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  1. Fulltext Familial adenomatous polyposis-associated papillary thyroid cancer
    Abdullah Suhaimi SN, Nazri N, Nani Harlina ML, Md Isa N, Muhammad R
    Malays J Med Sci, 2015 Jul-Aug;22(4):69-72.
    PMID: 26715910 MyJurnal
    Papillary thyroid carcinoma (PTC) associated with familial adenomatous polyposis (FAP) is rare. It is usually associated with the cribriform-morular variant of PTC, with unusual patterns on detailed histology examination. This variant is known to have a good prognosis. Papillary thyroid carcinoma associated with FAP commonly occurs in females in their 30s and rarely in the elderly. We report a case of a 69-year-old female presenting with thyroid swelling and a history of FAP.
  2. Fulltext Genotoxicity following Organophosphate Pesticides Exposure among Orang Asli Children Living in an Agricultural Island in Kuala Langat, Selangor, Malaysia
    Sutris JM, How V, Sumeri SA, Muhammad M, Sardi D, Mohd Mokhtar MT, et al.
    Int J Occup Environ Med, 2016 Jan;7(1):42-51.
    PMID: 26772597 DOI: 10.15171/ijoem.2016.705
    BACKGROUND: Agriculture is an important sector for the Malaysian economy. The use of pesticides in agriculture is crucial due to its function in keeping the crops from harmful insects. Children living near agricultural fields are at risk of pesticide poisoning.

    OBJECTIVE: To evaluate the genotoxic risk among children who exposed to pesticides and measure DNA damage due to pesticides exposure.

    METHODS: In a cross-sectional study 180 Orang Asli Mah Meri children aged between 7 and 12 years were studied. They were all living in an agricultural island in Kuala Langat, Selangor, Malaysia. The data for this study were collected via modified validated questionnaire and food frequency questionnaire, which consisted of 131 food items. 6 urinary organophosphate metabolites were used as biomarkers for pesticides exposure. For genotoxic risk or genetic damage assessment, the level of DNA damage from exfoliated buccal mucosa cells was measured using the comet assay electrophoresis method.

    RESULTS: Out of 180 respondents, 84 (46.7%) showed positive traces of organophosphate metabolites in their urine. Children with detectable urinary pesticide had a longer tail length (median 43.5; IQR 30.9 to 68.1 μm) than those with undetectable urinary pesticides (median 24.7; IQR 9.5 to 48.1 μm). There was a significant association between the extent of DNA damage and the children's age, length of residence in the area, pesticides detection, and frequency of apple consumption.

    CONCLUSION: The organophosphate genotoxicity among children is associated with the amount of exposure (detectability of urinary pesticide) and length of residence in (exposure) the study area.

  3. Fulltext Potent PPARγ Ligands from Swietenia macrophylla Are Capable of Stimulating Glucose Uptake in Muscle Cells
    Lau WK, Goh BH, Kadir HA, Shu-Chien AC, Muhammad TS
    Molecules, 2015;20(12):22301-14.
    PMID: 26703529 DOI: 10.3390/molecules201219847
    Numerous documented ethnopharmacological properties have been associated with Swietenia macrophylla (Meliaceae), with its seed extract reported to display anti-hypoglycemic activities in diabetic rats. In the present study, three compounds isolated from the seeds of S. macrophylla were tested on a modified ELISA binding assay and showed to possess PPARγ ligand activity. They were corresponded to PPARγ-mediated cellular response, stimulated adipocyte differentiation but produced lower amount of fat droplets compared to a conventional anti-diabetic agent, rosiglitazone. The up-regulation of adipocytes was followed by increased adipocyte-related gene expressions such as adiponectin, adipsin, and PPARγ. The S. macrophylla compounds also promoted cellular glucose uptake via the translocation of GLUT4 glucose transporter.
