Displaying publications 1 - 20 of 179 in total

Abstract:
Sort:
  1. Metallointercalator [Ru(dppz)2(PIP)]2+ Renders BRCA Wild-Type Triple-Negative Breast Cancer Cells Hypersensitive to PARP Inhibition
    Yusoh NA, Leong SW, Chia SL, Harun SN, Rahman MBA, Vallis KA, et al.
    ACS Chem. Biol., 2020 02 21;15(2):378-387.
    PMID: 31898884 DOI: 10.1021/acschembio.9b00843
    There is a need to improve and extend the use of clinically approved poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi), including for BRCA wild-type triple-negative breast cancer (TNBC). The demonstration that ruthenium(II) polypyridyl complex (RPC) metallointercalators can rapidly stall DNA replication fork progression provides the rationale for their combination alongside DNA damage response (DDR) inhibitors to achieve synergism in cancer cells. The aim of the present study was to evaluate use of the multi-intercalator [Ru(dppz)2(PIP)]2+ (dppz = dipyrido[3,2-a:2',3'-c]phenazine, PIP = (2-(phenyl)imidazo[4,5-f][1,10]phenanthroline, Ru-PIP) alongside the PARPi olaparib and NU1025. Cell proliferation and clonogenic survival assays indicated a synergistic relationship between Ru-PIP and olaparib in MDA-MB-231 TNBC and MCF7 human breast cancer cells. Strikingly, low dose Ru-PIP renders both cell lines hypersensitive to olaparib, with a >300-fold increase in olaparib potency in TNBC, the largest nongenetic PARPi enhancement effect described to date. A negligible impact on the viability of normal human fibroblasts was observed for any combination tested. Increased levels of DNA double-strand break (DSB) damage and olaparib abrogation of Ru-PIP-activated pChk1 signaling are consistent with PARPi-facilitated collapse of Ru-PIP-associated stalled replication forks. This results in enhanced G2/M cell-cycle arrest, apoptosis, and decreased cell motility for the combination treatment compared to single-agent conditions. This work establishes that an RPC metallointercalator can be combined with PARPi for potent synergy in BRCA-proficient breast cancer cells, including TNBC.
  2. Fulltext SOA-based multi-wavelength source
    Harun, S.W., Sulaiman, A.H., Ahmad, H.
    ASM Science Journal, 2009;3(1):27-30.
    MyJurnal
    We demonstrate a multi-wavelength light source using a semiconductor optical amplifier (SOA) in conjunction with an array waveguide grating (AWG). The experimental results showed more than 20 channels with a wavelength separation of 0.8 nm and an optical signal-to-noise ratio of more than 10 dB under room temperature. The channels operated at the wavelength region from 1530.4 nm to 1548.6 nm, which corresponded to AWG filtering wavelengths with SOA drive current of 350 mA. The proposed light source had the advantages of a simple and compact structure, multi-wavelength operation and the system could be upgraded to generate more wavelengths.
  3. Fulltext An erbium/ytterbium co-doped fibre amplifier using 1058 nm pumping
    Harun, S.W., Tamjis, M.R., Muhd-Yassin, S.Z., Abd-Rahman, M.K., Ahmad, H.
    ASM Science Journal, 2007;1(2):129-133.
    MyJurnal
    This paper demonstrates an erbium/ytterbium co-doped fi bre amplifi er (EYDFA) which used a pumping wavelength of 1058 nm, whereby the amplifi cation was assisted by the energy transfer between Yb and Er ions. The energy transfer increased the erbium doping concentration limit that was imposed by concentration quenching in erbium-doped fi bre. The optimum length was obtained at 4m~6m for erbium/ytterbium co-doped fi bre with Er ion concentration of 1000 p.p.m. This enabled the development of a compact amplifi er with a shorter gain medium compared to erbium-doped fi bre amplifi ers which use a gain medium of up to 15 m. A 1058 nm pumping wave-length was used for the EYDFA, as 1480 nm pumping resulted in severely degraded gain and noise fi gures because the energy transfer could not be achieved. The use of the optical isolator improved the small signal gain and noise fi gure by about 4.8 dB and 1.6 dB, respectively. Without the isolator, gain saturation and a noise fi gure penalty were observed due to the oscillating laser which was created at around 1534 nm by spurious refl ection. This showed that the usage of optical isolators was an important aspect to consider when designing an EYDFA.
