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Article ; Online: The Medicinal Mushroom Ganoderma neo-japonicum (Agaricomycetes) Polysaccharide Extract Prevents Obesity-Induced Diabetes in C57BL/6J Mice.

Subramaniam, Sarasvathy / Ong, Kien Chai / Sabaratnam, Vikineswary / Chua, Kek Heng / Kuppusamy, Umah Rani

International journal of medicinal mushrooms

2023 Volume 25, Issue 4, Page(s) 27–42

Abstract: Ganoderma neo-japonicum Imazeki is a medicinal mushroom consumed by the indigenous people in Malaysia as a remedy for diabetes. This study aims to validate the efficacy of G. neo-japonicum polysaccharides (GNJP) on obesity-induced type 2 diabetes ... ...

Abstract	Ganoderma neo-japonicum Imazeki is a medicinal mushroom consumed by the indigenous people in Malaysia as a remedy for diabetes. This study aims to validate the efficacy of G. neo-japonicum polysaccharides (GNJP) on obesity-induced type 2 diabetes mellitus (T2DM) in C57BL/6J mice. Mice were divided into seven groups; normal diet (ND)-control, high-fat-diet (HFD)-control, HFDGNJP-treated (50, 100, 200 mg/kg b.w.), HFDMET (metformin 50 mg/kg; positive-control) and ND-GNJP (200 mg/kg b.w.). Mice were administered GNJP or metformin orally for 10 weeks (thrice/week) and sacrificed after an oral glucose tolerance test. Body weight, serum biochemicals, liver histology, adipocyte gene expressions, glucose and insulin levels were measured. HFD caused obesity, dyslipidemia, and diabetes in the untreated groups. GNJP (50 mg/kg b.w.) supplementation prevented weight gain and liver steatosis, improved serum lipid profile and glucose tolerance and attenuated hyperglycemia and hyperinsulinemia more effectively when compared with the other treatment groups. The prevention of obesity and lipid dysregulation is plausibly attributed to the increased hormone-sensitive lipase and reduced Akt-1 and Ppary gene expressions while the up-regulation of AdipoQ (adiponectin), Prkag2 and Slc2a4 genes served to sensitize insulin and improve glucose uptake. Thus, supplementation with an appropriate dose of GNJP has promising efficacies in preventing HFD aka obesity-induced T2DM and associated metabolic abnormalities.
MeSH term(s)	Animals ; Mice ; Insulin Resistance ; Diabetes Mellitus, Type 2/prevention & control ; Agaricales/metabolism ; Mice, Inbred C57BL ; Blood Glucose/metabolism ; Obesity/complications ; Obesity/prevention & control ; Insulin/metabolism ; Polysaccharides ; Diet, High-Fat/adverse effects ; Metformin/therapeutic use ; Basidiomycota/metabolism ; Lipids
Chemical Substances	Blood Glucose ; Insulin ; Polysaccharides ; Metformin (9100L32L2N) ; Lipids
Language	English
Publishing date	2023-04-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2108803-2
ISSN	1940-4344 ; 1521-9437
ISSN (online)	1940-4344
ISSN	1521-9437
DOI	10.1615/IntJMedMushrooms.2023047595
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Article ; Online: Natural-derived compounds and their mechanisms in potential autosomal dominant polycystic kidney disease (ADPKD) treatment.

Mahendran, Rhubaniya / Lim, Soo Kun / Ong, Kien Chai / Chua, Kek Heng / Chai, Hwa Chia

Clinical and experimental nephrology

2021 Volume 25, Issue 11, Page(s) 1163–1172

Abstract: Background: Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic kidney disorder that impairs renal functions progressively leading to kidney failure. The disease affects between 1:400 and 1:1000 ratio of the people worldwide. It is ... ...

