Displaying publications 61 - 80 of 92 in total

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  1. Yap HY, Ariffeen Rosli MF, Tan SH, Kong BH, Fung SY
    Mycobiology, 2023;51(1):1-15.
    PMID: 36846625 DOI: 10.1080/12298093.2022.2164641
    Wound care has become increasingly important over the years. Various synthetic products for wound care treatment have been reported to cause toxic side effects and therefore natural products are in significant demand as they have minimal side effects. The presence of bioactive compounds in medicinal mushrooms contributes to various biological activities which assist in the early inflammatory phase, keratinocyte proliferation, and its migration enhancement which are pertinent to wound rehabilitation. Lignosus rhinocerus (tiger milk mushroom) can reduce the inflammation phase in wound healing by fighting off bacterial infection and modulating pro-inflammatory cytokines expression in the early stage to avoid prolonged inflammation and tissue damage. The antibacterial, immunomodulating, and anti-inflammatory activities exhibited by most macrofungi play a key role in enhancing wound healing. Several antibacterial and antifungal compounds sourced from traditional botanicals/products may prevent further complications and reoccurrence of injury to a wounded site. Scientific studies are actively underway to ascertain the potential use of macrofungi as a wound healing agent.
  2. Tan SH, King TL, Tan SSN, Lai WH, Bujang MA, Voon PJ
    Asia Pac J Clin Oncol, 2023 Nov 09.
    PMID: 37943536 DOI: 10.1111/ajco.14034
    AIM: Participant recruitment has always been a major challenge in clinical trials. This study aimed to develop and validate the Join Clinical Trial Questionnaire (JoinCT), exploring the willingness to join a clinical trial and associated factors in patients.

    METHODS: This questionnaire development study involved four phases: (i) exploring and understanding the subject matter, (ii) questionnaire development, (iii) content validity testing, and lastly, (iv) field-testing of the questionnaire. For the field-testing phase, a cross-sectional self-administered survey of JoinCT was conducted among cancer patients with various socio-demographic backgrounds and medical conditions. Besides content validity, Cronbach's alpha was used to evaluate the internal consistency of domains, and confirmatory factor analysis was used to evaluate the model fit of the JoinCT framework.

    RESULTS: A total of 389 respondents participated in the survey. Based on the results obtained from a field data collection phase, JoinCT consisted of four independent variables domains, namely "knowledge", "perception of benefits", "perception of risks", and "confidence". The only dependent variable was the willingness to participate in a clinical trial. The minimum Cronbach's alpha was 0.937, and the model fit for the overall framework of JoinCT is also excellent with Comparative Fit Index (> 0.90), root mean square error approximation (

  3. Murugan AC, Karim MR, Yusoff MB, Tan SH, Asras MF, Rashid SS
    Pharm Biol, 2015 Aug;53(8):1087-97.
    PMID: 25630358 DOI: 10.3109/13880209.2014.959615
    CONTEXT: Polyphenol-rich marine macroalgae are gaining dietary importance due to their influence over diabetes mellitus and the role as a vital source of high-value nutraceuticals. Their assorted beneficial effects on human health include competitive inhibition of digestive enzymes, varying the activity of hepatic glucose-metabolizing enzymes, lowering the plasma glucose levels, and lipid peroxidation, delaying the aging process.

    OBJECTIVE: In this paper, we review the health beneficial effects of polyphenols and phlorotannins from brown seaweeds with special emphasis on their inhibitory effects on carbohydrate-metabolizing enzymes.

    METHODS: A survey of literature from databases such as Sciencedirect, Scopus, Pubmed, Springerlink, and Google Scholar from the year 1973 to 2013 was done to bring together the information relating to drug discovery from brown seaweeds as a source for diabetes treatment.

    RESULTS: Over the past two decades, 20 different bioactive polyphenols/phlorotannins have been isolated and studied from 10 different brown algae. Discussion of the positive effect on the inhibition of enzymes metabolizing carbohydrates in both in vitro and in vivo experiments are included.

