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  1. Fulltext Pharmacokinetics and Biodistribution of Thymoquinone-loaded Nanostructured Lipid Carrier After Oral and Intravenous Administration into Rats
    Zakarial Ansar FH, Latifah SY, Wan Kamal WHB, Khong KC, Ng Y, Foong JN, et al.
    Int J Nanomedicine, 2020;15:7703-7717.
    PMID: 33116496 DOI: 10.2147/IJN.S262395
    Background: Thymoquinone (TQ), an active compound isolated from Nigella sativa, has been proven to exhibit various biological properties such as antioxidant. Although oral delivery of TQ is valuable, it is limited by poor oral bioavailability and low solubility. Recently, TQ-loaded nanostructured lipid carrier (TQ-NLC) was formulated with the aim of overcoming the limitations. TQ-NLC was successfully synthesized by the high-pressure homogenization method with remarkable physiochemical properties whereby the particle size is less than 100 nm, improved encapsulation efficiency and is stable up to 24 months of storage. Nevertheless, the pharmacokinetics and biodistribution of TQ-NLC have not been studied. This study determined the bioavailability of oral and intravenous administration of thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) in rats and its distribution to organs.

    Materials and Methods: TQ-NLC was radiolabeled with technetium-99m before the administration to the rats. The biodistribution and pharmacokinetics parameters were then evaluated at various time points. The rats were imaged at time intervals and the percentage of the injected dose/gram (%ID/g) in blood and each organ was analyzed.

    Results: Oral administration of TQ-NLC exhibited greater relative bioavailability compared to intravenous administration. It is postulated that the movement of TQ-NLC through the intestinal lymphatic system bypasses the first metabolism and therefore enhances the relative bioavailability. However, oral administration has a slower absorption rate compared to intravenous administration where the AUC0-∞ was 4.539 times lower than the latter.

    Conclusion: TQ-NLC had better absorption when administered intravenously compared to oral administration. However, oral administration showed greater bioavailability compared to the intravenous route. This study provides the pharmacokinetics and biodistribution profile of TQ-NLC in vivo which is useful to assist researchers in clinical use.

  2. Support vector machines for oil classification link with polyaromatic hydrocarbon contamination in the environment
    Ismail A, Juahir H, Mohamed SB, Toriman ME, Kassim AM, Zain SM, et al.
    Water Sci Technol, 2021 Mar;83(5):1039-1054.
    PMID: 33724935 DOI: 10.2166/wst.2021.038
    The main focus of this study is exploring the spatial distribution of polyaromatics hydrocarbon links between oil spills in the environment via Support Vector Machines based on Kernel-Radial Basis Function (RBF) approach for high precision classification of oil spill type from its sample fingerprinting in Peninsular Malaysia. The results show the highest concentrations of Σ Alkylated PAHs and Σ EPA PAHs in ΣTAH concentration in diesel from the oil samples PP3_liquid and GP6_Jetty achieving 100% classification output, corresponding to coherent decision boundary and projective subspace estimation. The high dimensional nature of this approach has led to the existence of a perfect separability of the oil type classification from four clustered oil type components; i.e diesel, bunker C, Mixture Oil (MO), lube oil and Waste Oil (WO) with the slack variables of ξ ≠ 0. Of the four clusters, only the SVs of two are correctly predicted, namely diesel and MO. The kernel-RBF approach provides efficient and reliable oil sample classification, enabling the oil classification to be optimally performed within a relatively short period of execution and a faster dataset classification where the slack variables ξ are non-zero.
  3. Source, distribution and emerging threat of micro- and nanoplastics to marine organism and human health: Socio-economic impact and management strategies
    Mofijur M, Ahmed SF, Rahman SMA, Arafat Siddiki SY, Islam ABMS, Shahabuddin M, et al.
    Environ Res, 2021 04;195:110857.
    PMID: 33581088 DOI: 10.1016/j.envres.2021.110857
    The nature of micro- and nanoplastics and their harmful consequences has drawn significant attention in recent years in the context of environmental protection. Therefore, this paper aims to provide an overview of the existing literature related to this evolving subject, focusing on the documented human health and marine environment impacts of micro- and nanoplastics and including a discussion of the economic challenges and strategies to mitigate this waste problem. The study highlights the micro- and nanoplastics distribution across various trophic levels of the food web, and in different organs in infected animals which is possible due to their reduced size and their lightweight, multi-coloured and abundant features. Consequently, micro- and nanoplastics pose significant risks to marine organisms and human health in the form of cytotoxicity, acute reactions, and undesirable immune responses. They affect several sectors including aquaculture, agriculture, fisheries, transportation, industrial sectors, power generation, tourism, and local authorities causing considerable economic losses. This can be minimised by identifying key sources of environmental plastic contamination and educating the public, thus reducing the transfer of micro- and nanoplastics into the environment. Furthermore, the exploitation of the potential of microorganisms, particularly those from marine origins that can degrade plastics, could offer an enhanced and environmentally sound approach to mitigate micro- and nanoplastics pollution.
  4. Fulltext Modulation of Ki67 and myogenic regulatory factor expression by tocotrienol-rich fraction ameliorates myogenic program of senescent human myoblasts
    Tan CM, Najib NAM, Suhaimi NF, Halid NA, Cho VV, Abdullah SI, et al.
    Arch Med Sci, 2021;17(3):752-763.
    PMID: 34025846 DOI: 10.5114/aoms.2019.85449
    Introduction: Replicative senescence results in dysregulation of cell proliferation and differentiation, which plays a role in the regenerative defects observed during age-related muscle atrophy. Vitamin E is a well-known antioxidant, which potentially ameliorates a wide range of age-related manifestations. The aim of this study was to determine the effects of tocotrienol-rich fraction (TRF) in modulating the expression of proliferation- and differentiation-associated proteins in senescent human myoblasts during the differentiation phase.

