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Fulltext Epstein-Barr Virus as a Promising Immunotherapeutic Target for Nasopharyngeal Carcinoma Treatment

Teow SY, Yap HY, Peh SC

J Pathog, 2017;2017:7349268.
PMID: 29464124 DOI: 10.1155/2017/7349268

Epstein-Barr virus (EBV) is a pathogen that infects more than 90% of global human population. EBV primarily targets B-lymphocytes and epithelial cells while some of them infect monocyte/macrophage, T-lymphocytes, and dendritic cells (DCs). EBV infection does not cause death by itself but the infection has been persistently associated with certain type of cancers such as nasopharyngeal carcinoma (NPC), Burkitt's lymphoma (BL), and Hodgkin's lymphoma (HL). Recent findings have shown promise on targeting EBV proteins for cancer therapy by immunotherapeutic approach. Some studies have also shown the success of adopting EBV-based therapeutic vaccines for the prevention of EBV-associated cancer particularly on NPC. In-depth investigations are in progress to refine the current therapeutic and vaccination strategies. In present review, we discuss the highly potential EBV targets for NPC immunotherapy and therapeutic vaccine development as well as addressing the underlying challenges in the process of bringing the therapy and vaccination from the bench to bedside.
Fulltext In-air Hand Gesture Signature Recognition: An iHGS Database Acquisition Protocol

Khoh WH, Pang YH, Yap HY

F1000Res, 2022;11:283.
PMID: 37600220 DOI: 10.12688/f1000research.74134.2

Background: With the advances in current technology, hand gesture recognition has gained considerable attention. It has been extended to recognize more distinctive movements, such as a signature, in human-computer interaction (HCI) which enables the computer to identify a person in a non-contact acquisition environment. This application is known as in-air hand gesture signature recognition. To our knowledge, there are no publicly accessible databases and no detailed descriptions of the acquisitional protocol in this domain. Methods: This paper aims to demonstrate the procedure for collecting the in-air hand gesture signature's database. This database is disseminated as a reference database in the relevant field for evaluation purposes. The database is constructed from the signatures of 100 volunteer participants, who contributed their signatures in two different sessions. Each session provided 10 genuine samples enrolled using a Microsoft Kinect sensor camera to generate a genuine dataset. In addition, a forgery dataset was also collected by imitating the genuine samples. For evaluation, each sample was preprocessed with hand localization and predictive hand segmentation algorithms to extract the hand region. Then, several vector-based features were extracted. Results: In this work, classification performance analysis and system robustness analysis were carried out. In the classification analysis, a multiclass Support Vector Machine (SVM) was employed to classify the samples and 97.43% accuracy was achieved; while the system robustness analysis demonstrated low error rates of 2.41% and 5.07% in random forgery and skilled forgery attacks, respectively. Conclusions: These findings indicate that hand gesture signature is not only feasible for human classification, but its properties are also robust against forgery attacks.
Fulltext Epstein-Barr Virus- (EBV-) Immortalized Lymphoblastoid Cell Lines (LCLs) Express High Level of CD23 but Low CD27 to Support Their Growth

Yap HY, Siow TS, Chow SK, Teow SY

Adv Virol, 2019;2019:6464521.
PMID: 31049064 DOI: 10.1155/2019/6464521

Epstein-Barr virus (EBV) is one of the common human herpesvirus types in the world. EBV is known to infect more than 95% of adults in the world. The virus mainly infects B lymphocytes and could immortalize and transform the cells into EBV-bearing lymphoblastoid cell lines (LCLs). Limited studies have been focused on characterizing the surface marker expression of the immortalized LCLs. This study demonstrates the generation of 15 LCLs from sixteen rheumatoid arthritis (RA) patients and a healthy volunteer using B95-8 marmoset-derived EBV. The success rate of LCL generation was 88.23%. All CD19+ LCLs expressed CD23 (16.94-58.9%) and CD27 (15.74-80.89%) on cell surface. Our data demonstrated two distinct categories of LCLs (fast- and slow-growing) (p<0.05) based on their doubling time. The slow-growing LCLs showed lower CD23 level (35.28%) compared to fast-growing LCLs (42.39%). In contrast, the slow-growing LCLs showed higher percentage in both CD27 alone and CD23+CD27+ in combination. Overall, these findings may suggest the correlations of cellular CD23 and CD27 expression with the proliferation rate of the generated LCLs. Increase expression of CD23 may play a role in EBV immortalization of B-cells and the growth and maintenance of the EBV-transformed LCLs while CD27 expression might have inhibitory effects on LCL proliferation. Further investigations are warranted to these speculations.