    CONCLUSION: Despite the recent advancements in isolating bioactive compounds from seaweeds with potential health benefit or pharmaceutical behavior, studies on the polyphenol effectiveness on glucose homeostasis in human beings are very few in response to their functional characterization. Added research in this area is required to confirm the close connection of polyphenol rich seaweed-based diet consumption with glucose homeostasis and the exciting possibility of prescribing polyphenols to treat the diabetes pandemic.

  4. Tan SH, Guan CA, Bujang MA, Lai WH, Voon PJ, Sim EUH
    Sci Rep, 2024 Jan 23;14(1):1997.
    PMID: 38263244 DOI: 10.1038/s41598-024-52421-9
    Gastrointestinal (GI) cancers account for a significant incidence and mortality rates of cancers globally. Utilization of a phenomic data approach allows researchers to reveal the mechanisms and molecular pathogenesis of these conditions. We aimed to investigate the association between the phenomic features and GI cancers in a large cohort study. We included 502,369 subjects aged 37-73 years in the UK Biobank recruited since 2006, followed until the date of the first cancer diagnosis, date of death, or the end of follow-up on December 31st, 2016, whichever occurred first. Socio-demographic factors, blood chemistry, anthropometric measurements and lifestyle factors of participants collected at baseline assessment were analysed. Unvariable and multivariable logistic regression were conducted to determine the significant risk factors for the outcomes of interest, based on the odds ratio (OR) and 95% confidence intervals (CI). The analysis included a total of 441,141 participants, of which 7952 (1.8%) were incident GI cancer cases and 433,189 were healthy controls. A marker, cystatin C was associated with total and each gastrointestinal cancer (adjusted OR 2.43; 95% CI 2.23-2.64). In this cohort, compared to Asians, the Whites appeared to have a higher risk of developing gastrointestinal cancers. Several other factors were associated with distinct GI cancers. Cystatin C and race appear to be important features in GI cancers, suggesting some overlap in the molecular pathogenesis of GI cancers. Given the small proportion of Asians within the UK Biobank, the association between race and GI cancers requires further confirmation.
  5. Anuar MA, Zainal Abidin M', Tan SH, Yeap CF, Yahaya NA
    Pediatr Neurol, 2024 Jan;150:10-14.
    PMID: 37931500 DOI: 10.1016/j.pediatrneurol.2023.10.004
    BACKGROUND: Epilepsy has a high incidence among infants during their first year of life, yet the prognosis can vary significantly. Although considerable research has been conducted on infantile spasms, studies examining infantile-onset epilepsy, excluding infantile spasms, remain limited, particularly concerning the factors influencing outcomes. Therefore, our study aims to elucidate seizure control, developmental outcomes, and prognostic factors in infants with epilepsy during their first year of life, within a single-center study in Malaysia.

    METHODS: We retrieved data from patients who experienced seizures before age 12 months and were followed for over two years, using electronic patient records at Hospital Raja Perempuan Zainab II in Kelantan, a state in Malaysia's east coast. We retrospectively reviewed these records and assessed clinical outcomes based on the last follow-up.

    RESULTS: Of 75 patients, 61 (81.3%) achieved good seizure control or remission. At the last follow-up, 24 (32%) exhibited developmental delay, whereas 19 (25.3%) displayed abnormal neuroimaging. Patients with abnormal background electroencephalographic (EEG) activity, as well as abnormal radiological findings, were more likely to experience poor seizure control and unfavorable developmental outcomes (P 

