Browse publications by year: 2017

  1. Comorbid association of antiphospholipid antibodies and migraine: A systematic review and meta-analysis
    Islam MA, Alam F, Wong KK
    Autoimmun Rev, 2017 May;16(5):512-522.
    PMID: 28279839 DOI: 10.1016/j.autrev.2017.03.005
    BACKGROUND: Antiphospholipid antibodies (aPLs) namely anticardiolipin (aCL) antibody, anti-β2-glycoprotein I (β2GPI) antibody and lupus anticoagulant (LA) are autoantibodies produced against anionic phospholipids and proteins on plasma membranes. Migraine is a primary headache disorder which has growing evidences of autoimmune-mediated pathogenesis and previous studies suggested the presence of aPLs in migraine patients.

    AIMS: The aim of this study was to evaluate the comorbid association between aPLs (aCL, anti-β2GPI and LA) and migraine compared to healthy controls.

    METHODS: Studies were searched through PubMed, ISI Web of Science and Google Scholar databases without restricting the languages and year (up to October 2016) and were selected based on the inclusion criteria. Two authors independently extracted data from the included studies. All analyses were conducted by using random effects model to calculate the odds ratio (OR) and 95% confidence interval (CI). Quality assessment was carried out by using the modified Newcastle-Ottawa Scale (NOS). Publication bias was evaluated via visualization of funnel plots, Begg's and Egger's tests.

    RESULTS: The database searches produced 1995 articles, 13 of which were selected (912 migraineurs and 822 healthy controls). 8.59%, 15.21% and 4.11% of the migraineurs exhibited aCL, anti-β2GPI and LA which was 4.83, 1.63 and 3.03 times higher, respectively, than healthy controls. A significant presence of aCL (OR: 3.55, 95% CI: 1.59-7.95; p=0.002) or anti-β2GPI antibodies (OR: 2.02, 95% CI: 1.20-3.42; p=0.008) was observed in migraine patients, however, LA was not significantly associated (OR: 2.02, 95% CI: 0.50-8.37; p=0.320). Majority of the studies (n=10 of 13) demonstrated NOS score of 7 or above and no significant publication bias was observed.

    CONCLUSION: Migraine might be an autoimmune-associated neurologic disorder. The presence of aCL or anti-β2GPI antibodies was significant in migraine patients compared to healthy controls, suggesting an involvement of these autoantibodies in migraine attack.
    MeSH terms: Adolescent; Adult; Autoantibodies/blood*; Child; Female; Humans; Migraine Disorders/complications*; Prospective Studies; Comorbidity; Case-Control Studies; Antiphospholipid Syndrome/complications*; Antiphospholipid Syndrome/immunology; Antibodies, Antiphospholipid/adverse effects*; Antibodies, Antiphospholipid/immunology; beta 2-Glycoprotein I/immunology
  2. Local gray level S-curve transformation - A generalized contrast enhancement technique for medical images
    Gandhamal A, Talbar S, Gajre S, Hani AF, Kumar D
    Comput Biol Med, 2017 04 01;83:120-133.
    PMID: 28279861 DOI: 10.1016/j.compbiomed.2017.03.001
    Most medical images suffer from inadequate contrast and brightness, which leads to blurred or weak edges (low contrast) between adjacent tissues resulting in poor segmentation and errors in classification of tissues. Thus, contrast enhancement to improve visual information is extremely important in the development of computational approaches for obtaining quantitative measurements from medical images. In this research, a contrast enhancement algorithm that applies gray-level S-curve transformation technique locally in medical images obtained from various modalities is investigated. The S-curve transformation is an extended gray level transformation technique that results into a curve similar to a sigmoid function through a pixel to pixel transformation. This curve essentially increases the difference between minimum and maximum gray values and the image gradient, locally thereby, strengthening edges between adjacent tissues. The performance of the proposed technique is determined by measuring several parameters namely, edge content (improvement in image gradient), enhancement measure (degree of contrast enhancement), absolute mean brightness error (luminance distortion caused by the enhancement), and feature similarity index measure (preservation of the original image features). Based on medical image datasets comprising 1937 images from various modalities such as ultrasound, mammograms, fluorescent images, fundus, X-ray radiographs and MR images, it is found that the local gray-level S-curve transformation outperforms existing techniques in terms of improved contrast and brightness, resulting in clear and strong edges between adjacent tissues. The proposed technique can be used as a preprocessing tool for effective segmentation and classification of tissue structures in medical images.
