Displaying publications 1 - 20 of 52 in total

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  1. The BRCA1 and BRCA2 Genes in Early-Onset Breast Cancer Patients
    Saleem M, Ghazali MB, Wahab MAMA, Yusoff NM, Mahsin H, Seng CE, et al.
    Adv Exp Med Biol, 2020;1292:1-12.
    PMID: 29687286 DOI: 10.1007/5584_2018_147
    Approximately 5-10% of breast cancers are attributable to genetic susceptibility. Mutations in the BRCA1 and BRCA2 genes are the best known genetic factors to date. The goal of this study was to determine the structure and distribution of haplotypes of the BRCA1 and BRCA2 genes in early-onset breast cancer patients. We enrolled 70 patients diagnosed with early-onset breast cancer. A total of 21 SNPs (11 on BRCA1 and 10 on BRCA2) and 1 dinucleotide deletion on BRCA1 were genotyped using nested allele-specific PCR methods. Linkage disequilibrium (LD) analysis was conducted, and haplotypes were deduced from the genotype data. Two tightly linked LD blocks were observed on each of the BRCA1 and BRCA2 genes. Variant-free haplotypes (TAT-AG for BRCA1 and ATA-AAT for BRCA2) were observed at a frequency of more than 50% on each gene along with variable frequencies of derived haplotypes. The variant 3'-subhaplotype CGC displayed strong LD with 5'-subhaplotypes GA, AA, and GG on BRCA1 gene. Haplotypes ATA-AGT, ATC-AAT, and ATA-AAC were the variant haplotypes frequent on BRCA2 gene. Although the clinical significance of these derived haplotypes has not yet been established, it is expected that some of these haplotypes, especially the less frequent subhaplotypes, eventually will be shown to be indicative of a predisposition to early-onset breast cancer.
  2. Adipose-Derived Mesenchymal Stem Cells Promote Growth and Migration of Lung Adenocarcinoma Cancer Cells
    Zakaria N, Yahaya BH
    Adv Exp Med Biol, 2020;1292:83-95.
    PMID: 31916234 DOI: 10.1007/5584_2019_464
    INTRODUCTION: Mesenchymal stem cells (MSCs) have been used in cancer therapy as vehicles to deliver therapeutic materials such as drugs, apoptosis inducers and cytokines due to their ability to migrate and home at the tumour site. Furthermore, MSCs have been genetically engineered to produce anticancer molecules such as TRAIL that can induce apoptosis of cancer cells. However, MSCs' presence in the tumour microenvironment has shown to be involved in promoting tumour growth and progression. Therefore, the roles of MSCs either promoting or suppressing tumorigenesis need to be investigated.

    METHODS: Human adipose-derived MSCs (Ad-MSCs) and A549 cells are co-cultured together in indirect co-culture system using Transwell insert. Following co-culture, both cells were analysed in terms of growth rate, migration ability, apoptosis and gene expression for genes involved in migration and stemness characteristics.

    RESULTS: The result shows that Ad-MSCs promoted the growth of A549 cells when indirectly co-cultured for 48 and 72 h. Furthermore, Ad-MSCs significantly enhanced the migration rate of A549 cells. The increased in migration rate was in parallel with the significant increase of MMP9. There are no significant changes observed in the expression of TWIST2, CDH2 and CDH1, genes involved in the epithelial-to-mesenchymal transition (EMT). Ad-MSCs also protect A549 cancer cells from undergoing apoptosis and increase the survival of cancer cells.

    CONCLUSION: Secretion of soluble factors from Ad-MSCs has been shown to promote the growth and metastatic characteristics of A549 cancer cells. Therefore, the use of Ad-MSCs in cancer therapy needs to be carefully evaluated in the long-term aspect.

  3. Acute Lung Injury: Disease Modelling and the Therapeutic Potential of Stem Cells
    Lian J, Lin J, Zakaria N, Yahaya BH
    Adv Exp Med Biol, 2020;1298:149-166.
