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  1. Stem Cells from Human Extracted Deciduous Teeth Expanded in Foetal Bovine and Human Sera Express Different Paracrine Factors After Exposure to Freshly Prepared Human Serum
    Haque N, Widera D, Abu Kasim NH
    Adv Exp Med Biol, 2019;1084:175-186.
    PMID: 30771186 DOI: 10.1007/5584_2018_299
    BACKGROUND: The response of stem cells to paracrine factors within the host's body plays an important role in the regeneration process after transplantation. The aim of this study was to determine the viability and paracrine factor profile of stem cells from human extracted deciduous teeth (SHED) pre-cultivated in media supplemented with either foetal bovine serum (FBS) or pooled human serum (pHS) in the presence of individual human sera (iHS).

    METHODS: SHED (n = 3) from passage 4 were expanded in FBS (FBS-SHED) or pHS (pHS-SHED) supplemented media until passage 7. During expansion, the proliferation of SHED was determined. Cells at passage 7 were further expanded in human serum from four individual donors (iHS) for 120 h followed by assessment of cell viability and profiling of the secreted paracrine factors.

    RESULTS: Proliferation of SHED was significantly higher (p 

  2. Pooled Human Serum Increases Regenerative Potential of In Vitro Expanded Stem Cells from Human Extracted Deciduous Teeth
    Haque N, Abu Kasim NH
    Adv Exp Med Biol, 2017 7 22;1083:29-44.
    PMID: 28730381 DOI: 10.1007/5584_2017_74
    In regenerative therapy, in vitro expansion of stem cells is critical to obtain a significantly higher number of cells for successful engraftment after transplantation. However, stem cells lose its regenerative potential and enter senescence during in vitro expansion. In this study, the influence of foetal bovine serum (FBS) and pooled human serum (pHS) on the proliferation, morphology and migration of stem cells from human extracted deciduous teeth (SHED) was compared. SHED (n = 3) was expanded in KnockOut DMEM supplemented with either pHS (pHS-SM) or FBS (FBS-SM). pHS was prepared using peripheral blood serum of six healthy male adults, aged between 21 and 35 years old. The number of live SHED was significantly higher, from passage 5 to 7, when cultured in pHS-SM compared to those cultured in FBS-SM (p 
  3. Regulatory Oversight of Cell and Gene Therapy Products in Malaysia
    Loh EYX, Ab Ghani A, Ahmad R
    Adv Exp Med Biol, 2023;1430:181-195.
    PMID: 37526848 DOI: 10.1007/978-3-031-34567-8_10
    The National Pharmaceutical Regulatory Agency (NPRA) is the agency responsible for the registration of pharmaceutical, natural, and health supplement products and notification of cosmetic products that are marketed in Malaysia. The implementation of regulatory oversight of the different types of product was in a progressive manner, with the latest addition to be regulated being the cell and gene therapy products (CGTPs), beginning January 1, 2021. CGTP can be classified as low risk (that does not require registration) or high risk (that needs to be registered). Generally, the regulation of high-risk CGTP is similar to other biological products. This chapter describes the chronology of the CGTP framework, classification of CGTP, how CGTPs fit into the current registration pathways and registration procedure, dossier requirements, and what is the current status and future direction of CGTP in Malaysia.
  4. Scaffolds for Cartilage Regeneration: To Use or Not to Use?
    Sha'ban M, Ahmad Radzi MA
    Adv Exp Med Biol, 2020;1249:97-114.
    PMID: 32602093 DOI: 10.1007/978-981-15-3258-0_7
    Joint cartilage has been a significant focus on the field of tissue engineering and regenerative medicine (TERM) since its inception in the 1980s. Represented by only one cell type, cartilage has been a simple tissue that is thought to be straightforward to deal with. After three decades, engineering cartilage has proven to be anything but easy. With the demographic shift in the distribution of world population towards ageing, it is expected that there is a growing need for more effective options for joint restoration and repair. Despite the increasing understanding of the factors governing cartilage development, there is still a lot to do to bridge the gap from bench to bedside. Dedicated methods to regenerate reliable articular cartilage that would be equivalent to the original tissue are still lacking. The use of cells, scaffolds and signalling factors has always been central to the TERM. However, without denying the importance of cells and signalling factors, the question posed in this chapter is whether the answer would come from the methods to use or not to use scaffold for cartilage TERM. This paper presents some efforts in TERM area and proposes a solution that will transpire from the ongoing attempts to understand certain aspects of cartilage development, degeneration and regeneration. While an ideal formulation for cartilage regeneration has yet to be resolved, it is felt that scaffold is still needed for cartilage TERM for years to come.