    Material and methods: Human skeletal muscle myoblasts were cultured until senescence. Young and senescent cells were treated with TRF for 24 h before and after differentiation induction, followed by evaluation of cellular morphology and efficiency of differentiation. Expression of cell proliferation marker Ki67 protein and myogenic regulatory factors MyoD and myogenin were determined.

    Results: Our findings showed that treatment with TRF significantly improved the morphology of senescent myoblasts. Promotion of differentiation was observed in young and senescent myoblasts with TRF treatment as shown by the increased fusion index and larger size of myotubes. Increased Ki67 and myogenin expression with TRF treatment was also observed in senescent myoblasts, suggesting amelioration of the myogenic program by TRF during replicative senescence.

    Conclusions: TRF modulates the expression of regulatory factors related to proliferation and differentiation in senescent human myoblasts and could be beneficial for ameliorating the regenerative defects during aging.

  5. Fulltext Preferred teaching styles of medical faculty: an international multi-center study
    Dash NR, Guraya SY, Al Bataineh MT, Abdalla ME, Yusoff MSB, Al-Qahtani MF, et al.
    BMC Med Educ, 2020 Nov 30;20(1):480.
    PMID: 33256705 DOI: 10.1186/s12909-020-02358-0
    BACKGROUND: In the current wave of educational reforms, understanding teaching styles of medical faculty can help modify instructional strategies for effective teaching. Few studies have probed distinctive teaching styles of medical faculty. We compared preferred teaching styles of faculty from seven medical schools in United Arab Emirates, the Netherlands, Saudi Arabia, Malaysia, Pakistan, and Sudan.

    METHODS: The validated Grasha-Riechmann teaching style inventory was administered online for data collection and used SPSS version 20.0 for statistical analysis.

    RESULTS: Of the 460 invitees, 248 responded (response rate; 54%). Delegator teaching style was most common with a highest median and mean of 2.38 and 2.45, respectively. There was a significant correlation between expert and authority teaching styles, correlation coefficient 0.62. Similarly, we found a significant correlation between authority teaching style and nature of curriculum, correlation coefficient 0.30. Multiple regression analysis showed that only authority teaching style and male gender had significant correlation. Interestingly, 117 (47%) teachers disagreed with the teaching philosophy of delivering course contents by strictly following learning outcomes. Female teachers (114/248) were more willing to negotiate with their students regarding how and what to teach in their course, while male teachers tended to allow more autonomy by allowing students to set their learning agenda.

    CONCLUSIONS: This study showed that the medical teachers preferred delegator teacher style that promotes students' collaboration and peer-to-peer learning. Most teachers are conscious of their teaching styles to motivate students for scientific curiosity. These findings can help medical educators to modify their teaching styles for effective learning.