    MeSH terms: Algorithms*; Humans; Image Enhancement/methods*; Image Interpretation, Computer-Assisted/methods*; Pattern Recognition, Automated/methods*; Sensitivity and Specificity; Reproducibility of Results
  3. Poor fisheries struggle with U.S. import rule
    Johnson AF, Caillat M, Verutes GM, Peter C, Junchompoo C, Long V, et al.
    Science, 2017 Mar 10;355(6329):1031-1032.
    PMID: 28280175 DOI: 10.1126/science.aam9153
  4. Fulltext Hepatoprotective Effects of Chinese Medicine Herbs Decoction on Liver Cirrhosis in Rats
    Mat-Rahim NA, Lim TH, Nor-Amdan NA, AbuBakar S
    Evid Based Complement Alternat Med, 2017;2017:6125829.
    PMID: 28280515 DOI: 10.1155/2017/6125829
    Hepatoprotective and curative activities of aqueous extract of decoction containing 10 Chinese medicinal herbs (HPE-XA-08) were evaluated in Sprague-Dawley albino rats with liver damage induced by thioacetamide (TAA). These activities were assessed by investigating the liver enzymes level and also histopathology investigation. Increases in alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels were observed in rats with cirrhotic liver. No significant alterations of the liver enzymes were observed following treatment with HPE-XA-08. Histopathology examination of rats treated with HPE-XA-08 at 250 mg/kg body weight, however, exhibited moderate liver protective effects. Reduced extracellular matrix (ECM) proteins within the hepatocytes were noted in comparison to the cirrhotic liver. The curative effects of HPE-XA-08 were observed with marked decrease in the level of ALP (more than 3x) and level of GGT (more than 2x) in cirrhotic rat treated with 600 mg/kg body weight HPE-XA-08 in comparison to cirrhotic rat treated with just water diluent. Reversion of cirrhotic liver to normal liver condition in rats treated with HPE-XA-08 was observed. Results from the present study suggest that HPE-XA-08 treatment assisted in the protection from liver cirrhosis and improved the recovery of cirrhotic liver.
    MeSH terms: Alkaline Phosphatase; Animals; Body Weight; Extracellular Matrix; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Plants, Medicinal; Thioacetamide; Transferases; Water; Extracellular Matrix Proteins; Rats, Sprague-Dawley; Hepatocytes; Rats
  5. Fulltext Rapid biodegradation of polycyclic aromatic hydrocarbons (PAHs) using effective Cronobacter sakazakii MM045 (KT933253)
    Umar ZD, Aziz NA, Zulkifli SZ, Mustafa M
    MethodsX, 2017;4:104-117.
    PMID: 28280689 DOI: 10.1016/j.mex.2017.02.003
    Polycyclic Aromatic Hydrocarbons (PAHs) are complex and widely distributed environmental pollutants that can affect living ecosystems. This study was conducted to rapidly degrade phenanthrene and pyrene representing low and high molecular weight of PAHs, respectively. Cronobacter sakazakii MM045 (KT933253) was identified from used engine oil of contaminated soil. PAHs biodegradation was carried out using 2,6-dichlorophenol indophenol (DCPIP) assay. Biodegradation influencing factors including agitation, temperature, pH, inoculums volume and salinity were enhanced using Response Surface Methodology (RSM) by Central Composite Design (CCD). Phenanthrene and pyrene biodegrading metabolites were identified using gas chromatography mass spectrophotometer (GCMS). •Initial biodegradation indicated 75.2% and 54.3% phenanthrene and pyrene degraded by C. sakazakii MM045 within 24 h. After CCD optimisation, 100% degradation was achieved for each of the phenanthrene and pyrene, resulting in the formation of intermediate metabolites.•The identified phenanthrene metabolites were 3,4-dihydroxyphenathrene, phthalic acid, pyruvic acid, acetic acid and oxalic acid. Pyrene intermediates comprised pyrene cis-4,5-dihydrodiol, 3,4-dihydroxyphenanthrene, phthalic acid, pyruvic acid, acetic acid and lactic acid.•Cronbacter sakazakii MM045 was proven to be rapid and effective in degrading PAHs within 24 h despite the unavailability of existing literatures on PAHs biodegradation.