  6. Khalid K, Lim HX, Anwar A, Tan SH, Hwang JS, Ong SK, et al.
    AAPS PharmSciTech, 2024 Mar 12;25(3):60.
    PMID: 38472523 DOI: 10.1208/s12249-024-02778-x
    The protective efficacies of current licensed vaccines against COVID-19 have significantly reduced as a result of SARS-CoV-2 variants of concern (VOCs) which carried multiple mutations in the Spike (S) protein. Considering that these vaccines were developed based on the S protein of the original SARS-CoV-2 Wuhan strain, we designed a recombinant plasmid DNA vaccine based on highly conserved and immunogenic B and T cell epitopes against SARS-CoV-2 Wuhan strain and the Omicron VOC. Literature mining and bioinformatics were used to identify 6 immunogenic peptides from conserved regions of the SARS-CoV-2 S and membrane (M) proteins. Nucleotide sequences encoding these peptides representing highly conserved B and T cell epitopes were cloned into a pVAX1 vector to form the pVAX1/S2-6EHGFP recombinant DNA plasmid vaccine. The DNA vaccine was intranasally or intramuscularly administered to BALB/c mice and evaluations of humoral and cellular immune responses were performed. The intramuscular administration of pVAX1/S2-6EHGFP was associated with a significantly higher percentage of CD8+ T cells expressing IFN-γ when compared with the empty vector and PBS controls. Intramuscular or intranasal administrations of pVAX1/S2-6EHGFP resulted in robust IgG antibody responses. Sera from mice intramuscularly immunized with pVAX1/S2-6EHGFP were found to elicit neutralizing antibodies capable of SARS-CoV-2 Omicron variant with the ACE2 cell surface receptor. This study demonstrated that the DNA vaccine construct encoding highly conserved immunogenic B and T cell epitopes was capable of eliciting potent humoral and cellular immune responses in mice.
  7. Kelly GM, Kong YH, Dobi A, Srivastava S, Sesterhenn IA, Pathmanathan R, et al.
    Molecular and clinical oncology, 2015 Jan;3(1):23-30.
    PMID: 25469265
    Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 (TMPRSS2)-ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed paraffin-embedded sections of transrectal ultrasound-guided prostate biopsy specimens, collected from 120 patients treated at the Sime Darby Medical Centre, Subang Jaya, Malaysia, were analyzed for ERG protein expression by immunohistochemistry using the anti-ERG monoclonal antibody 9FY as a surrogate for the detection of ERG fusion events. The overall frequency of ERG protein expression in the population evaluated in this study was 39.2%. Although seemingly similar to rates reported in other Asian communities, the expression of ERG was distinct amongst different ethnic groups (P=0.004). Malaysian Indian (MI) patients exhibited exceedingly high expression of ERG in their tumors, almost doubling that of Malaysian Chinese (MC) patients, whereas ERG expression was very low amongst Malay patients (12.5%). When collectively analyzing data, we observed a significant correlation between younger patients and higher ERG expression (P=0.04). The prevalence of ERG expression was significantly different amongst CaP patients of different ethnicities. The higher number of ERG-expressing tumors among MI patients suggested that the TMPRSS2-ERG fusion may be particularly important in the pathogenesis of CaP amongst this group of patients. Furthermore, the more frequent expression of ERG among the younger patients analyzed suggested an involvement of ERG in the early onset of CaP. The results of this study underline the value of using ERG status to better understand the differences in the etiology of CaP initiation and progression between ethnic groups.
  8. Ishak SD, Tan SH, Khong HK, Jaya-Ram A, Enyu YL, Kuah MK, et al.
    PMID: 19025614 DOI: 10.1186/1477-7827-6-56