Abstract	Background: Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic kidney disorder that impairs renal functions progressively leading to kidney failure. The disease affects between 1:400 and 1:1000 ratio of the people worldwide. It is caused by the mutated PKD1 and PKD2 genes which encode for the defective polycystins. Polycystins mimic the receptor protein or protein channel and mediate aberrant cell signaling that causes cystic development in the renal parenchyma. The cystic development is driven by the increased cyclic AMP stimulating fluid secretion and infinite cell growth. In recent years, natural product-derived small molecules or drugs targeting specific signaling pathways have caught attention in the drug discovery discipline. The advantages of natural products over synthetic drugs enthusiast researchers to utilize the medicinal benefits in various diseases including ADPKD. Conclusion: Overall, this review discusses some of the previously studied and reported natural products and their mechanisms of action which may potentially be redirected into ADPKD.
MeSH term(s)	Antioxidants/pharmacology ; Chalcones/pharmacology ; Curcumin/pharmacology ; Diterpenes/pharmacology ; Diterpenes, Kaurane/pharmacology ; Emodin/pharmacology ; Epoxy Compounds/pharmacology ; Estrogen Antagonists/pharmacology ; Flavanones/pharmacology ; Humans ; Hypoglycemic Agents/pharmacology ; Metformin/pharmacology ; Phenanthrenes/pharmacology ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use ; Polycystic Kidney, Autosomal Dominant/drug therapy ; Protein Kinase Inhibitors/pharmacology ; Quercetin/pharmacology ; Resveratrol/pharmacology
Chemical Substances	Antioxidants ; Chalcones ; Diterpenes ; Diterpenes, Kaurane ; Epoxy Compounds ; Estrogen Antagonists ; Flavanones ; Hypoglycemic Agents ; Phenanthrenes ; Plant Extracts ; Protein Kinase Inhibitors ; triptolide (19ALD1S53J) ; steviol (4741LYX6RT) ; Metformin (9100L32L2N) ; Quercetin (9IKM0I5T1E) ; cardamonin (H8KP1OJ8JX) ; naringenin (HN5425SBF2) ; Curcumin (IT942ZTH98) ; Emodin (KA46RNI6HN) ; Resveratrol (Q369O8926L)
Language	English
Publishing date	2021-07-12
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	1338768-6
ISSN	1437-7799 ; 1342-1751
ISSN (online)	1437-7799
ISSN	1342-1751
DOI	10.1007/s10157-021-02111-x
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Article ; Online: The magnitude of tyrosine kinase inhibitor induced cytopaenia on normal haematopoietic tissues in chronic myeloid leukaemia patients.

Kuan, Jew Win / Ng, Si Yuan / Hon, Siong Leng / Lim, Soo Min / Chai, Alvin Jung Mau / Teo, Hock Gin / Yong, Kar Ying / Tang, Andy Sing Ong / Chiang, Su Kien / Wilfred, Gilbert

International journal of laboratory hematology

2022 Volume 45, Issue 1, Page(s) e1–e5

MeSH term(s)	Humans ; Tyrosine Kinase Inhibitors ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myeloid ; Protein Kinase Inhibitors/adverse effects
Chemical Substances	Tyrosine Kinase Inhibitors ; Protein Kinase Inhibitors
Language	English
Publishing date	2022-07-27
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	2268590-X
ISSN	1751-553X ; 1751-5521 ; 0141-9854
ISSN (online)	1751-553X
ISSN	1751-5521 ; 0141-9854
DOI	10.1111/ijlh.13940
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Article ; Online: Neuronal infection is a major pathogenetic mechanism and cause of fatalities in human acute Nipah virus encephalitis.

Ong, Kien Chai / Ng, Khong Ying / Ng, Chiu Wan / Tan, Soon Hao / Teo, Woon Li / Karim, Norain / Kumar, Shalini / Wong, Kum Thong

Neuropathology and applied neurobiology

2022 Volume 48, Issue 6, Page(s) e12828

Abstract: Objectives: Acute Nipah (NiV) encephalitis is characterised by a dual pathogenetic mechanism of neuroglial infection and ischaemia-microinfarction associated with vasculitis-induced thrombotic occlusion. We investigated the contributions of these two ... ...

Abstract	Objectives: Acute Nipah (NiV) encephalitis is characterised by a dual pathogenetic mechanism of neuroglial infection and ischaemia-microinfarction associated with vasculitis-induced thrombotic occlusion. We investigated the contributions of these two mechanisms in fatal cases. Materials and methods: We analysed brain tissues (cerebrum, brainstem and cerebellum) from 15 autopsies using light microscopy, immunohistochemistry (IHC), in situ hybridisation and quantitative methods. Results: Three types of discrete plaque-like parenchymal lesions were identified: Type 1 with neuroglial IHC positivity for viral antigens and minimal or no necrosis; Type 2 with neuroglial immunopositivity and necrosis; and Type 3 with necrosis but no viral antigens. Most viral antigen/RNA-positive cells were neurons. Cerebral glial immunopositivity was rare, suggesting that microinfarction played a more important role in white matter injury. Type 1 lesions were also detected in the brainstem and cerebellum, but the differences between cerebral cortex and these two regions were not statistically significant. In the cerebral cortex, Type 1 lesions overwhelmingly predominated, and only 14% Type 1 vs 69% Type 2 lesions were associated with thrombosis. This suggests that neuronal infection as a mechanism of pathogenesis was more important than microinfarction, both in general and in Type 1 lesions in particular. Between the 'early' group (<8-day fever) and the 'late' group (≥8-day fever), there was a decrease of Type 1 and Type 2 lesions with a concomitant increase of Type 3 lesions, suggesting the latter possibly represented late-stage microinfarction and/or neuronal infection. Conclusion: Neuronal infection appears to play a more important role than vasculopathy-induced microinfarction in acute NiV encephalitis.
MeSH term(s)	Encephalitis/pathology ; Henipavirus Infections/pathology ; Humans ; Immunohistochemistry ; Neurons/pathology
Language	English
Publishing date	2022-06-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80371-6
ISSN	1365-2990 ; 0305-1846
ISSN (online)	1365-2990
ISSN	0305-1846
DOI	10.1111/nan.12828
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Zs.A 1241: Show issues

