Browse publications by year: 2019

  1. Alsaeedi HA, Koh AE, Lam C, Rashid MBA, Harun MHN, Saleh MFBM, et al.
    J. Photochem. Photobiol. B, Biol., 2019 Sep;198:111561.
    PMID: 31352000 DOI: 10.1016/j.jphotobiol.2019.111561
    Blindness and vision loss contribute to irreversible retinal degeneration, and cellular therapy for retinal cell replacement has the potential to treat individuals who have lost light sensitive photoreceptors in the retina. Retinal cells are well characterized in function, and are a subject of interest in cellular replacement therapy of photoreceptors and the retinal pigment epithelium. However, retinal cell transplantation is limited by various factors, including the choice of potential stem cell source that can show variability in plasticity as well as host tissue integration. Dental pulp is one such source that contains an abundance of stem cells. In this study we used dental pulp-derived mesenchymal stem cells (DPSCs) to mitigate sodium iodate (NaIO3) insult in a rat model of retinal degeneration. Sprague-Dawley rats were first given an intravitreal injection of 3 × 105 DPSCs as well as a single systemic administration of NaIO3 (40 mg/kg). Electroretinography (ERG) was performed for the next two months and was followed-up by histological analysis. The ERG recordings showed protection of DPSC-treated retinas within 4 weeks, which was statistically significant (* P ≤ .05) compared to the control. Retinal thickness of the control was also found to be thinner (*** P ≤ .001). The DPSCs were found integrated in the photoreceptor layer through immunohistochemical staining. Our findings showed that DPSCs have the potential to moderate retinal degeneration. In conclusion, DPSCs are a potential source of stem cells in the field of eye stem cell therapy due to its protective effects against retinal degeneration.
    MeSH terms: Animals; Dental Pulp/cytology; Disease Models, Animal; Electroretinography; Iodates/toxicity*; Male; Photoreceptor Cells/cytology; Retinal Degeneration/etiology; Retinal Degeneration/therapy*; Rats, Sprague-Dawley; Apoptosis/drug effects; Mesenchymal Stem Cell Transplantation*; Rats; Retinal Pigment Epithelium/drug effects*; Retinal Pigment Epithelium/pathology; Mesenchymal Stromal Cells/cytology; Mesenchymal Stromal Cells/metabolism
  2. Angelopoulou E, Paudel YN, Piperi C
    Transl Oncol, 2019 Jul 25;12(10):1357-1363.
    PMID: 31352198 DOI: 10.1016/j.tranon.2019.07.001
    Gliomas present the most common type of brain tumors in adults, characterized by high morbidity and mortality. In search of potential molecular targets, members of paired box (PAX) family have been found expressed in neural crest cells, regulating their proliferation, apoptosis, migration and differentiation. Recently, PAX3 overexpression has been implicated in glioma tumorigenesis by enhancing proliferation, increasing invasiveness and inducing resistance to apoptosis of glioma cells, while maintaining brain glioma stem cells (BGSCs) stemness. Although the oncogenic potential of PAX3 in gliomas is still under investigation, experimental evidence suggests that PAX3 function is mainly mediated through the canonical and non-canonical Wnt signaling pathway as well as through its interaction with GFAP and p53 proteins. In addition, PAX3 may contribute to the chemoresistance of glioma cells and modulates the effectiveness of novel experimental therapies. Further evidence indicates that PAX3 may represent a novel diagnostic and prognostic biomarker for gliomas, facilitating personalized treatment. This review addresses the emerging role of PAX3 in glioma diagnosis, prognosis and treatment, aiming to shed more light on the underlying molecular mechanisms that could lead to more effective treatment approaches.
    MeSH terms: Adult; Brain; Cell Differentiation; Glioma; Humans; Neural Crest; Prognosis; Neoplastic Stem Cells; Biomarkers; Tumor Suppressor Protein p53; Apoptosis; Drug Resistance, Neoplasm; Brain Stem Neoplasms; Therapies, Investigational; Cell Proliferation; Wnt Signaling Pathway; Carcinogenesis
  3. Adamu A, Abdul Wahab R, Aliyu F, Abdul Razak FI, Mienda BS, Shamsir MS, et al.
    J Mol Graph Model, 2019 11;92:131-139.
    PMID: 31352207 DOI: 10.1016/j.jmgm.2019.07.012
    Dehalogenases continue to garner interest of the scientific community due to their potential applications in bioremediation of halogen-contaminated environment and in synthesis of various industrially relevant products. Example of such enzymes is DehL, an L-2-haloacid dehalogenase (EC 3.8.1.2) from Rhizobium sp. RC1 that catalyses the specific cleavage of halide ion from L-2-halocarboxylic acids to produce the corresponding D-2-hydroxycarboxylic acids. Recently, the catalytic residues of DehL have been identified and its catalytic mechanism has been fully elucidated. However, the enantiospecificity determinants of the enzyme remain unclear. This information alongside a well-defined catalytic mechanism are required for rational engineering of DehL for substrate enantiospecificity. Therefore, using quantum mechanics/molecular mechanics and molecular mechanics Poisson-Boltzmann surface area calculations, the current study theoretically investigated the molecular basis of DehL enantiospecificity. The study found that R51L mutation cancelled out the dehalogenation activity of DehL towards it natural substrate, L-2-chloropropionate. The M48R mutation, however introduced a new activity towards D-2-chloropropionate, conveying the possibility of inverting the enantiospecificity of DehL from L-to d-enantiomer with a minimum of two simultaneous mutations. The findings presented here will play important role in the rational design of DehL dehalogenase for improving substrate utility.
    MeSH terms: Binding Sites; Hydrocarbons, Chlorinated/chemistry*; Hydrolases/genetics; Hydrolases/chemistry*; Models, Theoretical*; Mutation; Propionates/chemistry*; Protein Binding; Rhizobium/enzymology*; Rhizobium/genetics; Structure-Activity Relationship; Substrate Specificity; Molecular Dynamics Simulation; Molecular Docking Simulation
  4. Nastiti NA, Niam MS, Khoo PJ
    Int J Surg Case Rep, 2019;61:91-95.
    PMID: 31352320 DOI: 10.1016/j.ijscr.2019.07.021
    INTRODUCTION: Wandering spleen (WS) is an uncommon congenital or acquired condition where the spleen is displaced from its normal position at the left hypochondrium to anywhere within the abdominal or pelvic cavity. The incidence is extremely rare in the geriatric population.