  6. Fulltext Catalyst-Free Crosslinking Modification of Nata-de-Coco-Based Bacterial Cellulose Nanofibres Using Citric Acid for Biomedical Applications
    Salihu R, Ansari MNM, Abd Razak SI, Ahmad Zawawi N, Shahir S, Sani MH, et al.
    Polymers (Basel), 2021 Aug 31;13(17).
    PMID: 34503006 DOI: 10.3390/polym13172966
    Bacterial cellulose (BC) has gained attention among researchers in materials science and bio-medicine due to its fascinating properties. However, BC's fibre collapse phenomenon (i.e., its inability to reabsorb water after dehydration) is one of the drawbacks that limit its potential. To overcome this, a catalyst-free thermal crosslinking reaction was employed to modify BC using citric acid (CA) without compromising its biocompatibility. FTIR, XRD, SEM/EDX, TGA, and tensile analysis were carried out to evaluate the properties of the modified BC (MBC). The results confirm the fibre crosslinking phenomenon and the improvement of some properties that could be advantageous for various applications. The modified nanofibre displayed an improved crystallinity and thermal stability with increased water absorption/swelling and tensile modulus. The MBC reported here can be used for wound dressings and tissue scaffolding.
  7. Novel functional antimicrobial and biocompatible arabinoxylan/guar gum hydrogel for skin wound dressing applications
    Khan MUA, Raza MA, Razak SIA, Abdul Kadir MR, Haider A, Shah SA, et al.
    J Tissue Eng Regen Med, 2020 10;14(10):1488-1501.
    PMID: 32761978 DOI: 10.1002/term.3115
    It is a challenging task to develop active biomacromolecular wound dressing materials that are biocompatible and possesses antibacterial properties against the bacterial strains that cause severe skin disease. This work is focused on the preparation of a biocompatible and degradable hydrogel for wound dressing application using arabinoxylan (ARX) and guar gum (GG) natural polymers. Fourier transform infrared spectroscopy (FT-IR) confirmed that both ARX and GG interacted well with each other, and their interactions further increased with the addition of crosslinker tetraethyl orthosilicate. Scanning electron microscope (SEM) micrographs showed uniform porous morphologies of the hydrogels. The porous morphologies and uniform interconnected pores are attributed to the increased crosslinking of the hydrogel. Elastic modulus, tensile strength, and fracture strain of the hydrogels significantly improved (from ATG-1 to ATG-4) with crosslinking. Degradability tests showed that hydrogels lost maximum weight in 7 days. All the samples showed variation in swelling with pH. Maximum swelling was observed at pH 7. The hydrogel samples showed good antibacterial activity against Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus (Gram-positive) in PBS, good drug release profile (92% drug release), and nontoxic cellular behavior. The cells not only retained their cylindrical morphologies onto the hydrogel but were also performing their normal activities. It is, therefore, believed that as-developed hydrogel could be a potential material for wound dressing application.
  8. Fulltext Prediction of mortality in severe dengue cases
    Md-Sani SS, Md-Noor J, Han WH, Gan SP, Rani NS, Tan HL, et al.
    BMC Infect Dis, 2018 05 21;18(1):232.
    PMID: 29783955 DOI: 10.1186/s12879-018-3141-6
    BACKGROUND: Increasing incidence of dengue cases in Malaysia over the last few years has been paralleled by increased deaths. Mortality prediction models will therefore be useful in clinical management. The aim of this study is to identify factors at diagnosis of severe dengue that predicts mortality and assess predictive models based on these identified factors.

    METHOD: This is a retrospective cohort study of confirmed severe dengue patients that were admitted in 2014 to Hospital Kuala Lumpur. Data on baseline characteristics, clinical parameters, and laboratory findings at diagnosis of severe dengue were collected. The outcome of interest is death among patients diagnosed with severe dengue.

    RESULTS: There were 199 patients with severe dengue included in the study. Multivariate analysis found lethargy, OR 3.84 (95% CI 1.23-12.03); bleeding, OR 8.88 (95% CI 2.91-27.15); pulse rate, OR 1.04 (95% CI 1.01-1.07); serum bicarbonate, OR 0.79 (95% CI 0.70-0.89) and serum lactate OR 1.27 (95% CI 1.09-1.47), to be statistically significant predictors of death. The regression equation to our model with the highest AUROC, 83.5 (95% CI 72.4-94.6), is: Log odds of death amongst severe dengue cases = - 1.021 - 0.220(Serum bicarbonate) + 0.001(ALT) + 0.067(Age) - 0.190(Gender).

    CONCLUSION: This study showed that a large proportion of severe dengue occurred early, whilst patients were still febrile. The best prediction model to predict death at recognition of severe dengue is a model that incorporates serum bicarbonate and ALT levels.

