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  1. Fulltext A Degradable Inverse Vulcanized Copolymer as a Coating Material for Urea Produced under Optimized Conditions
    Ghumman ASM, Shamsuddin R, Nasef MM, Krivoborodov EG, Ahmad S, Zanin AA, et al.
    Polymers (Basel), 2021 Nov 22;13(22).
    PMID: 34833338 DOI: 10.3390/polym13224040
    Global enhancement of crop yield is achieved using chemical fertilizers; however, agro-economy is affected due to poor nutrient uptake efficacy (NUE), which also causes environmental pollution. Encapsulating urea granules with hydrophobic material can be one solution. Additionally, the inverse vulcanized copolymer obtained from vegetable oils are a new class of green sulfur-enriched polymer with good biodegradation and better sulfur oxidation potential, but they possess unreacted sulfur, which leads to void generations. In this study, inverse vulcanization reaction conditions to minimize the amount of unreacted sulfur through response surface methodology (RSM) is optimized. The copolymer obtained was then characterized using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). FTIR confirmed the formation of the copolymer, TGA demonstrated that copolymer is thermally stable up to 200 °C temperature, and DSC revealed the sulfur conversion of 82.2% (predicted conversion of 82.37%), which shows the goodness of the model developed to predict the sulfur conversion. To further maximize the sulfur conversion, 5 wt% diisopropenyl benzene (DIB) as a crosslinker is added during synthesis to produce terpolymer. The urea granule is then coated using terpolymer, and the nutrient release longevity of the coated urea is tested in distilled water, which revealed that only 65% of its total nutrient is released after 40 days of incubation. The soil burial of the terpolymer demonstrated its biodegradability, as 26% weight loss happens in 52 days of incubation. Thus, inverse vulcanized terpolymer as a coating material for urea demonstrated far better nutrient release longevity compared with other biopolymers with improved biodegradation; moreover, these copolymers also have potential to improve sulfur oxidation.
  2. Fulltext A Feasible Compatibilization Processing Technique for Improving the Mechanical and Thermal Performance of Rubbery Biopolymer/Graphene Nanocomposites
    Shahdan D, Rosli NA, Chen RS, Ahmad S
    Polymers (Basel), 2022 Nov 18;14(22).
    PMID: 36433138 DOI: 10.3390/polym14225009
    Over the last few decades, processing and compatibility have become challenging and interesting investigation areas of polymer matrix nanocomposites. This study investigated the addition of maleic anhydride (MAH) at different ratios with graphene nanoplatelets (GnPs) in poly(lactic acid)/modified natural rubber/polyaniline/GnP (PLA/m-NR/PANI/GnP) nanocomposites via two processing methods: a two-step technique and a one-pot technique. The former technique involved first preparing a master batch of PLA grafted with MAH, followed by a second step involving the melt blending of the nanocomposite (T1) using MAH-g-PLA. On the other hand, the one-pot technique involved the direct mixing of MAH during the melt-blending process (T2). The mechanical, morphological and thermal properties of the prepared nanocomposites were investigated. The findings showed that adding MAH significantly improved the tensile strength and elongation at break by about 25% for PLA/m-NR/PANi/GnP nanocomposites, with an optimal ratio of 1:1 of MAH-g-PLA to GnP loading using the T1 technique. FTIR analysis confirmed the chemical interaction between MAH and PLA for T1 nanocomposites, which exhibited improved phase morphology with smoother surfaces. MAH-compatibilized nanocomposites had enhanced thermal stabilities when compared to the sample without a compatibilizer. The findings show that the compatibilized PLA nanocomposite is potentially suitable for bio-inspired materials.
  3. Fulltext A Human Corneal Epithelial Cell Line Model for Limbal Stem Cell Biology and Limbal Immunobiology
    Shaharuddin B, Ahmad S, Md Latar N, Ali S, Meeson A
    Stem Cells Transl Med, 2017 03;6(3):761-766.