    PRESENTATION OF CASE: We present a rare case of WS torsion in a 69-year-old elderly patient who presented with an acute abdomen. Physical examination revealed a tender right lower quadrant abdominal mass. Imaging studies confirmed the diagnosis of WS torsion with features of infarction. Subsequently, an emergency laparoscopic splenectomy was performed.

    DISCUSSION: A WS occurs due to the hypermobility of the spleen secondary to the absence or laxity of splenic suspensory ligaments. It is more commonly seen in children and adults in the third decade of life. Symptoms are usually attributed to the consequences of splenic vascular pedicle torsion. Exhibited symptoms might be unspecific; thus, radiological modalities are essential to determine the diagnosis and aid in planning its management. The treatment of choice is either open or laparoscopic splenopexy or splenectomy.

    CONCLUSION: Due to potentially life-threatening consequences and the rarity of such cases, a thorough history, detailed physical examination, and objective investigation are the pillars to attain a prompt diagnosis for appropriate management to be conducted as soon as possible to minimise complications.

    MeSH terms: Abdomen; Abdomen, Acute; Adult; Child; Humans; Infarction; Ligaments; Pelvis; Laparoscopy; Physical Examination; Splenectomy; Splenic Diseases; Incidence; Wandering Spleen
  5. Chua TH, Manin BO, Vythilingam I, Fornace K, Drakeley CJ
    Parasit Vectors, 2019 Jul 25;12(1):364.
    PMID: 31345256 DOI: 10.1186/s13071-019-3627-0
    BACKGROUND: We investigated the effect of five common habitat types on the diversity and abundance of Anopheles spp. and on the biting rate and time of Anopheles balabacensis (currently the only known vector for Plasmodium knowlesi in Sabah) at Paradason village, Kudat, Sabah. The habitats were forest edge, playground area, longhouse, oil palm plantation and shrub-bushes area. Sampling of Anopheles was done monthly using the human landing catch method in all habitat types for 14 months (October 2013 to December 2014, excluding June 2014). The Anopheles species were morphologically identified and subjected to PCR assay for the detection of Plasmodium parasites. Generalised linear mixed models (GLMM) were applied to test the variation in abundance and biting rates of An. balabacensis in different habitat types.