  6. Fulltext Biotechnological Processes in Microbial Amylase Production
    Gopinath SC, Anbu P, Arshad MK, Lakshmipriya T, Voon CH, Hashim U, et al.
    Biomed Res Int, 2017;2017:1272193.
    PMID: 28280725 DOI: 10.1155/2017/1272193
    Amylase is an important and indispensable enzyme that plays a pivotal role in the field of biotechnology. It is produced mainly from microbial sources and is used in many industries. Industrial sectors with top-down and bottom-up approaches are currently focusing on improving microbial amylase production levels by implementing bioengineering technologies. The further support of energy consumption studies, such as those on thermodynamics, pinch technology, and environment-friendly technologies, has hastened the large-scale production of the enzyme. Herein, the importance of microbial (bacteria and fungi) amylase is discussed along with its production methods from the laboratory to industrial scales.
    MeSH terms: Amylases/biosynthesis*; Amylases/isolation & purification; Bacteria/enzymology*; Biotechnology/methods*; Fungi/enzymology*; Industry; Substrate Specificity
  7. Organosolv Processes
    Brosse N, Hussin MH, Rahim AA
    Adv. Biochem. Eng. Biotechnol., 2017 3 11;166:153-176.
    PMID: 28280848 DOI: 10.1007/10_2016_61
    Biofuels and chemicals can be produced from lignocellulosic feedstocks using biotechnological processes. The effective utilization of carbohydrates from biomass for the production of biofuels necessitates the development of pretreatment technologies to enhance their enzymatic digestibility. Among all the various pretreatment methods currently studied and developed, the organosolv processes, in which organic solvents or aqueous organic solvent mixtures are used as the pretreatment medium, appear to be specially promising in the context of the biorefinery because (1) they produce cellulosic pulp with a good enzymatic digestibility for monomeric glucose production and (2) they allow a clean fractionation of the major biomass components (cellulose, lignin, and hemicelluloses) into three process streams. In this chapter we give an updated overview of organosolv methods using conventional solvents and ionic liquids which have recently gained considerable interest as solvents for lignocellulosic biomass and pretreatment.
    MeSH terms: Hydrolysis; Lignin; Biomass; Ionic Liquids; Biofuels*
  8. Deficiency in Sperm-Egg Protein Interaction as a Major Cause of Fertilization Failure
    Sabetian S, Shamsir MS
    J. Membr. Biol., 2017 04;250(2):133-144.
    PMID: 28280854 DOI: 10.1007/s00232-017-9954-1
    Complete elucidation of fertilization process at molecular level is one of the unresolved challenges in sexual reproduction studies, and understanding the molecular mechanism is crucial in overcoming difficulties in infertility and unsuccessful in vitro fertilization. Sperm-oocyte interaction is one of the most remarkable events in fertilization process, and deficiency in protein-protein interactions which mediate this interaction is a major cause of unexplained infertility. Due to detection of how the various defects of sperm-oocyte interaction can affect fertilization failure, different experimental methods have been applied. This review summarizes the current understanding of sperm-egg interaction mechanism during fertilization and also accumulates the different types of sperm-egg interaction abnormalities and their association with infertility. Several detection approaches regarding sperm-egg protein interactions and the associated defects are reviewed in this paper.
    MeSH terms: Animals; Female; Humans; Infertility/metabolism*; Infertility/physiopathology*; Male; Oocytes/metabolism; Oocytes/physiology; Ovum/metabolism*; Ovum/physiology*; Spermatozoa/metabolism*; Spermatozoa/physiology*
  9. Biotechnological route for sustainable succinate production utilizing oil palm frond and kenaf as potential carbon sources
    Luthfi AAI, Manaf SFA, Illias RM, Harun S, Mohammad AW, Jahim JM
    Appl Microbiol Biotechnol, 2017 Apr;101(8):3055-3075.