Study site: Sunway Medical Centre, Malaysia
Fulltext Person authentication based on eye-closed and visual stimulation using EEG signals

Yap HY, Choo YH, Mohd Yusoh ZI, Khoh WH

Brain Inform, 2021 Oct 11;8(1):21.
PMID: 34633582 DOI: 10.1186/s40708-021-00142-4

The study of Electroencephalogram (EEG)-based biometric has gained the attention of researchers due to the neurons' unique electrical activity representation of an individual. However, the practical application of EEG-based biometrics is not currently widespread and there are some challenges to its implementation. Nowadays, the evaluation of a biometric system is user driven. Usability is one of the concerning issues that determine the success of the system. The basic elements of the usability of a biometric system are effectiveness, efficiency and user satisfaction. Apart from the mandatory consideration of the biometric system's performance, users also need an easy-to-use and easy-to-learn authentication system. Thus, to satisfy these user requirements, this paper proposes a reasonable acquisition period and employs a consumer-grade EEG device to authenticate an individual to identify the performances of two acquisition protocols: eyes-closed (EC) and visual stimulation. A self-collected database of eight subjects was utilized in the analysis. The recording process was divided into two sessions, which were the morning and afternoon sessions. In each session, the subject was requested to perform two different tasks: EC and visual stimulation. The pairwise correlation of the preprocessed EEG signals of each electrode channel was determined and a feature vector was formed. Support vector machine (SVM) was then used for classification purposes. In the performance analysis, promising results were obtained, where EC protocol achieved an accuracy performance of 83.70-96.42% while visual stimulation protocol attained an accuracy performance of 87.64-99.06%. These results have demonstrated the feasibility and reliability of our acquisition protocols with consumer-grade EEG devices.
An evaluation of transfer learning models in EEG-based authentication

Yap HY, Choo YH, Mohd Yusoh ZI, Khoh WH

Brain Inform, 2023 Aug 03;10(1):19.
PMID: 37535168 DOI: 10.1186/s40708-023-00198-4

Electroencephalogram(EEG)-based authentication has received increasing attention from researchers as they believe it could serve as an alternative to more conventional personal authentication methods. Unfortunately, EEG signals are non-stationary and could be easily contaminated by noise and artifacts. Therefore, further processing of data analysis is needed to retrieve useful information. Various machine learning approaches have been proposed and implemented in the EEG-based domain, with deep learning being the most current trend. However, retaining the performance of a deep learning model requires substantial computational effort and a vast amount of data, especially when the models go deeper to generate consistent results. Deep learning models trained with small data sets from scratch may experience an overfitting issue. Transfer learning becomes an alternative solution. It is a technique to recognize and apply the knowledge and skills learned from the previous tasks to a new domain with limited training data. This study attempts to explore the applicability of transferring various pre-trained models' knowledge to the EEG-based authentication domain. A self-collected database that consists of 30 subjects was utilized in the analysis. The database enrolment is divided into two sessions, with each session producing two sets of EEG recording data. The frequency spectrums of the preprocessed EEG signals are extracted and fed into the pre-trained models as the input data. Three experimental tests are carried out and the best performance is reported with accuracy in the range of 99.1-99.9%. The acquired results demonstrate the efficiency of transfer learning in authenticating an individual in this domain.
Fulltext Transcriptome Analysis Revealed Highly Expressed Genes Encoding Secondary Metabolite Pathways and Small Cysteine-Rich Proteins in the Sclerotium of Lignosus rhinocerotis