    RESULTS: A total of 1599 Anopheles specimens were collected in the village, of which about 90% were An. balabacensis. Anopheles balabacensis was present throughout the year and was the dominant Anopheles species in all habitat types. The shrub bushes habitat had the highest Anopheles species diversity while forest edge had the greatest number of Anopheles individuals caught. GLMM analysis indicated that An. balabacensis abundance was not affected by the type of habitats, and it was more active during the early and late night compared to predawn and dawn. PCR assay showed that 1.61% of the tested An. balabacensis were positive for malaria parasites, most of which were caught in oil palm estates and infected with one to two Plasmodium species.

    CONCLUSIONS: The identification of infected vectors in a range of habitats, including agricultural and farming areas, illustrates the potential for humans to be exposed to P. knowlesi outside forested areas. This finding contributes to a growing body of evidence implicating environmental changes due to deforestation, expansion of agricultural and farming areas, and development of human settlements near to forest fringes in the emergence of P. knowlesi in Sabah.

    MeSH terms: Animals; Anopheles/parasitology; Anopheles/physiology*; Insect Bites and Stings*; Malaria/prevention & control; Malaria/transmission; Malaysia; Linear Models; Plasmodium knowlesi/isolation & purification; Ecosystem*; Forests; Mosquito Vectors/parasitology; Mosquito Vectors/physiology*
  6. Chan WK, Wong VW
    Lancet Gastroenterol Hepatol, 2019 10;4(10):747-749.
    PMID: 31345779 DOI: 10.1016/S2468-1253(19)30183-9
    MeSH terms: Bile; Bile Acids and Salts; Double-Blind Method; Humans; Non-alcoholic Fatty Liver Disease*
  7. Sabri MZ, Abdul Hamid AA, Sayed Hitam SM, Abdul Rahim MZ
    Adv Bioinformatics, 2019;2019:6912914.
    PMID: 31346332 DOI: 10.1155/2019/6912914
    Aptamer has been long studied as a substitute of antibodies for many purposes. However, due to the exceeded length of the aptamers obtained in vitro, difficulties arise in its manipulation during its molecular conjugation on the matrix surfaces. Current study focuses on computational improvement for aptamers screening of hepatitis B surface antigen (HBsAg) through optimization of the length sequences obtained from SELEX. Three original aptamers with affinity against HBsAg were truncated into five short hairpin structured aptamers and their affinity against HBsAg was thoroughly studied by molecular docking, molecular dynamics (MD) simulation, and Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) method. The result shows that truncated aptamers binding on HBsAg "a" determinant region are stabilized by the dynamic H-bond formation between the active binding residues and nucleotides. Amino acids residues with the highest hydrogen bonds hydrogen bond interactions with all five aptamers were determined as the active binding residues and further characterized. The computational prediction of complexes binding will include validations through experimental assays in future studies. Current study will improve the current in vitro aptamers by minimizing the aptamer length for its easy manipulation.
    MeSH terms: Amino Acids; Antibodies; Hepatitis B Surface Antigens; Hydrogen; Hydrogen Bonding; Nucleotides; Oligonucleotides; SELEX Aptamer Technique; Molecular Dynamics Simulation; Molecular Docking Simulation
  8. Singh P, Mazumdar P, Harikrishna JA, Babu S
    Planta, 2019 Nov;250(5):1387-1407.
    PMID: 31346804 DOI: 10.1007/s00425-019-03246-8