    PMID: 28280869 DOI: 10.1007/s00253-017-8210-z
    Due to the world's dwindling energy supplies, greater thrust has been placed on the utilization of renewable resources for global succinate production. Exploration of such biotechnological route could be seen as an act of counterbalance to the continued fossil fuel dominance. Malaysia being a tropical country stands out among many other nations for its plenty of resources in the form of lignocellulosic biomass. To date, oil palm frond (OPF) contributes to the largest fraction of agricultural residues in Malaysia, while kenaf, a newly introduced fiber crop with relatively high growth rate, holds great potential for developing sustainable succinate production, apart from OPF. Utilization of non-food, inexhaustible, and low-cost derived biomass in the form of OPF and kenaf for bio-based succinate production remains largely untapped. Owing to the richness of carbohydrates in OPF and kenaf, bio-succinate commercialization using these sources appears as an attractive proposition for future sustainable developments. The aim of this paper was to review some research efforts in developing a biorefinery system based on OPF and kenaf as processing inputs. It presents the importance of the current progress in bio-succinate commercialization, in addition to describing the potential use of different succinate production hosts and various pretreatments-saccharifications under development for OPF and kenaf. Evaluations on the feasibility of OPF and kenaf as fermentation substrates are also discussed.
    MeSH terms: Agriculture; Biotechnology/economics; Biotechnology/methods*; Carbon/metabolism*; Escherichia coli/genetics; Fermentation; Hydrolysis; Lignin/metabolism; Malaysia; Succinates/economics; Succinates/metabolism*; Plant Leaves/metabolism*; Plant Leaves/chemistry; Biomass; Arecaceae/metabolism*; Hibiscus/metabolism*; Hibiscus/chemistry
  10. Characterization of two novel bacterial type A exo-chitobiose hydrolases having C-terminal 5/12-type carbohydrate-binding modules
    Jamek SB, Nyffenegger C, Muschiol J, Holck J, Meyer AS, Mikkelsen JD
    Appl Microbiol Biotechnol, 2017 Jun;101(11):4533-4546.
    PMID: 28280871 DOI: 10.1007/s00253-017-8198-4
    Type A chitinases (EC 3.2.1.14), GH family 18, attack chitin ((1 → 4)-2-acetamido-2-deoxy-β-D-glucan) and chito-oligosaccharides from the reducing end to catalyze release of chitobiose (N,N'-diacetylchitobiose) via hydrolytic cleavage of N-acetyl-β-D-glucosaminide (1 → 4)-β-linkages and are thus "exo-chitobiose hydrolases." In this study, the chitinase type A from Serratia marcescens (SmaChiA) was used as a template for identifying two novel exo-chitobiose hydrolase type A enzymes, FbalChi18A and MvarChi18A, originating from the marine organisms Ferrimonas balearica and Microbulbifer variabilis, respectively. Both FbalChi18A and MvarChi18A were recombinantly expressed in Escherichia coli and were confirmed to exert exo-chitobiose hydrolase activity on chito-oligosaccharides, but differed in temperature and pH activity response profiles. Amino acid sequence comparison of the catalytic β/α barrel domain of each of the new enzymes showed individual differences, but ~69% identity of each to that of SmaChiA and highly conserved active site residues. Superposition of a model substrate on 3D structural models of the catalytic domain of the enzymes corroborated exo-chitobiose hydrolase type A activity for FbalChi18A and MvarChi18A, i.e., substrate attack from the reducing end. A main feature of both of the new enzymes was the presence of C-terminal 5/12 type carbohydrate-binding modules (SmaChiA has no C-terminal carbohydrate binding module). These new enzymes may be useful tools for utilization of chitin as an N-acetylglucosamine donor substrate via chitobiose.
    MeSH terms: Chitin/metabolism*; Chitinase/genetics; Chitinase/metabolism; Disaccharides/genetics*; Disaccharides/metabolism; Escherichia coli/genetics; Hydrolases/genetics*; Hydrolases/metabolism*; Hydrolases/chemistry; Hydrolysis; Kinetics; Protein Binding; Serratia marcescens/enzymology; Serratia marcescens/genetics; Substrate Specificity; Sequence Analysis, DNA; Catalytic Domain; Gammaproteobacteria/enzymology*; Alteromonadaceae/enzymology*
  11. Effect of adding brewery wastewater to pulp and paper mill effluent to enhance the photofermentation process: wastewater characteristics, biohydrogen production, overall performance, and kinetic modeling
    Hay JX, Wu TY, Juan JC, Md Jahim J
    Environ Sci Pollut Res Int, 2017 Apr;24(11):10354-10363.
