Displaying publications 1 - 20 of 69 in total

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  1. Mechanistic insights into anti-inflammatory and immunosuppressive effects of plant secondary metabolites and their therapeutic potential for rheumatoid arthritis
    Yuandani, Jantan I, Salim E, Septama AW, Rullah K, Nainu F, et al.
    Phytother Res, 2024 Apr 10.
    PMID: 38600726 DOI: 10.1002/ptr.8147
    The anti-inflammatory and immunosuppressive activities of plant secondary metabolites are due to their diverse mechanisms of action against multifarious molecular targets such as modulation of the complex immune system associated with rheumatoid arthritis (RA). This review discussed and critically analyzed the potent anti-inflammatory and immunosuppressive effects of several phytochemicals and their underlying mechanisms in association with RA in experimental studies, including preliminary clinical studies of some of them. A wide range of phytochemicals including phenols, flavonoids, chalcones, xanthones, terpenoids, alkaloids, and glycosides have shown significant immunosuppressive and anti-inflammatory activities in experimental RA models and a few have undergone clinical trials for their efficacy and safety in reducing RA symptoms and improve patient outcomes. These phytochemicals have potential as safer alternatives to the existing drugs in the management of RA, which possess a wide range of serious side effects. Sufficient preclinical studies on safety and efficacy of these phytochemicals must be performed prior to proper clinical studies. Further studies are needed to address the barriers that have so far limited their human use before the therapeutic potential of these plant-based chemicals as anti-arthritic agents in the treatment of RA is fully realized.
  2. Evaluating climate change impacts on reef environments via multibeam echosounder and Acoustic Doppler Current profiler technology
    Abdullah MA, Chuah LF, Zakariya R, Syed A, Hasan RC, Mahmud SM, et al.
    Environ Res, 2024 Apr 10;252(Pt 3):118858.
    PMID: 38609066 DOI: 10.1016/j.envres.2024.118858
    Crucial to the Earth's oceans, ocean currents dynamically react to various factors, including rotation, wind patterns, temperature fluctuations, alterations in salinity and the gravitational pull of the moon. Climate change impacts coastal ecosystems, emphasizing the need for understanding these currents. This study explores multibeam echosounder (MBES), specifically R2-Sonic 2020 instrument, offering detailed seabed information. Investigating coral reefs, rocky reefs and artificial reefs aimed to map seafloor currents movement and their climate change responses. MBES data viz. Bathymetry and backscatter were classified and acoustic doppler current profiler (ADCP) ground data were validated using random forest regression. Results indicated high precision in currents speed measurement i.e. coral reefs with 0.96, artificial reefs with 0.94 and rocky reefs with 0.97. Currents direction accuracy was notable in coral reefs with 0.85, slightly lower in rocky reefs with 0.72 and artificial reefs with 0.60. Random forest identified sediment and backscatter as key for speed prediction while direction relies on bathymetry, slope and aspect. The study emphasizes integrating sediment size, backscatter, bathymetry and ADCP data for seafloor current analysis. This multibeam data on sediments and currents support better marine spatial planning and determine biodiversity patterns planning in the reef area.
  3. Fulltext Immunomodulating Phytochemicals: An Insight Into Their Potential Use in Cytokine Storm Situations
    Alarabei AA, Abd Aziz NAL, Ab Razak NI, Abas R, Bahari H, Abdullah MA, et al.
    Adv Pharm Bull, 2024 Mar;14(1):105-119.