    MAIN CONCLUSION: Rice sheath blight research should prioritise optimising biological control approaches, identification of resistance gene mechanisms and application in genetic improvement and smart farming for early disease detection. Rice sheath blight, caused by Rhizoctonia solani AG1-1A, is one of the most devasting diseases of the crop. To move forward with effective crop protection against sheath blight, it is important to review the published information related to pathogenicity and disease management and to determine areas of research that require deeper study. While progress has been made in the identification of pathogenesis-related genes both in rice and in the pathogen, the mechanisms remain unclear. Research related to disease management practices has addressed the use of agronomic practices, chemical control, biological control and genetic improvement: Optimising nitrogen fertiliser use in conjunction with plant spacing can reduce spread of infection while smart agriculture technologies such as crop monitoring with Unmanned Aerial Systems assist in early detection and management of sheath blight disease. Replacing older fungicides with natural fungicides and use of biological agents can provide effective sheath blight control, also minimising environmental impact. Genetic approaches that show promise for the control of sheath blight include treatment with exogenous dsRNA to silence pathogen gene expression, genome editing to develop rice lines with lower susceptibility to sheath blight and development of transgenic rice lines overexpressing or silencing pathogenesis related genes. The main challenges that were identified for effective crop protection against sheath blight are the adaptive flexibility of the pathogen, lack of resistant rice varieties, abscence of single resistance genes for use in breeding and low access of farmers to awareness programmes for optimal management practices.
    MeSH terms: Plant Breeding; Agriculture; Pest Control, Biological; Plant Diseases/immunology; Plant Diseases/microbiology; Plant Diseases/prevention & control*; Plant Proteins/genetics; Plant Proteins/metabolism; Rhizoctonia/pathogenicity*; Oryza/genetics*; Oryza/immunology; Oryza/microbiology; Transcription Factors/genetics; Transcription Factors/metabolism; Crops, Agricultural; Plants, Genetically Modified; Gene Editing
  9. Bongalov B, Burslem DFRP, Jucker T, Thompson SED, Rosindell J, Swinfield T, et al.
    Ecol Lett, 2019 Oct;22(10):1608-1619.
    PMID: 31347263 DOI: 10.1111/ele.13357
    Both niche and stochastic dispersal processes structure the extraordinary diversity of tropical plants, but determining their relative contributions has proven challenging. We address this question using airborne imaging spectroscopy to estimate canopy β-diversity for an extensive region of a Bornean rainforest and challenge these data with models incorporating niches and dispersal. We show that remotely sensed and field-derived estimates of pairwise dissimilarity in community composition are closely matched, proving the applicability of imaging spectroscopy to provide β-diversity data for entire landscapes of over 1000 ha containing contrasting forest types. Our model reproduces the empirical data well and shows that the ecological processes maintaining tropical forest diversity are scale dependent. Patterns of β-diversity are shaped by stochastic dispersal processes acting locally whilst environmental processes act over a wider range of scales.
    MeSH terms: Borneo; Spectrum Analysis*; Tropical Climate; Ecosystem*; Biodiversity*; Remote Sensing Technology; Rainforest*
  10. Rodzlan Hasani WS, Miaw Yn JL, Saminathan TA, Robert Lourdes TG, Ramly R, Abd Hamid HA, et al.
    Asia Pac J Public Health, 2019 11;31(8_suppl):48S-56S.
    PMID: 31347375 DOI: 10.1177/1010539519865053