  5. Metabolomics in Systems Biology
    Baharum SN, Azizan KA
    Adv Exp Med Biol, 2018 11 2;1102:51-68.
    PMID: 30382568 DOI: 10.1007/978-3-319-98758-3_4
    Over the last decade, metabolomics has continued to grow rapidly and is considered a dynamic technology in envisaging and elucidating complex phenotypes in systems biology area. The advantage of metabolomics compared to other omics technologies such as transcriptomics and proteomics is that these later omics only consider the intermediate steps in the central dogma pathway (mRNA and protein expression). Meanwhile, metabolomics reveals the downstream products of gene and expression of proteins. The most frequently used tools are nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Some of the common MS-based analyses are gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). These high-throughput instruments play an extremely crucial role in discovery metabolomics to generate data needed for further analysis. In this chapter, the concept of metabolomics in the context of systems biology is discussed and provides examples of its application in human disease studies, plant responses towards stress and abiotic resistance and also microbial metabolomics for biotechnology applications. Lastly, a few case studies of metabolomics analysis are also presented, for example, investigation of an aromatic herbal plant, Persicaria minor metabolome and microbial metabolomics for metabolic engineering applications.
  6. Collagen Type I: A Versatile Biomaterial
    Chowdhury SR, Mh Busra MF, Lokanathan Y, Ng MH, Law JX, Cletus UC, et al.
    Adv Exp Med Biol, 2018 10 26;1077:389-414.
    PMID: 30357700 DOI: 10.1007/978-981-13-0947-2_21
    Collagen type I is the most abundant matrix protein in the human body and is highly demanded in tissue engineering, regenerative medicine, and pharmaceutical applications. To meet the uprising demand in biomedical applications, collagen type I has been isolated from mammalians (bovine, porcine, goat and rat) and non-mammalians (fish, amphibian, and sea plant) source using various extraction techniques. Recent advancement enables fabrication of collagen scaffolds in multiple forms such as film, sponge, and hydrogel, with or without other biomaterials. The scaffolds are extensively used to develop tissue substitutes in regenerating or repairing diseased or damaged tissues. The 3D scaffolds are also used to develop in vitro model and as a vehicle for delivering drugs or active compounds.
  7. Natural Products as the Modulators of Oxidative Stress: An Herbal Approach in the Management of Prostate Cancer
    Nelson VK, Pullaiah CP, Saleem Ts M, Roychoudhury S, Chinnappan S, Vishnusai B, et al.
    Adv Exp Med Biol, 2022;1391:161-179.
    PMID: 36472822 DOI: 10.1007/978-3-031-12966-7_10
    Prostate cancer is the most commonly diagnosed and frequently occurred cancer in the males globally. The current treatment strategies available to treat prostate cancer are not much effective and express various adverse effects. Hence, there is an urgent need to identify novel treatment that can improve patient outcome. From times immemorial, natural products are highly recognized for novel drug development for various diseases including cancer. Cancer cells generally maintain higher basal levels of reactive oxygen species (ROS) when compared to normal cells due to its high metabolic rate. However, initiation of excess intracellular ROS production can not be tolerated by the cancer cells and induce several cell death signals which are in contrast to normal cells. Therefore, small molecules of natural origin that induce ROS can potentially kill cancer cells in specific and provide a better opportunity to develop a novel drug therapy. In this review, we elaborated various classes of medicinal compounds and their mechanism of killing prostate cancer cells through direct or indirect ROS generation. This can generate a novel thought to develop promising drug candidate to treat prostate cancer patients.
  8. Impact of Three-Dimentional Culture Systems on Hepatic Differentiation of Puripotent Stem Cells and Beyond
    Ramasamy TS, Ong ALC, Cui W
    Adv Exp Med Biol, 2018 10 26;1077:41-66.
    PMID: 30357683 DOI: 10.1007/978-981-13-0947-2_4
    Generation of functional hepatocytes from human pluripotent stem cells (hPSCs) is a vital tool to produce large amounts of human hepatocytes, which hold a great promise for biomedical and regenerative medicine applications. Despite a tremendous progress in developing the differentiation protocols recapitulating the developmental signalling and stages, these resulting hepatocytes from hPSCs yet achieve maturation and functionality comparable to those primary hepatocytes. The absence of 3D milieu in the culture and differentiation of these hepatocytes may account for this, at least partly, thus developing an optimal 3D culture could be a step forward to achieve this aim. Hence, review focuses on current development of 3D culture systems for hepatic differentiation and maturation and the future perspectives of its application.