Yap HY, Chooi YH, Fung SY, Ng ST, Tan CS, Tan NH

PLoS One, 2015;10(11):e0143549.
PMID: 26606395 DOI: 10.1371/journal.pone.0143549

Lignosus rhinocerotis (Cooke) Ryvarden (tiger milk mushroom) has long been known for its nutritional and medicinal benefits among the local communities in Southeast Asia. However, the molecular and genetic basis of its medicinal and nutraceutical properties at transcriptional level have not been investigated. In this study, the transcriptome of L. rhinocerotis sclerotium, the part with medicinal value, was analyzed using high-throughput Illumina HiSeqTM platform with good sequencing quality and alignment results. A total of 3,673, 117, and 59,649 events of alternative splicing, novel transcripts, and SNP variation were found to enrich its current genome database. A large number of transcripts were expressed and involved in the processing of gene information and carbohydrate metabolism. A few highly expressed genes encoding the cysteine-rich cerato-platanin, hydrophobins, and sugar-binding lectins were identified and their possible roles in L. rhinocerotis were discussed. Genes encoding enzymes involved in the biosynthesis of glucans, six gene clusters encoding four terpene synthases and one each of non-ribosomal peptide synthetase and polyketide synthase, and 109 transcribed cytochrome P450 sequences were also identified in the transcriptome. The data from this study forms a valuable foundation for future research in the exploitation of this mushroom in pharmacological and industrial applications.
Fulltext Genome-based proteomic analysis of Lignosus rhinocerotis (Cooke) Ryvarden sclerotium

Yap HY, Fung SY, Ng ST, Tan CS, Tan NH

Int J Med Sci, 2015;12(1):23-31.
PMID: 25552915 DOI: 10.7150/ijms.10019

Lignosus rhinocerotis (Cooke) Ryvarden (Polyporales, Basidiomycota), also known as the tiger milk mushroom, has received much interest in recent years owing to its wide-range ethnobotanical uses and the recent success in its domestication. The sclerotium is the part with medicinal value. Using two-dimensional gel electrophoresis coupled with mass spectrometry analysis, a total of 16 non-redundant, major proteins were identified with high confidence level in L. rhinocerotis sclerotium based on its genome as custom mapping database. Some of these proteins, such as the putative lectins, immunomodulatory proteins, superoxide dismutase, and aegerolysin may have pharmaceutical potential; while others are involved in nutrient mobilization and the protective antioxidant mechanism in the sclerotium. The findings from this study provide a molecular basis for future research on potential pharmacologically active proteins of L. rhinocerotis.
Fulltext Energy and nutritional composition of Tiger milk mushroom (Lignosus tigris Chon S. Tan) sclerotia and the antioxidant activity of its extracts

Yap HY, Aziz AA, Fung SY, Ng ST, Tan CS, Tan NH

Int J Med Sci, 2014;11(6):602-7.
PMID: 24782649 DOI: 10.7150/ijms.8341

The Lignosus is a genus of fungi that have useful medicinal properties. In Southeast Asia, three species of Lignosus (locally known collectively as Tiger milk mushrooms) have been reported including L. tigris, L. rhinocerotis, and L. cameronensis. All three have been used as important medicinal mushrooms by the natives of Peninsular Malaysia. In this work, the nutritional composition and antioxidant activities of the wild type and a cultivated strain of L. tigris sclerotial extracts were investigated. The sclerotia are rich in carbohydrates with moderate amount of protein and low fat content. Free radical scavenging activities of L. tigris sclerotial extracts correlate with their phenolic content, which ranges from 6.25 to 45.42 mg GAE/g extract. The FRAP values ranged from 0.002 to 0.041 mmol/min/g extract, while the DPPH(•), ABTS(•+), and superoxide anion (SOA) scavenging activities ranged from 0.18 to 2.53, 0.01 to 0.36, and -4.53 to 10.05 mmol Trolox equivalents/g extract, respectively. L. tigris cultivar shows good prospect to be developed into functional food due to its good nutritional value and potent SOA scavenging activity.
Fulltext Draft Genome Sequence of Pasteurella multocida subsp. multocida Strain PMTB, Isolated from a Buffalo

