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Selective isolation and characterisation of novel members of the family Nocardiopsaceae and other actinobacteria from a marine sediment of Tioman Island

Ng ZY, Tan GYA

Antonie Van Leeuwenhoek, 2018 May;111(5):727-742.
PMID: 29511956 DOI: 10.1007/s10482-018-1042-8

Tioman Island is one of many sources for underexplored actinobacterial diversity in Malaysia. Selective isolation, molecular profiling, 16S rRNA gene sequencing and phylogenetic analyses were carried out to highlight the diversity of the marine actinobacterial community in a sediment collected off Tioman Island. A high number of diverse actinobacteria were recovered using skim milk/HEPES pre-treatment on a mannitol-based medium. A total of 123 actinobacterial strains were isolated, including thirty obligate marine actinobacteria putatively identified as Salinispora spp. Molecular fingerprinting profiles obtained with a double digestion approach grouped the remaining non-Salinispora-like strains into 24 different clusters, with Streptomyces and Blastococcus as the major clusters. A total of 17 strains were identified as novel actinobacterial species within the genera Streptomyces (n = 6), Blastococcus (n = 5), Marinactinospora (n = 3), Nocardiopsis (n = 1), Agromyces (n = 1) and Nonomuraea (n = 1) based on 16S rRNA gene sequence analyses. Polyphasic data from three putative Marinactinospora spp. showed that the strains represent a new genus in the Nocardiopsaceae family. Crude extracts from the strains were also found to inhibit the growth of Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Providencia alcalifaciens) pathogens. Hierarchical clustering of the bioactivities of an active fraction revealed a unique profile, which is closely related that of fosfomycin.
Association of leptin/receptor and TNF-α gene variants with adolescent obesity in Malaysia

Ng ZY, Veerapen MK, Hon WM, Lim RL

Pediatr Int, 2014 Oct;56(5):689-97.
PMID: 24628746 DOI: 10.1111/ped.12336

BACKGROUND: Leptin (LEP) G-2548A (rs7799039), leptin receptor (LEPR) Q223R (rs1137101) and tumor necrosis factor (TNF)-α G-308A (rs1800629) gene variants have been reported to be associated with obesity, although results for subjects from different countries have been controversial. The aim of this study was to determine the prevalence of overweight and obesity in Malaysian adolescents and the association of these polymorphisms with overweight and obese or over-fat adolescents.
METHODS: A total of 613 adolescents (241 Malay, 219 Chinese, 153 Indian) were enrolled. Anthropometric measurements of body mass index (BMI) and body fat percentage were used to classify subjects as controls (non-overweight/obese or normal fat) or as cases (overweight/obese or over-fat). Genomic DNA was extracted from oral buccal mucosa cells for genotyping using polymerase chain reaction-restriction fragment length polymorphism and data obtained were statistically analyzed.
RESULTS: A total of 23.3% of subjects were overweight/obese whereas 11.4% were over-fat; there were significantly more overweight/obese and over-fat Indian and Malay adolescents compared to Chinese (P < 0.001). A allele was the minor one for LEPR Q223R and TNF-α G-308A in all ethnic groups, whereas G allele was minor for LEP G-2548A in Chinese and Malay adolescents, except for Indian adolescents. Indian male adolescents with AA genotype for LEP G-2548A were associated with overweight/obesity (P = 0.025; odds ratio, 3.64; 95% confidence interval: 1.15-11.54). Despite the lack of association observed for LEPR Q223R and TNF-α G-308A, Indian and Chinese subjects with AA risk genotype for LEPR Q223R/LEP G-2548A and TNF-α G-308A/LEP G-2548A, respectively, had increased mean BMI (P = 0.049, P = 0.016).
CONCLUSIONS: Genotype distribution and association of these polymorphisms with overweight/obesity vary between ethnic groups and genders. Nevertheless, the LEP G-2548A risk allele may be associated with overweight/obese Indian male adolescents in Malaysia.
KEYWORDS: adolescents; body fat percentage; body mass index; leptin; leptin receptor; single nucleotide polymorphism; tumor necrosis factor-α
Marinitenerispora sediminis gen. nov., sp. nov., a member of the family Nocardiopsaceae isolated from marine sediment