  4. Fulltext Er3+/Yb3+ co-doped fibre amplifier demonstrates significant gain enhancement with improved noise figure
    Muhd-Yassin, S.Z., Harun, S.W., Ahmad, H., Abd-Rahman, M.K.
    ASM Science Journal, 2008;2(2):163-168.
    MyJurnal
    An efficient erbium/ytterbium co-doped fibre amplifier was demonstrated by using a dual-stage partial doublepass structure with a band-pass filter (BPF). The amplifier achieved the maximum small signal gain of 56 dB and the corresponding noise figure of 4.66 dB at 1536 nm with an input signal power and total pump power of –50 dBm and 140 mW, respectively. Compared with a conventional single-stage amplifier, the maximum gain enhancement of 16.99 dB was obtained at 1544 nm with the corresponding noise figure was improved by 2 dB. The proposed amplifier structure only used a single pump source with a partial double pass scheme to provide a high gain and dual-stage structure to provide the low noise figure.
  5. Fulltext Distributed feedback Er-Yb co-doped phosphate fibre laser
    Harun, S.W., Hofmann, P., Schulzgen, A., Li, L., Peyghambarian, N., Ahmad, H.
    ASM Science Journal, 2008;2(2):149-152.
    MyJurnal
    A distributed feedback fibre laser made of highly Er-Yb co-doped phosphate glass fibre was demonstrated experimentally. The 45 mm long fibre laser device operated at 1540 nm with more than 50 dB side mode suppression ratio. However, the output power was still relatively lower due to un-optimized grating structure and thermal management.
  6. Occurrence of a mosquito vector in bird houses: Developmental consequences and potential epidemiological implications
    Dieng H, Hassan RB, Hassan AA, Ghani IA, Abang FB, Satho T, et al.
    Acta Trop, 2015 May;145:68-78.
    PMID: 25617636 DOI: 10.1016/j.actatropica.2015.01.004
    Even with continuous vector control, dengue is still a growing threat to public health in Southeast Asia. Main causes comprise difficulties in identifying productive breeding sites and inappropriate targeted chemical interventions. In this region, rural families keep live birds in backyards and dengue mosquitoes have been reported in containers in the cages. To focus on this particular breeding site, we examined the capacity of bird fecal matter (BFM) from the spotted dove, to support Aedes albopictus larval growth. The impact of BFM larval uptake on some adult fitness traits influencing vectorial capacity was also investigated. In serial bioassays involving a high and low larval density (HD and LD), BFM and larval standard food (LSF) affected differently larval development. At HD, development was longer in the BFM environment. There were no appreciable mortality differences between the two treatments, which resulted in similar pupation and adult emergence successes. BFM treatment produced a better gender balance. There were comparable levels of blood uptake and egg production in BFM and LSF females at LD; that was not the case for the HD one, which resulted in bigger adults. BFM and LSF females displayed equivalent lifespans; in males, this parameter was shorter in those derived from the BFM/LD treatment. Taken together these results suggest that bird defecations successfully support the development of Ae. albopictus. Due to their cryptic aspects, containers used to supply water to encaged birds may not have been targeted by chemical interventions.
  7. Indirect effects of cigarette butt waste on the dengue vector Aedes aegypti (Diptera: Culicidae)
    Dieng H, Rajasaygar S, Ahmad AH, Rawi CS, Ahmad H, Satho T, et al.
    Acta Trop, 2014 Feb;130:123-30.