    PMID: 32424492 DOI: 10.1007/5584_2020_538
    Acute lung injury (ALI) is a severe clinical condition with high morbidity and mortality that usually results in the development of multiple organ dysfunction. The complex pathophysiology of ALI seems to provide a wide range of targets that offer numerous therapeutic options. However, despite extensive studies of ALI pathophysiology and treatment, no effective pharmacotherapy is available. Increasing evidence from both preclinical and clinical studies supports the preventive and therapeutic effects of mesenchymal stem cells (MSCs) for treating ALI. As cell-based therapy poses the risk of occlusion in microvasculature or unregulated growth, MSC-derived extracellular vesicles (MSC-EVs) have been extensively studied as a new therapeutic strategy for non-cell based therapy. It is widely accepted that the therapeutic properties of MSCs are derived from soluble factors with paracrine or endocrine effects, and EVs are among the most important paracrine or endocrine vehicles that can deliver various soluble factors with a similar phenotype as the parent cell. Therapeutic effects of MSCs have been reported for various delivery approaches, diverse doses, multiple origins, and different times of administration, and MSC-EVs treatment may include but is not limited to these choices. The mechanisms by which MSCs and MSC-EVs may contribute to ALI treatment remain elusive and need further exploration. This review provides an overview of preclinical studies that support the application of MSC-EVs for treating ALI, and it discusses emerging opportunities and their associated challenges.
  4. Physico-Mechanical Properties of HA/TCP Pellets and Their Three-Dimensional Biological Evaluation In Vitro
    Kamalaldin N', Jaafar M, Zubairi SI, Yahaya BH
    Adv Exp Med Biol, 2019;1084:1-15.
    PMID: 29299875 DOI: 10.1007/5584_2017_130
    The use of bioceramics, especially the combination of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), as a three-dimensional scaffold in bone engineering is essential because together these elements constitute 60% of the bone content. Different ratios of HA and β-TCP were previously tested for their ability to produce suitable bioceramic scaffolds, which must be able to withstand high mechanical load. In this study, two ratios of HA/TCP (20:80 and 70:30) were used to create pellets, which then were evaluated in vitro to identify any adverse effects of using the material in bone grafting. Diametral tensile strength (DTS) and density testing was conducted to assess the mechanical strength and porosity of the pellets. The pellets then were tested for their toxicity to normal human fibroblast cells. In the toxicity assay, cells were incubated with the pellets for 3 days. At the end of the experiment, cell morphological changes were assessed, and the absorbance was read using PrestoBlue Cell Viability Reagent™. An inversely proportional relationship between DTS and porosity percentage was detected. Fibroblasts showed normal cell morphology in both treatments, which suggests that the HA/TCP pellets were not toxic. In the osteoblast cell attachment assay, cells were able to attach to the surface of both ratios, but cells were also able to penetrate inside the scaffold of the 70:30 pellets. This finding suggests that the 70:30 ratio had better osteoconduction properties than the 20:80 ratio.
  5. The Rapid Development of Airway Organoids: A Direct Culture Strategy
    Shaffi SC, Zakaria N, Halim NSSA, Ishtiah AA, Patar AA, Yahaya BH
    Adv Exp Med Biol, 2023 Mar 30.
    PMID: 36991294 DOI: 10.1007/5584_2023_767
    INTRODUCTION: The lung is a complex organ composed of numerous cell types. Exposure to air pollutants, cigarette smoke, bacteria, viruses, and many others may cause injury to the epithelial cells that line the conducting airways and alveoli. Organoids are the 3D self-organising structures grown from stem cells and generated from adult stem and progenitor cells. Lung organoids are fascinating tools to investigate human lung development in vitro. The objective of this study was to establish a rapid method for generating lung organoids with a direct culture strategy.

    METHODS: Trachea and lung organoids were derived from mixed cell populations of mice primary airway epithelial cells, fibroblasts, and lung microvascular endothelial cells and directly digested from the whole cell population in the distal lung.