Ng ZY, Fang BZ, Li WJ, Tan GYA

Int J Syst Evol Microbiol, 2019 Oct;69(10):3031-3040.
PMID: 31310190 DOI: 10.1099/ijsem.0.003587

Three novel actinobacterial strains, designated as TPS16T, TPS81 and TPS83, were isolated from a sample of marine sediment collected from Tioman Island, Malaysia. The strains formed abundant branched substrate mycelia without fragmentation along with production of blue spores and blue diffusible pigment on soybean meal agar. The strains could grow at pH ranging from pH 6 to 12 and in 0-8 % (w/v) NaCl. Cell-wall hydrolysis showed the presence of meso-diaminopimelic acid. The strains were closely related to Marinactinospora thermotolerans SCSIO 00652T (97.60 %) and Marinactinospora endophytica YIM 690053T (96.87 %) based on phylogenetic analysis of 16S rRNA gene sequences. Multilocus sequence analysis including gyrB, recA and rpoB genes further confirmed that strain TPS16T represented a distinct branch within the family Nocardiopsaceae. The predominant menaquinones were MK-11(H2), MK-10(H2), MK-11(H4) and MK-10(H4), while the major fatty acids were found to be iso-C16 : 0, anteiso-C17 : 0, iso-C15 : 0 and C18 : 1ω9c. Genome sequencing revealed genome sizes of approximately 6 Mb and G+C contents of 73.8 mol%. A new genus, Marinitenerispora gen. nov., is proposed within the family Nocardiopsaceae based on polyphasic data and the type species is Marinitenerispora sediminis gen. nov., sp. nov. The type strain is TPS16T (=DSM 46825T=TBRC 5138T).
Appropriateness of deep vein thrombosis (DVT) prophylaxis use among medical inpatients: a DVT risk alert tool (DRAT) study

Diana Yap FS, Ng ZY, Wong CY, Muhamad Saifuzzaman MK, Yang LB

Med J Malaysia, 2019 02;74(1):45-50.
PMID: 30846662

INTRODUCTION: Increasing incidence of Venous Thromboembolism (VTE) has complicated treatment courses for hospitalised patients. Despite recommendation to support deep vein thrombosis (DVT) risk assessment and appropriate use of prophylaxis in medical inpatients, it is either neglected or prescribed unnecessarily by the clinicians. This study aimed to assess and compare the appropriateness of DVT prophylaxis prescribing between usual care versus a pharmacist-driven DVT Risk Alert Tool (DRAT) intervention among hospitalised medical patients.
METHODS: A prospective pre- and post-intervention study was conducted among medical inpatients in a Malaysian secondary care hospital. DVT and bleeding risks were stratified using validated Padua Risk Assessment Model (RAM) and International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) Bleeding Risk Assessment Model. Pharmacist-driven DRAT was developed and implemented post-interventional phase. DVT prophylaxis use was determined and its appropriateness was compared between pre and post study using multivariate logistic regression with IBM SPSS software version 21.0.
RESULTS: Overall, 286 patients (n=142 pre-intervention versus n=144 post-intervention) were conveniently recruited. The prevalence of DVT prophylaxis use was 10.8%. Appropriate thromboprophylaxis prescribing increased from 64.8% to 68.1% post-DRAT implementation. Of note, among high DVT risk patients, DRAT intervention was observed to be a significant predictor of appropriate thromboprophylaxis use (14.3% versus 31.3%; adjusted odds ratio=2.80; 95% CI 1.01 to 7.80; p<0.05).
CONCLUSION: The appropriateness of DVT prophylaxis use was suboptimal but doubled after implementation of DRAT intervention. Thus, an integrated risk stratification checklist is an effective approach for the improvement of rational DVT prophylaxis use.
Towards circular economy: Potential of microalgae - bacterial-based biofertilizer on plants