  9. Improving oil classification quality from oil spill fingerprint beyond six sigma approach
    Juahir H, Ismail A, Mohamed SB, Toriman ME, Kassim AM, Zain SM, et al.
    Mar Pollut Bull, 2017 Jul 15;120(1-2):322-332.
    PMID: 28535957 DOI: 10.1016/j.marpolbul.2017.04.032
    This study involves the use of quality engineering in oil spill classification based on oil spill fingerprinting from GC-FID and GC-MS employing the six-sigma approach. The oil spills are recovered from various water areas of Peninsular Malaysia and Sabah (East Malaysia). The study approach used six sigma methodologies that effectively serve as the problem solving in oil classification extracted from the complex mixtures of oil spilled dataset. The analysis of six sigma link with the quality engineering improved the organizational performance to achieve its objectivity of the environmental forensics. The study reveals that oil spills are discriminated into four groups' viz. diesel, hydrocarbon fuel oil (HFO), mixture oil lubricant and fuel oil (MOLFO) and waste oil (WO) according to the similarity of the intrinsic chemical properties. Through the validation, it confirmed that four discriminant component, diesel, hydrocarbon fuel oil (HFO), mixture oil lubricant and fuel oil (MOLFO) and waste oil (WO) dominate the oil types with a total variance of 99.51% with ANOVA giving Fstat>Fcritical at 95% confidence level and a Chi Square goodness test of 74.87. Results obtained from this study reveals that by employing six-sigma approach in a data-driven problem such as in the case of oil spill classification, good decision making can be expedited.
  10. Anatomy education environment measurement inventory: A valid tool to measure the anatomy learning environment
    Hadie SNH, Hassan A, Ismail ZIM, Asari MA, Khan AA, Kasim F, et al.
    Anat Sci Educ, 2017 Sep;10(5):423-432.
    PMID: 28135037 DOI: 10.1002/ase.1683
    Students' perceptions of the education environment influence their learning. Ever since the major medical curriculum reform, anatomy education has undergone several changes in terms of its curriculum, teaching modalities, learning resources, and assessment methods. By measuring students' perceptions concerning anatomy education environment, valuable information can be obtained to facilitate improvements in teaching and learning. Hence, it is important to use a valid inventory that specifically measures attributes of the anatomy education environment. In this study, a new 11-factor, 132-items Anatomy Education Environment Measurement Inventory (AEEMI) was developed using Delphi technique and was validated in a Malaysian public medical school. The inventory was found to have satisfactory content evidence (scale-level content validity index [total] = 0.646); good response process evidence (scale-level face validity index [total] = 0.867); and acceptable to high internal consistency, with the Raykov composite reliability estimates of the six factors are in the range of 0.604-0.876. The best fit model of the AEEMI is achieved with six domains and 25 items (X2  = 415.67, P 
  11. Fulltext A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma
    Syafruddin SE, Rodrigues P, Vojtasova E, Patel SA, Zaini MN, Burge J, et al.
    Nat Commun, 2019 03 11;10(1):1152.
    PMID: 30858363 DOI: 10.1038/s41467-019-09116-x
    Transcriptional networks are critical for the establishment of tissue-specific cellular states in health and disease, including cancer. Yet, the transcriptional circuits that control carcinogenesis remain poorly understood. Here we report that Kruppel like factor 6 (KLF6), a transcription factor of the zinc finger family, regulates lipid homeostasis in clear cell renal cell carcinoma (ccRCC). We show that KLF6 supports the expression of lipid metabolism genes and promotes the expression of PDGFB, which activates mTOR signalling and the downstream lipid metabolism regulators SREBF1 and SREBF2. KLF6 expression is driven by a robust super enhancer that integrates signals from multiple pathways, including the ccRCC-initiating VHL-HIF2A pathway. These results suggest an underlying mechanism for high mTOR activity in ccRCC cells. More generally, the link between super enhancer-driven transcriptional networks and essential metabolic pathways may provide clues to the mechanisms that maintain the stability of cell identity-defining transcriptional programmes in cancer.
  12. Fulltext Profiling lysophosphatidic acid levels in plasma from head and neck cancer patients
    Abdul Rahman M, Mohamad Haron DE, Hollows RJ, Abdul Ghani ZDF, Ali Mohd M, Chai WL, et al.
    PeerJ, 2020;8:e9304.
    PMID: 32547888 DOI: 10.7717/peerj.9304