    Although unsaturated fatty acids such as eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (ARA, C20:4n-6), collectively known as the highly unsaturated fatty acids (HUFA), play pivotal roles in vertebrate reproduction, very little is known about their synthesis in the ovary. The zebrafish (Danio rerio) display capability to synthesize all three HUFA via pathways involving desaturation and elongation of two precursors, the linoleic acid (LA, C18:2n-6) and linolenic acid (LNA, C18:3n-3). As a prerequisite to gain full understanding on the importance and regulation of ovarian HUFA synthesis, we described here the mRNA expression pattern of two enzymes; desaturase (fadsd6) and elongase (elovl5), involved in HUFA biosynthesis pathway, in different zebrafish ovarian follicle stages. Concurrently, the fatty acid profile of each follicle stage was also analyzed.
  9. Dayrat B, Goulding TC, Apte D, Aslam S, Bourke A, Comendador J, et al.
    Zookeys, 2020;972:1-224.
    PMID: 33071542 DOI: 10.3897/zookeys.972.52853
    The genus Peronia Fleming, 1822 includes all the onchidiid slugs with dorsal gills. Its taxonomy is revised for the first time based on a large collection of fresh material from the entire Indo-West Pacific, from South Africa to Hawaii. Nine species are supported by mitochondrial (COI and 16S) and nuclear (ITS2 and 28S) sequences as well as comparative anatomy. All types available were examined and the nomenclatural status of each existing name in the genus is addressed. Of 31 Peronia species-group names available, 27 are regarded as invalid (twenty-one synonyms, sixteen of which are new, five nomina dubia, and one homonym), and four as valid: Peronia peronii (Cuvier, 1804), Peronia verruculata (Cuvier, 1830), Peronia platei (Hoffmann, 1928), and Peronia madagascariensis (Labbé, 1934a). Five new species names are created: P. griffithsi Dayrat & Goulding, sp. nov., P. okinawensis Dayrat & Goulding, sp. nov., P. setoensis Dayrat & Goulding, sp. nov., P. sydneyensis Dayrat & Goulding, sp. nov., and P. willani Dayrat & Goulding, sp. nov.Peronia species are cryptic externally but can be distinguished using internal characters, with the exception of P. platei and P. setoensis. The anatomy of most species is described in detail here for the first time. All the secondary literature is commented on and historical specimens from museum collections were also examined to better establish species distributions. The genus Peronia includes two species that are widespread across the Indo-West Pacific (P. verruculata and P. peronii) as well as endemic species: P. okinawensis and P. setoensis are endemic to Japan, and P. willani is endemic to Northern Territory, Australia. Many new geographical records are provided, as well as a key to the species using morphological traits.
  10. Tan SH, Karri V, Tay NWR, Chang KH, Ah HY, Ng PQ, et al.
    Biomed Pharmacother, 2019 Mar;111:765-777.
    PMID: 30612001 DOI: 10.1016/j.biopha.2018.12.101
    Neurodegenerative diseases are usually sporadic in nature and commonly influenced by a wide range of genetic, life style and environmental factors. A unifying feature of Alzheimer's disease (AD) and Parkinson's disease (PD) is the abnormal accumulation and processing of mutant or damaged intra and extracellular proteins; this leads to neuronal vulnerability and dysfunction in the brain. Through a detailed review of ubiquitin proteasome, mRNA splicing, mitochondrial dysfunction, and oxidative stress pathway interrelation on neurodegeneration can improve the understanding of the disease mechanism. The identified pathways common to AD and PD nominate promising new targets for further studies, and as well as biomarkers. These insights suggested would likely provide major stimuli for developing unified treatment approaches to combat neurodegeneration. More broadly, pathways can serve as vehicles for integrating findings from diverse studies of neurodegeneration. The evidence examined in this review provides a brief overview of the current literature on significant pathways in promoting in AD, PD. Additionally, these insights suggest that biomarkers and treatment strategies may require simultaneous targeting of multiple components.
  11. Chan CYW, Mohamad SM, Tan SH, Loh LH, Lim JN, Chiu CK, et al.
    Spine (Phila Pa 1976), 2019 03 15;44(6):389-396.
    PMID: 30153211 DOI: 10.1097/BRS.0000000000002853
    STUDY DESIGN: A retrospective study.