    This study was carried out to determine the prevalence of illicit drug use and its associated factors among male adolescents in Malaysia. Data of 13 135 adolescents were extracted from the National Health and Morbidity Survey 2017, a cross-sectional survey among school-going adolescents in Malaysia aged between 13 and 17 years, using a 2-stage stratified cluster sampling. A complex sample design analysis and multiple logistic regression analysis were applied. The overall prevalence of lifetime illicit drug use among male adolescents was 6.6%. The multivariable model showed that illicit drug use among male adolescents were associated with younger age, rural school area, marital status of parent, current smoker, ever having sex, truancy, involved in physical fight, and lack of peer support. The findings from this study can assist community and relevant authorities in their efforts to combat illicit drug usage among adolescents using intervention programs that diminishes risk factors and enhances the protective factors.
  11. Singh D, Narayanan S, Grundmann O, Dzulkapli EB, Vicknasingam B
    Subst Use Misuse, 2019;54(14):2284-2289.
    PMID: 31347441 DOI: 10.1080/10826084.2019.1645178
    Background: Mitragyna speciosa (Korth.) or kratom is an indigenous medicinal plant of Southeast Asia. Kratom is widely reported to have dose-dependent effects based on available literature, but to our knowledge, this has not been established conclusively. Objective: This study sought to evaluate if kratom use produces dose-dependent effects, with a stimulant effect at low doses and a sedative effect at high doses, in a sample of regular kratom users. Methods: A total of 63 regular kratom users participated in this cross-sectional study. The Brief-Biphasic Alcohol Effects Scale (B-BAES) was used to determine subjects self-report kratom use experiences. Results: Almost all in the sample were male (98%, n = 62/63), and the majority of subjects were Malays (94%, n = 59/63). The mean age of the subjects in the sample was 43.8 years (SD = 12.1). Seventy-five percent (n = 47/63) have >5 years kratom use history, and 65% (n = 41/63) consumed >3 glasses of kratom daily. Results from first test showed no significant difference in the stimulant (t61 =0.371, p 3 glasses a day or less than this amount, regardless of duration of use. In the second test, no significant differences in the mean scores were found among those who consumed >3 glasses daily or less than this amount among short-term or long-term uses. Conclusions: Daily kratom use produced both stimulant and sedative effects but they were not statistically significantly associated with the dose consumed, both among short-term and long-term users in our sample.
    MeSH terms: Adult; Central Nervous System Stimulants/administration & dosage*; Cross-Sectional Studies; Dose-Response Relationship, Drug; Female; Humans; Hypnotics and Sedatives/administration & dosage*; Malaysia; Male; Middle Aged; Mitragyna*; Self Report
  12. Khoo ACH, Yeoh KW
    Clin Nucl Med, 2019 Oct;44(10):808-809.
    PMID: 31348083 DOI: 10.1097/RLU.0000000000002739
    Extramammary Paget's disease (EMPD) is a rare disease with an estimated prevalence of 0.1 to 2.4 per 1,000,000 person-years. Metastatic EMPD has a poor prognosis with a 5-year survival of approximately 7%. Local therapy is the only curative option with surgery being recommended for resectable disease. It is therefore crucial to be able to stage such patients appropriately. The utility of F-FDG PET/CT for this disease is not well established. We share a case on how F-FDG PET/CT was used to stage metastatic EMPD.
    MeSH terms: Aged, 80 and over; Humans; Male; Neoplasm Metastasis; Neoplasm Staging; Paget Disease, Extramammary/pathology*; Fluorodeoxyglucose F18*; Positron Emission Tomography Computed Tomography*
  13. Abd Rahim MA, Johani FH, Shah SA, Hassan MR, Abdul Manaf MR
    Ann Glob Health, 2019 Jul 24;85(1).
    PMID: 31348624
    BACKGROUND: Helicobacter pylori (H. pylori) infection is known to be associated with peptic ulcer and gastric cancer. Detection of H. pylori infection is a significant part of peptic ulcer and gastric cancer prevention and management. 13C-urea breath test (UBT) provides a good option for the pathogen detection due to its accuracy and safety.