  9. Performance of univariate forecasting on seasonal diseases: the case of tuberculosis
    Permanasari AE, Rambli DR, Dominic PD
    Adv Exp Med Biol, 2011;696:171-9.
    PMID: 21431557 DOI: 10.1007/978-1-4419-7046-6_17
    The annual disease incident worldwide is desirable to be predicted for taking appropriate policy to prevent disease outbreak. This chapter considers the performance of different forecasting method to predict the future number of disease incidence, especially for seasonal disease. Six forecasting methods, namely linear regression, moving average, decomposition, Holt-Winter's, ARIMA, and artificial neural network (ANN), were used for disease forecasting on tuberculosis monthly data. The model derived met the requirement of time series with seasonality pattern and downward trend. The forecasting performance was compared using similar error measure in the base of the last 5 years forecast result. The findings indicate that ARIMA model was the most appropriate model since it obtained the less relatively error than the other model.
  10. An Overview of Circular RNAs
    Awasthi R, Singh AK, Mishra G, Maurya A, Chellappan DK, Gupta G, et al.
    Adv Exp Med Biol, 2018 9 28;1087:3-14.
    PMID: 30259353 DOI: 10.1007/978-981-13-1426-1_1
    Circular RNAs (cirRNAs) are long, noncoding endogenous RNA molecules and covalently closed continuous loop without 5'-3' polarity and polyadenylated tail which are largely concentrated in the nucleus. CirRNA regulates gene expression by modulating microRNAs and functions as potential biomarker. CirRNAs can translate in vivo to link between their expression and disease. They are resistant to RNA exonuclease and can convert to the linear RNA by microRNA which can then act as competitor to endogenous RNA. This chapter summarizes the evolutionary conservation and expression of cirRNAs, their identification, highlighting various computational approaches on cirRNA, and translation with a focus on the breakthroughs and the challenges in this new field.
  11. Integrative Multi-Omics Through Bioinformatics
    Goh HH
    Adv Exp Med Biol, 2018 11 2;1102:69-80.
    PMID: 30382569 DOI: 10.1007/978-3-319-98758-3_5
    This chapter introduces different aspects of bioinformatics with a brief discussion in the systems biology context. Example applications in network pharmacology of traditional Chinese medicine, systems metabolic engineering, and plant genome-scale modelling are described. Lastly, this chapter concludes on how bioinformatics helps to integrate omics data derived from various studies described in previous chapters for a holistic understanding of secondary metabolite production in P. minus.
  12. Synthesis and Characterization of PLGA-PEG Thymoquinone Nanoparticles and Its Cytotoxicity Effects in Tamoxifen-Resistant Breast Cancer Cells
    Ahmad R, Kaus NHM, Hamid S
    Adv Exp Med Biol, 2020;1292:65-82.
    PMID: 30560443 DOI: 10.1007/5584_2018_302
    INTRODUCTION: Drug resistance has been a continuous challenge in cancer treatment. The use of nanotechnology in the development of new cancer drugs has potential. One of the extensively studied compounds is thymoquinone (TQ), and this work aims to compare two types of TQ-nanoformulation and its cytotoxicity toward resistant breast cancer cells.

    METHOD: TQ-nanoparticles were prepared and optimized by using two different formulations with different drugs to PLGA-PEG ratio (1:20 and 1:7) and different PLGA-PEG to Pluronic F68 ratio (10:1 and 2:1). The morphology and size were determined using TEM and DLS. Characterization of particles was done using UV-VIS, ATR-IR, entrapment efficiency, and drug release. The effects of drug, polymer, and surfactants were compared between the two formulations. Cytotoxicity assay was performed using MTS assay.

    RESULTS: TEM finding showed 96% of particles produced with 1:7 drug to PLGA-PEG were less than 90 nm in size and spherical in shape. This was confirmed with DLS which showed smaller particle size than those formed with 1:20 drug to PLGA-PEG ratio. Further analysis showed zeta potential was negatively charged which could facilitate cellular uptake as reported previously. In addition, PDI value was less than 0.1 in both formulations indicating monodispersed and less broad in size distribution. The absorption peak of PLGA-PEG-TQ-Nps was at 255 nm. The 1:7 drug to polymer formulation was selected for further analysis where the entrapment efficiency was 79.9% and in vitro drug release showed a maximum release of TQ of 50%. Cytotoxicity result showed IC50 of TQ-nanoparticle at 20.05 μM and free TQ was 8.25 μM.

