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Chryseobacterium indologenes and Chryseobacterium gleum interact and multiply intracellularly in Acanthamoeba castellanii

Lim WG, Tong T, Chew J

Exp Parasitol, 2020 Feb 19;211:107862.
PMID: 32087220 DOI: 10.1016/j.exppara.2020.107862

Chryseobacterium indologenes and Chryseobacterium gleum are Gram negative environmental bacteria that have been frequently reported to implicate in fatal nosocomial infections, such as bacteraemia and ventilator-associated pneumonia in immunocompromised individuals in the past decades. The interaction between Chryseobacterium spp. and Acanthamoeba castellanii, a free-living amoeba ubiquitous in the environment, has not been explored previously. In this study, C. indologenes and C. gleum were co-cultured with A. castellanii trophozoites and their interactions were evaluated. Our results showed that when co-cultured with A. castellanii, bacterial numbers of C. indologenes and C. gleum increased significantly (p 0.05). Interestingly, the two Chryseobacterium spp. associated, invaded and/or taken up by A. castellanii at significantly higher rates than Escherichia coli K1, a neuropathogenic bacterial strain known to interact and replicate intracellularly in A. castellanii (p
Fulltext Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential

Yong SJ, Tong T, Chew J, Lim WL

Front Neurosci, 2019;13:1361.
PMID: 32009871 DOI: 10.3389/fnins.2019.01361

The accumulating knowledge of the host-microbiota interplay gives rise to the microbiota-gut-brain (MGB) axis. The MGB axis depicts the interkingdom communication between the gut microbiota and the brain. This communication process involves the endocrine, immune and neurotransmitters systems. Dysfunction of these systems, along with the presence of gut dysbiosis, have been detected among clinically depressed patients. This implicates the involvement of a maladaptive MGB axis in the pathophysiology of depression. Depression refers to symptoms that characterize major depressive disorder (MDD), a mood disorder with a disease burden that rivals that of heart diseases. The use of probiotics to treat depression has gained attention in recent years, as evidenced by increasing numbers of animal and human studies that have supported the antidepressive efficacy of probiotics. Physiological changes observed in these studies allow for the elucidation of probiotics antidepressive mechanisms, which ultimately aim to restore proper functioning of the MGB axis. However, the understanding of mechanisms does not yet complete the endeavor in applying probiotics to treat MDD. Other challenges remain which include the heterogeneous nature of both the gut microbiota composition and depressive symptoms in the clinical setting. Nevertheless, probiotics offer some advantages over standard pharmaceutical antidepressants, in terms of residual symptoms, side effects and stigma involved. This review outlines antidepressive mechanisms of probiotics based on the currently available literature and discusses therapeutic potentials of probiotics for depression.
Neuroprotective Effects of Lactoferrin in Alzheimer's and Parkinson's Diseases: A Narrative Review

Yong SJ, Veerakumarasivam A, Lim WL, Chew J

ACS Chem Neurosci, 2023 Mar 30.
PMID: 36995304 DOI: 10.1021/acschemneuro.2c00679

Recent advancements in lactoferrin research have uncovered that lactoferrin does function not only as an antimicrobial protein but also as an immunomodulatory, anticancer, and neuroprotective agent. Focusing on neuroprotection, this literature review delineates how lactoferrin interacts in the brain, specifically its neuroprotective effects and mechanisms against Alzheimer's and Parkinson's diseases (AD and PD), the two most common neurodegenerative diseases. The neuroprotective pathways involving surface receptors (heparan sulfate proteoglycan (HSPG) and lactoferrin receptor (LfR)), signaling pathways (extracellular regulated protein kinase-cAMP response element-binding protein (ERK-CREB) and phosphoinositide 3-kinase/Akt (PI3K/Akt)), and effector proteins (A disintegrin and metalloprotease10 (ADAM10) and hypoxia-inducible factor 1α (HIF-1α)) in cortical/hippocampal and dopaminergic neurons are described. These cellular effects of lactoferrin are likely responsible for attenuating cognitive and motor deficits, amyloid-β and α-synuclein accumulation, and neurodegeneration in animal and cellular models of AD and PD. This review also discusses the inconsistent findings related to the neuroprotective effects of lactoferrin against AD. Overall, this review contributes to the existing literature by clarifying the potential neuroprotective effects and mechanisms of lactoferrin in the context of AD and PD neuropathology.
Fulltext Comparable outcomes for β-lactam/β-lactamase inhibitor combinations and carbapenems in definitive treatment of bloodstream infections caused by cefotaxime-resistant Escherichia coli or Klebsiella pneumoniae

Harris PN, Yin M, Jureen R, Chew J, Ali J, Paynter S, et al.