    RESULTS: The formation of spheres appeared as early as 3 days and continued to proliferate until day 5. The generation of trachea and lung organoids self-organised into discrete epithelial structures was formed within less than 10 days.

    CONCLUSION: We conclude that researchers will be able to examine cellular involvement during organ formation and molecular networks because organoids come in a variety of morphologies and stages of development, and this organoid protocol may be used for modelling lung diseases as a platform for therapeutic purposes and suitable for personalised medicine for respiratory diseases.

  6. Tissue Engineering for Tracheal Replacement: Strategies and Challenges
    Samat AA, Hamid ZAA, Mariatti Jaafar @ Mustapha, Yahaya BH
    Adv Exp Med Biol, 2022 Apr 08.
    PMID: 35389199 DOI: 10.1007/5584_2022_707
    The critical feature in trachea replacement is to provide a hollow cylindrical framework that is laterally stable and longitudinally flexible, facilitating cartilage and epithelial tissue formation. Despite advanced techniques and sources of materials used, most inherent challenges are related to the complexity of its anatomy. Limited blood supply leads to insufficient regenerative capacity for cartilage and epithelium. Natural and synthetic scaffolds, different types of cells, and growth factors are part of tissue engineering approaches with varying outcomes. Pre-vascularization remains one of the crucial factors to expedite the regenerative process in tracheal reconstruction. This review discusses the challenges and strategies used in tracheal tissue engineering, focusing on scaffold implantation in clinical and preclinical studies conducted in recent decades.
  7. Metabolomics, Lipidomics and Pharmacometabolomics of Human Hypertension
    Au A, Cheng KK, Wei LK
    Adv Exp Med Biol, 2017;956:599-613.
    PMID: 27722964 DOI: 10.1007/5584_2016_79
    Hypertension is a common but complex human disease, which can lead to a heart attack, stroke, kidney disease or other complications. Since the pathogenesis of hypertension is heterogeneous and multifactorial, it is crucial to establish a comprehensive metabolomic approach to elucidate the molecular mechanism of hypertension. Although there have been limited metabolomic, lipidomic and pharmacometabolomic studies investigating this disease to date, metabolomic studies on hypertension have provided greater insights into the identification of disease-specific biomarkers, predicting treatment outcome and monitor drug safety and efficacy. Therefore, we discuss recent updates on the applications of metabolomics technology in human hypertension with a focus on metabolic biomarker discovery.
  8. Biobanking of Human Mesenchymal Stem Cells: Future Strategy to Facilitate Clinical Applications
    Yong KW, Choi JR, Wan Safwani WK
    Adv Exp Med Biol, 2016;951:99-110.
    PMID: 27837557
    Human mesenchymal stem cells (hMSCs), a type of adult stem cells that hold great potential in clinical applications (e.g., regenerative medicine and cell-based therapy) due to their ability to differentiate into multiple types of specialized cells and secrete soluble factors which can initiate tissue repair and regulate immune response. hMSCs need to be expanded in vitro or cryopreserved to obtain sufficient cell numbers required for clinical applications. However, long-term in vitro culture-expanded hMSCs may raise some biosafety concerns (e.g., chromosomal abnormality and malignant transformation) and compromised functional properties, limiting their use in clinical applications. To avoid those adverse effects, it is essential to cryopreserve hMSCs at early passage and pool them for off-the-shelf use in clinical applications. However, the existing cryopreservation methods for hMSCs have some notable limitations. To address these limitations, several approaches have to be taken in order to produce healthy and efficacious cryopreserved hMSCs for clinical trials, which remains challenging to date. Therefore, a noteworthy amount of resources has been utilized in research in optimization of the cryopreservation methods, development of freezing devices, and formulation of cryopreservation media to ensure that hMSCs maintain their therapeutic characteristics without raising biosafety concerns following cryopreservation. Biobanking of hMSCs would be a crucial strategy to facilitate clinical applications in the future.