  4. Synthesis of novel benzohydrazone-oxadiazole hybrids as β-glucuronidase inhibitors and molecular modeling studies
    Taha M, Ismail NH, Imran S, Selvaraj M, Rahim A, Ali M, et al.
    Bioorg Med Chem, 2015 Dec 1;23(23):7394-404.
    PMID: 26526743 DOI: 10.1016/j.bmc.2015.10.037
    A series of compounds consisting of 25 novel oxadiazole-benzohydrazone hybrids (6-30) were synthesized through a five-step reaction sequence and evaluated for their β-glucuronidase inhibitory potential. The IC50 values of compounds 6-30 were found to be in the range of 7.14-44.16μM. Compounds 6, 7, 8, 9, 11, 13, 18, and 25 were found to be more potent than d-saccharic acid 1,4-lactone (48.4±1.25μM). These compounds were further subjected for molecular docking studies to confirm the binding mode towards human β-d-glucuronidase active site. Docking study for compound 13 (IC50=7.14±0.30μM) revealed that it adopts a binding mode that fits within the entire pocket of the binding site of β-d-glucuronidase. Compound 13 has the maximum number of hydrogens bonded to the residues of the active site as compared to the other compounds, that is, the ortho-hydroxyl group forms hydrogen bond with carboxyl side chain of Asp207 (2.1Å) and with hydroxyl group of Tyr508 (2.6Å). The other hydroxyl group forms hydrogen bond with His385 side chain (2.8Å), side chain carboxyl oxygen of Glu540 (2.2Å) and Asn450 side-chain's carboxamide NH (2.1Å).
  5. Synthesis of potent urease inhibitors based on disulfide scaffold and their molecular docking studies
    Taha M, Ismail NH, Imran S, Wadood A, Rahim F, Riaz M
    Bioorg Med Chem, 2015 Nov 15;23(22):7211-8.
    PMID: 26507431 DOI: 10.1016/j.bmc.2015.10.017
    Disulfide analogs (1-20) have been synthesized, characterized by HR-MS, (1)H NMR and (13)C NMR and screened for urease inhibitory potential. All compounds were found to have varied degree of urease inhibitory potential ranging in between 0.4 ± 0.01 and 18.60 ± 1.24 μM when compared with standard inhibitor thiourea with IC50 19.46 ± 1.20 μM. Structure activity relationship has been established. The binding interactions of compounds with enzyme were confirmed through molecular docking. All the synthesized compounds 1-20 are new. Our compounds are cheaply synthesizable with high yield and can further be studied to discovery lead compounds. We further, tested for carbonic anhydrase, PDE1 and butyrylcholinesterase but they show no activity. On the other hand we evaluated all compounds for cytotoxicity they showed no toxicity.
  6. Fulltext Synthesis and Consecutive Reactions of α-Azido Ketones: A Review
    Faiz S, Zahoor AF, Rasool N, Yousaf M, Mansha A, Zia-Ul-Haq M, et al.
    Molecules, 2015 Aug 13;20(8):14699-745.
    PMID: 26287135 DOI: 10.3390/molecules200814699
    This review paper covers the major synthetic approaches attempted towards the synthesis of α-azido ketones, as well as the synthetic applications/consecutive reactions of α-azido ketones.
  7. Determination of CYP3A4 Inducing Properties of Compounds Using a Laboratory-Developed Cell-Based Assay
    Seah TC, Tay YL, Tan HK, Muhammad TS, Wahab HA, Tan ML
    Int J Toxicol, 2015 08 12;34(5):454-68.