    PMID: 38585461 DOI: 10.34172/apb.2024.001
    Phytochemicals are compounds found in plants that possess a variety of bioactive properties, including antioxidant and immunomodulatory properties. Recent studies have highlighted the potential of phytochemicals in targeting specific signalling pathways involved in cytokine storm, a life-threatening clinical condition resulting from excessive immune cell activation and oversupply of proinflammatory cytokines. Several studies have documented the immunomodulatory effects of phytochemicals on immune function, including their ability to regulate essential cellular and molecular interactions of immune system cells. This makes them a promising alternative for cytokine storm management, especially when combined with existing chemotherapies. Furthermore, phytochemicals have been found to target multiple signalling pathways, including the TNF-α/NF-κB, IL-1/NF-κB, IFN-γ/JAK/STAT, and IL-6/JAK-STAT. These pathways play critical roles in the development and progression of cytokine storm, and targeting them with phytochemicals represents a promising strategy for controlling cytokine release and the subsequent inflammation. Studies have also investigated certain families of plant-related constituents and their potential immunomodulatory actions. In vivo and in vitro studies have reported the immunomodulatory effects of phytochemicals, which provide viable alternatives in the management of cytokine storm syndrome. The collective data from previous studies suggest that phytochemicals represent a potentially functional source of cytokine storm treatment and promote further exploration of these compounds as immunomodulatory agents for suppressing specific signalling cascade responses. Overall, the previous research findings support the use of phytochemicals as a complementary approach in managing cytokine storm and improving patient outcomes.
  4. Assessing coastal bathymetry and climate change impacts on coastal ecosystems using Landsat 8 and Sentinel-2 satellite imagery
    Mokhtar K, Chuah LF, Abdullah MA, Oloruntobi O, Ruslan SMM, Albasher G, et al.
    Environ Res, 2023 Dec 15;239(Pt 2):117314.
    PMID: 37805186 DOI: 10.1016/j.envres.2023.117314
    Coastal ecosystems are facing heightened risks due to human-induced climate change, including rising water levels and intensified storm events. Accurate bathymetry data is crucial for assessing the impacts of these threats. Traditional data collection methods can be cost-prohibitive. This study investigates the feasibility of using freely accessible Landsat and Sentinel satellite imagery to estimate bathymetry and its correlation with hydrographic chart soundings in Port Klang, Malaysia. Through analysis of the blue and green spectral bands from the Landsat 8 and Sentinel 2 datasets, a bathymetry map of Port Klang's seabed is generated. The precision of this derived bathymetry is evaluated using statistical metrics like Root Mean Square Error (RMSE) and the coefficient of determination. The results reveal a strong statistical connection (R2 = 0.9411) and correlation (R2 = 0.7958) between bathymetry data derived from hydrographic chart soundings and satellite imagery. This research not only advances our understanding of employing Landsat imagery for bathymetry assessment but also underscores the significance of such assessments in the context of climate change's impact on coastal ecosystems. The primary goal of this research is to contribute to the comprehension of Landsat imagery's utility in bathymetry evaluation, with the potential to enhance safety protocols in seaport terminals and provide valuable insights for decision-making concerning the management of coastal ecosystems amidst climate-related challenges. The findings of this research have practical implications for a wide range of stakeholders involved in coastal management, environmental protection, climate adaptation and disaster preparedness.
  5. Zika virus antibody-positivity among symptomatic/asymptomatic pregnant women in the Aseer region displays pre-exposure to dengue viruses
    Harish CC, Ayed AA, Alhanshani AA, Youssef AA, Esther P, Riyad AAM, et al.
    Trop Biomed, 2023 Sep 01;40(3):337-343.
    PMID: 37897167 DOI: 10.47665/tb.40.3.010
    Antibody cross-reactivity among flaviviruses is a major limitation in understanding the prevalence without vector control measures. In this study, we investigated the presence of Zika virus (ZIKV)-specific antibodies and the significance of their cross-reactivity with other flaviviruses, which could affect the serological specificity in both symptomatic and asymptomatic pregnant women. Among the results obtained from 217 serum samples tested for ZIKV-specific IgM and IgG, no specific predictions regarding seropositivity or exposure due to extensive cross-reactivity with dengue virus (DENV) serology could be made. Clear-cut positivity was observed in 1.8% (n = 4) and 1.0% (n = 2) for ZIKV IgM and IgG, respectively. The same samples assessed for DENV showed 1.3% (n = 3) seropositivity each for IgM and IgG levels. None of the samples were positive for ZIKV and DENV IgM or IgG. However, one sample (0.4%) tested positive for ZIKV and DENV IgM. No significant correlation was observed between DENV IgM and IgG when comparing the overlapped serotiters. On the other hand, the ZIKV IgG-positive sample showed higher serotiters for DENV IgG, indicating cross-reactivity with ZIKV but without statistical significance. Therefore, screening for the incidence of ZIKV becomes particularly challenging in a population where the presence or pre-exposure to DENV is observed. Our observations further suggest that unless flavivirus prevalence is properly addressed, determining the prevalence of ZIKV antibodies, which may be confounded with other uninvestigated flaviviruses, will be complicated.