    PMID: 28281053 DOI: 10.1007/s11356-017-8557-9
    Although a significant amount of brewery wastewater (BW) is generated during beer production, the nutrients in the BW could be reused as a potential bio-resource for biohydrogen production. Therefore, improvements in photofermentative biohydrogen production due to a combination of BW and pulp and paper mill effluent (PPME) as a mixed production medium were investigated comprehensively in this study. The experimental results showed that both the biohydrogen yield and the chemical oxygen demand removal were improved through the combination of BW and PPME. The best biohydrogen yield of 0.69 mol H2/L medium was obtained using the combination of 10 % BW + 90 % PPME (10B90P), while the reuse of the wastewater alone (100 % BW and 100 % PPME) resulted in 42.3 and 44.0 % less biohydrogen yields than the highest yield, respectively. The greatest light efficiency was 1.97 % and was also achieved using the combination of both wastewaters at 10B90P. This study revealed the potential of reusing and combining two different effluents together, in which the combination of BW and PPME improved the nutrients and light penetration into the mixed production medium.
    MeSH terms: Industrial Waste; Kinetics; Paper*; Biological Oxygen Demand Analysis; Waste Water*
  12. Fulltext Sandhoff disease in two siblings of a Malaysian family: Description of novel beta hexosaminidase mutations, magnetic resonance imaging, and spectroscopic findings
    Antony CD, Thong MK, Rahmat K, Muridan R
    Neurol India, 2017 3 11;65(Supplement):S98-S100.
    PMID: 28281504 DOI: 10.4103/neuroindia.NI_1121_15
  13. Fulltext SrCo1-xTixO3-δ perovskites as excellent catalysts for fast degradation of water contaminants in neutral and alkaline solutions
    Miao J, Sunarso J, Su C, Zhou W, Wang S, Shao Z
    Sci Rep, 2017 03 10;7:44215.
    PMID: 28281656 DOI: 10.1038/srep44215
    Perovskite-like oxides SrCo1-xTixO3-δ (SCTx, x = 0.1, 0.2, 0.4, 0.6) were used as heterogeneous catalysts to activate peroxymonosulfate (PMS) for phenol degradation under a wide pH range, exhibiting more rapid phenol oxidation than Co3O4 and TiO2. The SCT0.4/PMS system produced a high activity at increased initial pH, achieving optimized performance at pH ≥ 7 in terms of total organic carbon removal, the minimum Co leaching and good catalytic stability. Kinetic studies showed that the phenol oxidation kinetics on SCT0.4/PMS system followed the pseudo-zero order kinetics and the rate on SCT0.4/PMS system decreased with increasing initial phenol concentration, decreased PMS amount, catalyst loading and solution temperature. Quenching tests using ethanol and tert-butyl alcohol demonstrated sulfate and hydroxyl radicals for phenol oxidation. This investigation suggested promising heterogeneous catalysts for organic oxidation with PMS, showing a breakthrough in the barriers of metal leaching, acidic pH, and low efficiency of heterogeneous catalysis.
    MeSH terms: Ethanol; Cobalt; Kinetics; Oxides; Peroxides; Temperature; Titanium; Calcium Compounds; Hydroxyl Radical; Phenol; tert-Butyl Alcohol
  14. Fulltext Regions of very low H3K27me3 partition the Drosophila genome into topological domains
    El-Sharnouby S, Fischer B, Magbanua JP, Umans B, Flower R, Choo SW, et al.
    PLoS One, 2017;12(3):e0172725.
    PMID: 28282436 DOI: 10.1371/journal.pone.0172725
    It is now well established that eukaryote genomes have a common architectural organization into topologically associated domains (TADs) and evidence is accumulating that this organization plays an important role in gene regulation. However, the mechanisms that partition the genome into TADs and the nature of domain boundaries are still poorly understood. We have investigated boundary regions in the Drosophila genome and find that they can be identified as domains of very low H3K27me3. The genome-wide H3K27me3 profile partitions into two states; very low H3K27me3 identifies Depleted (D) domains that contain housekeeping genes and their regulators such as the histone acetyltransferase-containing NSL complex, whereas domains containing moderate-to-high levels of H3K27me3 (Enriched or E domains) are associated with regulated genes, irrespective of whether they are active or inactive. The D domains correlate with the boundaries of TADs and are enriched in a subset of architectural proteins, particularly Chromator, BEAF-32, and Z4/Putzig. However, rather than being clustered at the borders of these domains, these proteins bind throughout the H3K27me3-depleted regions and are much more strongly associated with the transcription start sites of housekeeping genes than with the H3K27me3 domain boundaries. While we have not demonstrated causality, we suggest that the D domain chromatin state, characterised by very low or absent H3K27me3 and established by housekeeping gene regulators, acts to separate topological domains thereby setting up the domain architecture of the genome.