    PMID: 24239749 DOI: 10.1016/j.actatropica.2013.11.001
    Despite major insecticide-based vector control programs, dengue continues to be a major threat to public health in urban areas. The reasons for this failure include the emergence of insecticide resistance and the narrowing of the spectrum of efficient products. Cigarette butts (CBs), the most commonly discarded piece of waste, also represent a major health hazard to human and animal life. CBs are impregnated with thousands of chemical compounds, many of which are highly toxic and none of which has history of resistance in mosquitoes. This study was performed to examine whether exposure to CB alters various biological parameters of parents and their progeny. We examined whether the mosquito changes its ovipositional behaviors, egg hatching, reproductive capacity, longevity and fecundity in response to CB exposure at three different concentrations. Females tended to prefer microcosms containing CBs for egg deposition than those with water only. There were equivalent rates of eclosion success among larvae from eggs that matured in CB and water environments. We also observed decreased life span among adults that survived CB exposure. Extracts of CB waste have detrimental effects on the fecundity and longevity of its offspring, while being attractive to its gravid females. These results altogether indicate that CB waste indirectly affect key adult life traits of Aedes aegypti and could conceivably be developed as a novel dengue vector control strategy, referring to previously documented direct toxicity on the larval stage. But this will require further research on CB waste effects on non-target organisms including humans.
  8. Turning cigarette butt waste into an alternative control tool against an insecticide-resistant mosquito vector
    Dieng H, Rajasaygar S, Ahmad AH, Ahmad H, Rawi CS, Zuharah WF, et al.
    Acta Trop, 2013 Dec;128(3):584-90.
    PMID: 23999373 DOI: 10.1016/j.actatropica.2013.08.013
    Annually, 4.5 trillion cigarette butts (CBs) are flicked into our environment. Evidence exists that CB waste is deadly to aquatic life, but their lethality to the aquatic life of the main dengue vector is unknown. CBs are full of toxicants that occur naturally, during planting and manufacturing, which may act as larvicidal agents. We assessed Aedes aegypti vulnerability to Marlboro butts during its development. Overall, CBs showed insecticidal activities against larvae. At early phases of development, mortality rates were much higher in two CBs solution (2CBSol) and 3CBSol microcosms (MICRs). Larval survival gradually decreased with development in 1CBSol-MICRs. However, in great presence of CBs, mortality was high even for the late developmental stages. These results suggest that A. aegypti larvae are vulnerable to CB presence in their habitats, but this effect was seen most during the early developmental phases and in the presence of increased amounts of cigarette remnants. CB filters are being used as raw material in many sectors, i.e., brick, art, fashion, plastic industries, as a practical solution to the pollution problem, the observed butt waste toxicity to mosquito larvae open new avenues for the identification of novel insecticide products.
  9. A new antigen detection ELISA for the diagnosis of Strongyloides infection
    Balachandra D, Rahumatullah A, Lim TS, Mustafa FH, Ahmad H, Anuar NS, et al.
    Acta Trop, 2021 Sep;221:105986.
    PMID: 34058161 DOI: 10.1016/j.actatropica.2021.105986
    Serodiagnosis is an essential component of the laboratory diagnosis of Strongyloides infection and is usually performed using an indirect IgG antibody test. A direct antigen detection method can complement the IgG assay, particularly for detecting early infection and post-treatment follow-up. In the present study, a recombinant scFv monoclonal antibody against NIE recombinant protein (rMAb23) that we had previously produced was used to develop a Strongyloides antigen detection ELISA (SsAg-ELISA). The assay is based on detecting immune complexes of circulating NIE antigens bound to Strongyloides-specific IgG antibodies. The optimized ELISA parameters were 10 µg/mL of rMAb23 coated on microtitre plate wells, 2% skim milk as blocking reagent, 1:100 serum dilution, and 1:1000 goat anti-human IgG F(ab')2 conjugated to horseradish peroxidase. Four groups of serum samples were used, i.e., Strongyloides-positive serum samples categorized into Groups IA and IB; the former were from probable chronic infections and the latter from probable early/acute infections. Strongyloides-negative samples comprising Groups II (healthy samples) and III (other infections); the latter were from eleven different types of other parasitic infections. The receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 1.00, cut-off optical density (OD405) of 0.5002, and 100% diagnostic sensitivity and specificity. The results of the commercial IgG-ELISA and SsAg-ELISA from Group IA were found to be moderately correlated (r = 0.416; p 
  10. Sweet waste extract uptake by a mosquito vector: Survival, biting, fecundity responses, and potential epidemiological significance
    Dieng H, Satho T, Abang F, Meli NKKB, Ghani IA, Nolasco-Hipolito C, et al.