  6. Physicians' professionalism from the patients' perspective: a qualitative study at a single-family practice in Saudi Arabia
    AlFaris E, Irfan F, Abouammoh N, Zakaria N, Ahmed AM, Kasule O, et al.
    BMC Med Ethics, 2023 Jun 07;24(1):39.
    PMID: 37287002 DOI: 10.1186/s12910-023-00918-9
    INTRODUCTION: Professionalism is a crucial component of medical practice. It is a culturally sensitive notion that generally consists of behaviors, values, communication, and relationships. This study is a qualitative study exploring physician professionalism from the patients' perspective.

    METHODS: Focus group discussions with patients attending a family medicine center attached to a tertiary care hospital were carried out using the four gates model of Arabian medical professionalism that is appropriate to Arab culture. Discussions with patients were recorded and transcribed. Data were thematically analyzed using NVivo software.

    RESULTS: Three main themes emerged from the data. (1) In dealing with patients, participants expected respect but understood delays in seeing physicians due to their busy schedules. In communication, participants expected to be informed about their health conditions and to have their questions answered. (2) In dealing with tasks, participants expected proper examination and transparency of diagnosis, but some expected the physician to know everything and did not appreciate them seeking outside opinions. They expected to see the same physician at every visit. (3) In physician characteristics preferences, participants preferred friendly smiling physicians. Some cared about the outer appearance of the physician whereas others did not.

    DISCUSSION/CONCLUSIONS: The findings of the study explained only two themes of the four gates model namely dealing with patients and dealing with tasks. Cultural competence and how to benefit from patients' perceptions to be an ideal physician should be incorporated into the process of physicians' training.

  7. Implementation of the energy efficiency existing ship index and carbon intensity indicator on domestic ship for marine environmental protection
    Chuah LF, Mokhtar K, Mhd Ruslan SM, Bakar AA, Abdullah MA, Osman NH, et al.
    Environ Res, 2023 Apr 01;222:115348.
    PMID: 36731596 DOI: 10.1016/j.envres.2023.115348
    The International Maritime Organization has set a goal to achieve a 50% reduction of total annual greenhouse gas emission related to the international shipping by 2050 compared to the 2008 baseline emissions. Malaysia government has taken an initiative to investigate the assessment (cost-effectiveness) of this International Maritime Organization's short-term measure on Malaysian-registered domestic ships although this measure is only for international merchant ship. To achieve this, this paper collected the ship's data from the shipowners from 25 sample ships. Engine power limitation is the most cost-effective option, but low power limits can lead to substantially increased sailing times. Based on cost-efficiency analysis, it creates for the purpose of compliance with the operational carbon intensity indicator. It found that even if it is possible to bring an asset back into service, it may not be possible to do so in a manner that generates a profit or complies with applicable regulations. In these situations, it may be more prudent to scrap the asset rather than run the risk of having it become a stranded asset. This is especially true for older tankers. Alternatives with lengthy payback periods are not desirable for the domestic tanker fleet that is already in operation.
  8. Fulltext Amoxicillin-docosahexaenoic acid encapsulated chitosan-alginate nanoparticles as a delivery system with enhanced biocidal activities against Helicobacter pylori and improved ulcer healing
    Khoshnood S, Negahdari B, Kaviar VH, Sadeghifard N, Abdullah MA, El-Shazly M, et al.
    Front Microbiol, 2023;14:1083330.