    PMID: 26268769 DOI: 10.1177/1091581815599335
    A cell-based assay to measure cytochrome P450 3A4 (CYP3A4) induction was developed to screen for potential CYP3A4 inducers. This 96-well format assay utilizes HepG2 cells transfected with a gene construct of CYP3A4 proximal promoter linked to green fluorescence protein (GFP) gene, and the expression of the GFP is then measured quantitatively. Bergamottin at 5 to 25 µmol/L produced low induction relative to the positive control. Both curcumin and lycopene were not found to affect the expression of GFP, suggesting no induction properties toward CYP3A4. Interestingly, resveratrol produced significant induction from 25 µmol/L onward, which was similar to omeprazole and may warrant further studies. In conclusion, the present study demonstrated that this cell-based assay can be used as a tool to evaluate the potential CYP3A4 induction properties of compounds. However, molecular docking data have not provided satisfactory pointers to differentiate between CYP3A4 inducers from noninducers or from inhibitors, more comprehensive molecular screening may be indicated.
  8. Effect of donor strength of extended alkyl auxiliary groups on optoelectronic and charge transport properties of novel naphtha[2,1-b:6,5-b']difuran derivatives: simple yet effective strategy
    Chaudhry AR, Ahmed R, Irfan A, Shaari A, Isa AR, Muhammad S, et al.
    J Mol Model, 2015 Aug;21(8):199.
    PMID: 26177706 DOI: 10.1007/s00894-015-2743-9
    The present study spotlights the designing of new derivatives of 2,7-bis (4-octylphenyl) naphtho [2,1-b:6,5-b'] difuran (C8-DPNDF) by substituting the alkyl groups (methyl, ethyl, propyl, butyl, pentyl, hexyl, and heptyl groups) at para position. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) methods are employed to optimize the molecular structures in ground and first excited states, respectively. Several electro-optical properties including hole/electron reorganization energies (λh/λe), electron affinities (EAs), ionization potentials (IPs), molecular electrostatic potentials (MEP), and frontier molecular orbitals (FMOs) have been evaluated. Furthermore their transfer integrals and intrinsic mobilities values have also been calculated. From this study, it is found that hole mobility of octyl containing derivative is raised to 4.69 cm(2) V(-1) s(-1). Moreover with attaching octyl group, hole transfer integral values have also been enhanced in newly designed derivatives. The balanced hole and electron reorganization energies, and improved transfer integrals lead to enhanced mobility in derivatives with octyl group, highlighting them as an efficient hole transfer material. Unlike the other electro-optical properties, the intrinsic hole mobility has increased because of transfer integral values of octyl containing derivative C8-DPNDF due to the dense and close crystal packing of C8-DPNDF. However, photostability of furan-based materials has not changed by increasing length of extended alkyl chain. Thus our present investigation highlights the importance of alkyl auxiliary groups that are often neglected/replaced with simple methyl group to save computation costs. Graphical Abstract The hole and electron reorganization energies of naphtho[2,1-b:6,5-b']difuran derivatives.
  9. Fulltext Investigation on the Redox Properties of a Novel Cu-Based Pr-Modified Oxygen Carrier for Chemical Looping Combustion
    Qasim M, Ayoub M, Aqsha A, Ghazali NA, Ullah S, Ando Y, et al.
    ACS Omega, 2022 Nov 15;7(45):40789-40798.
    PMID: 36406530 DOI: 10.1021/acsomega.2c02993
    CO2 levels in the atmosphere are growing as a result of the burning of fossil fuels to meet energy demands. The introduction of chemical looping combustion (CLC) as an alternative to traditional combustion by transporting oxygen emphasizes the need to develop greener and more economical energy systems. Metal oxide, also defined as an oxygen carrier (OC), transports oxygen from the air to the fuel. Several attempts are being made to develop an OC with a reasonable material cost for superior fuel conversion and high oxygen transport capacity (OTC). This study aims to synthesize a potential OC using the wet impregnation method for the CLC process. Thermogravimetric analysis (TGA) was used to determine the cyclic redox properties using 5% CH4/N2 and air as reducing and oxidizing gases, respectively. The 10CuPA-based OC retained a high OTC of about 0.0267 mg O2/mg of OC for 10 cycles that was higher than 10CuA-based OC. Furthermore, the oxygen transfer rate for 10CuPA-based OC was relatively higher compared to 10CuA-based OC over 10 cycles. In comparison to 10CuA-based OC, the 10CuPA-based OC presented a steady X-ray diffraction (XRD) pattern after 10 redox cycles, implying that the phase was stably restored due to praseodymium-modified γ alumina support.