    OBJECTIVE: This review aims to evaluate the 13C-UBT diagnostic accuracy studies conducted among Asian population and validate its use for the Asian population.

    METHODS: Original articles were systematically searched in PubMed, Scopus, and Google Scholar using the PICOS strategy by applying relevant keywords. Only studies published in English and conducted in Asia were included. Our search returned 276 articles. After assessment, 11 articles which answered our research question and met the criteria set for systematic review and meta-analysis were accepted. A total of 15 study protocols were extracted from the 11 accepted articles.

    FINDINGS: Majority of the studies were conducted in Hong Kong (six), followed by Taiwan (five), Japan (two), and one each in Singapore and Israel. All studies had used histology as part of its gold standard of reference. All but one study was performed on adult populations. The summary estimate for sensitivity was 97% (95% CI: 96, 98%), and specificity was 96% (95% CI: 95, 97%), with significant heterogeneity between studies. Adjusting for the dose (50 mg) and breath sample collection time (20 minutes) had improved both accuracy estimates and significantly reduced heterogeneity.

    CONCLUSION: This review supports the test-and-treat strategy for H. pylori infection management. Prevalence and cost-effectiveness studies are mandatory for health authorities to adopt this strategy into national policy.

    MeSH terms: Asia; Breath Tests*; Carbon Isotopes; Humans; Sensitivity and Specificity; Urea/analysis*; Reproducibility of Results; Helicobacter pylori*; Helicobacter Infections/diagnosis*
  14. Fahrni ML, Azmy MT, Usir E, Aziz NA, Hassan Y
    PLoS One, 2019;14(7):e0219898.
    PMID: 31348784 DOI: 10.1371/journal.pone.0219898
    OBJECTIVES: To provide baseline information on inappropriate prescribing (IP), and to evaluate whether potentially inappropriate medications (PIMs), as defined by STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions) criteria, were associated with preventable adverse drug events (ADEs) and/or hospitalization.

    METHODS: We prospectively studied older patients (n = 301) admitted to three urban, public-funded hospitals. We scrutinized their medical records and used STOPP-START (Screening Tool to Alert Prescribers to Right Treatment) criteria to determine PIM and potential prescribing omissions (PPO) respectively- together these constitute IP. Prescriptions with PIM(s) were subjected to a pharmacist medication review, aimed at detecting cases of ADE(s). The vetted cases were further assessed by an expert consensus panel to ascertain: i) causality between the ADE and hospitalization, using, the World Health Organization Uppsala Monitoring Centre criteria, and, ii) whether the ADEs were avoidable (using Hallas criteria). Finally, percentages of PIM-associated ADEs that were both preventable and linked to hospitalization were calculated.

    RESULTS: IP prevalence was 58.5% (n = 176). A majority (49.5%, n = 150) had moderate to severe degree of comorbidities (Charlson Comorbidity Index score ≥ 3). Median age was 72 years. Median number of medications was 6 and 30.9% (n = 93) had ≥8 medications. PIM prevalence was 34.9% (117 PIMs, n = 105) and PPO 37.9% (191 PPOs, n = 114). Most PIMs and PPOs involved overuse of aspirin and underuse of both antiplatelets and statins respectively. With every increase in the number of medications prescribed, the likelihood of PIM occurrence increased by 20%, i.e.1.2 fold (OR 1.20, 95% CI: 1.1-1.3). Among the 105 patients with PIMs, 33 ADEs (n = 33); 31 ADEs (n = 31) considered "causal" or "contributory" to hospitalization; 27 ADEs (n = 27) deemed "avoidable" or "potentially avoidable"; and 25 PIM-associated ADEs, preventable, and that induced hospitalization (n = 25), were identified: these equated to prevalence of 31.4%, 29.5%, 25.7%, and 23.8% respectively. The most common ADEs were masked hypoglycemia and gastrointestinal bleed. With every additional PIM prescribed, the odds for ADE occurrence increased by 12 folds (OR 11.8, 95% CI 5.20-25.3).

    CONCLUSION: The majority of the older patients who were admitted to secondary care for acute illnesses were potentially exposed to IP. Approximately a quarter of the patients were prescribed with PIMs, which were plausibly linked with preventable ADEs that directly caused or contributed to hospitalization.