    PMID: 28297580 DOI: 10.5966/sctm.2016-0175
    Limbal stem cell (LSC) deficiency is a visually debilitating condition caused by abnormal maintenance of LSCs. It is treated by transplantation of donor-derived limbal epithelial cells (LECs), the success of which depends on the presence and quality of LSCs within the transplant. Understanding the immunobiological responses of these cells within the transplants could improve cell engraftment and survival. However, human corneal rings used as a source of LSCs are not always readily available for research purposes. As an alternative, we hypothesized that a human telomerase-immortalized corneal epithelial cell (HTCEC) line could be used as a model for studying LSC immunobiology. HTCEC constitutively expressed human leukocyte antigen (HLA) class I but not class II molecules. However, when stimulated by interferon-γ, HTCECs then expressed HLA class II antigens. Some HTCECs were also migratory in response to CXCL12 and expressed stem cell markers, Nanog, Oct4, and Sox2. In addition because both HTCECs and LECs contain side population (SP) cells, which are an enriched LSC population, we used these SP cells to show that some HTCEC SP cells coexpressed ABCG2 and ABCB5. HTCEC SP and non-side population (NSP) cells also expressed CXCR4, but the SP cells expressed higher levels. Both were capable of colony formation, but the NSP colonies were smaller and contained fewer cells. In addition, HTCECs expressed ΔNp63α. These results suggest the HTCEC line is a useful model for further understanding LSC biology by using an in vitro approach without reliance on a supply of human tissue. Stem Cells Translational Medicine 2017;6:761-766.
  4. Fulltext A Perspective Review on the Role of Nanomedicine in the Modulation of TNF-TNFR2 Axis in Breast Cancer Immunotherapy
    Al-Hatamleh MAI, Ahmad S, Boer JC, Lim J, Chen X, Plebanski M, et al.
    J Oncol, 2019;2019:6313242.
    PMID: 31239840 DOI: 10.1155/2019/6313242
    In the past decade, nanomedicine research has provided us with highly useful agents (nanoparticles) delivering therapeutic drugs to target cancer cells. The present review highlights nanomedicine applications for breast cancer immunotherapy. Recent studies have suggested that tumour necrosis factor (TNF) and its receptor 2 (TNFR2) expressed on breast cancer cells have important functional consequences. This cytokine/receptor interaction is also critical for promoting highly immune-suppressive phenotypes by regulatory T cells (Tregs). This review generally provides a background for nanoparticles as potential drug delivery agents for immunomodulators and further discusses in depth the potential of TNF antagonists delivery to modulate TNF-TNFR2 interactions and inhibit breast cancer progression.
  5. Fulltext A Polymer Blend Electrolyte Based on CS with Enhanced Ion Transport and Electrochemical Properties for Electrical Double Layer Capacitor Applications
    Aziz SB, Dannoun EMA, Hamsan MH, Ghareeb HO, Nofal MM, Karim WO, et al.
    Polymers (Basel), 2021 Mar 17;13(6).
    PMID: 33803001 DOI: 10.3390/polym13060930
    The fabrication of energy storage EDLC in this work is achieved with the implementation of a conducting chitosan-methylcellulose-NH4NO3-glycerol polymer electrolyte system. The simple solution cast method has been used to prepare the electrolyte. The impedance of the samples was fitted with equivalent circuits to design the circuit diagram. The parameters associated with ion transport are well studied at various plasticizer concentrations. The FTIR investigation has been done on the films to detect the interaction that occurs among plasticizer and polymer electrolyte. To get more insights into ion transport parameters, the FTIR was deconvoluted. The transport properties achieved from both impedance and FTIR are discussed in detail. It was discovered that the transport parameter findings are in good agreement with both impedance and FTIR studies. A sample with high transport properties was characterized for ion dominancy and stability through the TNM and LSV investigations. The dominancy of ions in the electrolyte verified as the tion of the electrolyte is established to be 0.933 whereas it is potentially stable up to 1.87 V. The rechargeability of the EDLC is steady up to 500 cycles. The internal resistance, energy density, and power density of the EDLC at the 1st cycle are 53 ohms, 6.97 Wh/kg, and 1941 W/kg, respectively.