Yap HY, Ghazali K, Wan Mohamad Nazarie WF, Mat Isa MN, Zakaria Z, Omar AR

Genome Announc, 2013;1(5).
PMID: 24136854 DOI: 10.1128/genomeA.00872-13

Pasteurella multocida serotypes B:2 and E:2 are the main causative agents of ruminant hemorrhagic septicemia in Asia and Africa, respectively. Pasteurella multocida strain PMTB was isolated from a buffalo with hemorrhagic septicemia and has been determined to be serotype B:2. Here we report the draft genome sequence of strain PMTB.
Shotgun proteomic analysis of tiger milk mushroom (Lignosus rhinocerotis) and the isolation of a cytotoxic fungal serine protease from its sclerotium

Yap HY, Fung SY, Ng ST, Tan CS, Tan NH

J Ethnopharmacol, 2015 Nov 4;174:437-51.
PMID: 26320692 DOI: 10.1016/j.jep.2015.08.042

The sclerotium of Lignosus rhinocerotis (Cooke) Ryvarden (tiger milk mushroom) has been traditionally used as a complementary and alternative medicine for cancer treatment by the local communities of Southeast Asia. Despite the continuous research interest in its antiproliferative activity, the identity of the bioactive compound(s) responsible has yet to be determined. This study aims to bridge the gap in existing research literature by using proteomics approach for investigation of the nature of the anticancer substance of L. rhinocerotis.
Fulltext Bactericidal Properties of Plants-Derived Metal and Metal Oxide Nanoparticles (NPs)

Teow SY, Wong MM, Yap HY, Peh SC, Shameli K

Molecules, 2018 06 06;23(6).
PMID: 29882775 DOI: 10.3390/molecules23061366

Nanoparticles (NPs) are nano-sized particles (generally 1⁻100 nm) that can be synthesized through various methods. The wide range of physicochemical characteristics of NPs permit them to have diverse biological functions. These particles are versatile and can be adopted into various applications, particularly in biomedical field. In the past five years, NPs’ roles in biomedical applications have drawn considerable attentions, and novel NPs with improved functions and reduced toxicity are continuously increasing. Extensive studies have been carried out in evaluating antibacterial potentials of NPs. The promising antibacterial effects exhibited by NPs highlight the potential of developing them into future generation of antimicrobial agents. There are various methods to synthesize NPs, and each of the method has significant implication on the biological action of NPs. Among all synthetic methods, green technology is the least toxic biological route, which is particularly suitable for biomedical applications. This mini-review provides current update on the antibacterial effects of NPs synthesized by green technology using plants. Underlying challenges in developing NPs into future antibacterials in clinics are also discussed at the present review.
Fulltext Pathogenic role of immune cells in rheumatoid arthritis: implications in clinical treatment and biomarker development

Yap HY, Tee SZ, Wong MM, Chow SK, Peh SC, Teow SY

Cells, 2018 Oct 09;7(10).
PMID: 30304822 DOI: 10.3390/cells7100161

Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, inflammatory disorder that affects synovial joints, both small and large joints, in a symmetric pattern. This disorder usually does not directly cause death but significantly reduces the quality of life and life expectancy of patients if left untreated. There is no cure for RA but, patients are usually on long-term disease modifying anti-rheumatic drugs (DMARDs) to suppress the joint inflammation, to minimize joint damage, to preserve joint function, and to keep the disease in remission. RA is strongly associated with various immune cells and each of the cell type contributes differently to the disease pathogenesis. Several types of immunomodulatory molecules mainly cytokines secreted from immune cells mediate pathogenesis of RA, hence complicating the disease treatment and management. There are various treatments for RA depending on the severity of the disease and more importantly, the patient's response towards the given drugs. Early diagnosis of RA and treatment with (DMARDs) are known to significantly improve the treatment outcome of patients. Sensitive biomarkers are crucial in early detection of disease as well as to monitor the disease activity and progress. This review aims to discuss the pathogenic role of various immune cells and immunological molecules in RA. This review also highlights the importance of understanding the immune cells in treating RA and in exploring novel biomarkers.
Fulltext Inhibition of Protein Glycation by Tiger Milk Mushroom [Lignosus rhinocerus(Cooke) Ryvarden] and Search for Potential Anti-diabetic Activity-Related Metabolic Pathways by Genomic and Transcriptomic Data Mining