    MeSH terms: Potentially Inappropriate Medication List; Aged; Aged, 80 and over; Female; Hospitalization/statistics & numerical data*; Humans; Male; Prospective Studies; Prevalence; Inappropriate Prescribing/statistics & numerical data*; Secondary Care; Drug-Related Side Effects and Adverse Reactions/epidemiology*; Polypharmacology
  15. Anwar A, Khan NA, Siddiqui R
    PLoS Negl Trop Dis, 2019 07;13(7):e0007385.
    PMID: 31348789 DOI: 10.1371/journal.pntd.0007385
    MeSH terms: Acanthamoeba/drug effects*; alpha-Galactosidase/metabolism; Galactose/antagonists & inhibitors*; Galactose/metabolism; Humans; Oocysts/drug effects*; Trophozoites/drug effects*
  16. H S N, Paudel YN, K L K
    Life Sci, 2019 Sep 15;233:116686.
    PMID: 31348946 DOI: 10.1016/j.lfs.2019.116686
    Epilepsy is a neurological disorder characterized by an enduring predisposition to generate and aggravate epileptic seizures affecting around 1% of global population making it a serious health concern. Despite the recent advances in epilepsy research, no disease-modifying treatment able to terminate epileptogenesis have been reported yet reflecting the complexity in understanding the disease pathogenesis. To overcome the current treatment gap against epilepsy, one effective approach is to explore anti-epileptic effects from a drug that are approved to treat non-epileptic diseases. In this regard, Metformin emerged as an ideal candidate which is a first line treatment option for type 2 diabetes mellitus (T2DM), has conferred neuroprotection in several in vivo neurological disorders such as Alzheimer's diseases (AD), Parkinson's disease (PD), Stroke, Huntington's diseases (HD) including epilepsy. In addition, Metformin has ameliorated cognitive alteration, learning and memory induced by epilepsy as well as in animal model of AD. Herein, we review the promising findings demonstrated upon Metformin treatment against animal model of epilepsy however, the precise underlying mechanism of anti-epileptic potential of Metformin is not well understood. However, there is a growing understanding that Metformin demonstrates its anti-epileptic effect mainly via ameliorating brain oxidative damage, activation of AMPK, inhibition of mTOR pathway, downregulation of α-synuclein, reducing apoptosis, downregulation of BDNF and TrkB level. These reflects that Metformin being non-anti-epileptic drug (AED) has a potential to ameliorate the cellular pathways that were impaired in epilepsy reflecting its therapeutical potential against epileptic seizure that might plausibly overcome the limitations of today epilepsy treatment.
    MeSH terms: Animals; Diabetes Mellitus, Type 2/complications; Diabetes Mellitus, Type 2/drug therapy*; Disease Models, Animal*; Epilepsy/drug therapy*; Epilepsy/etiology; Hypoglycemic Agents/pharmacology*; Metformin/pharmacology*; Neuroprotective Agents/pharmacology*
  17. Rahim F, Taha M, Ullah H, Wadood A, Selvaraj M, Rab A, et al.
    Bioorg Chem, 2019 10;91:103112.
    PMID: 31349115 DOI: 10.1016/j.bioorg.2019.103112
    Alpha-amylase and urease enzyme over expression endorses various complications like rheumatoid arthritis, urinary tract infection, colon cancer, metabolic disorder, cardiovascular risk, and chronic kidney disease. To overcome these complications, we have synthesized new arylhydrazide bearing Schiff bases/thiazolidinone analogues as α-amylase and urease inhibitors. The analogues 1a-r were evaluated for α-amylase inhibitory potential. All analogues were found active and show IC50 value ranging between 0.8 ± 0.05 and 12.50 ± 0.5 μM as compare to standard acarbose (IC50 = 1.70 ± 0.10 μM). Among the synthesized analogs, compound 1j, 1r, 1k, 1e, 1b and 1f having IC50 values 0.8 ± 0.05, 0.9 ± 0.05, 1.00 ± 0.05, 1.10 ± 0.10, 1.20 ± 0.10 and 1.30 ± 0.10 μM respectively showed an excellent inhibitory potential. Analogs 2a-o were evaluated against urease activity. All analogues were found active and show IC50 value ranging between 4.10 ± 0.02 and 38.20 ± 1.10 μM as compare to standard thiourea (IC50 = 21.40 ± 0.21 μM). Among the synthesized analogs, compound 2k, 2a, 2h, 2j, 2f, 2e, 2g, 2b and 2l having IC50 values 4.10 ± 0.02, 4.60 ± 0.02, 4.70 ± 0.03, 5.40 ± 0.02, 6.70 ± 0.05, 8.30 ± 0.3, 11.20 ± 0.04, 16.90 ± 0.8 and 19.80 ± 0.60 μM respectively showed an excellent inhibitory potential. All compounds were characterized through 1H, 13C NMR and HR-EIMS analysis. Structure activity relationship of the synthesized analogs were recognized and confirmed through molecular docking studies.