  6. Fulltext A Review on Antimicrobial Packaging from Biodegradable Polymer Composites
    Kamarudin SH, Rayung M, Abu F, Ahmad S, Fadil F, Karim AA, et al.
    Polymers (Basel), 2022 Jan 02;14(1).
    PMID: 35012197 DOI: 10.3390/polym14010174
    The development of antimicrobial packaging has been growing rapidly due to an increase in awareness and demands for sustainable active packaging that could preserve the quality and prolong the shelf life of foods and products. The addition of highly efficient antibacterial nanoparticles, antifungals, and antioxidants to biodegradable and environmentally friendly green polymers has become a significant advancement trend for the packaging evolution. Impregnation of antimicrobial agents into the packaging film is essential for impeding or destroying the pathogenic microorganisms causing food illness and deterioration. Higher safety and quality as well as an extended shelf life of sustainable active packaging desired by the industry are further enhanced by applying the different types of antimicrobial packaging systems. Antimicrobial packaging not only can offer a wide range of advantages, but also preserves the environment through usage of renewable and biodegradable polymers instead of common synthetic polymers, thus reducing plastic pollution generated by humankind. This review intended to provide a summary of current trends and applications of antimicrobial, biodegradable films in the packaging industry as well as the innovation of nanotechnology to increase efficiency of novel, bio-based packaging systems.
  7. Fulltext A Study of Methylcellulose Based Polymer Electrolyte Impregnated with Potassium Ion Conducting Carrier: Impedance, EEC Modeling, FTIR, Dielectric, and Device Characteristics
    Nofal MM, Hadi JM, Aziz SB, Brza MA, Asnawi ASFM, Dannoun EMA, et al.
    Materials (Basel), 2021 Aug 26;14(17).
    PMID: 34500952 DOI: 10.3390/ma14174859
    In this research, a biopolymer-based electrolyte system involving methylcellulose (MC) as a host polymeric material and potassium iodide (KI) salt as the ionic source was prepared by solution cast technique. The electrolyte with the highest conductivity was used for device application of electrochemical double-layer capacitor (EDLC) with high specific capacitance. The electrical, structural, and electrochemical characteristics of the electrolyte systems were investigated using various techniques. According to electrochemical impedance spectroscopy (EIS), the bulk resistance (Rb) decreased from 3.3 × 105 to 8 × 102 Ω with the increase of salt concentration from 10 wt % to 40 wt % and the ionic conductivity was found to be 1.93 ×10-5 S/cm. The dielectric analysis further verified the conductivity trends. Low-frequency regions showed high dielectric constant, ε' and loss, ε″ values. The polymer-salt complexation between (MC) and (KI) was shown through a Fourier transformed infrared spectroscopy (FTIR) studies. The analysis of transference number measurement (TNM) supported ions were predominantly responsible for the transport process in the MC-KI electrolyte. The highest conducting sample was observed to be electrochemically constant as the potential was swept linearly up to 1.8 V using linear sweep voltammetry (LSV). The cyclic voltammetry (CV) profile reveals the absence of a redox peak, indicating the presence of a charge double-layer between the surface of activated carbon electrodes and electrolytes. The maximum specific capacitance, Cs value was obtained as 118.4 F/g at the sweep rate of 10 mV/s.
  8. Fulltext A curcumin derivative, 2,6-bis(2,5-dimethoxybenzylidene)-cyclohexanone (BDMC33) attenuates prostaglandin E2 synthesis via selective suppression of cyclooxygenase-2 in IFN-γ/LPS-stimulated macrophages
    Lee KH, Abas F, Alitheen NB, Shaari K, Lajis NH, Ahmad S
    Molecules, 2011 Nov 23;16(11):9728-38.