    Acta Trop, 2017 May;169:84-92.
    PMID: 28174057 DOI: 10.1016/j.actatropica.2017.01.022
    In nature, adult mosquitoes typically utilize nectar as their main energy source, but they can switch to other as yet unidentified sugary fluids. Contemporary lifestyles, with their associated unwillingness to consume leftovers and improper disposal of waste, have resulted in the disposal of huge amounts of waste into the environment. Such refuse often contains unfinished food items, many of which contain sugar and some of which can collect water from rain and generate juices. Despite evidence that mosquitoes can feed on sugar-rich suspensions, semi-liquids, and decaying fruits, which can be abundant in garbage sites, the impacts of sweet waste fluids on dengue vectors are unknown. Here, we investigated the effects of extracts from some familiar sweet home waste items on key components of vectorial capacity of Aedes aegypti. Adult mosquitoes were fed one of five diets in this study: water (WAT); sucrose (SUG); bakery product (remnant of chocolate cake, BAK); dairy product (yogurt, YOG); and fruit (banana (BAN). Differences in survival, response time to host, and egg production were examined between groups. For both males and females, maintenance on BAK extract resulted in marked survival levels that were similar to those seen with SUG. Sweet waste extracts provided better substrates for survival compared to water, but this superiority was mostly seen with BAK. Females maintained on BAK, YOG, and BAN exhibited shorter response times to a host compared to their counterparts maintained on SUG. The levels of egg production were equivalent in waste extract- and SUG-fed females. The findings presented here illustrate the potential of sweet waste-derived fluids to contribute to the vectorial capacity of dengue vectors and suggest the necessity of readdressing the issue of waste disposal, especially that of unfinished sweet foods. Such approaches can be particularly relevant in dengue endemic areas where rainfall is frequent and waste collection infrequent.
  11. Fulltext Ethnopharmacology, Biological Evaluation, and Chemical Composition of Ziziphus spina-christi (L.) Desf.: A Review
    Abdulrahman MD, Zakariya AM, Hama HA, Hamad SW, Al-Rawi SS, Bradosty SW, et al.
    Adv Pharmacol Pharm Sci, 2022;2022:4495688.
    PMID: 35677711 DOI: 10.1155/2022/4495688
    Medicinal plants are the primary raw materials used in the production of medicinal products all over the world. As a result, more study on plants with therapeutic potential is required. The tropical tree Ziziphus spina belongs to the Rhamnaceae family. Biological reports and traditional applications including management of diabetes and treatment of malaria, digestive issues, typhoid, liver complaints, weakness, skin infections, urinary disorders, obesity, diarrhoea, and sleeplessness have all been treated with different parts of Z. spina all over the globe. The plant is identified as a rich source of diverse chemical compounds. This study is a comprehensive yet detailed review of Z. spina based on major findings from around the world regarding ethnopharmacology, biological evaluation, and chemical composition. Scopus, Web of Science, BioMed Central, ScienceDirect, PubMed, Springer Link, and Google Scholar were searched to find published articles. From the 186 research articles reviewed, we revealed the leaf extract to be significant against free radicals, microbes, parasites, inflammation-related cases, obesity, and cancer. Chemically, polyphenols/flavonoids were the most reported compounds with a composition of 66 compounds out of the total 193 compounds reported from different parts of the plant. However, the safety and efficacy of Z. spina have not been wholly assessed in humans, and further well-designed clinical trials are needed to corroborate preclinical findings. The mechanism of action of the leaf extract should be examined. The standard dose and safety of the leaf should be established.