  10. Fulltext Combined 3D-QSAR, molecular docking and dynamics simulations studies to model and design TTK inhibitors
    Ashraf N, Asari A, Yousaf N, Ahmad M, Ahmed M, Faisal A, et al.
    Front Chem, 2022;10:1003816.
    PMID: 36405310 DOI: 10.3389/fchem.2022.1003816
    Tyrosine threonine kinase (TTK) is the key component of the spindle assembly checkpoint (SAC) that ensures correct attachment of chromosomes to the mitotic spindle and thereby their precise segregation into daughter cells by phosphorylating specific substrate proteins. The overexpression of TTK has been associated with various human malignancies, including breast, colorectal and thyroid carcinomas. TTK has been validated as a target for drug development, and several TTK inhibitors have been discovered. In this study, ligand and structure-based alignment as well as various partial charge models were used to perform 3D-QSAR modelling on 1H-Pyrrolo[3,2-c] pyridine core containing reported inhibitors of TTK protein using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches to design better active compounds. Different statistical methods i.e., correlation coefficient of non-cross validation (r2), correlation coefficient of leave-one-out cross-validation (q2), Fisher's test (F) and bootstrapping were used to validate the developed models. Out of several charge models and alignment-based approaches, Merck Molecular Force Field (MMFF94) charges using structure-based alignment yielded highly predictive CoMFA (q2 = 0.583, Predr2 = 0.751) and CoMSIA (q2 = 0.690, Predr2 = 0.767) models. The models exhibited that electrostatic, steric, HBA, HBD, and hydrophobic fields play a key role in structure activity relationship of these compounds. Using the contour maps information of the best predictive model, new compounds were designed and docked at the TTK active site to predict their plausible binding modes. The structural stability of the TTK complexes with new compounds was confirmed using MD simulations. The simulation studies revealed that all compounds formed stable complexes. Similarly, MM/PBSA method based free energy calculations showed that these compounds bind with reasonably good affinity to the TTK protein. Overall molecular modelling results suggest that newly designed compounds can act as lead compounds for the optimization of TTK inhibitors.
  11. Fulltext Characterization of Sphingobacterium sp. Ab3 Lipase and Its Coexpression with LEA Peptides
    Ng YK, Ikeno S, Kadhim Almansoori AK, Muhammad I, Abdul Rahim R
    Microbiol Spectr, 2022 Dec 21;10(6):e0142221.
    PMID: 36314920 DOI: 10.1128/spectrum.01422-21
    Sphingobacterium sp. is a yellowish Gram-negative bacterium that is usually characterized by high concentrations of sphingophospholipids as lipid components. As microbial enzymes have been in high demand in industrial fields in the past few decades, this study hopes to provide significant information on lipase activities of Sphingobacterium sp., since limited studies have been conducted on the Sphingobacterium sp. lipase. A microbe from one collected Artic soil sample, ARC4, was identified as psychrotolerant Sphingobacterium sp., and it could grow in temperatures ranging from 0°C to 24°C. The expression of Sphingobacterium sp. lipase was successfully performed through an efficient approach of utilizing mutated group 3 late embryogenesis abundant (G3LEA) proteins developed from Polypedilum vanderplanki. Purified enzyme was characterized using a few parameters, such as temperature, pH, metal ion cofactors, organic solvents, and detergents. The expressed enzyme is reported to be cold adapted and has the capability to work efficiently under neutral pH (pH 5.0 to 7.0), cofactors like Na+ ion, and the water-like solvent methanol. Addition of nonionic detergents greatly enhanced the activity of purified enzyme. IMPORTANCE The mechanism of action of LEA proteins has remained unknown to many; in this study we reveal their presence and improved protein expression due to the molecular shielding effect reported by others. This paper should be regarded as a useful example of using such proteins to influence an existing expression system to produce difficult-to-express proteins.