    PMID: 22113581 DOI: 10.3390/molecules16119728
    Our preliminary screening had shown that the curcumin derivative [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] or BDMC33 exhibited improved anti-inflammatory activity by inhibiting nitric oxide synthesis in activated macrophage cells. In this study, we further investigated the anti-inflammatory properties of BDMC33 on PGE(2 )synthesis and cyclooxygenase (COX) expression in IFN-γ/LPS-stimulated macrophages. We found that BDMC33 significantly inhibited PGE(2) synthesis in a concentration-dependent manner albeit at a low inhibition level with an IC(50) value of 47.33 ± 1.00 µM. Interestingly, the PGE(2) inhibitory activity of BDMC33 is not attributed to inhibition of the COX enzyme activities, but rather BDMC33 selectively down-regulated the expression of COX-2. In addition, BDMC33 modulates the COX expression by sustaining the constitutively COX-1 expression in IFN-γ/LPS-treated macrophage cells. Collectively, the experimental data suggest an immunodulatory action of BDMC33 on PGE(2) synthesis and COX expression, making it a possible treatment for inflammatory disorders with minimal gastrointestinal-related side effects.
  9. A profile of TNFR2+ regulatory T cells and CD103+ dendritic cells in the peripheral blood of patients with asthma
    Azid NA, Ahmad S, Boer JC, Al-Hatamleh MAI, Mohammad N, Mohd Ashari NS, et al.
    Hum Immunol, 2020 08 06;81(10-11):634-643.
    PMID: 32771274 DOI: 10.1016/j.humimm.2020.07.006
    The interaction of tolerogenic CD103+ dendritic cells (DCs) with regulatory T (Tregs) cells modulates immune responses by inducing immune tolerance. Hence, we determined the proportion of these cells in the peripheral blood mononuclear cells (PBMC) of asthmatic patients. We observed lower trends of CD11b-CD103+ DCs and CD86 within CD11b-CD103+ DCs, while increased levels of Foxp3 expressing CD25+/-TNFR2+ cells in asthmatics. There was a positive correlation in the expression of Foxp3 within CD3+CD4+CD25+TNFR2+ Tregs and CD11b-CD103+ as well as the expression of CD86 within HLA-DR+CD11c+CD11b-CD103+ DCs. In conclusion, we suggest that the increased levels of Tregs in blood could continuously suppress the T helper 2 (Th2) cells activation in the circulation which is also supported by the increase of anti-inflammatory cytokines IL-10 and TNF. Overall, functional immunoregulation of the regulatory cells, particularly Tregs, exhibit immune suppression and induce immune tolerance linked with the immune activation by the antigen presenting cells (APC).
  10. A randomized control trial evaluating the prevalence of obstetrical anal sphincter injuries in primigravida in routine versus selective mediolateral episiotomy
    Sulaiman AS, Ahmad S, Ismail NA, Rahman RA, Jamil MA, Mohd Dali AZ
    Saudi Med J, 2013 Aug;34(8):819-23.
    PMID: 23974453
    To evaluate the prevalence of obstetrical anal sphincter injuries (OASIS), which include third and fourth degree perineal tears in primigravida in routine versus selective mediolateral episiotomy. Secondly, to determine the rate of episiotomy in local settings.
  11. Fulltext A review: electrochemical performance of LSCF composite cathodes – influence of Ceria Electrolyte and metal elements
    Bakar, M. S. A., Ahmad, S., Muchtar, A., Rahman, H. A .
    Journal of Advanced Review on Scientific Research, 2014;1(1):1-9.