  9. Greek Nurses' Perception of Hospital Ethical Climate: A Cross-Sectional Study
    Fradelos EC, Latsou D, Alikari V, Papathanasiou IV, Roupa A, Balang V, et al.
    Adv Exp Med Biol, 2021;1337:17-25.
    PMID: 34972887 DOI: 10.1007/978-3-030-78771-4_3
    This study aimed to examine Greek nurses' perceptions about hospital ethical climate and to investigate the possible difference of those perceptions regarding their demographic and work-related characteristics. The cross-sectional study design was employed in this study in which 286 nurses and nurse assistants participated. Data were collected by a sheet containing demographic and work-related characteristics and the Greek version of the Oslons' Hospital Ethical Climate Scale. IBM Statistical Package for Social Sciences 25 was used in data analysis. Frequencies, means, percentages, and standard deviations summarized the data. For the statistical differences, parametric tests were performed. Independent Samples t and Pearson correlation analysis were used to determine the relationship between the ethical climate of the hospital and the nurses' characteristics. The p-values 0.05 were considered statistically significant. The mean age of the nurses was 44 years (SD: 8.5 years; range 24-66 years). The majority of them were women (77.3%). A percent of 57.7% of the sample was married. Most positive perceptions were concerning managers (4.01) following by peers (3.82), patients (3.69), hospitals (3.29) while the least positive perceptions of the ethical climate were concerning the physicians (3.16). The factors associated with hospital ethical perception were: working experience and responsible position. The highest score of ethical climate reported to managers subscale, while the minimum score was related to physicians. In general, Greek nurses reported positive perceptions regarding hospital ethical climate. The positive ethical climate is associated with a better working environment, fewer nurses' experience of moral distress, fewer chances for nursing turnover, high quality of nursing care, and fewer errors in nursing practice.
  10. Tracking of EEG activity using motion estimation to understand brain wiring
    Nisar H, Malik AS, Ullah R, Shim SO, Bawakid A, Khan MB, et al.
    Adv Exp Med Biol, 2015;823:159-74.
    PMID: 25381107 DOI: 10.1007/978-3-319-10984-8_9
    The fundamental step in brain research deals with recording electroencephalogram (EEG) signals and then investigating the recorded signals quantitatively. Topographic EEG (visual spatial representation of EEG signal) is commonly referred to as brain topomaps or brain EEG maps. In this chapter, full search full search block motion estimation algorithm has been employed to track the brain activity in brain topomaps to understand the mechanism of brain wiring. The behavior of EEG topomaps is examined throughout a particular brain activation with respect to time. Motion vectors are used to track the brain activation over the scalp during the activation period. Using motion estimation it is possible to track the path from the starting point of activation to the final point of activation. Thus it is possible to track the path of a signal across various lobes.
  11. Tocotrienol and Its Role in Chronic Diseases
    Chin KY, Pang KL, Soelaiman IN
    Adv Exp Med Biol, 2016;928:97-130.
    PMID: 27671814
    Tocotrienol is a member of vitamin E family and is well-known for its antioxidant and anti-inflammatory properties. It is also a suppressor of mevalonate pathway responsible for cholesterol and prenylated protein synthesis. This review aimed to discuss the health beneficial effects of tocotrienol, specifically in preventing or treating hyperlipidaemia, diabetes mellitus, osteoporosis and cancer with respect to these properties. Evidence from in vitro, in vivo and human studies has been examined. It is revealed that tocotrienol shows promising effects in preventing or treating the health conditions previously mentioned in in vivo and in vitro models. In some cases, alpha-tocopherol attenuates the biological activity of tocotrienol. Except for its cholesterol-lowering effects, data on the health-promoting effects of tocotrienol in human are limited. As a conclusion, the encouraging results on the health beneficial effects of tocotrienol should motivate researchers to explore its potential use in human.
  12. Group A streptococcal infections in hospitalized patients
    Jamal F, Pit S, Kasni S, Yasin MS, Aton SB, Singh K
    Adv Exp Med Biol, 1997;418:35-7.