Antimicrob Resist Infect Control, 2015;4:14.
PMID: 25932324 DOI: 10.1186/s13756-015-0055-6

Extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae are often susceptible in vitro to β-lactam/β-lactamase inhibitor (BLBLI) combination antibiotics, but their use has been limited by concerns of clinical inefficacy. We aimed to compare outcomes between patients treated with BLBLIs and carbapenems for bloodstream infection (BSI) caused by cefotaxime non-susceptible (likely ESBL- or AmpC β-lactamase-producing) Escherichia coli and Klebsiella pneumoniae.
Antibacterial and cytotoxic effect of honey mediated copper nanoparticles synthesized using ultrasonic assistance

Ismail NA, Shameli K, Wong MM, Teow SY, Chew J, Sukri SNAM

Mater Sci Eng C Mater Biol Appl, 2019 Nov;104:109899.
PMID: 31499959 DOI: 10.1016/j.msec.2019.109899

In this study, a comparative study of effect using honey on copper nanoparticles (Cu-NPs) via simple, environmentally friendly process and inexpensive route was reported. Honey and ascorbic acid act as stabilizing and reducing agents with the assistance of sonochemical method. The products were characterized using UV-visible (UV-vis) spectroscopy, X-Ray Diffraction (XRD), High-Resolution Transmission Electron Microscopy (HRTEM), Field-Emission Scanning Electron Microscopy (FESEM) and Fourier Transform Infrared (FTIR) spectroscopy. The reddish brown colour demonstrated the formation of Cu-NPs and UV-visible proved the plasmon resonance of Cu-NPs. XRD also confirmed a highly pure Cu-NPs obtained with absence of copper oxide in which the structure is crystalline. The spherical size of the Cu-NPs was acquire in the presence of honey which is 3.68 ± 0.78 nm with narrow particle distribution. The antibacterial activity was seen against gram-positive and gram-negative bacteria which are Enterococcus faecalis (E. faecalis) and Escherichia coli (E. coli). At higher concentration of Cu-NPs, they were more effective in killing both bacteria. The Cu-NPs without and with honey exhibited toxicities toward normal and cancerous cells. However, Cu-NPs without honey showed more potent killing activity against normal and cancer cells.
Fulltext Decoding Antioxidant and Antibacterial Potentials of Malaysian Green Seaweeds: Caulerpa racemosa and Caulerpa lentillifera

Yap WF, Tay V, Tan SH, Yow YY, Chew J

Antibiotics (Basel), 2019 Sep 17;8(3).
PMID: 31533237 DOI: 10.3390/antibiotics8030152

Seaweeds are gaining a considerable amount of attention for their antioxidant and antibacterial properties. Caulerpa racemosa and Caulerpa lentillifera, also known as 'sea grapes', are green seaweeds commonly found in different parts of the world, but the antioxidant and antibacterial potentials of Malaysian C. racemosa and C. lentillifera have not been thoroughly explored. In this study, crude extracts of the seaweeds were prepared using chloroform, methanol, and water. Total phenolic content (TPC) and total flavonoid content (TFC) were measured, followed by in vitro antioxidant activity determination using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Antibacterial activities of these extracts were tested against Methicillin-resistant Staphylococcus aureus (MRSA) and neuropathogenic Escherichia coli K1. Liquid chromatography-mass spectrometry (LCMS) analysis was then used to determine the possible compounds present in the extract with the most potent antioxidant and antibacterial activity. Results showed that C. racemosa chloroform extract had the highest TPC (13.41 ± 0.86 mg GAE/g), antioxidant effect (EC50 at 0.65 ± 0.03 mg/mL), and the strongest antibacterial effect (97.7 ± 0.30%) against MRSA. LCMS analysis proposed that the chloroform extracts of C. racemosa are mainly polyunsaturated and monounsaturated fatty acids, terpenes, and alkaloids. In conclusion, C. racemosa can be a great source of novel antioxidant and antibacterial agents, but isolation and purification of the bioactive compounds are needed to study their mechanism of action.
In vitro anti-bacterial and time kill evaluation of binuclear tricyclohexylphosphanesilver(I) dithiocarbamates, {Cy3PAg(S2CNRR')}2

Tan YJ, Tan YS, Yeo CI, Chew J, Tiekink ERT

J Inorg Biochem, 2019 03;192:107-118.
PMID: 30640150 DOI: 10.1016/j.jinorgbio.2018.12.017