Ng ZY, Ajeng AA, Cheah WY, Ng EP, Abdullah R, Ling TC

J Environ Manage, 2024 Jan 01;349:119445.
PMID: 37890301 DOI: 10.1016/j.jenvman.2023.119445

Biofertilizers encompass microorganisms that can be applied to plants, subsequently establishing themselves within the plant's rhizosphere or internal structures. This colonization stimulates plant development by enhancing nutrient absorption from the host. While there is growing literature documenting the applications of microalgae-based and bacterial-based biofertilizers, the research focusing on the effectiveness of consortia formed by these microorganisms as short-term plant biofertilizers is notably insufficient. This study seeks to assess the effectiveness of microalgae-bacterial biofertilizers in promoting plant growth and their potential contribution to the circular economy. The review sheds light on the impact of microalgae-bacterial biofertilizers on plant growth parameters, delving into factors influencing their efficiency, microalgae-bacteria interactions, and effects on soil health. The insights from this review are poised to offer valuable guidance to stakeholders in agriculture, including farmers, environmental technologists, and businesses. These insights will aid in the development and investment in more efficient and sustainable methods for enhancing crop yields, aligning with the Sustainable Development Goals and principles of the circular economy.
Vesicular Systems Containing Curcumin and Their Applications in Respiratory Disorders - A Mini Review

Chellappan DK, Hansbro PM, Dua K, Hsu A, Gupta G, Ng ZY, et al.

Pharm Nanotechnol, 2017;5(4):250-254.
PMID: 28786351 DOI: 10.2174/2211738505666170808094635

BACKGROUND: Vesicular systems like nanotechnology and liposomes are gaining tremendous attention lately in the field of respiratory diseases. These formulations enhance bioavailability of the drug candidate, which could be achieved through a novel drug delivery mechanism. Moreover, the therapeutic potential achieved through these systems is highly controllable over long durations of time providing better efficacy and patient compliance.
OBJECTIVE: The objective of this paper is to review the recent literature on vesicular drug delivery systems containing curcumin.
METHODS: We have collated and summarized various recent attempts made to develop different controlled release drug delivery systems containing curcumin which would be of great interest for herbal, formulation and biological scientists. There are several vesicular nanotechnological techniques involving curcumin which have been studied recently, targeting pulmonary diseases.
RESULTS: Different vesicular systems containing curcumin are being studied for their therapeutic potential in different respiratory diseases. There has been a renewed interest in formulations containing curcumin recently, primarily owing to the broad spectrum therapeutic potential of this miracle substance. Various types of formulations, containing curcumin, targeting different bodily systems have recently emerged and, nevertheless, the search for newer frontiers with this drug goes on.
CONCLUSION: This mini review, in this direction, tries to highlight the key research interventions employing vesicular systems of drug delivery with curcumin.
Immunological axis of curcumin-loaded vesicular drug delivery systems

Chellappan DK, Ng ZY, Wong JY, Hsu A, Wark P, Hansbro N, et al.

Future Med Chem, 2018 04 01;10(8):839-844.
PMID: 29620416 DOI: 10.4155/fmc-2017-0245

Several vesicular systems loaded with curcumin have found their way in the therapeutic applications of several diseases, primarily acting through their immunological pathways. Such systems use particles at a nanoscale range, bringing about their intended use through a range of complex mechanisms. Apart from delivering drug substances into target tissues, these vesicular systems also effectively overcome problems like insolubility and unequal drug distribution. Several mechanisms are explored lately by different workers, and interest over vesicular curcumin has been renewed in the past decade. This commentary discusses several immunological targets in which curcumin is employed in a vesicular form.
Assessing the potential of liposomes loaded with curcumin as a therapeutic intervention in asthma

Ng ZY, Wong JY, Panneerselvam J, Madheswaran T, Kumar P, Pillay V, et al.