    Head and neck squamous cell carcinoma (HNSCC) represents a significant world health problem, with approximately 600,000 new cases being diagnosed annually. The prognosis for patients with HNSCC is poor and, therefore, the identification of biomarkers for screening, diagnosis and prognostication would be clinically beneficial. A limited number of studies have used lipidomics to profile lipid species in the plasma of cancer patients. However, the profile and levels of lysophosphatidic acid (LPA) species have not been examined in HNSCC. In this study, a targeted lipidomics approach using liquid chromatography triple quadrupole mass spectrometry (LCMS/MS) was used to analyse the concentration of LPA (16:0 LPA, 18:0 LPA, 18:1 LPA, 18:2 LPA and 20:4 LPA) in the plasma of patients with oral squamous cell carcinoma (OSCC) and nasopharyngeal carcinoma (NPC), together with healthy controls. The levels of three LPA species (18:1 LPA, 18:2 LPA and 20:4 LPA) were significantly lower in the plasma of OSCC patients, whilst the concentrations of all five LPA species tested were significantly lower in plasma from NPC patients. Furthermore, the order of abundance of LPA species in plasma was different between the control and cancer groups, with 16:0 LPA, 18:0 LPA levels being more abundant in OSCC and NPC patients. Medium to strong correlations were observed using all pairs of LPA species and a clear separation of the normal and tumour groups was observed using PCA analysis. In summary, the results of this study showed that the levels of several LPA species in the plasma of patients with OSCC and NPC were lower than those from healthy individuals. Understanding these variations may provide novel insights into the role of LPA in these cancers.
  13. Gellan Gum Hydrogels Filled Edible Oil Microemulsion for Biomedical Materials: Phase Diagram, Mechanical Behavior, and In Vivo Studies
    Muktar MZ, Bakar MAA, Amin KAM, Che Rose L, Wan Ismail WI, Razali MH, et al.
    Polymers (Basel), 2021 Sep 26;13(19).
    PMID: 34641095 DOI: 10.3390/polym13193281
    The demand for wound care products, especially advanced and active wound care products is huge. In this study, gellan gum (GG) and virgin coconut oil (VCO) were utilized to develop microemulsion-based hydrogel for wound dressing materials. A ternary phase diagram was constructed to obtain an optimized ratio of VCO, water, and surfactant to produce VCO microemulsion. The VCO microemulsion was incorporated into gellan gum (GG) hydrogel (GVCO) and their chemical interaction, mechanical performance, physical properties, and thermal behavior were examined. The stress-at-break (σ) and Young's modulus (YM) of GVCO hydrogel films were increased along with thermal behavior with the inclusion of VCO microemulsion. The swelling degree of GVCO hydrogel decreased as the VCO microemulsion increased and the water vapor transmission rate of GVCO hydrogels was comparable to commercial dressing in the range of 332-391 g m-2 d-1. The qualitative antibacterial activities do not show any inhibition against Gram-negative (Escherichia coli and Klebsiella pneumoniae) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria. In vivo studies on Sprague-Dawley rats show the wound contraction of GVCO hydrogel is best (95 ± 2%) after the 14th day compared to a commercial dressing of Smith and Nephew Opsite post-op waterproof dressing, and this result is supported by the ultrasound images of wound skin and histological evaluation of the wound. The findings suggest that GVCO hydrogel has the potential to be developed as a biomedical material.
  14. Advocating Electrically Conductive Scaffolds with Low Immunogenicity for Biomedical Applications: A Review
    Ahmad Ruzaidi DA, Mahat MM, Shafiee SA, Mohamed Sofian Z, Mohmad Sabere AS, Ramli R, et al.
    Polymers (Basel), 2021 Oct 02;13(19).
    PMID: 34641210 DOI: 10.3390/polym13193395
    Scaffolds support and promote the formation of new functional tissues through cellular interactions with living cells. Various types of scaffolds have found their way into biomedical science, particularly in tissue engineering. Scaffolds with a superior tissue regenerative capacity must be biocompatible and biodegradable, and must possess excellent functionality and bioactivity. The different polymers that are used in fabricating scaffolds can influence these parameters. Polysaccharide-based polymers, such as collagen and chitosan, exhibit exceptional biocompatibility and biodegradability, while the degradability of synthetic polymers can be improved using chemical modifications. However, these modifications require multiple steps of chemical reactions to be carried out, which could potentially compromise the end product's biosafety. At present, conducting polymers, such as poly(3,4-ethylenedioxythiophene) poly(4-styrenesulfonate) (PEDOT: PSS), polyaniline, and polypyrrole, are often incorporated into matrix scaffolds to produce electrically conductive scaffold composites. However, this will reduce the biodegradability rate of scaffolds and, therefore, agitate their biocompatibility. This article discusses the current trends in fabricating electrically conductive scaffolds, and provides some insight regarding how their immunogenicity performance can be interlinked with their physical and biodegradability properties.
  15. Fulltext Barrier to contraceptive use among childbearing age women in rural Indonesia
    Rohmah N, Yusuf A, Hargono R, Laksono AD, Masruroh, Sujoso ADP, et al.
    Malays Fam Physician, 2021 Nov 30;16(3):16-22.
    PMID: 34938389 DOI: 10.51866/oa1020
    Introduction: The contraceptive prevalence rate in Indonesia has not experienced much improvement, which has led to an increase in the number of pregnancies. This study aimed to analyse the barriers to contraception use among women of childbearing age in rural Indonesia.