  12. Angiogenic and wound healing potency of fermented virgin coconut oil: in vitro and in vivo studies
    Ibrahim AH, Li H, Al-Rawi SS, Majid ASA, Al-Habib OA, Xia X, et al.
    Am J Transl Res, 2017;9(11):4936-4944.
    PMID: 29218091
    OBJECTIVE: The process of wound healing involves activation of keratinocytes, fibroblasts, endothelial cells, etc. Angiogenesis is crucial during the process of wound healing. Virgin coconut oil is widely utilized in South Asia for various purposes including food, medicinal and industrial applications. This study aimed to evaluate the potency of fermented virgin coconut oil (FVCO) in angiogenesis and wound healing via both in vitro and in vivo assays.

    METHODS: Human umbilical vein endothelial (HUVEC), fibroblast (CCD-18) and retinal ganglion (RGC-5) cells were cultured in medium containing different concentrations of FVCO. The proliferation, migration and morphological changes of cells were determined. The angiogenic effect of FVCO was evaluated by rat aortic assay. The therapeutic effect of FVCO on wound healing was further assessed in a wound excision model in Sprague Dawley rats. The expression of phospho-VEGFR2 (vascular endothelial growth factor receptor 2) in HUVECs was detected by Western blot.

    RESULTS: FVCO (6 and 12 µg/mL) significantly improved the proliferation of HUVEC, CCD-18 and RGC-5 cells (P < 0.05 or 0.01). FVCO (25 µg/mL) markedly increased the migration ability of CCD-18 and RGC-5 cells (P < 0.05). FVCO did not affect cell morphology as indicated by fluorescein diacetate (FDA), rhodamine 123 and Hoechst staining. FVCO (25, 50 and 100 µg/mL) significantly stimulated the ex vivo blood vessel formation as compared with negative control (P < 0.05). Rats in FVCO group had significantly smaller wound size, higher wound healing percentage, and shorter wound closure time when compared with control group since day 8 (P < 0.05), suggesting that oral FVCO administration notably promoted the wound healing process. FVCO treatment (6 and 12 µg/mL) significantly enhanced the phospho-VEGFR2 expression in HUVECs (P = 0.006 and 0.000, respectively).

    CONCLUSION: Our study confirms a high angiogenic and wound healing potency of FVCO that might be mediated by the regulation of VEGF signing pathway.

  13. Fulltext The Impact of Feed Supplementations on Asian Buffaloes: A Review
    Mohd Azmi AF, Ahmad H, Mohd Nor N, Goh YM, Zamri-Saad M, Abu Bakar MZ, et al.
    Animals (Basel), 2021 Jul 07;11(7).
    PMID: 34359160 DOI: 10.3390/ani11072033
    With the increase in the global buffalo herd, the use of supplementation in the ruminant feeding has become an important area for many researchers who are looking for an isocaloric and isonitrogenous diet to improve production parameters. In order to improve the performance of the Asian water buffalo, the optimal balance of all nutrients, including energy and protein, are important as macronutrients. Dietary supplementation is one of the alternatives to enhance the essential nutrient content in the buffalo diet and to improve the rumen metabolism of the animal. Researchers have found that supplementation of concentrate and rumen bypass fat could change growth performance and carcass traits without causing any adverse effects on the buffalo growth. Some studies showed that dry matter intake, body condition score and some blood parameters and hormones related to growth responded positively to concentrate and rumen bypass fat supplementation. In addition, changes of feeding management by adding the supplement to the ruminant basal diet helped to increase the profit of the local farmers due to the increased performance and productivity of the animals. Nevertheless, the effects of dietary supplementation on the performance of ruminants are inconsistent. Thus, its long-term effects on the health and productivity of buffaloes still need to be further investigated.