    PMID: 9331592
  13. Contribution of kinin system to the antihypertensive action of angiotensin converting enzyme inhibitors
    Sharma JN
    Adv Exp Med Biol, 1989;247A:197-205.
    PMID: 2690588
  14. Functional Analysis of Circular RNAs
    Shanmugapriya, Huda HA, Vijayarathna S, Oon CE, Chen Y, Kanwar JR, et al.
    Adv Exp Med Biol, 2018 9 28;1087:95-105.
    PMID: 30259360 DOI: 10.1007/978-981-13-1426-1_8
    Circular RNAs characterize a class of widespread and diverse endogenous RNAs which are non-coding RNAs that are made by back-splicing events and have covalently closed loops with no polyadenylated tails. Various indications specify that circular RNAs (circRNAs) are plentiful in the human transcriptome. However, their participation in biological processes remains mostly undescribed. To date thousands of circRNAs have been revealed in organisms ranging from Drosophila melanogaster to Homo sapiens. Functional studies specify that these transcripts control expression of protein-coding linear transcripts and thus encompass a key component of gene expression regulation. This chapter provide a comprehensive overview on functional validation of circRNAs. Furthermore, we discuss the recent modern methodologies for the functional validation of circRNAs such as RNA interference (RNAi) gene silencing assay, luciferase reporter assays, circRNA gain-of-function investigation via overexpression of circular transcript assay, RT-q-PCR quantification, and other latest applicable assays. The methods described in this chapter are demonstrated on the cellular model.
  15. Anticoagulation Therapy in Patients with Chronic Kidney Disease
    Saheb Sharif-Askari F, Syed Sulaiman SA, Saheb Sharif-Askari N
    Adv Exp Med Biol, 2017;906:101-114.
    PMID: 27628006
    Patients with chronic kidney disease (CKD) are at increased risk for both thrombotic events and bleeding. The early stages of CKD are mainly associated with prothrombotic tendency, whereas in its more advanced stages, beside the prothrombotic state, platelets can become dysfunctional due to uremic-related toxin exposure leading to an increased bleeding tendency. Patients with CKD usually require anticoagulation therapy for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of anticoagulant-induced bleeding. Treatment of patients with CKD should be based on evidence from randomized clinical trials, but usually CKD patients are excluded from these trials. In the past, unfractionated heparins were the anticoagulant of choice for patients with CKD because of its independence of kidney elimination. However, currently low-molecular-weight heparins have largely replaced the use of unfractionated heparins owing to fewer incidences of heparin-induced thrombocytopenia and bleeding. We undertook this review in order to explain the practical considerations for the management of anticoagulation in these high risk population.
  16. Socialization During the COVID-19 Pandemic: The Role of Social and Scientific Networks During Social Distancing
    Momtazmanesh S, Samieefar N, Uddin LQ, Ulrichs T, Kelishadi R, Roudenok V, et al.
    Adv Exp Med Biol, 2021;1318:911-921.
    PMID: 33973219 DOI: 10.1007/978-3-030-63761-3_51
    In the COVID-19 era, while we are encouraged to be physically far away from each other, social and scientific networking is needed more than ever. The dire consequences of social distancing can be diminished by social networking. Social media, a quintessential component of social networking, facilitates the dissemination of reliable information and fighting against misinformation by health authorities. Distance learning, telemedicine, and telehealth are among the most prominent applications of networking during this pandemic. Additionally, the COVID-19 pandemic highlights the importance of collaborative scientific efforts. In this chapter, we summarize the advantages of harnessing both social and scientific networking in minimizing the harms of this pandemic. We also discuss the extra collaborative measures we can take in our fight against COVID-19, particularly in the scientific field.
  17. Metabolic Engineering and Synthetic Biology
    Ramzi AB
    Adv Exp Med Biol, 2018 11 2;1102:81-95.