    Methods: This study used a cross-sectional design with data from the Indonesian Demographic and Health Survey (IDHS) of 2017. The independent variables were age, employment status, education, marital status, wealth status, health insurance and parity. The dependent variable was the use of contraception. The statistical significance was set at p <0.05 using bivariate analysis and binary logistic regression.

    Results: The study showed that the age group of 45-49 years (OR 0.199; 95% CI 0.149-0.266), secondary education (OR 2.227; 95% CI 2.060-2.514), women married/living with their partner (OR 43.752; 95% CI: 35.484-53.946), wealth status: middle (OR 1.492; 95% CI 1.400-1.589) and multipara (OR 2.524; 95% CI: 2.328-2.737) exhibited the increased use of contraception among women of childbearing age in rural Indonesia.

    Conclusion: The variables proven to represent obstacles to contraceptive use among women of childbearing age in rural Indonesia include old age, no education, no husband/partner, poverty and already having one child.

  16. Arabinoxylan/graphene-oxide/nHAp-NPs/PVA bionano composite scaffolds for fractured bone healing
    Aslam Khan MU, Haider A, Abd Razak SI, Abdul Kadir MR, Haider S, Shah SA, et al.
    J Tissue Eng Regen Med, 2021 04;15(4):322-335.
    PMID: 33432773 DOI: 10.1002/term.3168
    The importance of bone scaffolds has increased many folds in the last few years; however, during bone implantation, bacterial infections compromise the implantation and tissue regeneration. This work is focused on this issue while not compromising on the properties of a scaffold for bone regeneration. Biocomposite scaffolds (BS) were fabricated via the freeze-drying technique. The samples were characterized for structural changes, surface morphology, porosity, and mechanical properties through spectroscopic (Fourier transform-infrared [FT-IR]), microscopic (scanning electron microscope [SEM]), X-ray (powder X-ray diffraction and energy-dispersive X-ray), and other analytical (Brunauer-Emmett-Teller, universal testing machine Instron) techniques. Antibacterial, cellular, and hemocompatibility assays were performed using standard protocols. FT-IR confirmed the interactions of all the components. SEM illustrated porous and interconnected porous morphology. The percentage porosity was in the range of 49.75%-67.28%, and the pore size was 215.65-470.87 µm. The pore size was perfect for cellular penetration. Thus, cells showed significant proliferation onto these scaffolds. X-ray studies confirmed the presence of nanohydroxyapatite and graphene oxide (GO). The cell viability was 85%-98% (BS1-BS3), which shows no significant toxicity of the biocomposite. Furthermore, the biocomposites exhibited better antibacterial activity, no effect on the blood clotting (normal in vitro blood clotting), and less than 5% hemolysis. The ultimate compression strength for the biocomposites increased from 4.05 to 7.94 with an increase in the GO content. These exciting results revealed that this material has the potential for possible application in bone tissue engineering.
  17. Bone tissue engineering potentials of 3D printed magnesium-hydroxyapatite in polylactic acid composite scaffolds
    Anita Lett J, Sagadevan S, Léonard E, Fatimah I, Motalib Hossain MA, Mohammad F, et al.
    Artif Organs, 2021 Dec;45(12):1501-1512.
    PMID: 34309044 DOI: 10.1111/aor.14045
    The primary role of bone tissue engineering is to reconcile the damaged bones and facilitate the speedy recovery of the injured bones. However, some of the investigated metallic implants suffer from stress-shielding, palpability, biocompatibility, etc. Consequently, the biodegradable scaffolds fabricated from polymers have gathered much attention from researchers and thus helped the tissue engineering sector by providing many alternative materials whose functionality is similar to that of natural bones. Herein, we present the fabrication and testing of a novel composite, magnesium (Mg)-doped hydroxyapatite (HAp) glazed onto polylactic acid (PLA) scaffolds where polyvinyl alcohol (PVA) used as a binder. For the composite formation, Creality Ender-3 pro High Precision 3D Printer with Shape tool 3D Technology on an FSD machine operated by Catia design software was employed. The