  12. Fulltext Cancer and Disease Diagnosis - Biosensor as Potential Diagnostic Tool for Biomarker Detection
    Chaudhry GE, Akim AM, Safdar N, Yasmin A, Begum S, Sung YY, et al.
    J Adv Pharm Technol Res, 2022;13(4):243-247.
    PMID: 36568055 DOI: 10.4103/japtr.japtr_106_22
    Analysis of cancer biomarkers has enormous promise for advancing our molecular understanding of illness and facilitating more precise and timely diagnosis and follow-up care. MicroRNA, exosomes, ctDNA, CTCs, and proteins are only some of the circulating biomarkers that can be detected by liquid biopsy instead of the more intrusive and time-consuming process of doing a tissue biopsy. As the cancer diagnosis bio-markers reveal ultra-low levels in the early stages of the disease, highly sensitive approaches are urgently required. Researchers have taken an interest in a optical biosensor for detecting cancer biomarkers as a potential tool for early disease diagnosis. These techniques have the potential to aid in the development of effective treatments, ultimately leading to a higher rate of patient survival. This review briefly discuss the i) understanding of cancer and biomarkers for early diagonosis purpose ii) Molecular methods and ii) biosensor-based diagnostics. The reseach primary focus on advancement in biosensor design using various concepts ie., Electrochemical, Chemiluminescence and Colorimetric, Surface plasmons (SP), Surface plasmon resonance (SPR), localized surface plasmon resonance (LSPR), Fluorescence, Fiber-based sensors, Terahertz based biosensors, and Surface enhanced Raman spectroscopy (SERS). As a result of the local electric field amplification around plasmonic (usually gold and silver) nanostructures, surface-enhanced Raman spectroscopy (SERS) has emerged as a rapid, selective, and sensitive alternative to conventional laboratory analytical methods, making significant strides in a number of biosensing applications but still under developing stage to be used as diagnostic tool in clinical research.
  13. Fulltext Clinical Audit on Badminton-Related Ocular Injuries in a Tertiary Hospital in Malaysia
    Mohd Rasidin AH, Muhammad-Ikmal MK, Raja Omar RN, Yaakub A, Ahmad Tajudin LS
    Cureus, 2022 Oct;14(10):e30769.
    PMID: 36447729 DOI: 10.7759/cureus.30769
    Background Badminton-related ocular injuries are among the commonest causes of blunt trauma to the eye, which can lead to significant damage to the ocular structures. This study aimed to assess the clinical presentations, complications, and visual outcomes of patients who sustained ocular injuries related to badminton treated in a single tertiary center in Malaysia. Materials and methods A retrospective clinical audit was conducted in Hospital Universiti Sains Malaysia (HUSM), Malaysia, involving patients diagnosed with ocular injuries related to badminton, either as players or spectators, between January 1, 2003 and December 31, 2017. The demographic data, mechanism of injury, and clinical presentation were recorded. In addition, visual acuity, anterior and posterior segment, and intraocular pressure (IOP) measurements were recorded at the initial presentation and at the present recruitment period. Management at the initial presentation was also obtained and recorded. The final visual outcome and complications were based on the finding of the most recent follow-up. Visual acuity was categorized as follows: mild or no visual impairment (6/18 or better), moderate and severe visual impairment (<6/18 and worse). Results A total of 23 patients (23 eyes) were included in this clinical audit. The average age was 24 years, with a range of 6-56 years, with the highest incidence occurring at the age of 20 years old and younger. The majority of the injuries were sustained during the single-player game. All the injuries were caused by shuttlecock hits. In 18 cases (78%), the trauma was caused by an opponent, in four cases (17%) by a partner, and in one case involving a bystander. Most of the patients in this series were not using any protective eyewear while playing the game 96% (22). Most injuries (22 eyes) involved the anterior segment, with hyphaema as the commonest clinical presentation. The mean IOP at presentation was 23.5 (11.2) mmHg. Angle recession was detected as early as one-week post initial presentation in 17 eyes. Commotio retinae (5 eyes) and vitreous hemorrhage (4 eyes) were the common posterior segment findings. There were eight eyes with visual acuity of worse than 6/18 at the initial presentation, but only three eyes had poor final visual acuity. There was a statistically significant improvement in visual acuity at the last follow-up compared to the initial presentation (Fisher's exact test) (p=0.032). Conclusion Ocular injuries related to badminton is common and cause a detrimental effect on the long-term visual outcome. Traumatic hyphaema and commotio retinae are the most common presenting signs related to poor visual outcomes. Therefore, protective eyewear and promoting awareness of badminton-related ocular injuries are essential to prevent monocular blindness in young adults.