    MeSH terms: Animals; Cells, Cultured; Chromatin/metabolism; Chromatin/chemistry; Drosophila/genetics*; Drosophila/metabolism; Embryo, Nonmammalian/metabolism; Histones/genetics; Histones/metabolism*; Histones/chemistry; Male; Markov Chains; Protein Binding; Spermatocytes/cytology; Spermatocytes/metabolism; Transcription Initiation Site; Drosophila Proteins/genetics; Drosophila Proteins/metabolism*; Drosophila Proteins/chemistry; Chromatin Immunoprecipitation; Genome, Insect; Transcriptome; Polycomb-Group Proteins/genetics; Polycomb-Group Proteins/metabolism; Protein Domains
  15. Total syntheses of Prelactone V and Prelactone B
    Raghavendra S, Tadiparthi K, Yadav JS
    Carbohydr Res, 2017 Apr 10;442:17-19.
    PMID: 28282511 DOI: 10.1016/j.carres.2017.02.008
    The total syntheses of natural products Prelactone-V and Prelactone-B have been accomplished by a novel Chiron approach starting from d-glucose. The synthesis involves isopropylidene acetal formation of d-glucose using Poly(4-vinylpyridine) supported iodine as a catalyst, Tebbe olefination, Grignard reaction, Wittig olefination, selective mono deprotection of acetal using PMA/SiO2, hydrogenation and anti-1,3-diol formation are as key steps.
    MeSH terms: Lactones/chemical synthesis*; Lactones/chemistry; Molecular Conformation
  16. Cytochrome P450 2W1 (CYP2W1) - ready for use as the biomarker and drug target for cancer?
    Pan Y, Ong EC
    Xenobiotica, 2017 Oct;47(10):923-932.
    PMID: 27690753 DOI: 10.1080/00498254.2016.1244370
    1. This article aims to evaluate the potentials of using cytochrome P450 2W1 (CYP2W1) as a biomarker and a drug target of cancer because of its characteristic cancer-specific expression. 2. Discrepant findings comparing the expression levels of CYP2W1 in cancer and non-cancer samples were reported. In general, the expression followed a developmental pattern. The demethylation status of CpG island and the expression levels of CYP2W1 genes was positively correlated. 3. CYP2W1 was able to activate several procarcinogens, anticancer pro-drugs and to metabolise many endogenous substances including fatty acids and lysophospholipids. 4. CYP2W1 expression level was suggested to serve as an independent prognostic biomarker in colorectal cancer and hepatocellular carcinoma. The correlation of genetic polymorphisms of CYP2W1 and cancer risk was uncertain. 5. Further characterisation of CYP2W1 structure is suggested to link to its functions. More studies are warranted to reveal the true status and the regulation of CYP2W1 expression across normal and cancer tissues. Catalytic activity of CYP2W1 should be tested on a wider spectrum of endogenous and exogenous substances before its use as the drug target. Larger size of clinical samples can be included to verify the potential of CYP2W1 as the prognostic or cancer risk biomarker.
    MeSH terms: Antineoplastic Agents/metabolism*; Antineoplastic Agents/therapeutic use; Carcinoma, Hepatocellular/metabolism; Humans; Liver Neoplasms/metabolism; Prodrugs; Colorectal Neoplasms/metabolism; Biomarkers/metabolism; Cell Line, Tumor; Cytochrome P450 Family 2/metabolism*
  17. Fulltext Innovative Approaches to Hypertension Control in Low- and Middle-Income Countries
    Vedanthan R, Bernabe-Ortiz A, Herasme OI, Joshi R, Lopez-Jaramillo P, Thrift AG, et al.
    Cardiol Clin, 2017 Feb;35(1):99-115.
    PMID: 27886793 DOI: 10.1016/j.ccl.2016.08.010
    Elevated blood pressure, a major risk factor for ischemic heart disease, heart failure, and stroke, is the leading global risk for mortality. Treatment and control rates are very low in low- and middle-income countries. There is an urgent need to address this problem. The Global Alliance for Chronic Diseases sponsored research projects focus on controlling hypertension, including community engagement, salt reduction, salt substitution, task redistribution, mHealth, and fixed-dose combination therapies. This paper reviews the rationale for each approach and summarizes the experience of some of the research teams. The studies demonstrate innovative and practical methods for improving hypertension control.