composite has been characterized for the crystallinity (XRD), surface functionality (FTIR), morphology (FESEM), biocompatibility (hemolytic and protein absorption), and mechanical properties (stress-strain and maximum compressive strength). The powder XRD analysis confirmed the semicrystalline nature and intact structure of HAp even after doping with Mg, while FTIR studies for the successful formation of Mg-HAp/PVA@PLA composite. The FESEM provided analysis indicated for the 3D porous architecture and well-defined morphology to efficiently transport the nutrients, and the biocompatibility studies are supporting that the composite for blood compatible with the surface being suitable enough for the protein absorption. Finally, the composite's antibacterial activity (against Staphylococcus aureus and Escherichia coli) and the test of mechanical properties supported for the enhanced inhibition of active growth of microorganisms and maximum compressive strength, respectively. Based on the research outcomes of biocompatibility, antibacterial activity, and mechanical resistance, the fabricated Mg-HAp/PVA@PLA composite suits well as a promising biomaterial platform for orthopedic applications by functioning towards the open reduction internal fixation of bone fractures and internal repairs.
  18. Fulltext Molecular Characterization of Somatic Alterations in Dukes' B and C Colorectal Cancers by Targeted Sequencing
    Abdul SN, Ab Mutalib NS, Sean KS, Syafruddin SE, Ishak M, Sagap I, et al.
    Front Pharmacol, 2017;8:465.
    PMID: 28769798 DOI: 10.3389/fphar.2017.00465
    Despite global progress in research, improved screening and refined treatment strategies, colorectal cancer (CRC) remains as the third most common malignancy. As each type of cancer is different and exhibits unique alteration patterns, identifying and characterizing gene alterations in CRC that may serve as biomarkers might help to improve diagnosis, prognosis and predict potential response to therapy. With the emergence of next generation sequencing technologies (NGS), it is now possible to extensively and rapidly identify the gene profile of individual tumors. In this study, we aimed to identify actionable somatic alterations in Dukes' B and C in CRC via NGS. Targeted sequencing of 409 cancer-related genes using the Ion Ampliseq(TM) Comprehensive Cancer Panel was performed on genomic DNA obtained from paired fresh frozen tissues, cancer and normal, of Dukes' B (n = 10) and Dukes' C (n = 9) CRC. The sequencing results were analyzed using Torrent Suite, annotated using ANNOVAR and validated using Sanger sequencing. A total of 141 somatic non-synonymous sequence variations were identified in 86 genes. Among these, 64 variants (45%) were predicted to be deleterious, 38 variants (27%) possibly deleterious while the other 39 variants (28%) have low or neutral protein impact. Seventeen genes have alterations with frequencies of ≥10% in the patient cohort and with 14 overlapped genes in both Dukes' B and C. The adenomatous polyposis coli gene (APC) was the most frequently altered gene in both groups (n = 6 in Dukes' B and C). In addition, TP53 was more frequently altered in Dukes' C (n = 7) compared to Dukes' B (n = 4). Ten variants in APC, namely p.R283(∗), p.N778fs, p.R805(∗), p.Y935fs, p.E941fs, p.E1057(∗), p.I1401fs, p.Q1378(∗), p.E1379(∗), and p.A1485fs were predicted to be driver variants. APC remains as the most frequently altered gene in the intermediate stages of CRC. Wnt signaling pathway is the major affected pathway followed by P53, RAS, TGF-β, and PI3K signaling. We reported the alteration profiles in each of the patient which has the potential to affect the clinical decision. We believe that this study will add further to the understanding of CRC molecular landscape.
  19. Fulltext Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines
    Zamrus SNH, Akhtar MN, Yeap SK, Quah CK, Loh WS, Alitheen NB, et al.
    Chem Cent J, 2018 Mar 19;12(1):31.
    PMID: 29556774 DOI: 10.1186/s13065-018-0398-1
    BACKGROUND: Curcumin is one of the leading compound extracted from the dry powder of Curcuma longa (Zingiberaceae family), which possess several pharmacological properties. However, in vivo administration exhibited limited applications in cancer therapies.