    PMID: 36846798 DOI: 10.3389/fmicb.2023.1083330
    Encapsulation of amoxicillin (AMX) for drug delivery against Helicobacter pylori infection and aspirin-induced ulcers in rat's stomachs was performed using docosahexaenoic acid (DHA)-loaded chitosan/alginate (CA) nanoparticles (NPs) developed by ionotropic gelation method. The physicochemical analyses of the composite NPs were performed by scanning electron microscopy, Fourier transform infrared spectroscopy, zeta potential, X-ray diffraction, and atomic force microscopy. The encapsulation efficiency of AMX was increased to 76% by incorporating DHA, which resulted in a reduction in the particle size. The formed CA-DHA-AMX NPs effectively adhered to the bacteria and rat gastric mucosa. Their antibacterial properties were more potent than those of the single AMX and CA-DHA NPs as demonstrated by the in vivo assay. The composite NPs attained higher mucoadhesive potential during food intake than during fasting (p = 0.029). At 10 and 20 mg/kg AMX, the CA-AMX-DHA showed more potent activities against H. pylori than the CA-AMX, CA-DHA, and single AMX. The in vivo study showed that the effective dose of AMX was lower when DHA was included, indicating better drug delivery and stability of the encapsulated AMX. Both mucosal thickening and ulcer index were significantly higher in the groups receiving CA-DHA-AMX than in the groups receiving CA-AMX and single AMX. The presence of DHA declines the pro-inflammatory cytokines including IL-1β, IL-6, and IL-17A. The synergistic effects of AMX and the CA-DHA formulation increased the biocidal activities against H. pylori infection and improved ulcer healing properties.
  9. Fulltext Exogenous L-Glutathione Improves Vitrification Outcomes in Murine Preimplantation Embryos
    Abdul Rahman NS, Mohamed Noor Khan NA, Eshak Z, Sarbandi MS, Mohammad Kamal AA, Abd Malek M, et al.
    Antioxidants (Basel), 2022 Oct 25;11(11).
    PMID: 36358471 DOI: 10.3390/antiox11112100
    Vitrification is an important tool to store surplus embryos in assisted reproductive technology (ART). However, vitrification increases oxidative damage and results in decreased viability. Studies have reported that L-glutathione (GSH) supplementation improves the preimplantation development of murine embryos. Glutathione constitutes the major non-protein sulphydryl compound in mammalian cells, which confers protection against oxidative damage. However, the effect of GSH supplementation on embryonic vitrification outcomes has yet to be reported. This study aims to determine whether GSH supplementation in culture media improves in vitro culture and vitrification outcomes, as observed through embryo morphology and preimplantation development. Female BALB/c mice aged 6−8 weeks were superovulated through an intraperitoneal injection of 10 IU of pregnant mare serum gonadotrophin (PMSG), followed by 10 IU of human chorionic gonadotrophin (hCG) 48 h later. The mated mice were euthanized by cervical dislocation 48 h after hCG to harvest embryos. Two-cell embryos were randomly assigned to be cultured in either Group 1 (GSH-free medium), Group 2 (GSH-free medium with vitrification), Group 3 (0.01 mM GSH-supplemented medium), or Group 4 (0.01 mM GSH-supplemented medium with vitrification). Non-vitrified (Groups 1 and 3) and vitrified (Groups 2 and 4) embryos were observed for morphological quality and preimplantation development at 24, 48, 72, and 96 h. In the non-vitrified groups, there were significant increases in the number of Grade-1 blastocysts in GSH cultures (p < 0.05). Similarly, in the vitrified groups, GSH supplementation was also seen to significantly increase blastocyst formation. Exogenous GSH supplementation resulted in a significant increase in intracellular GSH, a release of cytochrome c from mitochondria, and a parallel decrease in intracellular reactive oxygen species (ROS) levels in vitrified eight-cell embryos (p < 0.05). GSH supplementation was shown to upregulate Bcl2 expression and downregulate Bax expression in the vitrified preimplantation embryo group. The action of exogenous GSH was concomitant with an increase in the relative abundance of Gpx1 and Sod1. In conclusion, our study demonstrated the novel use and practical applicability of GSH supplementation for improving embryonic cryotolerance via a decrease in ROS levels and the inhibition of apoptotic events by improvement in oxidative status.