    MeSH terms: Antihypertensive Agents/therapeutic use*; Blood Pressure*; Developing Countries*; Humans; Risk Factors; Incidence; Telemedicine/methods*
  18. Chemical composition and cytotoxic properties of Clinacanthus nutans root extracts
    Teoh PL, Cheng AY, Liau M, Lem FF, Kaling GP, Chua FN, et al.
    Pharm Biol, 2017 Dec;55(1):394-401.
    PMID: 27931178
    CONTEXT: Clinacanthus nutans Lindau (Acanthaceae) is a medicinal plant that has been reported to have anti-inflammatory, antiviral, antimicrobial and antivenom activities. In Malaysia, it has been widely claimed to be effective in various cancer treatments but scientific evidence is lacking.

    OBJECTIVE: This study investigates the chemical constituents, anti-proliferative, and apoptotic properties of C. nutans root extracts.

    MATERIALS AND METHODS: The roots were subjected to solvent extraction using methanol and ethyl acetate. The anti-proliferative effects of root extracts were tested at the concentrations of 10 to 50 μg/mL on MCF-7 and HeLa by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay for 72 h. Morphological changes were observed under light microscope. Pro-apoptotic effects of root extracts were examined using flow cytometric analysis and RT-PCR. The chemical compositions of root extracts were detected using GC-MS.

    RESULTS: The proliferation of MCF-7 cells was inhibited with the IC50 values of 35 and 30 μg/mL, respectively, for methanol and ethyl acetate root extracts. The average inhibition of HeLa cells was ∼25%. Induction of apoptosis in MCF-7 was supported by chromatin condensation, down-regulation of BCL2 and unaltered expression of BAX. However, only ethyl acetate extract caused the loss of mitochondrial membrane potential. GC-MS analysis revealed the roots extracts were rich with terpenoids and phytosterols.

    DISCUSSION AND CONCLUSIONS: The results demonstrated that root extracts promote apoptosis by suppressing BCL2 via mitochondria-dependent or independent manner. The identified compounds might work solely or cooperatively in regulating apoptosis. However, further studies are required to address this.

    MeSH terms: Animals; Antineoplastic Agents, Phytogenic/isolation & purification; Antineoplastic Agents, Phytogenic/pharmacology*; Breast Neoplasms/drug therapy*; Breast Neoplasms/genetics; Breast Neoplasms/metabolism; Breast Neoplasms/pathology; Uterine Cervical Neoplasms/drug therapy*; Uterine Cervical Neoplasms/genetics; Uterine Cervical Neoplasms/metabolism; Uterine Cervical Neoplasms/pathology; Dose-Response Relationship, Drug; Female; Flow Cytometry; HeLa Cells; Humans; Gas Chromatography-Mass Spectrometry; Phytotherapy; Plant Extracts/isolation & purification; Plant Extracts/pharmacology*; Plants, Medicinal; Solvents/chemistry; Apoptosis/drug effects*; Plant Roots/chemistry*; Inhibitory Concentration 50; Reverse Transcriptase Polymerase Chain Reaction; Acanthaceae/chemistry*; NIH 3T3 Cells; Chromatin Assembly and Disassembly/drug effects; Cell Proliferation/drug effects*; Apoptosis Regulatory Proteins/genetics; Apoptosis Regulatory Proteins/metabolism; Mice; Membrane Potential, Mitochondrial/drug effects; Cell Nucleus Shape/drug effects; MCF-7 Cells
  19. Insight into the molecular mechanism of P-glycoprotein mediated drug toxicity induced by bioflavonoids: an integrated computational approach
    Wongrattanakamon P, Lee VS, Nimmanpipug P, Sirithunyalug B, Chansakaow S, Jiranusornkul S
    Toxicol. Mech. Methods, 2017 May;27(4):253-271.