    CONCLUSION: This study showed that nanoparticle synthesized with 1:7 drug to PLGA-PEG ratio and 2:1 PLGA-PEG to Pluronic F68 formed nanoparticles with less than 100 nm and had spherical shape as confirmed with DLS. This could facilitate its transportation and absorption to reach its target. There was conserved TQ stability as exhibited slow release of this volatile oil. The TQ-nanoparticles showed selective cytotoxic effect toward UACC 732 cells compared to MCF-7 breast cancer cells.

  13. Proteomics in Systems Biology
    Aizat WM, Hassan M
    Adv Exp Med Biol, 2018 11 2;1102:31-49.
    PMID: 30382567 DOI: 10.1007/978-3-319-98758-3_3
    Proteomics is the study of proteins, the workhorses of cells. Proteins can be subjected to various post-translational modifications, making them dynamic to external perturbation. Proteomics can be divided into four areas: sequence, structural, functional and interaction and expression proteomics. These different areas used different instrumentations and have different focuses. For example, sequence and structural proteomics mainly focus on elucidating a particular protein sequence and structure, respectively. Meanwhile, functional and interaction proteomics concentrate on protein function and interaction partners, whereas expression proteomics allows the cataloguing of total proteins in any given samples, hence providing a holistic overview of various proteins in a cell. The application of expression proteomics in cancer and crop research is detailed in this chapter. The general workflow of expression proteomics consisting the use of mass spectrometry instrumentation has also been described, and some examples of proteomics studies are also presented.
  14. Natural Variation in Freezing Tolerance and Cold Acclimation Response in Arabidopsis thaliana and Related Species
    Zuther E, Lee YP, Erban A, Kopka J, Hincha DK
    Adv Exp Med Biol, 2018 10 6;1081:81-98.
    PMID: 30288705 DOI: 10.1007/978-981-13-1244-1_5
    During low-temperature exposure, temperate plant species increase their freezing tolerance in a process termed cold acclimation. The molecular mechanisms involved in cold acclimation have been mostly investigated in Arabidopsis thaliana. In addition, other Brassicaceae species related to A. thaliana have been employed in recent years to study plant stress responses on a phylogenetically broader basis and in some cases with extremophile species with a much higher stress tolerance. In this paper, we briefly summarize cold acclimation responses in A. thaliana and current knowledge about cold acclimation in A. thaliana relatives with special emphasis on Eutrema salsugineum and two closely related Thellungiella species. We then present a transcriptomic and metabolomic analysis of cold acclimation in five A. thaliana and two E. salsugineum accessions that differ widely in their freezing tolerance. Differences in the cold responses of the two species are discussed.
  15. A study on discrete wavelet-based noise removal from EEG signals
    Asaduzzaman K, Reaz MB, Mohd-Yasin F, Sim KS, Hussain MS
    Adv Exp Med Biol, 2010;680:593-9.
    PMID: 20865544 DOI: 10.1007/978-1-4419-5913-3_65
    Electroencephalogram (EEG) serves as an extremely valuable tool for clinicians and researchers to study the activity of the brain in a non-invasive manner. It has long been used for the diagnosis of various central nervous system disorders like seizures, epilepsy, and brain damage and for categorizing sleep stages in patients. The artifacts caused by various factors such as Electrooculogram (EOG), eye blink, and Electromyogram (EMG) in EEG signal increases the difficulty in analyzing them. Discrete wavelet transform has been applied in this research for removing noise from the EEG signal. The effectiveness of the noise removal is quantitatively measured using Root Mean Square (RMS) Difference. This paper reports on the effectiveness of wavelet transform applied to the EEG signal as a means of removing noise to retrieve important information related to both healthy and epileptic patients. Wavelet-based noise removal on the EEG signal of both healthy and epileptic subjects was performed using four discrete wavelet functions. With the appropriate choice of the wavelet function (WF), it is possible to remove noise effectively to analyze EEG significantly. Result of this study shows that WF Daubechies 8 (db8) provides the best noise removal from the raw EEG signal of healthy patients, while WF orthogonal Meyer does the same for epileptic patients. This algorithm is intended for FPGA implementation of portable biomedical equipments to detect different brain state in different circumstances.
  16. Prospective Advances in Circular RNA Investigation
    Sulaiman SA, Abdul Murad NA, Mohamad Hanif EA, Abu N, Jamal R
    Adv Exp Med Biol, 2018 9 28;1087:357-370.