    OBJECTIVE: The aim of this study was to compare the perioperative outcome of posterior spinal fusion (PSF) between overweight (OW) adolescent idiopathic scoliosis (AIS) patients and the healthy-weight (HW) patients using propensity score matching analysis.

    SUMMARY OF BACKGROUND DATA: Obesity was found to increase postoperative surgical complications compared with the nonobese group. In scoliosis correction surgery, association of OW and perioperative risks had been explored, but most studies were retrospective in nature.

    METHODS: From 374 patients, two comparable groups were matched using propensity score matching analysis with one-to-one nearest neighbor matching and a caliper of 0.2. There were 46 HW and OW patients in each group. The main outcome measures were intraoperative blood loss, use of allogeneic blood transfusion, operative time, duration of hospital stay post-surgery, total patient-controlled analgesia (PCA) morphine usage, perioperative complications, side bending flexibility (SBF), and correction rate (%).

    RESULTS: The mean age was 13.3 ± 1.7 and 13.2 ± 1.7 years for HW and OW groups, respectively. The majority of the patients were Lenke 1 curves; 32.6% (HW) and 26.1% (OW) with an average Cobb angle of 69.0 ± 19.1° and 68.8 ± 18.4° for each group, respectively. The two groups were comparable. The operation time was 145.2 ± 42.2 and 154.4 ± 48.3 minutes for HW and OW groups, respectively (P > 0.05). The intraoperative blood loss was almost similar in both groups; 955.1 ± 497.7 mL (HW group) and 1011.8 ± 552.7 mL (OW group) (P > 0.05). Total PCA morphine used was higher in OW group (30.4 ± 22.7 mg) than in the HW group (16.2 ± 11.3 mg). No complication was observed in HW group, while in OW group, one patient (2.2%) developed intraoperative seizure.

    CONCLUSION: OW AIS patients (≥85th percentile) had similar mean operative time, intraoperative blood loss, allogeneic transfusion rate, length of stay, and perioperative complications compared with HW AIS patients.

    LEVEL OF EVIDENCE: 3.

  12. Kwan MK, Chiu CK, Hasan MS, Tan SH, Loh LH, Yeo KS, et al.
    Spine (Phila Pa 1976), 2019 03 15;44(6):E348-E356.
    PMID: 30130336 DOI: 10.1097/BRS.0000000000002848
    STUDY DESIGN: Retrospective study.

    OBJECTIVE: To evaluate the perioperative outcome of dual attending surgeon strategy for severe adolescent idiopathic scoliosis (AIS) patients with Cobb angle more than or equal to 90°.

    SUMMARY OF BACKGROUND DATA: The overall complication rate for AIS remains significant and is higher in severe scoliosis. Various operative strategies had been reported for severe scoliosis. However the role of dual attending surgeon strategy in improving the perioperative outcome in severe scoliosis has not been investigated.

    METHODS: The patients were stratified into two groups, Cobb angles 90° to 100° (Group 1) and more than 100° (Group 2). Demographic, intraoperative, preoperative, and postoperative day 2 data were collected. The main outcome measures were intraoperative blood loss, use of allogeneic blood transfusion, operative time, duration of hospital stay postsurgery, and documentation of any perioperative complications.

    RESULTS: Eighty-five patients were recruited. The mean age for the whole cohort was 16.2 ± 5.2 years old. The mean age of Group 1 was 16.7 ± 5.7 and Group 2 was 15.6 ± 4.8 years old. The majority of the patients in both groups were Lenke 2 curves with the average Cobb angle of 93.9 ± 3.0° in Group 1 and 114.2 ± 10.2° in Group 2. The average operative time was 198.5 ± 47.5 minutes with an average blood loss of 1699.5 ± 939.3 mL. The allogeneic blood transfusion rate was 17.6%. The average length of stay postoperation was 71.6 ± 22.5 hours. When comparing the patients between Group 1 and Group 2, the operating time, total blood loss, allogeneic transfusion rate showed significant intergroup differences. Five complications were documented (one intraoperative seizure, one massive blood loss, one intraoperative loss of somatosensory evoked potential (SSEP) signal, and two superficial wound breakdown).

    CONCLUSION: Dual attending surgeon strategy in severe AIS more than or equal to 90° demonstrated an average operative time of 199 minutes, intraoperative blood loss of 1.7 L, postoperative hospital stay of 71.6 hours, and a complication rate of 5.9% (5/85 patients). Curves with Cobb angle more than 100° lead to longer operating time, greater blood loss, and allogeneic transfusion rate.

    LEVEL OF EVIDENCE: 4.