  14. Fulltext Effects of Concentrate and Bypass Fat Supplementations on Growth Performance, Blood Profile, and Rearing Cost of Feedlot Buffaloes
    Mohd Azmi AF, Ahmad H, Mohd Nor N, Meng GY, Saad MZ, Abu Bakar MZ, et al.
    Animals (Basel), 2021 Jul 15;11(7).
    PMID: 34359233 DOI: 10.3390/ani11072105
    This study investigates the effects of supplementation of the basal diet with concentrate and rumen bypass fat on the dry matter intake (DMI), growth performance, blood metabolites and hormonal changes, and the feeding cost of feedlot water buffaloes. Thirty-six healthy, three- to four-month-old male Murrah crossbred (n = 18) and Swamp (n = 18) buffaloes with a similar average initial body weight of 98.64 ± 1.93 kg were each randomly allocated into three dietary experimental groups. Buffaloes were fed with Diet A, which consisted of 100% Brachiaria decumbens, Diet B, consisting of 70% Brachiaria decumbens and 30% concentrate, and Diet C, consisting of 70% Brachiaria decumbens, 26% concentrate, and 4% rumen bypass fat for a period of 730 days. Feed intake was measured daily, while blood samples were collected for every eight months. Furthermore, body scores were noted prior to and at the end of the experimental period. The results showed that the average daily gain for buffaloes fed with Diet C was the highest. The DMI, BCS, FI, and FCR for the three groups showed significant (p < 0.05) differences, in the following order: Diet C > Diet B > Diet A. At the end of the two-year feeding trial, buffaloes fed with Diet B had significantly (p < 0.05) higher cholesterol levels than Diet A and Diet C. In addition, buffaloes fed with Diet C had significantly (p < 0.05) higher levels of serum total protein, growth hormone, and insulin-like growth factor-I hormone compared to Diet A and Diet B. On the other hand, buffaloes fed with Diet B and Diet C showed significant (p < 0.05) decrease in glucose levels. Supplemented diet improved the buffalos' weight gain to achieve the market weight in a shorter period of time, thus, giving farmers a greater return. In conclusion, concentrate and bypass fat supplementations in the diet of water buffaloes improved the growth performance without adverse effect on the blood metabolites, which enabled better farmer profitability.
  15. Fulltext Blood Profiling of Captive and Semi-Wild False Gharial in Peninsular Malaysia
    Latip MQA, Tengku Azizan TRP, Ahmad H, Abu Hassim H, Noor MHM, Mikail M
    Animals (Basel), 2021 May 21;11(6).
    PMID: 34063794 DOI: 10.3390/ani11061481
    The involvement of veterinary medicine in wildlife research has played an important role in understanding the health status of various wildlife species. Health status is a very important aspect of species conservation. However, it requires a widely employed knowledge of veterinary clinical pathology, as a diagnostic tool in diagnosing the various disease conditions of wildlife species. Notwithstanding, a gap exists in the literature about the clinical pathology of the false gharial, due to the lack of normal reference values for hematological and serum biochemical analysis. The present study investigated the normal blood profile of 10 healthy false gharials, from two different zoos, and wildlife conservation centers located in three different states of Peninsular Malaysia. Blood samples were collected from the lateral caudal vein and divided into a vacutainer without anticoagulant for biochemical analysis, and a lithium heparin vacutainer (containing sodium heparin) for hematological studies. The results of the study indicated that the false gharial has a smaller erythrocyte dimension compared to other crocodilian species. At the same time the study revealed that the false gharial in a natural captive pond showed more leukocytes than false gharial kept in zoos, hence, habitat and environmental factors significantly affect hematological values. The biochemistry values also showed differences between the false gharial in different environmental conditions. Total protein, albumin (Alb), globulin (Glob), and Alb: Glob ratio were higher in false gharials kept in wildlife conservation centers than in false gharials kept in zoos. The values obtained in this study provide baseline data of hematological and serum biochemical values of the false gharial for future research and routine clinical diagnosis.