  14. Fulltext Total Synthesis of Terpenes and Their Biological Significance: A Critical Review
    Kanwal A, Bilal M, Rasool N, Zubair M, Shah SAA, Zakaria ZA
    Pharmaceuticals (Basel), 2022 Nov 11;15(11).
    PMID: 36422521 DOI: 10.3390/ph15111392
    Terpenes are a group of natural products made up of molecules with the formula (C5H8)n that are typically found in plants. They are widely employed in the medicinal, flavor, and fragrance industries. The total synthesis of terpenes as well as their origin and biological potential are discussed in this review.
  15. Fulltext Estimating the incidence of spontaneous breathing effort of mechanically ventilated patients using a non-linear auto regressive (NARX) model
    Zainol NM, Damanhuri NS, Othman NA, Chiew YS, Nor MBM, Muhammad Z, et al.
    Comput Methods Programs Biomed, 2022 Jun;220:106835.
    PMID: 35512627 DOI: 10.1016/j.cmpb.2022.106835
    BACKGROUND AND OBJECTIVE: Mechanical ventilation (MV) provides breathing support for acute respiratory distress syndrome (ARDS) patients in the intensive care unit, but is difficult to optimize. Too much, or too little of pressure or volume support can cause further ventilator-induced lung injury, increasing length of MV, cost and mortality. Patient-specific respiratory mechanics can help optimize MV settings. However, model-based estimation of respiratory mechanics is less accurate when patient exhibit un-modeled spontaneous breathing (SB) efforts on top of ventilator support. This study aims to estimate and quantify SB efforts by reconstructing the unaltered passive mechanics airway pressure using NARX model.

    METHODS: Non-linear autoregressive (NARX) model is used to reconstruct missing airway pressure due to the presence of spontaneous breathing effort in mv patients. Then, the incidence of SB patients is estimated. The study uses a total of 10,000 breathing cycles collected from 10 ARDS patients from IIUM Hospital in Kuantan, Malaysia. In this study, there are 2 different ratios of training and validating methods. Firstly, the initial ratio used is 60:40 which indicates 600 breath cycles for training and remaining 400 breath cycles used for testing. Then, the ratio is varied using 70:30 ratio for training and testing data.

    RESULTS AND DISCUSSION: The mean residual error between original airway pressure and reconstructed airway pressure is denoted as the magnitude of effort. The median and interquartile range of mean residual error for both ratio are 0.0557 [0.0230 - 0.0874] and 0.0534 [0.0219 - 0.0870] respectively for all patients. The results also show that Patient 2 has the highest percentage of SB incidence and Patient 10 with the lowest percentage of SB incidence which proved that NARX model is able to perform for both higher incidence of SB effort or when there is a lack of SB effort.

    CONCLUSION: This model is able to produce the SB incidence rate based on 10% threshold. Hence, the proposed NARX model is potentially useful to estimate and identify patient-specific SB effort, which has the potential to further assist clinical decisions and optimize MV settings.