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Article ; Online: Understanding Enterovirus 71 Neuropathogenesis and Its Impact on Other Neurotropic Enteroviruses.

Ong, Kien Chai / Wong, Kum Thong

Brain pathology (Zurich, Switzerland)

2015 Volume 25, Issue 5, Page(s) 614–624

Abstract: Enterovirus A71 (EV-A71) belongs to the species group A in the Enterovirus genus within the Picornaviridae family. EV-A71 usually causes self-limiting hand, foot and mouth disease or herpangina but rarely causes severe neurological complications such as ... ...

Abstract	Enterovirus A71 (EV-A71) belongs to the species group A in the Enterovirus genus within the Picornaviridae family. EV-A71 usually causes self-limiting hand, foot and mouth disease or herpangina but rarely causes severe neurological complications such as acute flaccid paralysis and encephalomyelitis. The pathology and neuropathogenesis of these neurological syndromes is beginning to be understood. EV-A71 neurotropism for motor neurons in the spinal cord and brainstem, and other neurons, is mainly responsible for central nervous system damage. This review on the general aspects, recent developments and advances of EV-A71 infection will focus on neuropathogenesis and its implications on other neurotropic enteroviruses, such as poliovirus and the newly emergent Enterovirus D68. With the imminent eradication of poliovirus, EV-A71 is likely to replace it as an important neurotropic enterovirus of worldwide importance.
MeSH term(s)	Animals ; Brain/pathology ; Brain/virology ; Coxsackievirus Infections/pathology ; Encephalitis, Viral/pathology ; Enterovirus A, Human/pathogenicity ; Enterovirus D, Human/pathogenicity ; Enterovirus Infections/pathology ; Humans ; Neurons/pathology ; Neurons/virology ; Poliomyelitis/pathology
Language	English
Publishing date	2015-09-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1051484-3
ISSN	1750-3639 ; 1015-6305
ISSN (online)	1750-3639
ISSN	1015-6305
DOI	10.1111/bpa.12279
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Article ; Online: Japanese Encephalitis Virus Infects the Thalamus Early Followed by Sensory-Associated Cortex and Other Parts of the Central and Peripheral Nervous Systems.

Fu, Tzeh Long / Ong, Kien Chai / Tan, Soon Hao / Wong, Kum Thong

Journal of neuropathology and experimental neurology

2019 Volume 78, Issue 12, Page(s) 1160–1170

Abstract: Japanese encephalitis (JE) is a known CNS viral infection that often involves the thalamus early. To investigate the possible role of sensory peripheral nervous system (PNS) in early neuroinvasion, we developed a left hindlimb footpad-inoculation mouse ... ...