  16. Differential receptor dependencies: expression and significance of muscarinic M1 receptors in the biology of prostate cancer
    Mannan Baig A, Khan NA, Effendi V, Rana Z, Ahmad HR, Abbas F
    Anticancer Drugs, 2017 01;28(1):75-87.
    PMID: 27606721
    Recent reports on acetylcholine muscarinic receptor subtype 3 (CHRM3) have shown its growth-promoting role in prostate cancer. Additional studies report the proliferative effect of the cholinergic agonist carbachol on prostate cancer by its agonistic action on CHRM3. This study shows that the type 1 acetylcholine muscarinic receptor (CHRM1) contributes toward the proliferation and growth of prostate cancer. We used growth and cytotoxic assays, the prostate cancer microarray database and CHRM downstream pathways' homology of CHRM subtypes to uncover multiple signals leading to the growth of prostate cancer. Growth assays showed that pilocarpine stimulates the proliferation of prostate cancer. Moreover, it shows that carbachol exerts an additional agonistic action on nicotinic cholinergic receptor of prostate cancer cells that can be blocked by tubocurarine. With the use of selective CHRM1 antagonists such as pirenzepine and dicyclomine, a considerable inhibition of proliferation of prostate cancer cell lines was observed in dose ranging from 15-60 µg/ml of dicyclomine. The microarray database of prostate cancer shows a dominant expression of CHRM1 in prostate cancer compared with other cholinergic subtypes. The bioinformatics of prostate cancer and CHRM pathways show that the downstream signalling include PIP3-AKT-CaM-mediated growth in LNCaP and PC3 cells. Our study suggests that antagonism of CHRM1 may be a potential therapeutic target against prostate cancer.
  17. Fulltext Pharmacotherapeutic Potential of Natural Products to Target the SARS-CoV-2 PLpro Using Molecular Screening and Simulation Approaches
    Sayaf AM, Ahmad H, Aslam MA, Ghani SA, Bano S, Yousafi Q, et al.
    Appl Biochem Biotechnol, 2023 Nov;195(11):6959-6978.
    PMID: 36961512 DOI: 10.1007/s12010-023-04466-1
    Because of the essential role of PLpro in the regulation of replication and dysregulation of the host immune sensing, it is considered a therapeutic target for novel drug development. To reduce the risk of immune evasion and vaccine effectiveness, small molecular therapeutics are the best complementary approach. Hence, we used a structure-based drug-designing approach to identify potential small molecular inhibitors for PLpro of SARS-CoV-2. Initial scoring and re-scoring of the best hits revealed that three compounds NPC320891 (2,2-Dihydroxyindene-1,3-Dione), NPC474594 (Isonarciclasine), and NPC474595 (7-Deoxyisonarciclasine) exhibit higher docking scores than the control GRL0617. Investigation of the binding modes revealed that alongside the essential contacts, i.e., Asp164, Glu167, Tyr264, and Gln269, these molecules also target Lys157 and Tyr268 residues in the active site. Moreover, molecular simulation demonstrated that the reported top hits also possess stable dynamics and structural packing. Furthermore, the residues' flexibility revealed that all the complexes demonstrated higher flexibility in the regions 120-140, 160-180, and 205-215. The 120-140 and 160-180 lie in the finger region of PLpro, which may open/close during the simulation to cover the active site and push the ligand inside. In addition, the total binding free energy was reported to be - 32.65 ± 0.17 kcal/mol for the GRL0617-PLpro, for the NPC320891-PLpro complex, the TBE was - 35.58 ± 0.14 kcal/mol, for the NPC474594-PLpro, the TBE was - 43.72 ± 0.22 kcal/mol, while for NPC474595-PLpro complex, the TBE was calculated to be - 41.61 ± 0.20 kcal/mol, respectively. Clustering of the protein's motion and FEL further revealed that in NPC474594 and NPC474595 complexes, the drug was seen to have moved inside the binding cavity along with the loop in the palm region harboring the catalytic triad, thus justifying the higher binding of these two molecules particularly. In conclusion, the overall results reflect favorable binding of the identified hits strongly than the control drug, thus demanding in vitro and in vivo validation for clinical purposes.