  16. Fulltext Biofilm Signaling, Composition and Regulation in Burkholderia pseudomallei
    Nyanasegran PK, Nathan S, Firdaus-Raih M, Muhammad NAN, Ng CL
    J Microbiol Biotechnol, 2023 Jan 28;33(1):15-27.
    PMID: 36451302 DOI: 10.4014/jmb.2207.07032
    The incidence of melioidosis cases caused by the gram-negative pathogen Burkholderia pseudomallei (BP) is seeing an increasing trend that has spread beyond its previously known endemic regions. Biofilms produced by BP have been associated with antimicrobial therapy limitation and relapse melioidosis, thus making it urgently necessary to understand the mechanisms of biofilm formation and their role in BP biology. Microbial cells aggregate and enclose within a self-produced matrix of extracellular polymeric substances (EPSs) to form biofilm. The transition mechanism of bacterial cells from planktonic state to initiate biofilm formation, which involves the formation of surface attachment microcolonies and the maturation of the biofilm matrix, is a dynamic and complex process. Despite the emerging findings on the biofilm formation process, systemic knowledge on the molecular mechanisms of biofilm formation in BP remains fractured. This review provides insights into the signaling systems, matrix composition, and the biosynthesis regulation of EPSs (exopolysaccharide, eDNA and proteins) that facilitate the formation of biofilms in order to present an overview of our current knowledge and the questions that remain regarding BP biofilms.
  17. Fulltext Corporate social responsibility, financial fraud, and firm's value in Indonesia and Malaysia
    Tarjo T, Anggono A, Yuliana R, Prasetyono P, Syarif M, Alkirom Wildan M, et al.
    Heliyon, 2022 Dec;8(12):e11907.
    PMID: 36471844 DOI: 10.1016/j.heliyon.2022.e11907
    The purpose of this research is to determine if financial fraud can lessen the direct impact of Corporate Social Responsibility (CSR) on firm value. Proxies of the CSR are fourth-generation of the Initiative Global Reporting, religiosity, Philanthropy, Voluntary Environmental Disclosure Index, and ISO 26000. The company's value proxy is Price Book Value and Profit Margin. At the same time, the proxy of financial fraud is the F-Score model. This researcher researches mining companies engaged in Indonesia and Malaysia's oil and gas sectors. This study uses a fixed effect model based on the Hausman diagnostic test statistics. This research reveals evidence that financial fraud can reduce the impact of CSR on a firm's value.
  18. Dissecting the Biology of Rafflesia Species: Current Progress and Future Directions Made Possible with High-Throughput Sequencing Data
    Mursyidah AK, Hafizzudin-Fedeli M, Nor Muhammad NA, Latiff A, Firdaus-Raih M, Wan KL
    Plant Cell Physiol, 2023 Apr 17;64(4):368-377.
    PMID: 36611267 DOI: 10.1093/pcp/pcad004
    The angiosperm Rafflesia exhibits a unique biology, including a growth strategy that involves endophytic parasitism of a specific host, with only the gigantic flower externally visible. The Rafflesia possesses many unique evolutionary, developmental and morphological features that are rooted in yet-to-be-explained physiological processes. Although studies on the molecular biology of Rafflesia are limited by sampling difficulties due to its rarity in the wild and the short life span of its flower, current advances in high-throughput sequencing technology have allowed for the genome- and transcriptome-level dissection of the molecular mechanisms behind the unique characteristics of this parasitic plant. In this review, we summarize major findings on the cryptic biology of Rafflesia and provide insights into future research directions. The wealth of data obtained can improve our understanding of Rafflesia species and contribute toward the conservation strategy of this endangered plant.