  10. Fulltext Preparation and Characterization of Novel Schiff Base Derived From 4-Nitro Benzaldehyde and Its Cytotoxic Activities
    Abdul Majeed RH, Hussein HA, Abdullah MA
    Int J Mol Cell Med, 2022;11(4):285-296.
    PMID: 37727641 DOI: 10.22088/IJMCM.BUMS.11.4.285
    Normal drugs exhibit activities against both normal and cancer cells. Furthermore, cancer cells may develop resistance to these drugs that alternative treatment must be explored. The main objective of this study was to examine the anticancer activity of Schiff base against Tongue Squamous Cell Carcinoma Fibroblasts (TSCCF) and normal human gingival fibroblasts (NHGF) and to propose its mechanism. A Novel Schiff base ligand was synthesized from the reaction of 5-C-2-4-NABA (5-chloro-2-((4-nitrobenzylidene) amino) benzoic acid). These Schiff bases possessed azomethine group (-HC=N-) and aromatic group (CH) as analyzed by Fourier transforms infrared (FTIR) spectroscopy and UV-Vis spectra. The in vitro cytotoxicity screening assay suggested promising activity against TSCCF with IC50 of 446.68 µg/mL, but insignificant activity against NHGF cells (IC50 of 977.24 µg/mL) after 72 h. The evidence of apoptotic induction was supported by DAPI staining of apoptotic nuclei with reduced cell numbers, suggesting that Schiff base could induce apoptotic bodies in cancer cells being observed. Based on the Schiff base structure, the anti-cancer mechanism may be attributed to the -HC=N- azomethine group. For the first time, our findings highlighted the anticancer activities of the new Schiff base against oral cancer cell lines.
  11. Heavy Metal Concentrations in Malaysian Adults' Hair and Associated Variables in Bukit Mertajam, Penang, Malaysia
    Aziz MY, Hussain SH, Ishak AR, Abdullah MA, Mohamed R, Ruzi II, et al.
    Biol Trace Elem Res, 2021 Sep 30.
    PMID: 34591221 DOI: 10.1007/s12011-021-02942-5
    The presence of heavy metals in human hair is being tracked to predict health risk, forensics, and environmental monitoring. Heavy metals are typically non-biodegradable and have a lengthy half-life, allowing them to linger in humans and the environment for many years. Heavy metal exposure in hair has been attributed to multiple sources from the environment and food intake. In this study, copper (Cu), nickel (Ni), zinc (Zn), chromium (Cr), manganese (Mn), lead (Pb), and cadmium (Cd) levels were measured in the scalp hair of 50 individuals in Bukit Mertajam, Penang, Malaysia. In conjunction with sampling, subjects' age, gender, lifestyle, diet, and working environment were also obtained through the questionnaire. The Atomic Absorption Spectrometry (AAS) method was used to extract all the metals in the hair samples. The mean concentrations of heavy metals were found to be in the following order (unit of mg/kg): Cr > Zn > Pb > Ni > Cd > Cu. Manganese was detected below the limit of quantitation among the elements (
  12. Hedgehog signalling molecule, SMO is a poor prognostic marker in bladder cancer
    Mohd Ariffin K, Abd Ghani F, Hussin H, Md Said S, Yunus R, Veerakumarasivam A, et al.
    Malays J Pathol, 2021 Apr;43(1):49-54.
    PMID: 33903305
    INTRODUCTION: Hedgehog (HH) pathway is an important signalling cascade for growth and patterning during embryonic development. Constitutive activation of Hedgehog pathway can be found in various types of malignancies including medulloblastoma, basal cell carcinoma, gastrointestinal, breast, pancreatic, prostate cancer and leukaemia. Little is known about the expression and role of Hedgehog signalling in bladder cancer.

    MATERIALS AND METHODS: The purpose of this study was to investigate the immunohistochemical expression of SMO in 112 bladder cancer cases and determine their association with demographic and clinicopathological parameters. Bladder cancer tissues were obtained from the Hospital Kuala Lumpur.