    MyJurnal
    Solid oxide fuel cells (SOFC) are efficient and clean power generation devices. Lowtemperature
    SOFC (LTSOFC) has been developed since high-temperature SOFC (HTSOFC) is not
    feasible to be commercialized due to cost. Lowering the operation temperature reduces its substantial
    performance resulting from cathode polarization resistance and overpotential of cathode. The
    development of composite cathodes regarding mixed ionic-electronic conductor (MIEC) and ceriabased
    materials for LTSOFC minimizes the problems significantly and leads to an increase in
    electrocatalytic activity for the occurrence of oxygen reduction reaction (ORR). Lanthanum-based
    materials such as lanthanum strontium cobalt ferrite (La0.6Sr0.4Co0.2Fe0.8O3-δ) have been discovered
    recently, which offer great compatibility with ceria-based electrolyte to be applied as composite
    cathode materials for LTSOFC. Cell performance at lower operating temperature can be maintained
    and further improved by enhancing the ORR. This paper reviews recent development of various ceriabased
    composite cathodes especially related to the ceria-carbonate composite electrolytes for
    LTSOFC. The influence of the addition of metallic elements such as silver (Ag), platinum (Pt) and
    palladium (Pd) towards the electrochemical properties and performance of LSCF composite cathodes
    are also discussed.
  12. Fulltext A tale of two boys: case report on nonconsanguineous siblings with cerebral palsy
    Leelavathi, M., Lim, J.L., Ahmad, S.
    Medicine & Health, 2014;9(1):74-79.
    MyJurnal
    Cerebral palsy is a common cause of childhood disability. It has a great impact on parents and caregivers, especially when it reoccurs in the same family. Although familial cerebral palsy is relatively uncommon, cases have been reported among children from consanguineous, non-consanguineous marriages and multiple pregnancies suggesting a possible complex genetic mode of inheritance. Physicians need to be aware of the possibility of familial cerebral palsy for early detection and counseling. We describe a rare case of two male siblings from a non-consanguineous marriage affected by cerebral palsy.
  13. Acetylsalicylic acid-sulfa drugs conjugates as potential urease inhibitors and anti-inflammatory agents: bio-oriented drug synthesis, molecular docking, and dynamics simulation studies
    Ahmad S, Abdul Qadir M, Ahmed M, Imran M, Yousaf N, Asari A, et al.
    J Biomol Struct Dyn, 2023 Aug 29.
    PMID: 37643014 DOI: 10.1080/07391102.2023.2252083
    To explore the new mode of action and reduce side effects, making conjugates of existing drugs is becoming an attractive tool in the realm of medicinal chemistry. In this work, we exploited this approach and synthesized new conjugates to assess their activities against the enzymes involved in different pathological conditions. Specifically, we design and synthesized conjugates involving acetylsalicylic acid and sulfa drugs, validating the newly crafted conjugates using techniques like IR, 1HNMR, 13CNMR, and elemental analysis. These conjugates underwent assessment for their ability to inhibit cyclooxygenase-2 (COX-2), urease enzymes, and their anti-inflammatory potential. A competitive mode of urease inhibition was observed for acetylsalicylic acid conjugated with sulfanilamide, sulfacetamide, and sulfadiazine with IC50 of 2.49 ± 0.35 µM, 6.21 ± 0.28 µM, and 6.57 ± 0.44 µM, respectively. Remarkably, the acetylsalicylic acid-sulfamethoxazole conjugate exhibited exceptional anti-inflammatory activity, effectively curtailing induced edema by 83.7%, a result akin to the reference anti-inflammatory drug indomethacin's performance (86.8%). Additionally, it demonstrated comparable COX-2 inhibition (75.8%) to the reference selective COX-2 inhibitor celecoxib that exhibited 77.1% inhibition at 10 µM concentration. To deepen our understanding, we employed molecular docking techniques to predict the binding interactions of competitive inhibitors with COX-2 and urease receptors. Additionally, MD simulations were carried out, confirming the stability of inhibitor-target complexes throughout the simulation period, devoid of significant conformational changes. Collectively, our research underscores the potential of coupling approved medicinal compounds to usher in novel categories of pharmacological agents, holding promise for addressing a wide spectrum of pathological disorders involving COX-2 and urease enzymes.Communicated by Ramaswamy H. Sarma.