    PMID: 27996361 DOI: 10.1080/15376516.2016.1273428
    In this work, molecular docking, pharmacophore modeling and molecular dynamics (MD) simulation were rendered for the mouse P-glycoprotein (P-gp) (code: 4Q9H) and bioflavonoids; amorphigenin, chrysin, epigallocatechin, formononetin and rotenone including a positive control; verapamil to identify protein-ligand interaction features including binding affinities, interaction characteristics, hot-spot amino acid residues and complex stabilities. These flavonoids occupied the same binding site with high binding affinities and shared the same key residues for their binding interactions and the binding region of the flavonoids was revealed that overlapped the ATP binding region with hydrophobic and hydrophilic interactions suggesting a competitive inhibition mechanism of the compounds. Root mean square deviations (RMSDs) analysis of MD trajectories of the protein-ligand complexes and NBD2 residues, and ligands pointed out these residues were stable throughout the duration of MD simulations. Thus, the applied preliminary structure-based molecular modeling approach of interactions between NBD2 and flavonoids may be gainful to realize the intimate inhibition mechanism of P-gp at NBD2 level and on the basis of the obtained data, it can be concluded that these bioflavonoids have the potential to cause herb-drug interactions or be used as lead molecules for the inhibition of P-gp (as anti-multidrug resistance agents) via the NBD2 blocking mechanism in future.
    MeSH terms: Amino Acid Sequence; Animals; Binding Sites; Flavonoids/toxicity*; Flavonoids/chemistry; Humans; Ligands; Protein Binding; Sequence Alignment; Computational Biology/methods*; P-Glycoprotein/antagonists & inhibitors; P-Glycoprotein/chemistry*; Structural Homology, Protein; Herb-Drug Interactions; Mice; Protein Interaction Domains and Motifs; Molecular Dynamics Simulation; Molecular Docking Simulation
  20. Genoproteomics-assisted improvement of Andrographis paniculata: toward a promising molecular and conventional breeding platform for autogamous plants affecting the pharmaceutical industry
    Valdiani A, Talei D, Lattoo SK, Ortiz R, Rasmussen SK, Batley J, et al.
    Crit Rev Biotechnol, 2017 Sep;37(6):803-816.
    PMID: 28049346 DOI: 10.1080/07388551.2016.1260525
    Andrographis paniculata (Burm. f.) Wall. ex Nees. (AP) is a hermaphroditic, self-compatible, and habitual inbreeding plant. Its main bioactive component is andrographolide, which is capable of inducing autophagic cell death in some human cancer cells and helps fight HIV/AIDS. Increasing the andrographolide content by investigating the genetic mechanisms controlling its biosynthesis in order to improve and develop high-yielding cultivars are the main breeding targets for AP. However, there might exist some limitations or barriers for crossability within AP accessions. Recently, this problem was addressed in AP by using a combination of crossbreeding and biotechnology-aided genetic methods. This review emphasizes that development of a breeding platform in a hard-to-breed plant, such as AP, requires the involvement of a broad range of methods from classical genetics to molecular breeding. To this end, a phenological stage (for example, flowering and stigma development) can be simplified to a quantitative morphological trait (for example, bud or stigma length) to be used as an index to express the highest level of receptivity in order to manage outcrossing. The outcomes of the basic crossability research can be then employed in diallel mating and crossbreeding. This review explains how genomic data could produce useful information regarding genetic distance and its influence on the crossability of AP accessions. Our review indicates that co-dominant DNA markers, such as microsatellites, are also capable of resolving the evolutionary pathway and cryptic features of plant populations and such information can be used to select the best breeding strategy. This review also highlights the importance of proteomic analysis as a breeding tool. In this regard, protein diversification, as well as the impact of normal and stress-responsive proteins on morphometric and physiological behaviors, could be used in breeding programs. These findings have immense potential for improving plant production and, therefore, can be regarded as prospective breeding platforms for medicinal plants that have an autogamous mode of reproduction. Finally, this review suggests that novel site-directed genome editing approaches such as TALENs (Transcription Activator-Like Effector Nucleases) and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein-9 nuclease) systems together with other new plant breeding technologies (NPBT) should simultaneously be taken into consideration for improvement of pharmaceutical plants.
    MeSH terms: Plant Breeding; Genetic Markers; Heat-Shock Proteins; Humans; Inbreeding; Plants, Medicinal; Prospective Studies; DNA Shuffling; Andrographis; Proteomics; Clustered Regularly Interspaced Short Palindromic Repeats; CRISPR-Cas Systems; Transcription Activator-Like Effector Nucleases; Gene Editing
External Links