Yap HY, Tan NH, Ng ST, Tan CS, Fung SY

Front Pharmacol, 2018;9:103.
PMID: 29491836 DOI: 10.3389/fphar.2018.00103

Naturally occurring anti-glycation compounds have drawn much interest in recent years as they show potential in reducing or preventing the risk of chronic complications for diabetic patients. In this study, annotation of the genome-transcriptome data from tiger milk mushroom (Lignosus rhinocerus, syn.Lignosus rhinocerotis) to PlantCyc enzymes database identified transcripts that are related to anti-diabetic properties, and these include genes that are involved in carotenoid and abscisic acid biosynthesis as well as genes that code for glyoxalase I, catalase-peroxidases, and superoxide dismutases. The existence of these genes suggests thatL. rhinocerusmay contain bioactive compound(s) with anti-glycation properties that can be exploited for management of diabetic complications. A medium-molecular-weight (MMW) fraction which was obtained from a combination of cold water extraction and Sephadex®G-50 (fine) gel filtration chromatography ofL. rhinocerussclerotia powder was demonstrated to exhibit potent anti-glycation activity. The fraction specifically inhibited the formation of N𝜀-(carboxymethyl)lysine, pentosidine, and other advanced glycation end-product (AGE) structures in a human serum albumin-glucose system, with an IC50value of 0.001 mg/ml, almost 520 times lower than that of the positive control, aminoguanidine hydrochloride (IC50= 0.52 mg/ml). Its ability to suppress protein glycation may be partly associated with its strong superoxide anion radical scavenging activity (10.16 ± 0.12 mmol TE/g). Our results suggest that the MMW fraction ofL. rhinocerusshows potential to be developed into a potent glycation inhibitor for preventing AGE-mediated diabetic complications.
Fulltext The Wound Healing Potential of Lignosus rhinocerus and Other Ethno-myco Wound Healing Agents

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.
Fulltext The genome of the Tiger Milk mushroom, Lignosus rhinocerotis, provides insights into the genetic basis of its medicinal properties

Yap HY, Chooi YH, Firdaus-Raih M, Fung SY, Ng ST, Tan CS, et al.

BMC Genomics, 2014;15:635.
PMID: 25073817 DOI: 10.1186/1471-2164-15-635

The sclerotium of Lignosus rhinocerotis (Cooke) Ryvarden or Tiger milk mushroom (Polyporales, Basidiomycota) is a valuable folk medicine for indigenous peoples in Southeast Asia. Despite the increasing interest in this ethnobotanical mushroom, very little is known about the molecular and genetic basis of its medicinal and nutraceutical properties.
Fulltext Complete Genome Sequence Analysis and Characterization of Selected Iron Regulation Genes of Pasteurella Multocida Serotype A Strain PMTB2.1

Jabeen S, Yap HY, Abdullah FFJ, Zakaria Z, Isa NM, Tan YC, et al.

Genes (Basel), 2019 01 25;10(2).
PMID: 30691021 DOI: 10.3390/genes10020081

Although more than 100 genome sequences of Pasteurella multocida are available, comprehensive and complete genome sequence analysis is limited. This study describes the analysis of complete genome sequence and pathogenomics of P. multocida strain PMTB2.1. The genome of PMTB2.1 has 2176 genes with more than 40 coding sequences associated with iron regulation and 140 virulence genes including the complete tad locus. The tad locus includes several previously uncharacterized genes such as flp2, rcpC and tadV genes. A transposable phage resembling to Mu phages was identified in P. multocida that has not been identified in any other serotype yet. The multi-locus sequence typing analysis assigned the PMTB2.1 genome sequence as type ST101, while the comparative genome analysis showed that PMTB2.1 is closely related to other P. multocida strains with the genomic distance of less than 0.13. The expression profiling of iron regulating-genes of PMTB2.1 was characterized under iron-limited environment. Results showed significant changes in the expression profiles of iron-regulating genes (p < 0.05) whereas the highest expression of fecE gene (281 fold) at 30 min suggests utilization of the outer-membrane proteins system in iron acquisition at an early stage of growth. This study showed the phylogenomic relatedness of P. multocida and improved annotation of important genes and functional characterization of iron-regulating genes of importance to the bacterial growth.
Association between autophagy and KRAS mutation with clinicopathological variables in colorectal cancer patients

Awi NJ, Yap HY, Armon S, Low JSH, Peh KB, Peh SC, et al.