  13. Tan SH, Normi YM, Leow AT, Salleh AB, Murad AM, Mahadi NM, et al.
    J. Biochem., 2017 02 01;161(2):167-186.
    PMID: 28175318 DOI: 10.1093/jb/mvw058
    The effectiveness of β-lactam antibiotics as chemotherapeutic agents to treat bacterial infections is gradually threatened with the emergence of antibiotic resistance mechanism among pathogenic bacteria through the production metallo-β-lactamase (MBL). In this study, we discovered a novel hypothetical protein (HP) termed Bleg1_2437 from the genome of alkaliphilic Bacillus lehensis G1 which exhibited MBL-like properties of B3 subclass; but evolutionary divergent from other circulating B3 MBLs. Domain and sequence analysis of HP Bleg1_2437 revealed that it contains highly conserved Zn2+-binding residues such as H54, H56, D58, H59, H131 and H191, important for catalysis, similar with the subclass B3 of MBL. Built 3-D Bleg1_2437 structure exhibited an αββα sandwich layer similar to the well-conserved global topology of MBL superfamily. Other features include a ceiling and floor in the model which are important for accommodation and orientation of β-lactam antibiotics docked to the protein model showed interactions at varying degrees with residues in the binding pocket of Bleg1_2437. Hydrolysis activity towards several β-lactam antibiotics was proven through an in vitro assay using purified recombinant Bleg1_2437 protein. These findings highlight the presence of a clinically important and evolutionary divergent antibiotics-degrading enzyme within the pools of uncharacterized HPs.
  14. Ling MH, Ivorra T, Heo CC, Wardhana AH, Hall MJR, Tan SH, et al.
    Med Vet Entomol, 2023 Dec;37(4):767-781.
    PMID: 37477152 DOI: 10.1111/mve.12682
    In medical, veterinary and forensic entomology, the ease and affordability of image data acquisition have resulted in whole-image analysis becoming an invaluable approach for species identification. Krawtchouk moment invariants are a classical mathematical transformation that can extract local features from an image, thus allowing subtle species-specific biological variations to be accentuated for subsequent analyses. We extracted Krawtchouk moment invariant features from binarised wing images of 759 male fly specimens from the Calliphoridae, Sarcophagidae and Muscidae families (13 species and a species variant). Subsequently, we trained the Generalized, Unbiased, Interaction Detection and Estimation random forests classifier using linear discriminants derived from these features and inferred the species identity of specimens from the test samples. Fivefold cross-validation results show a 98.56 ± 0.38% (standard error) mean identification accuracy at the family level and a 91.04 ± 1.33% mean identification accuracy at the species level. The mean F1-score of 0.89 ± 0.02 reflects good balance of precision and recall properties of the model. The present study consolidates findings from previous small pilot studies of the usefulness of wing venation patterns for inferring species identities. Thus, the stage is set for the development of a mature data analytic ecosystem for routine computer image-based identification of fly species that are of medical, veterinary and forensic importance.
  15. Tan SH, Normi YM, Leow AT, Salleh AB, Karjiban RA, Murad AM, et al.
    BMC Struct Biol, 2014 Mar 19;14:11.
    PMID: 24641837 DOI: 10.1186/1472-6807-14-11
    BACKGROUND: At least a quarter of any complete genome encodes for hypothetical proteins (HPs) which are largely non-similar to other known, well-characterized proteins. Predicting and solving their structures and functions is imperative to aid understanding of any given organism as a complete biological system. The present study highlights the primary effort to classify and cluster 1202 HPs of Bacillus lehensis G1 alkaliphile to serve as a platform to mine and select specific HP(s) to be studied further in greater detail.

    RESULTS: All HPs of B. lehensis G1 were grouped according to their predicted functions based on the presence of functional domains in their sequences. From the metal-binding group of HPs of the cluster, an HP termed Bleg1_2507 was discovered to contain a thioredoxin (Trx) domain and highly-conserved metal-binding ligands represented by Cys69, Cys73 and His159, similar to all prokaryotic and eukaryotic Sco proteins. The built 3D structure of Bleg1_2507 showed that it shared the βαβαββ core structure of Trx-like proteins as well as three flanking β-sheets, a 310 -helix at the N-terminus and a hairpin structure unique to Sco proteins. Docking simulations provided an interesting view of Bleg1_2507 in association with its putative cytochrome c oxidase subunit II (COXII) redox partner, Bleg1_2337, where the latter can be seen to hold its partner in an embrace, facilitated by hydrophobic and ionic interactions between the proteins. Although Bleg1_2507 shares relatively low sequence identity (47%) to BsSco, interestingly, the predicted metal-binding residues of Bleg1_2507 i.e. Cys-69, Cys-73 and His-159 were located at flexible active loops similar to other Sco proteins across biological taxa. This highlights structural conservation of Sco despite their various functions in prokaryotes and eukaryotes.