  14. Fulltext Acute Oral, Subacute, and Developmental Toxicity Profiling of Naphthalene 2-Yl, 2-Chloro, 5-Nitrobenzoate: Assessment Based on Stress Response, Toxicity, and Adverse Outcome Pathways
    Anwar F, Saleem U, Rehman AU, Ahmad B, Ismail T, Mirza MU, et al.
    Front Pharmacol, 2021;12:810704.
    PMID: 35126145 DOI: 10.3389/fphar.2021.810704
    The U.S. National Research Council (NRC) introduced new approaches to report toxicity studies. The NRC vision is to explore the toxicity pathways leading to the adverse effects in intact organisms by the exposure of the chemicals. This study examines the toxicity profiling of the naphthalene-2-yl 2-chloro-5-dinitrobenzoate (SF5) by adopting the vision of NRC that moves from traditional animal studies to the cellular pathways. Acute, subacute, and developmental toxicity studies were assayed according to the Organization for Economic Cooperation and Development (OECD) guidelines. The stress response pathway, toxicity pathway, and adverse effects outcome parameters were analyzed by using their standard protocols. The results showed that the acute toxicity study increases the liver enzyme levels. In a subacute toxicity study, alkaline phosphatase (ALP) levels were raised in both male and female animals. SF5 significantly increases the normal sperm count in the male animals corresponding to a decrease in the abnormality count. Developmental toxicity showed the normal skeletal and morphological parameters, except little hydrocephalus was observed in developmental toxicity. Doses of 20 mg/kg in males and 4 mg/kg in females showed decreased glutathione (GSH) levels in the kidney and liver. MDA levels were also increased in the kidney and liver. However, histopathological studies did not show any cellular change in these organs. No statistical difference was observed in histamine levels, testosterone, nuclear factor erythroid two-related factor-2 (Nrf2), and nuclear factor-kappa B (NF-κB), which showed no initiation of the stress response, toxicity, and adverse effect pathways. Immunomodulation was observed at low doses in subacute toxicity studies. It was concluded that SF5 did not produce abrupt and high-toxicity levels in organs and biochemical parameters. So, it is safe for further studies.
  15. Advanced abdominal pregnancy resulting from late uterine rupture
    Naim NM, Ahmad S, Siraj HH, Ng P, Mahdy ZA, Razi ZR
    Obstet Gynecol, 2008 Feb;111(2 Pt 2):502-4.
    PMID: 18239000 DOI: 10.1097/01.AOG.0000279451.51446.c1
    Advanced abdominal pregnancy is rare, and one that occurs after uterine rupture with delivery of a viable fetus is exceptional.
  16. Fulltext Age-dependent atrial arrhythmic phenotype secondary to mitochondrial dysfunction in Pgc-1β deficient murine hearts
    Valli H, Ahmad S, Chadda KR, Al-Hadithi ABAK, Grace AA, Jeevaratnam K, et al.
    Mech Ageing Dev, 2017 Oct;167:30-45.
    PMID: 28919427 DOI: 10.1016/j.mad.2017.09.002
    INTRODUCTION: Ageing and several age-related chronic conditions including obesity, insulin resistance and hypertension are associated with mitochondrial dysfunction and represent independent risk factors for atrial fibrillation (AF).

    MATERIALS AND METHODS: Atrial arrhythmogenesis was investigated in Langendorff-perfused young (3-4 month) and aged (>12 month), wild type (WT) and peroxisome proliferator activated receptor-γ coactivator-1β deficient (Pgc-1β-/-) murine hearts modeling age-dependent chronic mitochondrial dysfunction during regular pacing and programmed electrical stimulation (PES).