Four binuclear phosphanesilver(I) dithiocarbamates, {cyclohexyl3PAg(S2CNRR')}2 for R = R' = Et (1), CH2CH2 (2), CH2CH2OH (3) and R = Me, R' = CH2CH2OH (4) have been synthesised and characterised by spectroscopy and crystallography, and feature tri-connective, μ2-bridging dithiocarbamate ligands and distorted tetrahedral geometries based on PS3 donor sets. The compounds were evaluated for anti-bacterial activity against a total of 12 clinically important pathogens. Based on minimum inhibitory concentration (MIC) and cell viability tests (human embryonic kidney cells, HEK 293), 1-4 are specifically active against Gram-positive bacteria while demonstrating low toxicity; 3 and 4 are active against methicillin resistant S. aureus (MRSA). Across the series, 4 was most effective and was more active than the standard anti-biotic chloramphenicol. Time kill assays reveal 1-4 to exhibit both time- and concentration-dependent pharmacokinetics against susceptible bacteria. Compound 4 demonstrates rapid (within 2 h) bactericidal activity at 1 and 2 × MIC to reach a maximum decrease of 5.2 log10 CFU/mL against S. aureus (MRSA).
Fulltext The Hippocampal Vulnerability to Herpes Simplex Virus Type I Infection: Relevance to Alzheimer's Disease and Memory Impairment

Yong SJ, Yong MH, Teoh SL, Soga T, Parhar I, Chew J, et al.

Front Cell Neurosci, 2021;15:695738.
PMID: 34483839 DOI: 10.3389/fncel.2021.695738

Herpes simplex virus type 1 (HSV-1) as a possible infectious etiology in Alzheimer's disease (AD) has been proposed since the 1980s. The accumulating research thus far continues to support the association and a possible causal role of HSV-1 in the development of AD. HSV-1 has been shown to induce neuropathological and behavioral changes of AD, such as amyloid-beta accumulation, tau hyperphosphorylation, as well as memory and learning impairments in experimental settings. However, a neuroanatomical standpoint of HSV-1 tropism in the brain has not been emphasized in detail. In this review, we propose that the hippocampal vulnerability to HSV-1 infection plays a part in the development of AD and amnestic mild cognitive impairment (aMCI). Henceforth, this review draws on human studies to bridge HSV-1 to hippocampal-related brain disorders, namely AD and aMCI/MCI. Next, experimental models and clinical observations supporting the neurotropism or predilection of HSV-1 to infect the hippocampus are examined. Following this, factors and mechanisms predisposing the hippocampus to HSV-1 infection are discussed. In brief, the hippocampus has high levels of viral cellular receptors, neural stem or progenitor cells (NSCs/NPCs), glucocorticoid receptors (GRs) and amyloid precursor protein (APP) that support HSV-1 infectivity, as well as inadequate antiviral immunity against HSV-1. Currently, the established diseases HSV-1 causes are mucocutaneous lesions and encephalitis; however, this review revises that HSV-1 may also induce and/or contribute to hippocampal-related brain disorders, especially AD and aMCI/MCI.
Fulltext Applications of Polyaniline-Based Molybdenum Disulfide Nanoparticles against Brain-Eating Amoebae

Abdelnasir S, Mungroo MR, Chew J, Siddiqui R, Khan NA, Ahmad I, et al.

ACS Omega, 2023 Mar 07;8(9):8237-8247.
PMID: 36910978 DOI: 10.1021/acsomega.2c06050

Primary amoebic meningoencephalitis and granulomatous amoebic encephalitis are distressing infections of the central nervous system caused by brain-eating amoebae, namely, Naegleria fowleri and Acanthamoeba spp., respectively, and present mortality rates of over 90%. No single drug has been approved for use against these infections, and current therapy is met with an array of obstacles including high toxicity and limited specificity. Thus, the development of alternative effective chemotherapeutic agents for the management of infections due to brain-eating amoebae is a crucial requirement to avert future mortalities. In this paper, we synthesized a conducting polymer-based nanocomposite entailing polyaniline (PANI) and molybdenum disulfide (MoS2) and explored its anti-trophozoite and anti-cyst potentials against Acanthamoeba castellanii and Naegleria fowleri. The intracellular generation of reactive oxygen species (ROS) and ultrastructural appearances of amoeba were also evaluated with treatment. Throughout, treatment with the 1:2 and 1:5 ratios of PANI/MoS2 at 100 μg/mL demonstrated significant anti-amoebic effects toward A. castellanii as well as N. fowleri, appraised to be ROS mediated and effectuate physical alterations to amoeba morphology. Further, cytocompatibility toward human keratinocyte skin cells (HaCaT) and primary human corneal epithelial cells (pHCEC) was noted. For the first time, polymer-based nanocomposites such as PANI/MoS2 are reported in this study as appealing options in the drug discovery for brain-eating amoebae infections.
Mitochondrial DNA Profiling Reveals Two Lineages of Sun Bears in East and West Malaysia

Lai WL, Chew J, Gatherer D, Ngoprasert D, Rahman S, Ayub Q, et al.