Abstract	Japanese encephalitis (JE) is a known CNS viral infection that often involves the thalamus early. To investigate the possible role of sensory peripheral nervous system (PNS) in early neuroinvasion, we developed a left hindlimb footpad-inoculation mouse model to recapitulate human infection by a mosquito bite. A 1-5 days postinfection (dpi) study, demonstrated focal viral antigens/RNA in contralateral thalamic neurons at 3 dpi in 50% of the animals. From 4 to 5 dpi, gradual increase in viral antigens/RNA was observed in bilateral thalami, somatosensory, and piriform cortices, and then the entire CNS. Infection of neuronal bodies and adjacent nerves in dorsal root ganglia (DRGs), trigeminal ganglia, and autonomic ganglia (intestine, etc.) was also observed from 5 dpi. Infection of explant organotypic whole brain slice cultures demonstrated no viral predilection for the thalamus, while DRG and intestinal ganglia organotypic cultures confirmed sensory and autonomic ganglia susceptibility to infection, respectively. Early thalamus and sensory-associated cortex involvement suggest an important role for sensory pathways in neuroinvasion. Our results suggest that JE virus neuronotropism is much more extensive than previously known, and that the sensory PNS and autonomic system are susceptible to infection.
MeSH term(s)	Animals ; Brain/pathology ; Brain/virology ; Cells, Cultured ; Central Nervous System Infections/pathology ; Central Nervous System Infections/virology ; Disease Models, Animal ; Encephalitis Virus, Japanese/isolation & purification ; Encephalitis Virus, Japanese/physiology ; Mice, Inbred ICR ; Neurons/pathology ; Neurons/virology ; Peripheral Nervous System/pathology ; Peripheral Nervous System/virology ; Piriform Cortex/pathology ; Piriform Cortex/virology ; Somatosensory Cortex/pathology ; Somatosensory Cortex/virology ; Thalamus/pathology ; Thalamus/virology
Language	English
Publishing date	2019-10-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3088-0
ISSN	1554-6578 ; 0022-3069
ISSN (online)	1554-6578
ISSN	0022-3069
DOI	10.1093/jnen/nlz103
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Article ; Online: Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis.

Phyu, Win Kyaw / Ong, Kien Chai / Wong, Kum Thong

Emerging microbes & infections

2017 Volume 6, Issue 7, Page(s) e62

Abstract: Enterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be complicated by fatal encephalomyelitis. Although fecal-oral or oral-oral routes are important in person-to-person transmission, how viral shedding and exposure may ... ...

Abstract	Enterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be complicated by fatal encephalomyelitis. Although fecal-oral or oral-oral routes are important in person-to-person transmission, how viral shedding and exposure may predispose individuals to infection remains unknown. We investigated person-to-person transmission by using a model of HFMD and encephalomyelitis based on EV-A71 oral infection of 2-week-old hamsters. Animals (index animals) infected with 10
Language	English
Publishing date	2017-07-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2681359-2
ISSN	2222-1751 ; 2222-1751
ISSN (online)	2222-1751
ISSN	2222-1751
DOI	10.1038/emi.2017.49
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Article ; Online: Henipavirus Encephalitis: Recent Developments and Advances.

Ong, Kien Chai / Wong, Kum Thong

Brain pathology (Zurich, Switzerland)

2015 Volume 25, Issue 5, Page(s) 605–613

Abstract: The genus Henipavirus within the family Paramyxoviridae includes the Hendra virus (HeV) and Nipah virus (NiV) which were discovered in the 1990s in Australia and Malaysia, respectively, after emerging to cause severe and often fatal outbreaks in humans ... ...

Abstract	The genus Henipavirus within the family Paramyxoviridae includes the Hendra virus (HeV) and Nipah virus (NiV) which were discovered in the 1990s in Australia and Malaysia, respectively, after emerging to cause severe and often fatal outbreaks in humans and animals. While HeV is confined to Australia, more recent NiV outbreaks have been reported in Bangladesh, India and the Philippines. The clinical manifestations of both henipaviruses in humans appear similar, with a predominance of an acute encephalitic syndrome. Likewise, the pathological features are similar and characterized by disseminated, multi-organ vasculopathy comprising endothelial infection/ulceration, vasculitis, vasculitis-induced thrombosis/occlusion, parenchymal ischemia/microinfarction, and parenchymal cell infection in the central nervous system (CNS), lung, kidney and other major organs. This unique dual pathogenetic mechanism of vasculitis-induced microinfarction and neuronal infection causes severe tissue damage in the CNS. Both viruses can also cause relapsing encephalitis months and years after the acute infection. Many animal models studied to date have largely confirmed the pathology of henipavirus infection, and provided the means to test new therapeutic agents and vaccines. As the bat is the natural host of henipaviruses and has worldwide distribution, spillover events into human populations are expected to occur in the future.
MeSH term(s)	Animals ; Antiviral Agents/therapeutic use ; Brain/pathology ; Encephalitis, Viral/diagnosis ; Encephalitis, Viral/pathology ; Encephalitis, Viral/therapy ; Hendra Virus/pathogenicity ; Henipavirus Infections/diagnosis ; Henipavirus Infections/pathology ; Henipavirus Infections/therapy ; Humans ; Immunization, Passive ; Nipah Virus/pathogenicity
Chemical Substances	Antiviral Agents
Keywords	covid19
Language	English
Publishing date	2015-08-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1051484-3
ISSN	1750-3639 ; 1015-6305
ISSN (online)	1750-3639
ISSN	1015-6305
DOI	10.1111/bpa.12278
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Article ; Online: Myricetin derivative-rich fraction from