    PMID: 30382570 DOI: 10.1007/978-3-319-98758-3_6
    In the modern era of next-generation genomics and Fourth Industrial Revolution, there is a growing demand for translational research that brings about not only impactful research but also potential commercialisation of R- and D-based products. Advancement of metabolic engineering and synthetic biology has put forward a viable and innovative biotechnological platform for bioproduct development especially using microbial chassis. In this chapter, readers will be introduced on the concepts of metabolic engineering, synthetic biology and microbial chassis and the applications of these biological engineering (BioE) components in the advancement of industrial and agricultural biotechnology. Main strategies in employing BioE platform are discussed especially for waste bioconversion and value-added product development. More importantly, this chapter will also discuss current endeavours in integrating systems and synthetic biology for microbial production of natural products by introducing flavonoid biosynthesis genes of Polygonum minus, a medicinally important tropical plant in engineered yeast.
  18. Benign Disorders of the Breast in Pregnancy and Lactation
    Taib NA, Rahmat K
    Adv Exp Med Biol, 2020;1252:43-51.
    PMID: 32816261 DOI: 10.1007/978-3-030-41596-9_6
    Benign cystic or solid lumps frequently occur in the breasts of young women, and consequently can also be seen during pregnancy and lactation. Simple cysts do not increase the risk of malignancy. The current management is routine follow-up. Complex cysts are thick walled or contain a mass, and should be followed by a US-guided biopsy and then treated similar to any non-gravid, non-lactating patient.Galactoceles can be detected during the last trimester of pregnancy and during or after stopping lactation. Aspiration can be done to confirm the content. Co-existence of galactocele and malignancy is extremely rare, and the key is to follow up until it resolves.Fibroadenoma is the most frequent lesion found during pregnancy and lactation. Management is usually conservative after triple assessment. Surgery is usually not recommended in pregnant and lactating women unless rapid increase in size occurs or there is discordance in the triple assessment.Lactating adenomas are sometimes interpreted as a variant of fibroadenoma . They can naturally disappear at the end of pregnancy or lactation. Management is usually conservative, and an excisional biopsy is only mandated if it is rapidly enlarging or if there is discordance in the triple assessment.Gestational gigantomastia is a rare condition consisting of diffuse severe hypertrophy of both breasts during pregnancy . Mastectomy and reconstruction may rarely be required in such cases.
  19. Current Perspectives on Nasopharyngeal Carcinoma
    Lee HM, Okuda KS, González FE, Patel V
    Adv Exp Med Biol, 2019;1164:11-34.
    PMID: 31576537 DOI: 10.1007/978-3-030-22254-3_2
    Of the ~129,079 new cases of nasopharyngeal carcinoma (NPC) and 72,987 associated deaths estimated for 2018, the majority will be geographically localized to South East Asia, and likely to show an upward trend annually. It is thought that disparities in dietary habits, lifestyle, and exposures to harmful environmental factors are likely the root cause of NPC incidence rates to differ geographically. Genetic differences due to ethnicity and the Epstein Barr virus (EBV) are likely contributing factors. Pertinently, NPC is associated with poor prognosis which is largely attributed to lack of awareness of the salient symptoms of NPC. These include nose hemorrhage and headaches and coupled with detection and the limited therapeutic options. Treatment options include radiotherapy or chemotherapy or combination of both. Surgical excision is generally the last option considered for advanced and metastatic disease, given the close proximity of nasopharynx to brain stem cell area, major blood vessels, and nerves. To improve outcome of NPC patients, novel cellular and in vivo systems are needed to allow an understanding of the underling molecular events causal for NPC pathogenesis and for identifying novel therapeutic targets and effective therapies. While challenges and gaps in current NPC research are noted, some advances in targeted therapies and immunotherapies targeting EBV NPCs are discussed in this chapter, which may offer improvements in outcome of NPC patients.
  20. Pathogenesis of dengue haemorrhagic fever: current perspectives
    Pang T
    Adv Exp Med Biol, 1989;257:155-68.
    PMID: 2694815 DOI: 10.1007/978-1-4684-5712-4_15
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