J Hered, 2021 03 29;112(2):214-220.
PMID: 33439997 DOI: 10.1093/jhered/esab004

Sun bear populations are fragmented and at risk from habitat loss and exploitation for body parts. These threats are made worse by significant gaps in knowledge of sun bear population genetic diversity, population connectivity, and taxonomically significant management units. Using a complete sun bear mitochondrial genome, we developed a set of mitochondrial markers to assess haplotype variation and the evolutionary history of sun bears from Peninsular (West) Malaysia and Sabah (East Malaysia). Genetic samples from 28 sun bears from Peninsular Malaysia, 36 from Sabah, and 18 from Thailand were amplified with primers targeting a 1800 bp region of the mitochondrial genome including the complete mitochondrial control region and adjacent genes. Sequences were analyzed using phylogenetic methods. We identified 51 mitochondrial haplotypes among 82 sun bears. Phylogenetic and network analyses provided strong support for a deep split between Malaysian sun bears and sun bears in East Thailand and Yunnan province in China. The Malaysian lineage was further subdivided into two clades: Peninsular Malaysian and Malaysian Borneo (Sabah). Sun bears from Thailand occurred in both Sabah and Peninsular Malaysian clades. Our study supports recent findings that sun bears from Sundaland form a distinct clade from those in China and Indochina with Thailand possessing lineages from the three clades. Importantly, we demonstrate a more recent and clear genetic delineation between sun bears from the Malay Peninsula and Sabah indicating historical barriers to gene flow within the Sundaic region.
Fulltext Enhanced antibacterial and anticancer activities of plant extract mediated green synthesized zinc oxide-silver nanoparticles

Mohamad Sukri SNA, Shameli K, Teow SY, Chew J, Ooi LT, Lee-Kiun Soon M, et al.

Front Microbiol, 2023;14:1194292.
PMID: 37577438 DOI: 10.3389/fmicb.2023.1194292

This study presents a green synthesis approach for the fabrication of zinc oxide-silver nanoparticles (ZnO-Ag-NPs) using Punica granatum fruit peels extract as a natural reducing and stabilizing agent. This eco-friendly method offers a sustainable alternative to conventional methods that often employ toxic or hazardous chemicals. Antibacterial and anti-cancer activities of the green synthesized nanoparticles were then assessed in vitro. X-ray diffraction confirmed the production of ZnO-Ag-NPs with increasing crystallinity in higher pH values. The ZnO-Ag-NPs were found to be agglomerated with spherical Ag-NPs. Fourier Transform Infrared (FTIR) spectra revealed a broad band in ZnO-Ag-NPs ranging from 400-1 to 530 cm-1 with reduced intensity as compared to ZnO-NPs, indicating the formation of Ag-NPs on the surface of ZnO-NPs. The synthesized ZnO-Ag-NPs exhibited potent antibacterial activity against a broad spectrum of bacterial strains, particularly Gram-positive bacteria, with superior inhibition activity compared to ZnO-NPs. Moreover, ZnO-Ag-NPs showed a dose-dependent anti-proliferative effect on colorectal-, lung-, and cervical cancer cells. ZnO-Ag-NPs showed significantly greater efficacy in inhibiting cancer cell growth at a lower concentration of 31.25 μg/mL, compared to ZnO-NPs which required over 500 μg/mL, possibly due to the presence of silver nanoparticles (Ag-NPs). The results obtained from this study demonstrate the potential of green synthesis approaches in the fabrication of therapeutic nanomaterials for cancer treatment, as well as other biomedical applications.
Association of Fusobacterium nucleatum infection with the clinicopathological characteristics in colorectal cancer patients

Pang SW, Armon S, Chook JB, Chew J, Peh KB, Lim WW, et al.