    CONCLUSIONS: We propose that HP Bleg1_2507 is a Sco protein which is able to interact with COXII, its redox partner and therefore, may possess metallochaperone and redox functions similar to other documented bacterial Sco proteins. It is hoped that this scientific effort will help to spur the search for other physiologically relevant proteins among the so-called "orphan" proteins of any given organism.

  16. Tan BS, Tiong KH, Choo HL, Chung FF, Hii LW, Tan SH, et al.
    Cell Death Dis, 2015;6:e1826.
    PMID: 26181206 DOI: 10.1038/cddis.2015.191
    p53 is the most frequently mutated tumor-suppressor gene in human cancers. Unlike other tumor-suppressor genes, p53 mutations mainly occur as missense mutations within the DNA-binding domain, leading to the expression of full-length mutant p53 protein. Mutant p53 proteins not only lose their tumor-suppressor function, but may also gain new oncogenic functions and promote tumorigenesis. Here, we showed that silencing of endogenous p53-R273H contact mutant, but not p53-R175H conformational mutant, reduced AKT phosphorylation, induced BCL2-modifying factor (BMF) expression, sensitized BIM dissociation from BCL-XL and induced mitochondria-dependent apoptosis in cancer cells. Importantly, cancer cells harboring endogenous p53-R273H mutant were also found to be inherently resistant to anoikis and lack BMF induction following culture in suspension. Underlying these activities is the ability of p53-R273H mutant to suppress BMF expression that is dependent on constitutively active PI3K/AKT signaling. Collectively, these findings suggest that p53-R273H can specifically drive AKT signaling and suppress BMF expression, resulting in enhanced cell survivability and anoikis resistance. These findings open the possibility that blocking of PI3K/AKT will have therapeutic benefit in mutant p53-R273H expressing cancers.
  17. Lee ECS, Elhassan SAM, Lim GPL, Kok WH, Tan SW, Leong EN, et al.
    Biomed Pharmacother, 2019 Mar;111:198-208.
    PMID: 30583227 DOI: 10.1016/j.biopha.2018.12.052
    For many years, circular ribonucleic acids (circRNAs) have been counted as aberrant splicing by-products. Advanced bioinformatics analysis and deep sequencing techniques have allowed researchers to discover more interesting facts about circRNAs. Intriguing evidence has shed light on the functions of circRNAs in many tissues. Furthermore, emerging reports showed that circRNAs are found abundantly in saliva and blood samples, suggesting that circRNAs are potential clinical biomarkers for human embryonic development, diseases progression and prognosis, in addition to its role in organogenesis and pathogenesis. The implementation of circRNAs in human developmental stages and diseases would be a tremendous discovery in the science and medical field. Therefore, circRNAs have been studied for its biological function as well as its implication in various human diseases. The aim of this review is to highlight the importance of circRNAs in cardiac, respiratory, nervous, endocrine and digestive systems. In addition, the role and impact of circRNAs in, cardiogenesis, neurogenesis and cancer have been discussed.
  18. Tan SY, Mei Wong JL, Sim YJ, Wong SS, Mohamed Elhassan SA, Tan SH, et al.
    Diabetes Metab Syndr, 2018 10 10;13(1):364-372.
    PMID: 30641727 DOI: 10.1016/j.dsx.2018.10.008
    Type 1 and type 2 diabetes mellitus is a serious and lifelong condition commonly characterised by abnormally elevated blood glucose levels due to a failure in insulin production or a decrease in insulin sensitivity and function. Over the years, prevalence of diabetes has increased globally and it is classified as one of the leading cause of high mortality and morbidity rate. Furthermore, diabetes confers a huge economic burden due to its management costs as well as its complications are skyrocketing. The conventional medications in diabetes treatment focusing on insulin secretion and insulin sensitisation cause unwanted side effects to patients and lead to incompliance as well as treatment failure. Besides insulin and oral hypoglycaemic agents, other treatments such as gene therapy and induced β-cells regeneration have not been widely introduced to manage diabetes. Therefore, this review aims to deliver an overview of the current conventional medications in diabetes, discovery of newer pharmacological drugs and gene therapy as a potential intervention of diabetes in the future.
  19. Raziff HHA, Tan D, Tan SH, Wong YH, Lim KS, Yeong CH, et al.
    Phys Med, 2021 Feb;82:40-45.
    PMID: 33581616 DOI: 10.1016/j.ejmp.2021.01.067
    PURPOSE: To investigate the efficacy of a newly-developed laser-heated core biopsy needle in the thermal ablation of biopsy tract to reduce hemorrhage after biopsy using in vivo rabbit's liver model.

