA: Studies had found that current recommendations for UIV selection were not predictive of good postoperative shoulder balance.

    METHODS: A total of 98 patients with adolescent idiopathic scoliosis with Lenke 1/2 curves who underwent posterior spinal fusion between 2013 and 2014 with minimum follow-up of 2 years were recruited. Radiological parameters: UIV tilt angle, T1 tilt, cervical axis, and clavicle angle were measured preoperatively, postoperatively, and at final follow-up.

    RESULTS: Mean age was 16.2 ± 6.2 years. Mean follow-up was 37.9 ± 6.5 months. There were 73.5% Lenke 1 and 26.5% Lenke 2 curves. Significant factors affecting postoperative T1 Tilt were postoperative UIV tilt angle, preoperative T1 tilt, and preoperative UIV tilt angle. Postoperative UIV tilt angle and preoperative cervical axis were significant factors affecting cervical axis at final follow-up. UIV level was not significant independent factor that affected postoperative T1 tilt and cervical axis. There was strong correlation between postoperative UIV tilt angle and T1 tilt for the whole cohort (P 

    MeSH terms: Adolescent; Child; Female; Follow-Up Studies; Humans; Male; Postoperative Period; Posture; Retrospective Studies; Scoliosis/surgery*; Spinal Fusion/methods*; Thoracic Vertebrae/surgery*; Young Adult
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