Mol Biol Rep, 2024 Jan 16;51(1):124.
PMID: 38227097 DOI: 10.1007/s11033-023-09150-5

BACKGROUND: Colorectal cancer (CRC) is a global health problem. The gut microbiome is now recognized as an important underlying factor to the initiation and progression of CRC. Fusobacterium nucleatum (FN) is one of the most studied bacteria in the aetiology of CRC. This study provided cohort evidence on the association of FN infection with clinicopathologic features in CRC patients.
METHODS: We analysed the cancerous and adjacent non-cancerous formalin-fixed paraffin embedded (FFPE) tissue of 83 CRC patients from a single medical centre in Malaysia. TaqMan probe-based qPCR targeting the 16S rRNA gene was used to detect the presence of FN in the extracted FFPE DNA. The differences in FN expression between cancer and non-cancer tissues were evaluated. Association studies between FN infection in the tumour and relative FN abundance with available clinical data were conducted.
RESULTS: FN was more abundant in the cancerous tissue compared to non-cancerous tissue (p = 0.0025). FN infection in the tumour was significantly associated with lymph node metastasis (p = 0.047) and cancer staging (p = 0.032), but not with other clinicopathologic variables. In double-positive patients where FN was detected in both cancerous and non-cancerous tissue, the expression fold-change of FN, calculated using 2-ΔΔCT formula, was significantly higher in patients with tumour size equal to or greater than 5 cm (p = 0.033) and in KRAS-mutated patients (p = 0.046).
CONCLUSIONS: FN is enriched in CRC tumour tissue and is associated with tumour size, lymph node metastasis, cancer staging, and KRAS mutation in this single-centre small cohort study.
Fulltext Severe Pediatric Adenovirus 7 Disease in Singapore Linked to Recent Outbreaks across Asia

Ng OT, Thoon KC, Chua HY, Tan NW, Chong CY, Tee NW, et al.

Emerg Infect Dis, 2015 Jul;21(7):1192-6.
PMID: 26079293 DOI: 10.3201/eid2107.141443

During November 2012-July 2013, a marked increase of adenovirus type 7 (Ad7) infections associated with severe disease was documented among pediatric patients in Singapore. Phylogenetic analysis revealed close genetic links with severe Ad7 outbreaks in China, Taiwan, and other parts of Asia.
Fulltext Diagnosis and outcomes of cachexia in Asia: Working Consensus Report from the Asian Working Group for Cachexia

Arai H, Maeda K, Wakabayashi H, Naito T, Konishi M, Assantachai P, et al.

J Cachexia Sarcopenia Muscle, 2023 Oct;14(5):1949-1958.
PMID: 37667992 DOI: 10.1002/jcsm.13323

Chronic diseases often lead to metabolic disorders, causing anabolic resistance and increased energy consumption, which result in cachexia. Cachexia, in turn, can lead to major clinical consequences such as impaired quality of life, shortened life expectancy, and increased healthcare expenditure. Existing international diagnostic criteria for cachexia employ thresholds derived from Western populations, which may not apply to Asians due to differing body compositions. To address this issue, the Asian Working Group for Cachexia (AWGC) was initiated. The AWGC comprises experts in cachexia research and clinical practice from various Asian countries and aims to develop a consensus on diagnostic criteria and significant clinical outcomes for cachexia in Asia. The AWGC, composed of experts in cachexia research and clinical practice from several Asian countries, undertook three-round Delphi surveys and five meetings to reach a consensus. Discussions were held on etiological diseases, essential diagnostic items for cachexia, including subjective and objective symptoms and biomarkers, and significant clinical outcomes. The consensus highlighted the importance of multiple diagnostic factors for cachexia, including chronic diseases, either or both weight loss or low body mass index, and at least one of the following: anorexia, decreased grip strength (<28 kg in men and <18 kg in women), or elevated C-reactive protein levels (>5 mg/L [0.5 mg/dL]). The AWGC proposed a significant weight change of 2% or more over a 3-6 month period and suggested a tentative cut-off value of 21 kg/m2 for low body mass index in diagnosing cachexia. Critical clinical outcomes were determined to be mortality, quality of life as assessed by tools such as EQ-5D or the Functional Assessment of Anorexia/Cachexia Therapy, and functional status as measured by the Clinical Frailty Scale or Barthel Index, with significant emphasis on patient-reported outcomes. The AWGC consensus offers a comprehensive definition and user-friendly diagnostic criteria for cachexia, tailored specifically for Asian populations. This consensus is set to stimulate future research and enhance the multidisciplinary approach to managing cachexia. With plans to develop further guidelines for the optimal treatment, prevention, and care of cachexia in Asians, the AWGC criteria are expected to drive research across chronic co-morbidities and cancer in Asia, leading to future refinement of diagnostic criteria.

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