  19. Ensemble-based, high-throughput virtual screening of potential inhibitor targeting putative farnesol dehydrogenase of Metisa plana (Lepidoptera: Psychidae)
    Zifruddin AN, Mohamad Yusoff MA, Abd Ghani NS, Nor Muhammad NA, Lam KW, Hassan M
    Comput Biol Chem, 2023 Apr;103:107811.
    PMID: 36645937 DOI: 10.1016/j.compbiolchem.2023.107811
    Metisa plana (Lepidoptera: Psychidae) bagworm is a leaf-eater caterpillar ubiquitously found as a damaging pest in oil palm plantations, specifically in Malaysia. Various strategies have been implemented, including the usage of chemical insecticides. However, the main challenges include the development of insecticide resistance and its detrimental effects on the environment and non-target organisms. Therefore, a biorational insecticide is introduced by targeting the juvenile hormone (JH) biosynthetic pathway, which is mainly present in the insect and vital for the insect's growth, diapause, metamorphosis, and adult reproduction. This study aimed to investigate the potential inhibitor for the rate-limiting enzyme involved in the JH pathway known as farnesol dehydrogenase. A 255 amino acids sequence encoded for the putative M. plana farnesol dehydrogenase (MpFolDH) open reading frame had been identified and isolated. The three-dimensional structure of MpFolDH was predicted to have seven β- sheets with α-helices at both sides, showing typical characteristics for classical short-chain dehydrogenase and associated with oxidoreductase activity. Then, the ensemble-based virtual screening was conducted based on the ZINC20 database, in which 43 768 compounds that fulfilled pesticide-likeness criteria were screened by site-specific molecular docking. After a short molecular dynamics simulation (5 ns) was conducted towards 102 compounds, only the top 10 compounds based on their most favourable binding energy were selected for a more extended simulation (100 ns). Based on the protein-ligand stability, protein compactness, residues rigidity, binding interaction, binding energy throughout the 100 ns simulation, and physicochemical analysis, ZINC000408743205 was selected as a potential inhibitor for this enzyme. Amino acids decomposition analysis indicates Ile18, Ala95, Val198 and Val202 were the critical contributor residues for MpFolDH-inhibitors(s) complex.
  20. Explorations of CRISPR/Cas9 for improving the long-term efficacy of universal CAR-T cells in tumor immunotherapy
    Naeem M, Hazafa A, Bano N, Ali R, Farooq M, Razak SIA, et al.
    Life Sci, 2023 Mar 01;316:121409.
    PMID: 36681183 DOI: 10.1016/j.lfs.2023.121409
    Chimeric antigen receptor (CAR) T therapy has shown remarkable success in discovering novel CAR-T cell products for treating malignancies. Despite of successful results from clinical trials, CAR-T cell therapy is ineffective for long-term disease progression. Numerous challenges of CAR-T cell immunotherapy such as cell dysfunction, cytokine-related toxicities, TGF-β resistance, GvHD risks, antigen escape, restricted trafficking, and tumor cell infiltration still exist that hamper the safety and efficacy of CAR-T cells for malignancies. The accumulated data revealed that these challenges could be overcome with the advanced CRISPR genome editing technology, which is the most promising tool to knockout TRAC and HLA genes, inhibiting the effects of dominant negative receptors (PD-1, TGF-β, and B2M), lowering the risks of cytokine release syndrome (CRS), and regulating CAR-T cell function in the tumor microenvironment (TME). CRISPR technology employs DSB-free genome editing methods that robustly allow efficient and controllable genetic modification. The present review explored the innovative aspects of CRISPR/Cas9 technology for developing next-generation/universal allogeneic CAR-T cells. The present manuscript addressed the ongoing status of clinical trials of CRISPR/Cas9-engineered CAR-T cells against cancer and pointed out the off-target effects associated with CRISPR/Cas9 genome editing. It is concluded that CAR-T cells modified by CRISPR/Cas9 significantly improved antitumor efficacy in a cost-effective manner that provides opportunities for novel cancer immunotherapies.
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