    MATERIALS AND METHODS: Five male New Zealand White rabbits weighed between 1.5 and 4.0 kg were anesthetized and their livers were exposed. 18 liver biopsies were performed under control group (without tract ablation, n = 9) and study group (with tract ablation, n = 9) settings. The needle insertion depth (~3 cm) and rate of retraction (~3 mm/s) were fixed in all the experiments. For tract ablation, three different needle temperatures (100, 120 and 150 °C) were compared. The blood loss at each biopsy site was measured by weighing the gauze pads before and after blood absorption. The rabbits were euthanized immediately and the liver specimens were stained with hematoxylin-eosin (H&E) for further histopathological examination (HPE).

    RESULTS: The average blood loss in the study group was reduced significantly (p 

  20. Soo HC, Chung FF, Lim KH, Yap VA, Bradshaw TD, Hii LW, et al.
    PLoS One, 2017;12(1):e0170551.
    PMID: 28107519 DOI: 10.1371/journal.pone.0170551
    Cudraflavone C (Cud C) is a naturally-occurring flavonol with reported anti-proliferative activities. However, the mechanisms by which Cud C induced cytotoxicity have yet to be fully elucidated. Here, we investigated the effects of Cud C on cell proliferation, caspase activation andapoptosis induction in colorectal cancer cells (CRC). We show that Cud C inhibits cell proliferation in KM12, Caco-2, HT29, HCC2998, HCT116 and SW48 CRC but not in the non-transformed colorectal epithelial cells, CCD CoN 841. Cud C induces tumor-selective apoptosis via mitochondrial depolarization and activation of the intrinsic caspase pathway. Gene expression profiling by microarray analyses revealed that tumor suppressor genes EGR1, HUWE1 and SMG1 were significantly up-regulated while oncogenes such as MYB1, CCNB1 and GPX2 were down-regulated following treatment with Cud C. Further analyses using Connectivity Map revealed that Cud C induced a gene signature highly similar to that of protein synthesis inhibitors and phosphoinositide 3-kinase (PI3K)-AKT inhibitors, suggesting that Cud C might inhibit PI3K-AKT signaling. A luminescent cell free PI3K lipid kinase assay revealed that Cud C significantly inhibited p110β/p85α PI3K activity, followed by p120γ, p110δ/p85α, and p110α/p85α PI3K activities. The inhibition by Cud C on p110β/p85α PI3K activity was comparable to LY-294002, a known PI3K inhibitor. Cud C also inhibited phosphorylation of AKT independent of NFκB activity in CRC cells, while ectopic expression of myristoylated AKT completely abrogated the anti-proliferative effects, and apoptosis induced by Cud C in CRC. These findings demonstrate that Cud C induces tumor-selective cytotoxicity by targeting the PI3K-AKT pathway. These findings provide novel insights into the mechanism of action of Cud C, and indicate that Cud C further development of Cud C derivatives as potential therapeutic agents is warranted.
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