    PMID: 30259380 DOI: 10.1007/978-981-13-1426-1_28
    circRNAs have emerged as one of the key regulators in many cellular mechanisms and pathogenesis of diseases. However, with the limited knowledge and current technologies for circRNA investigations, there are several challenges that need to be addressed for. These include challenges in understanding the regulation of circRNA biogenesis, experimental designs, and sample preparations to characterize the circRNAs in diseases as well as the bioinformatics pipelines and algorithms. In this chapter, we discussed the above challenges and possible strategies to overcome those limitations. We also addressed the differences between the existing applications and technologies to study the circRNAs in diseases. By addressing these challenges, further understanding of circRNAs roles and regulations as well as the discovery of novel circRNAs could be achieved.
  17. Arsenic-Induced Sex Hormone Disruption: An Insight into Male Infertility
    Choudhury BP, Roychoudhury S, Sengupta P, Toman R, Dutta S, Kesari KK
    Adv Exp Med Biol, 2022;1391:83-95.
    PMID: 36472818 DOI: 10.1007/978-3-031-12966-7_6
    Arsenic (As) is one of the most potent natural as well as anthropogenic metalloid toxicants that have various implications in the everyday life of humans. It is found in several chemical forms such as inorganic salt, organic salt, and arsine (gaseous form). Although it is mostly released via natural causes, there are many ways through which humans come in contact with As. Drinking water contamination by As is one of the major health concerns in various parts of the world. Arsenic exposure has the ability to induce adverse health effects including reproductive problems. Globally, around 15% of the couples are affected with infertility, of which about 20-30% are attributed to the male factor. Arsenic affects the normal development and function of sperm cells, tissue organization of the gonads, and also the sex hormone parameters. Stress induction is one of the implications of As exposure. Excessive stress leads to the release of glucocorticoids, which impact the oxidative balance in the body leading to overproduction of reactive oxygen species (ROS). This may in turn result in oxidative stress (OS) ultimately interfering with normal sperm and hormonal parameters. This study deals with As-induced OS and its association with sex hormone disruption as well as its effect on sperm and semen quality.
  18. Studies on variation in Lancefield group A type 50 streptococcal cell-wall carbohydrate
    Kurl DN
    Adv Exp Med Biol, 1997;418:607-10.
    PMID: 9331725
  19. Immune Human Antibody Libraries for Infectious Diseases
    Chan SK, Lim TS
    Adv Exp Med Biol, 2017;1053:61-78.
    PMID: 29549635 DOI: 10.1007/978-3-319-72077-7_4
    The incident of two children in Europe who died of diphtheria due to a shortage of anti-toxin drugs has highlighted the need for alternative anti-toxins. Historically, antiserum produced from immunised horses have been used to treat diphtheria. Despite the potential of antiserum, the economical and medial concerns associated with the use of animal antiserum has led to its slow market demise. Over the years, new and emerging infectious diseases have grown to be a major global health threat. The emergence of drug-resistant superbugs has also pushed the boundaries of available therapeutics to deal with new infectious diseases. Antibodies have emerged as a possible alternative to combat the continuous onslaught of various infectious agents. The isolation of antibodies against pathogens of infectious diseases isolated from immune libraries utilising phage display has yielded promising results in terms of affinities and neutralizing activities. This chapter focuses on the concept of immune antibody libraries and highlights the application of immune antibody libraries to generate antibodies for various infectious diseases.
  20. Fulltext Naïve Human Antibody Libraries for Infectious Diseases
    Chan SK, Rahumatullah A, Lai JY, Lim TS
    Adv Exp Med Biol, 2017;1053:35-59.
    PMID: 29549634 DOI: 10.1007/978-3-319-72077-7_3
    Many countries are facing an uphill battle in combating the spread of infectious diseases. The constant evolution of microorganisms magnifies the problem as it facilitates the re-emergence of old infectious diseases as well as promote the introduction of new and more deadly variants. Evidently, infectious diseases have contributed to an alarming rate of mortality worldwide making it a growing concern. Historically, antibodies have been used successfully to prevent and treat infectious diseases since the nineteenth century using antisera collected from immunized animals. The inherent ability of antibodies to trigger effector mechanisms aids the immune system to fight off pathogens that invades the host. Immune libraries have always been an important source of antibodies for infectious diseases due to the skewed repertoire generated post infection. Even so, the role and ability of naïve antibody libraries should not be underestimated. The naïve repertoire has its own unique advantages in generating antibodies against target antigens. This chapter will highlight the concept, advantages and application of human naïve libraries as a source to isolate antibodies against infectious disease target antigens.
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