Nallappan, Devi / Ong, Kien Chai / Palanisamy, Uma Devi / Chua, Kek Heng / Kuppusamy, Umah Rani

Archives of physiology and biochemistry

2020 Volume 129, Issue 1, Page(s) 186–197

Abstract: Aim: A high-fat diet (HFD) can lead to obesity and related metabolic disorders. This study evaluated the preventive efficacy of myricetin derivative-rich fraction (MD) from : Methods: HFD-fed mice were administered MD (50 mg/kg, 100 mg/kg, and 150 mg/ ...

Abstract	Aim: A high-fat diet (HFD) can lead to obesity and related metabolic disorders. This study evaluated the preventive efficacy of myricetin derivative-rich fraction (MD) from Methods: HFD-fed mice were administered MD (50 mg/kg, 100 mg/kg, and 150 mg/kg) or 2 mg/kg metformin (positive control) orally for 16 weeks. Normal diet and HFD-fed control groups received normal saline. Results: MD dose of 50 mg/kg was better than 100 mg/kg and 150 mg/kg in significantly reducing weight-gain, glucose intolerance, insulin resistance, lipid accumulation in liver and kidney, and improving the serum lipid profile. Lowered protein carbonyls and lipid hydroperoxides in urine and tissue homogenates and elevated reduced glutathione, ferric reducing antioxidant power (FRAP), and Trolox equivalent antioxidant capacity (TEAC) levels in tissue homogenates indicated amelioration of oxidative stress. Conclusion: MD has therapeutic value in the prevention and management of obesity, hyperglycaemia, and oxidative stress.
MeSH term(s)	Mice ; Animals ; Glucose Intolerance/etiology ; Glucose Intolerance/prevention & control ; Antioxidants/metabolism ; Diet, High-Fat/adverse effects ; Syzygium/metabolism ; Mice, Inbred C57BL ; Obesity/etiology ; Obesity/prevention & control ; Obesity/drug therapy ; Oxidative Stress ; Insulin Resistance ; Lipids
Chemical Substances	Antioxidants ; myricetin (76XC01FTOJ) ; Lipids
Language	English
Publishing date	2020-08-19
Publishing country	England
Document type	Journal Article
ZDB-ID	1238320-x
ISSN	1744-4160 ; 1381-3455
ISSN (online)	1744-4160
ISSN	1381-3455
DOI	10.1080/13813455.2020.1808019
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Article: Immunomodulatory Effect and an Intervention of TNF Signalling Leading to Apoptotic and Cell Cycle Arrest on ORL-204 Oral Cancer Cells by Tiger Milk Mushroom,

Yap, Hui Yeng Yeannie / Kong, Boon Hong / Yap, Chee Sum Alvin / Ong, Kien Chai / Zain, Rosnah Binti / Tan, Soon Hao / Zaini, Zuraiza Mohamad / Ng, Szu Ting / Tan, Chon Seng / Fung, Shin Yee

Food technology and biotechnology

2022 Volume 60, Issue 1, Page(s) 80–88

Abstract: Research background: Tiger milk mushroom (: Experimental approach: Mushroom sclerotial powder of cultivar TM02® was extracted and fractionated in a chromatographic column prior to cytotoxicity testing against a panel of human oral cancer cell lines. ... ...

Abstract	Research background: Tiger milk mushroom ( Experimental approach: Mushroom sclerotial powder of cultivar TM02® was extracted and fractionated in a chromatographic column prior to cytotoxicity testing against a panel of human oral cancer cell lines. The capability of the identified bioactive fraction in regulating several molecules associated with its tumour necrosis factor (TNF) pathway was investigated. Results and conclusions: 2,5-Diphenyl-2H-tetrazolium bromide (MTT) proliferation assay indicated that cell lines ORL-48 (derived from gingiva), ORL-188 (derived from the tongue) and ORL-204 (derived from buccal mucosa) were inhibited by cold water extract of Novelty and scientific contribution: Using ORL-204, we showed that HMM mushroom extract may act
Language	English
Publishing date	2022-04-12
Publishing country	Croatia
Document type	Journal Article
ZDB-ID	1340467-2
ISSN	1330-9862
ISSN	1330-9862
DOI	10.17113/ftb.60.01.22.7296
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