    RESULTS: Twenty-four curcumin derivatives have synthesized, which comprises cyclohexanone 1-10, acetone 11-17 and cyclopentanone 18-24 series. All the curcuminoids were synthesized by the acid or base catalyzed Claisen Schmidt condenstion reactions, in which β-diketone moiety of curcumin was modified with mono-ketone. These curcuminoids 1-24 were screened against HeLa, K562, MCF-7 (an estrogen-dependent) and MDA-MB-231 (an estrogen-independent) cancer cell lines. Among them, acetone series 11-17 were found to be more selective and potential cytotoxic agents. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines. Among the cyclohexanone series, the compound 4 exhibited (IC50 = 11.04 ± 2.80, 6.50 ± 01.80, 8.70 ± 3.10 and 2.30 ± 1.60 µg/mL) potential cytotoxicity against four proposed cancer cell lines, respectively. All the curcucminoids were characterized with the detailed1H NMR, IR, UV-Vis, and mass spectroscopic techniques. The structure of compound 4 was confirmed by using the single X-ray crystallography. Additionally, we are going to report the first time spectral data of (2E,6E)-2,6-bis(2-methoxybenzylidene)cyclohexanone (1). Structure-activity relationships revealed that the mono-carbonyl with 2,5-dimethoxy substituted curcuminoids could be an essential for the future drugs against cancer diseases.

    CONCLUSIONS: Curcuminoids with diferuloyl(4-hydroxy-3-methoxycinnamoyl) moiety with mono carbonyl exhibiting potential cytotoxic properties. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines.

  20. Fulltext Determination and Quantification of Phytochemicals from the Leaf Extract of Parthenium hysterophorus L. and Their Physio-Biochemical Responses to Several Crop and Weed Species
    Bashar HMK, Juraimi AS, Ahmad-Hamdani MS, Uddin MK, Asib N, Anwar MP, et al.
    Plants (Basel), 2022 Nov 23;11(23).
    PMID: 36501249 DOI: 10.3390/plants11233209
    This current investigation was undertaken both in laboratory and glasshouse for documentation and quantification of phytochemicals from different parts of the parthenium (Parthenium hysterophorus L.) plant through LC-MS and HPLC to study their effect on two crops namely, Bambara groundnut (Vigna subterranean L.) and maize (Zea mays L.), and six different types of weed e.g., Digitaria sanguinalis, Eleusine indica, Ageratum conyzoides, Cyperus iria, Euphorbia hirta, and Cyperus difformis. The parthenium methanolic leaf extracts at 25, 50, 75, and 100 g L-1 were sprayed in the test crops and weeds to assess their physiological and biochemical reactions after 6, 24, 48, and 72 h of spraying these compounds (HAS). The LC-MS analysis confirmed seven types of phytochemicals (caffeic acid, ferulic acid, vanillic acid, parthenin, chlorogenic acid, quinic acid, and p-anisic acid) in the parthenium leaf extract that were responsible for the inhibition of tested crops and weeds. From the HPLC analysis, higher amounts in leaf methanol extracts (40,752.52 ppm) than those of the stem (2664.09 ppm) and flower extracts (30,454.33 ppm) were recorded. Parthenium leaf extract at 100 g L-1 had observed higher phytotoxicity on all weed species except C. difformis. However, all crops were found safe under this dose of extraction. Although both crops were also affected to some extent, they could recover from the stress after a few days. The photosynthetic rate, transpiration rate, stomatal conductance, carotenoid and chlorophyll content were decreased due to the application of parthenium leaf extract. However, when parthenium leaf extract was applied at 100 g L-1 for 72 h, the malondialdehyde (MDA) and proline content were increased in all weeds. Enzymatic antioxidant activity (e.g., superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) contents) were also elevated as a result of the sprayed parthenium leaf extract. The negative impact of physiological and biochemical responses as a consequence of the parthenium leaf extract led the weed species to be stressed and finally killed. The current findings show the feasibility of developing bioherbicide from the methanolic extract of parthenium leaf for controlling weeds, which will be cost-effective, sustainable, and environment friendly for crop production during the future changing climate.
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