    RESULTS: SMO was expressed in the cytoplasm of all cases of bladder cancer. 6 cases (5.4%) showed low expression, while 106 cases (94.6%) showed high expression. Positive expression of SMO protein was correlated with a few variables which include grade and stage of tumour, lymph node metastasis and distant metastasis. SMO expression showed statistically significant association with higher grade (p=0.001) and higher stage (p=0.042) of bladder cancer. SMO expression also showed borderline association with lymph node metastasis (p=0.056).

    CONCLUSION: These findings indicate that SMO expression may be a poor prognostic marker in bladder cancer.

  13. Fulltext Stimulated Ag Nanoparticles by Pulsed Laser Ablation for Breast Cancer Treatment
    Wan Mohd Shukri WN, Bakhtiar H, Islam S, Bidin N, Baba S, Hamdan S, et al.
    Biomed Environ Sci, 2021 Feb 20;34(2):119-123.
    PMID: 33685570 DOI: 10.3967/bes2021.017
  14. Fulltext Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice
    Lee HC, Hamzah H, Leong MP, Md Yusof H, Habib O, Zainal Abidin S, et al.
    Sci Rep, 2021 Feb 15;11(1):3847.
    PMID: 33589712 DOI: 10.1038/s41598-021-83222-z
    Ruxolitinib is the first janus kinase 1 (JAK1) and JAK2 inhibitor that was approved by the United States Food and Drug Administration (FDA) agency for the treatment of myeloproliferative neoplasms. The drug targets the JAK/STAT signalling pathway, which is critical in regulating the gliogenesis process during nervous system development. In the study, we assessed the effect of non-maternal toxic dosages of ruxolitinib (0-30 mg/kg/day between E7.5-E20.5) on the brain of the developing mouse embryos. While the pregnant mice did not show any apparent adverse effects, the Gfap protein marker for glial cells and S100β mRNA marker for astrocytes were reduced in the postnatal day (P) 1.5 pups' brains. Gfap expression and Gfap+ cells were also suppressed in the differentiating neurospheres culture treated with ruxolitinib. Compared to the control group, adult mice treated with ruxolitinib prenatally showed no changes in motor coordination, locomotor function, and recognition memory. However, increased explorative behaviour within an open field and improved spatial learning and long-term memory retention were observed in the treated group. We demonstrated transplacental effects of ruxolitinib on astrogenesis, suggesting the potential use of ruxolitinib to revert pathological conditions caused by gliogenic-shift in early brain development such as Down and Noonan syndromes.
  15. Fulltext Functional food mixtures: Inhibition of lipid peroxidation, HMGCoA reductase, and ACAT2 in hypercholesterolemia-induced rats
    Mohd Rosmi NSA, Shafie NH, Azlan A, Abdullah MA
    Food Sci Nutr, 2021 Feb;9(2):875-887.
    PMID: 33598171 DOI: 10.1002/fsn3.2051
    Mixtures of selected functional foods (MSFF) were composed of nattokinase (fermented soybean), red yeast rice extract, Ginkgo biloba, oat fiber, garlic, bee pollen, and propolis as anti-hypercholesterolemic were studied. The goal of this study was to determine the bioactive compounds in these mixtures and their cholesterol-lowering potential effects (biochemical profiles, lipid peroxidation, liver tissue histopathology, and enzymatic activity analysis; HMGCoA reductase and ACAT2. The LC-MS/MS analysis showed that bioactive compounds such as Monacolin K, naringin, tocopherol, and glutamate, which have potential as anti-hypercholesterolemic agents, were present in these functional food mixtures. MSFF supplementation at 50 mg/kg 100 mg/kg and 200 mg/kg showed substantial reductions in serum lipid profiles (TC and LDL) (p 
  16. A Review on Biological Properties and Synthetic Methodologies of Diarylpentadienones
    Abdullah MA, Mohd Faudzi SM, Nasir NM
    Mini Rev Med Chem, 2021;21(9):1058-1070.