    MeSH terms: alpha-Amylases/antagonists & inhibitors*; alpha-Amylases/metabolism; Dose-Response Relationship, Drug; Enzyme Inhibitors/chemical synthesis; Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/chemistry; Humans; Hydrazines/chemical synthesis; Hydrazines/pharmacology*; Hydrazines/chemistry; Schiff Bases/pharmacology; Schiff Bases/chemistry; Structure-Activity Relationship; Urease/antagonists & inhibitors*; Urease/metabolism; Molecular Structure; Thiazolidines/pharmacology*; Thiazolidines/chemistry; Molecular Docking Simulation*
  18. Irfan M, Irfan M, Shah SM, Baig N, Saleh TA, Ahmed M, et al.
    Mater Sci Eng C Mater Biol Appl, 2019 Oct;103:109769.
    PMID: 31349444 DOI: 10.1016/j.msec.2019.109769
    Non-covalent electrostatic interaction between amide nitrogen and carbonyl carbon of shorter chain length of polyvinylpyrrolidone (PVP-k25) was developed with in-house carboxylic oxidized multiwall carbon nanotubes (O-MWCNT) and then blended with Polyethersulfone (PES) polymer. FTIR analysis was utilized to confirm bonding nature of nano-composites (NCs) of O-MWCNT/PVP-k25 and casting membranes. Non-solvent induces phase separation process developed regular finger-like channels in composite membranes whereas pristine PES exhibited spongy entities as studied by cross sectional analysis report of FESEM. Further, FESEM instrument was also utilized to observe the dispersion of O-MWCNT/PVP based nanocomposite (NCs) with PES and membranes leaching phenomena analysis. Contact angle experiments described 24% improvement of hydrophilic behaviour, leaching ratio of additives was reduced to 1.89%, whereas water flux enhanced up to 6 times. Bovine serum albumin (BSA) and lysozyme based antifouling analysis shown up to 25% improvement, whereas 84% of water flux was regained after protein fouling than pristine PES. Anticoagulant activity was reported by estimating prothrombin, thrombin, plasma re-calcification times and production of fibrinogen cluster with platelets-adhesions photographs and hemolysis experiments. Composite membranes exhibited 3.4 and 3 times better dialysis clearance ratios of urea and creatinine solutes as compared to the raw PES membrane.
    MeSH terms: Anticoagulants/chemistry*; Renal Dialysis/instrumentation*; Humans; Membranes, Artificial*; Polymers/chemistry*; Sulfones/chemistry*; Nanotubes/chemistry*; Nanocomposites/chemistry*
  19. Tariq U, Hussain R, Tufail K, Haider Z, Tariq R, Ali J
    Mater Sci Eng C Mater Biol Appl, 2019 Oct;103:109863.
    PMID: 31349467 DOI: 10.1016/j.msec.2019.109863
    Quick setting and poor injectability due to liquid-solid phase separation have limited the clinical use of brushite and monetite cements. The presence of certain ions in the cement during the setting reaction moderate the setting time and properties of the cement. This study reports the preparation of injectable bone cement by using biphasic calcium phosphate (BCP) extracted from femur lamb bone by calcination at 1450 °C. EDX analysis infers the presence of Mg and Na ions as trace elements in BCP. X-ray diffraction patterns of the prepared cement confirmed the formation of brushite (DCPD) along with monetite (DCPA) as a minor phase. DCPA phase diminished gradually with a decrease in powder to liquid ratio (PLR). Initial and final setting time of 5.3 ± 0.5 and 14.67 ± 0.5 min respectively are obtained and within the acceptable recommended range for orthopedic applications. Exceptional injectability of ≈90% is achieved for all prepared bone cement samples. A decrease in compressive strength was observed with increase in the liquid phase of the cement, which is attributed to the higher degree of porosity in the set cement. Immersion of bone cement in simulated body fluid (SBF) for up to 7 days resulted in the formation of apatite layer on the surface of cement with Ca/P ratio 1.71, which enhanced the compressive strength from 2.88 to 9.15 MPa. The results demonstrate that bone cement produced from BCP extracted from femur lamb bone can be considered as potential bone substitute for regeneration and repair of bone defects.
    MeSH terms: Animals; Calcium Phosphates/chemistry*; Femur/chemistry*; Hydroxyapatites/chemistry*; Sheep
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