  18. Direct period measurement for fiber Bragg grating using an optical imaging technique
    Ali MM, Lim KS, Yang HZ, Chong WY, Lim WS, Ahmad H
    Appl Opt, 2013 Aug 1;52(22):5393-7.
    PMID: 23913056 DOI: 10.1364/AO.52.005393
    This paper proposes an approach based on an optical imaging technique for the period measurement of fiber Bragg gratings (FBG). The simple, direct technique involves a differential interface contrast (DIC) microscope and a high-resolution CCD camera. Image processing is performed on the microscope images to obtain low-noise grating profiles and then the grating periods. Adopting a large image sample size in the image processing can reduce uncertainty. During the investigation, FBGs of different grating periods are fabricated by prestraining the photosensitive fibers during the UV-writing process. A good linearity between the measured Bragg wavelengths and grating periods is observed and the measured strain-optics coefficient was found to be in agreement with reported literature.
  19. S-band multiwavelength Brillouin/Raman distributed Bragg reflector fiber lasers
    Zulkifli MZ, Ahmad H, Taib JM, Muhammad FD, Dimyati K, Harun SW
    Appl Opt, 2013 Jun 1;52(16):3753-6.
    PMID: 23736330 DOI: 10.1364/AO.52.003753
    A multiwavelength Brillouin/Raman distributed Bragg reflector fiber laser operating in the S-band region is proposed and demonstrated. The laser uses a 7.7 km long dispersion-shifted fiber with an effective mode area of 15 μm(2) as the Brillouin and Raman gain media simultaneously. Two 1420 nm laser diodes with a combined power of 372 mW are used as pump sources, while a fiber Bragg grating with a center wavelength of 1500 nm is used as a reflector in the cavity. The setup is capable of generating 6 clearly defined Stokes lines at the highest pump power, spanning from 1499.8 to 1500.3 nm with the even Stokes having relatively higher peak powers, between 1.4 and 3.5 dBm as compared to the odd Stokes, which have peak powers between -4.7 and -5.0 dBm. The output of the laser is very stable and shows little to no fluctuations over a monitoring period of 50 min.
  20. S-band multiwavelength ring Brillouin/Raman fiber laser with 20 GHz channel spacing
    Ahmad H, Zulkifli MZ, Hassan NA, Harun SW
    Appl Opt, 2012 Apr 10;51(11):1811-5.
    PMID: 22505174 DOI: 10.1364/AO.51.001811
    We propose and demonstrate a tunable S-band multiwavelength Brillouin/Raman fiber laser (MBRFL) with a tuning range of between 1490 to 1530 nm. The proposed MBRFL is designed around a 7.7 km long dispersion compensating fiber in a simple ring configuration, acting as a nonlinear medium for the generation of multiple wavelengths from stimulated Brillouin scattering (SBS) and also as a nonlinear gain medium for stimulated Raman scattering (SRS) amplification. A laser source with a maximum power of 12 dBm acts as the Brillouin pump (BP), while two 1420 nm laser diodes with a total power of 26 dBm act as the Raman pumps (RPs). The MBRFL can generate a multiwavelength comb consisting of even and odd Stokes at an average power of -12 dBm and -14 dBm respectively, and by separating the even and odd Stokes outputs, a 20 GHz channel spacing is obtained between two consecutive wavelengths. Due to the four-wave mixing (FWM) effect, anti-Stokes lines are also observed. The multiwavelength comb generated is not dependent on the BP, thus providing high stability and repeatability and making it a highly potential source for many real-world applications. This is the first time, to the knowledge of the authors, that a tunable MBRFL has been developed using SRS to obtain gain in the S-band region.
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links