    PMID: 33272171 DOI: 10.2174/1389557520999201203213957
    Medicinal chemists have continuously shown interest in new curcuminoid derivatives, diarylpentadienones, owing to their enhanced stability feature and easy preparation using a one-pot synthesis. Thus far, methods such as Claisen-Schmidt condensation and Julia- Kocienski olefination have been utilised for the synthesis of these compounds. Diarylpentadienones possess a high potential as a chemical source for designing and developing new and effective drugs for the treatment of diseases, including inflammation, cancer, and malaria. In brief, this review article focuses on the broad pharmacological applications and the summary of the structure-activity relationship of molecules, which can be employed to further explore the structure of diarylpentadienone. The current methodological developments towards the synthesis of diarylpentadienones are also discussed.
  17. Fulltext Expression of Autophagy and Mitophagy Markers in Breast Cancer Tissues
    Mustafa MF, Saliluddin SM, Fakurazi S, Tizen Laim NMS, Md Pauzi SH, Nik Yahya NH, et al.
    Front Oncol, 2021;11:612009.
    PMID: 34490076 DOI: 10.3389/fonc.2021.612009
    Mitochondria play important roles in regulating cell bioenergetics status and reactive oxygen species (ROS) generation. ROS-induced mitochondrial damage is among the main intracellular signal inducers of autophagy. Autophagy is a cellular catabolic process that regulates protein and organelle turnover, while a selective form of autophagy, mitophagy, specifically targets dysfunctional mitochondrial degradation. This study aims to measure the levels of autophagy, mitophagy, oxidative stress, and apoptosis in invasive breast carcinoma tissues using immunohistochemistry (IHC). Tissue microarrays of 76 patients with breast cancer were stained with six IHC markers (MnSOD, Beclin-1, LC3, BNIP3, Parkin, and cleaved caspase 3). The expression intensity was determined for each tumor tissue and the adjacent tumor-matched control tissues. Intermediate and strong staining scores of MnSOD, Beclin-1, LC-3, BNIP-3, and Parkin were significantly higher in tumor tissues compared to the adjacent matched control. The scoring intensity was further classified into tissues with negative staining and positive staining, which showed that positive scores of Beclin-1 and Parkin were significantly high in tumor tissues compared to other markers. Positive association was also noted between BNIP-3 and Beclin-1 as well as LC-3 and cleaved caspase-3 immunostaining. To our knowledge, this is one of the first studies that measure both mitophagy and autophagy in the same breast cancer tissues and the adjacent matched control. The findings from this study will be of great potential in identifying new cancer biomarkers and inspire significant interest in applying anti-autophagy therapies as a possible treatment for breast cancer.
  18. Fulltext The classification of skateboarding tricks via transfer learning pipelines
    Abdullah MA, Ibrahim MAR, Shapiee MNA, Zakaria MA, Mohd Razman MA, Muazu Musa R, et al.
    PeerJ Comput Sci, 2021;7:e680.
    PMID: 34497873 DOI: 10.7717/peerj-cs.680
    This study aims at classifying flat ground tricks, namely Ollie, Kickflip, Shove-it, Nollie and Frontside 180, through the identification of significant input image transformation on different transfer learning models with optimized Support Vector Machine (SVM) classifier. A total of six amateur skateboarders (20 ± 7 years of age with at least 5.0 years of experience) executed five tricks for each type of trick repeatedly on a customized ORY skateboard (IMU sensor fused) on a cemented ground. From the IMU data, a total of six raw signals extracted. A total of two input image type, namely raw data (RAW) and Continous Wavelet Transform (CWT), as well as six transfer learning models from three different families along with grid-searched optimized SVM, were investigated towards its efficacy in classifying the skateboarding tricks. It was shown from the study that RAW and CWT input images on MobileNet, MobileNetV2 and ResNet101 transfer learning models demonstrated the best test accuracy at 100% on the test dataset. Nonetheless, by evaluating the computational time amongst the best models, it was established that the CWT-MobileNet-Optimized SVM pipeline was found to be the best. It could be concluded that the proposed method is able to facilitate the judges as well as coaches in identifying skateboarding tricks execution.