Malays J Pathol, 2021 Aug;43(2):269-279.
PMID: 34448791

Autophagy is a host defensive mechanism responsible for eliminating harmful cellular components through lysosomal degradation. Autophagy has been known to either promote or suppress various cancers including colorectal cancer (CRC). KRAS mutation serves as an important predictive marker for epidermal growth factor receptor (EGFR)-targeted therapies in CRC. However, the relationship between autophagy and KRAS mutation in CRC is not well-studied. In this single-centre study, 92 formalin-fixed paraffin-embedded (FFPE) tissues of CRC patients (42 Malaysian Chinese and 50 Indonesian) were collected and KRAS mutational status was determined by quantitative PCR (qPCR) (n=92) while the expression of autophagy effector (p62, LC3A and LC3B) was examined by immunohistochemistry (IHC) (n=48). The outcomes of each were then associated with the clinicopathological variables (n=48). Our findings demonstrated that the female CRC patients have a higher tendency in developing KRAS mutation in the Malaysian Chinese population (p<0.05). Expression of autophagy effector LC3A was highly associated with the tumour grade in CRC (p<0.001) but not with other clinicopathological parameters. Lastly, the survival analysis did not yield a statistically significant outcome. Overall, this small cohort study concluded that KRAS mutation and autophagy effectors are not good prognostic markers for CRC patients.
Fulltext An assessment of oral cancer knowledge, attitudes, and practices among undergraduate students in Malaysian dental schools

Chan ZW, Phuan YF, Ooi PY, Nor Azmi N, Pateel DGS, Yap HY, et al.

BMC Oral Health, 2023 Aug 31;23(1):617.
PMID: 37653402 DOI: 10.1186/s12903-023-03354-8

BACKGROUND: Oral cancer is a significant public health concern worldwide. Early detection and prevention are crucial in reducing the morbidity and mortality rates associated with this disease. As future dental professionals, dental undergraduates play a vital role in promoting oral health and identifying potential oral cancer cases.
METHODS: This study aimed to evaluate the level of oral cancer awareness, knowledge, attitudes, and practices among dental undergraduates in Malaysia. A total of 595 students from years 3, 4, and 5 in both public and private universities participated.
RESULTS: The results showed that a higher percentage of dental undergraduates from private universities were aware of oral cancer and had satisfactory knowledge compared to those from public universities (p
RNA-seq transcriptome and pathway analysis of the medicinal mushroom Lignosus tigris (Polyporaceae) offer insights into its bioactive compounds with anticancer and antioxidant potential

Ng MJ, Mohamad Razif MF, Kong BH, Yap HY, Ng ST, Tan CS, et al.

J Ethnopharmacol, 2024 Jun 28;328:118073.
PMID: 38513780 DOI: 10.1016/j.jep.2024.118073