    RESULTS AND DISCUSSION: The Pgc-1β-/- genotype was associated with a pro-arrhythmic phenotype progressing with age. Young and aged Pgc-1β-/- hearts showed compromised maximum action potential (AP) depolarization rates, (dV/dt)max, prolonged AP latencies reflecting slowed action potential (AP) conduction, similar effective refractory periods and baseline action potential durations (APD90) but shortened APD90 in APs in response to extrasystolic stimuli at short stimulation intervals. Electrical properties of APs triggering arrhythmia were similar in WT and Pgc-1β-/- hearts. Pgc-1β-/- hearts showed accelerated age-dependent fibrotic change relative to WT, with young Pgc-1β-/- hearts displaying similar fibrotic change as aged WT, and aged Pgc-1β-/- hearts the greatest fibrotic change. Mitochondrial deficits thus result in an arrhythmic substrate, through slowed AP conduction and altered repolarisation characteristics, arising from alterations in electrophysiological properties and accelerated structural change.

  17. Fulltext Age-dependent electrocardiographic changes in Pgc-1β deficient murine hearts
    Ahmad S, Valli H, Salvage SC, Grace AA, Jeevaratnam K, Huang CL
    Clin Exp Pharmacol Physiol, 2018 02;45(2):174-186.
    PMID: 28949414 DOI: 10.1111/1440-1681.12863
    Increasing evidence implicates chronic energetic dysfunction in human cardiac arrhythmias. Mitochondrial impairment through Pgc-1β knockout is known to produce a murine arrhythmic phenotype. However, the cumulative effect of this with advancing age and its electrocardiographic basis have not been previously studied. Young (12-16 weeks) and aged (>52 weeks), wild type (WT) (n = 5 and 8) and Pgc-1β-/- (n = 9 and 6), mice were anaesthetised and used for electrocardiographic (ECG) recordings. Time intervals separating successive ECG deflections were analysed for differences between groups before and after β1-adrenergic (intraperitoneal dobutamine 3 mg/kg) challenge. Heart rates before dobutamine challenge were indistinguishable between groups. The Pgc-1β-/- genotype however displayed compromised nodal function in response to adrenergic challenge. This manifested as an impaired heart rate response suggesting a functional defect at the level of the sino-atrial node, and a negative dromotropic response suggesting an atrioventricular conduction defect. Incidences of the latter were most pronounced in the aged Pgc-1β-/- mice. Moreover, Pgc-1β-/- mice displayed electrocardiographic features consistent with the existence of a pro-arrhythmic substrate. Firstly, ventricular activation was prolonged in these mice consistent with slowed action potential conduction and is reported here for the first time. Additionally, Pgc-1β-/- mice had shorter repolarisation intervals. These were likely attributable to altered K+ conductance properties, ultimately resulting in a shortened QTc interval, which is also known to be associated with increased arrhythmic risk. ECG analysis thus yielded electrophysiological findings bearing on potential arrhythmogenicity in intact Pgc-1β-/- systems in widespread cardiac regions.
  18. Fulltext Ageing in Pgc-1β-/- mice modelling mitochondrial dysfunction induces differential expression of a range of genes regulating ventricular electrophysiology
    Edling CE, Fazmin IT, Chadda KR, Ahmad S, Valli H, Grace AA, et al.
    Biosci Rep, 2019 04 30;39(4).