  19. Development of diarylpentadienone analogues as alpha-glucosidase inhibitor: Synthesis, in vitro biological and in vivo toxicity evaluations, and molecular docking analysis
    Abdullah MA, Lee YR, Mastuki SN, Leong SW, Wan Ibrahim WN, Mohammad Latif MA, et al.
    Bioorg Chem, 2020 11;104:104277.
    PMID: 32971414 DOI: 10.1016/j.bioorg.2020.104277
    A series of aminated- (1-9) and sulfonamide-containing diarylpentadienones (10-18) were synthesized, structurally characterized, and evaluated for their in vitro anti-diabetic potential on α-glucosidase and DPP-4 enzymes. It was found that all the new molecules were non-associated PAINS compounds. The sulfonamide-containing series (compounds 10-18) selectively inhibited α-glucosidase over DPP-4, in which compound 18 demonstrated the highest activity with an IC50 value of 5.69 ± 0.5 µM through a competitive inhibition mechanism. Structure-activity relationship (SAR) studies concluded that the introduction of the trifluoromethylbenzene sulfonamide moiety was essential for the suppression of α-glucosidase. The most active compound 18, was then further tested for in vivo toxicities using the zebrafish animal model, with no toxic effects detected in the normal embryonic development, blood vessel formation, and apoptosis of zebrafish. Docking simulation studies were also carried out to better understand the binding interactions of compound 18 towards the homology modeled α -glucosidase and the human lysosomal α -glucosidase enzymes. The overall results suggest that the new sulfonamide-containing diarylpentadienones, compound 18, could be a promising candidate in the search for a new α-glucosidase inhibitor, and can serve as a basis for further studies involving hit-to-lead optimization, in vivo efficacy and safety assessment in an animal model and mechanism of action for the treatment of T2DM patients.
  20. Synthetic nanoparticle-conjugated bisindoles and hydrazinyl arylthiazole as novel antiamoebic agents against brain-eating amoebae
    Kanwal, Mungroo MR, Anwar A, Ali F, Khan S, Abdullah MA, et al.
    Exp Parasitol, 2020 Nov;218:107979.
    PMID: 32866583 DOI: 10.1016/j.exppara.2020.107979
    Balamuthia mandrillaris and Naegleria fowleri are free-living amoebae that can cause life-threatening infections involving the central nervous system. The high mortality rates of these infections demonstrate an urgent need for novel treatment options against the amoebae. Considering that indole and thiazole compounds possess wide range of antiparasitic properties, novel bisindole and thiazole derivatives were synthesized and evaluated against the amoebae. The antiamoebic properties of four synthetic compounds i.e., two new bisindoles (2-Bromo-4-(di (1H-indol-3-yl)methyl)phenol (denoted as A1) and 2-Bromo-4-(di (1H-indol-3-yl)methyl)-6-methoxyphenol (A2)) and two known thiazole (4-(3-Nitrophenyl)-2-(2-(pyridin-3-ylmethylene)hydrazinyl)thiazole (A3) and 4-(Biphenyl-4-yl)-2-(2-(1-(pyridin-4-yl)ethylidene)hydrazinyl)thiazole (A4)) were evaluated against B. mandrillaris and N. fowleri. The ability of silver nanoparticle (AgNPs) conjugation to enrich antiamoebic activities of the compounds was also investigated. The synthetic heterocyclic compounds demonstrated up to 53% and 69% antiamoebic activities against B. mandrillaris and N. fowleri respectively, while resulting in up to 57% and 68% amoebistatic activities, respectively. Antiamoebic activities of the compounds were enhanced by up to 71% and 51% against B. mandrillaris and N. fowleri respectively, after conjugation with AgNPs. These compounds exhibited potential antiamoebic effects against B. mandrillaris and N. fowleri and conjugation of synthetic heterocyclic compounds with AgNPs enhanced their activity against the amoebae.
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