Colloids Surf B Biointerfaces, 2018 Dec 01;172:51-59.
PMID: 30134219 DOI: 10.1016/j.colsurfb.2018.08.027

Curcumin a component of turmeric, which is derived from Curcuma longa is used as a colouring agent and as a dietary spice for centuries. Extensive studies have been done on the anti-inflammatory activity of curcumin along with its molecular mechanism involving different signalling pathways. However, the physicochemical and biological properties such as poor solubility and rapid metabolism of curcumin have led to low bioavailability and hence limits its application. Current therapies for asthma such as bronchodilators and inhaled corticosteroids (ICS) are aimed at controlling disease symptoms and prevent asthma exacerbation. However, this approach requires lifetime therapy and is associated with a constellation of side effects. This creates a clear unmet medical need and there is an urgent demand for new and more-effective treatments. The present study is aimed to formulate liposomes containing curcumin and evaluate for its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation on BCi-NS1.1 cell line. Curcumin and salbutamol liposomes were formulated using lipid hydration method. The prepared liposomes were characterized in terms of particle size, zeta potential, encapsulation efficiency and in-vitro release profile. The liposomes were tested on BCI-NS1.1 cell line to evaluate its anti-inflammatory properties. The various pro-inflammatory markers studied were Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1β (IL-1β) and Tumour Necrosis Factor-a (TNF-a). Additionally, molecular mechanics simulations were used to elucidate the positioning, energy minimization, and aqueous dispersion of the liposomal architecture involving lecithin and curcumin. The prepared curcumin formulation showed an average size and zeta potential of 271.3 ± 3.06 nm and -61.0 mV, respectively. The drug encapsulation efficiency of liposomal curcumin is 81.1%. Both curcumin-loaded liposomes formulation (1 μg/mL, 5 μg/mL) resulted in significant (p
The role of pazopanib on tumour angiogenesis and in the management of cancers: A review

Chellappan DK, Chellian J, Ng ZY, Sim YJ, Theng CW, Ling J, et al.

Biomed Pharmacother, 2017 Dec;96:768-781.
PMID: 29054093 DOI: 10.1016/j.biopha.2017.10.058

Pazopanib is a relatively new compound to be introduced into the chemotherapy field. It is thought to have decent anti-angiogenic properties, which gives an additional hope for the treatment of certain types of cancers. A systematic review solely discussing about pazopanib and its anti-angiogenic effect is yet to be published to date, despite several relevant clinical trials being conducted over the recent years. In this review, we aim to investigate the mechanism of pazopanib's anti-angiogenic effect and its effectiveness in treating several cancers. We have included, in this study, findings from electronically searchable data from randomized clinical trials, clinical studies, cohort studies and other relevant articles. A total of 352 studies were included in this review. From the studies, the effect of pazopanib in various cancers or models was observed and recorded. Study quality is indefinite, with a few decent quality articles. The most elaborately studied cancers include renal cell carcinoma, solid tumors, advanced solid tumors, soft tissue sarcoma, breast cancer and gynecological cancers. In addition, several less commonly studied cancers are included in the studies as well. Pazopanib had demonstrated its anti-angiogenic effect based on favorable results observed in cancers, which are caused by angiogenesis-related mechanisms, such as renal cell carcinoma, solid tumors, advanced solid tumors and soft tissue sarcoma. This review was conducted to study, analyze and review the anti-angiogenic properties of pazopanib in various cancers. The results obtained can provide a decent reference when considering treatment options for angiogenesis-related malignancies. Furthermore, the definite observations of the anti-angiogenic effects of pazopanib could provide newer insights leading to the future development of drugs of the same mechanism with increased efficiency and reduced adverse effects.