    PMID: 30914453 DOI: 10.1042/BSR20190127
    Mice deficient in mitochondrial promoter peroxisome proliferator activated receptor-γ co-activator-1β (Pgc-1β-/- ) is a valuable model for metabolic diseases and has been found to present with several pathologies including ventricular arrhythmia. In the present study, our aim was to shed light on the molecular mechanisms behind the observed arrhythmic substrate by studying how the expression of selected genes critical for cardiac function differs in wild-type (WT) compared with Pgc-1β knockout mice and young compared with aged mice. We found that a clear majority of genes are down-regulated in the Pgc-1β-/- ventricular tissue compared with the WT. Although most individual genes are not significantly differentially expressed, a pattern is apparent when the genes are grouped according to their functional properties. Genes encoding proteins relating to ATPase activity, potassium ion channels relating to repolarisation and resting membrane potential, and genes encoding proteins in the cAMP pathway are found to be significantly down-regulated in the Pgc-1β deficient mice. On the contrary, the pacemaker channel genes Hcn3 and Hcn4 are up-regulated in subsets of the Pgc-1β deficient tissue. Furthermore, we found that with age, especially in the Pgc-1β-/- genotype, most genes are up-regulated including genes relating to the resting membrane potential, calcium homeostasis, the cAMP pathway, and most of the tested adrenoceptors. In conclusion, we here demonstrate how a complex pattern of many modest changes at gene level may explain major functional differences of the action potential related to ageing and mitochondrial dysfunction.
  19. Fulltext Alteration in morphological features of Puntius javanicus liver exposed to copper sulfate
    Sabullah, M. K., Gansau, A. J., Ahmad, S. A., Shamaan, N. A., Khalid, A., Sulaiman, M. R.
    International Food Research Journal, 2017;24(3):1314-1320.
    MyJurnal
    The environmental toxicants such as copper are known to affect vital organ especially liver.
    This study examined the effects of copper sulfate (CuSO4) on the liver morphological structure
    of P. javanicus. The untreated control, 0.1 and 0.3 mg/L CuSO4 treated groups displayed normal
    polygonal structure of the hepatocyte. However, at the concentrations of 0.5, 1.0 and 5.0 mg/L
    CuSO4, the hepatostructure was significantly affected, as shown by the increasing number of
    dilation and congestion of sinusoids, vacuolation, macrophage activities and peliosis. The
    damage level and HSI value were increased while the number of hepatic nuclei per mm2 was
    decreased with the increasing of copper concentration. In conclusion, this study shows that the
    degree of liver damage in P.javanicus is dependent to the dose exposure.
  20. Fulltext Alterations in Herbage Yield, Antioxidant Activities, Phytochemical Contents, and Bioactive Compounds of Sabah Snake Grass (Clinacanthus Nutans L.) with Regards to Harvesting Age and Harvesting Frequency
    Abd Samat NMA, Ahmad S, Awang Y, Bakar RAH, Hakiman M
    Molecules, 2020 Jun 19;25(12).
    PMID: 32575450 DOI: 10.3390/molecules25122833
    Sabah snake grass or Clinacanthus nutans has drawn public interest having significant economic benefits attributable to the presence of phytochemicals and several interesting bioactive constituents that may differ according to harvesting age and harvesting frequency. The current study was aimed to evaluate the effect of harvesting age and harvesting frequency towards herbal yield, antioxidant activities, phytochemicals synthesis, and bioactive compounds of C. nutans. A factorial randomized completely block design with five replications was used to illustrate the relationship between herbal yield, DPPH (2, 2-diphenyl-1-picrylhydrazyl) and ferric reducing antioxidant power (FRAP) assays, total phenolic and flavonoid content affected by harvesting age (week 8, 12, and 16 after transplanting), and harvesting frequency (harvest 1, 2, and 3). The bioactive compounds by HPLC were also determined to describe the interaction effect between both harvesting age and harvesting frequency. The yield, antioxidant activities, and phytochemical contents were gradually increased as the plant grew, with the highest recorded during week 16. However, the synthesis and activities of phytochemicals were reduced in subsequent harvests despite the increment of the herbal yield. All bioactive compounds were found to be influenced insignificantly and significantly by harvesting age and harvesting frequency, respectively, specifically to shaftoside, iso-orientin, and orientin. Among all constituents, shaftoside was the main compound at various harvesting ages and harvesting frequencies. These results indicated that harvesting at week 16 with 1st harvest frequency might enhance the yield while sustaining the high synthesis of polyphenols and antioxidant activities of C. nutans.
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