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal mushrooms belonging to the Lignosus spp., colloquially known as Tiger Milk mushrooms (TMMs), are used as traditional medicine by communities across various regions of China and Southeast Asia to enhance immunity and to treat various diseases. At present, three Lignosus species have been identified in Malaysia: L. rhinocerus, L. tigris, and L. cameronensis. Similarities in their macroscopic morphologies and the nearly indistinguishable appearance of their sclerotia often lead to interchangeability between them. Hence, substantiation of their traditional applications via identification of their individual bioactive properties is imperative in ensuring that they are safe for consumption. L. tigris was first identified in 2013. Thus far, studies on L. tigris cultivar sclerotia (Ligno TG-K) have shown that it possesses significant antioxidant activities and has greater antiproliferative action against selected cancer cells in vitro compared to its sister species, L. rhinocerus TM02®. Our previous genomics study also revealed significant genetic dissimilarities between them. Further omics investigations on Ligno TG-K hold immense potential in facilitating the identification of its bioactive compounds and their associated bioactivities.
AIM OF STUDY: The overall aim of this study was to investigate the gene expression profile of Ligno TG-K via de novo RNA-seq and pathway analysis. We also aimed to identify highly expressed genes encoding compounds that contribute to its cytotoxic and antioxidant properties, as well as perform a comparative transcriptomics analysis between Ligno TG-K and its sister species, L. rhinocerus TM02®.
MATERIALS AND METHODS: Total RNA from fresh 3-month-old cultivated L. tigris sclerotia (Ligno TG-K) was extracted and analyzed via de novo RNA sequencing. Expressed genes were analyzed using InterPro and NCBI-Nr databases for domain identification and homology search. Functional categorization based on gene functions and pathways was performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Clusters of Orthologous Genes (COG) databases. Selected genes were subsequently subjected to phylogenetic analysis.
RESULTS: Our transcriptomics analysis of Ligno TG-K revealed that 68.06% of its genes are expressed in the sclerotium; 80.38% of these were coding transcripts. Our analysis identified highly expressed transcripts encoding proteins with prospective medicinal properties. These included serine proteases (FPKM = 7356.68), deoxyribonucleases (FPKM = 3777.98), lectins (FPKM = 3690.87), and fungal immunomodulatory proteins (FPKM = 2337.84), all of which have known associations with anticancer activities. Transcripts linked to proteins with antioxidant activities, such as superoxide dismutase (FPKM = 1161.69) and catalase (FPKM = 1905.83), were also highly expressed. Results of our sequence alignments revealed that these genes and their orthologs can be found in other mushrooms. They exhibit significant sequence similarities, suggesting possible parallels in their anticancer and antioxidant bioactivities.
CONCLUSION: This study is the first to provide a reference transcriptome profile of genes expressed in the sclerotia of L. tigris. The current study also presents distinct COG profiles of highly expressed genes in Ligno TG-K and L. rhinocerus TM02®, highlighting that any distinctions uncovered may be attributed to their interspecies variations and inherent characteristics that are unique to each species. Our findings suggest that Ligno TG-K contains bioactive compounds with prospective medicinal properties that warrant further investigations.
CLASSIFICATION: Systems biology and omics.
Fulltext Heterologous expression of cytotoxic sesquiterpenoids from the medicinal mushroom Lignosus rhinocerotis in yeast

Yap HY, Muria-Gonzalez MJ, Kong BH, Stubbs KA, Tan CS, Ng ST, et al.

Microb Cell Fact, 2017 Jun 12;16(1):103.
PMID: 28606152 DOI: 10.1186/s12934-017-0713-x

BACKGROUND: Genome mining facilitated by heterologous systems is an emerging approach to access the chemical diversity encoded in basidiomycete genomes. In this study, three sesquiterpene synthase genes, GME3634, GME3638, and GME9210, which were highly expressed in the sclerotium of the medicinal mushroom Lignosus rhinocerotis, were cloned and heterologously expressed in a yeast system.
RESULTS: Metabolite profile analysis of the yeast culture extracts by GC-MS showed the production of several sesquiterpene alcohols (C15H26O), including cadinols and germacrene D-4-ol as major products. Other detected sesquiterpenes include selina-6-en-4-ol, β-elemene, β-cubebene, and cedrene. Two purified major compounds namely (+)-torreyol and α-cadinol synthesised by GME3638 and GME3634 respectively, are stereoisomers and their chemical structures were confirmed by 1H and 13C NMR. Phylogenetic analysis revealed that GME3638 and GME3634 are a pair of orthologues, and are grouped together with terpene synthases that synthesise cadinenes and related sesquiterpenes. (+)-Torreyol and α-cadinol were tested against a panel of human cancer cell lines and the latter was found to exhibit selective potent cytotoxicity in breast adenocarcinoma cells (MCF7) with IC50 value of 3.5 ± 0.58 μg/ml while α-cadinol is less active (IC50 = 18.0 ± 3.27 μg/ml).
CONCLUSIONS: This demonstrates that yeast-based genome mining, guided by transcriptomics, is a promising approach for uncovering bioactive compounds from medicinal mushrooms.

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