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Zinc (II) complex with a cationic Schiff base ligand: synthesis, characterization, and biological studies

Lee SK, Tan KW, Ng SW, Ooi KK, Ang KP, Abdah MA

Spectrochim Acta A Mol Biomol Spectrosc, 2014;121:101-8.
PMID: 24231745 DOI: 10.1016/j.saa.2013.10.084

A cationic Schiff base ligand, TSB (L) and its Zn (II) complex (1) were synthesized and characterized by using CHN, (1)H-NMR, FT-IR, UV, LC-MS, and X-ray methods. Their ability to inhibit topoisomerase I, DNA cleavage activities, and cytotoxicity were studied. X-ray diffraction study shows that the mononuclear complex 1 is four coordinated with distorted tetrahedral geometry. The singly deprotonated Schiff base ligand L acts as a bidentate ON-donor ligand. Complexation of L increases the inhibitory strength on topoisomerase I activity. Complex 1 could fully inhibit topoisomerase I activity at 250 μM, while L did not show any inhibitory effect on topoisomerase I activity. In addition, L and complex 1 could cleave pBR322 DNA in a concentration and time dependent profile. Surprisingly, L has better DNA cleavage activity than complex 1. The cleavage of DNA by complex 1 is altered in the presence of hydrogen peroxide. Furthermore, L and complex 1 are mildly cytotoxic towards human ovarian cancer A2780 and hepatocellular carcinoma HepG2.
Radiological monitoring: terrestrial natural radionuclides in Kinta District, Perak, Malaysia

Lee SK, Wagiran H, Ramli AT, Apriantoro NH, Wood AK

J Environ Radioact, 2009 May;100(5):368-74.
PMID: 19299052 DOI: 10.1016/j.jenvrad.2009.01.001

Natural background gamma radiation and radioactivity concentrations were investigated from 2003 to 2005 in Kinta District, Perak, Malaysia. Sample locations were distant from any 'amang' processing plants. The external gamma dose rates ranged from 39 to 1039 nGy h(-1). The mean external gamma dose rate was 222+/-191 nG yh(-1). Small areas of relatively enhanced activity were located having external gamma dose rates of up to 1039+/-104 nGy h(-1). The activity concentrations of (238)U, (232)Th and (40)K were analyzed by using a high-resolution co-axial HPGe detector system. The activity concentration ranges were 12-426 Bq kg(-1) for (238)U, 19-1377 Bq kg(-1) for (232)Th and <19-2204 Bq kg(-1) for (40)K. Based on the radioactivity levels determined, the gamma-absorbed dose rates in air at 1m above the ground were calculated. The calculated dose rates and measured dose rates had a good correlation coefficient, R of 0.94. To evaluate the radiological hazard of the natural radioactivity, the radium equivalent activity, the gamma-absorbed dose rate and the mean population weighted dose rate were calculated. An isodose map for the Kinta District was also produced.
Effects of antenatal, postpartum and post-weaning melatonin supplementation on blood pressure and renal antioxidant enzyme activities in spontaneously hypertensive rats

Lee SK, Sirajudeen KN, Sundaram A, Zakaria R, Singh HJ

J Physiol Biochem, 2011 Jun;67(2):249-57.
PMID: 21210316 DOI: 10.1007/s13105-010-0070-2

Although melatonin lowers blood pressure in spontaneously hypertensive rats (SHR), its effect following antenatal and postpartum supplementation on the subsequent development of hypertension in SHR pups remains unknown. To investigate this, SHR dams were given melatonin in drinking water (10 mg/kg body weight/day) from day 1 of pregnancy until day 21 postpartum. After weaning, a group of male pups continued to receive melatonin till the age of 16 weeks (Mel-SHR), while no further melatonin was given to another group of male pups (Maternal-Mel-SHR). Controls received plain drinking water. Systolic blood pressure (SBP) was measured at 4, 6, 8, 12 and 16 weeks of age, after which the kidneys were collected for analysis of antioxidant enzyme profiles. SBP was significantly lower till the age of 8 weeks in Maternal-Mel-SHR and Mel-SHR than that in the controls, after which no significant difference was evident in SBP between the controls and Maternal-Mel-SHR. SBP in Mel-SHR was lower than that in controls and Maternal-Mel-SHR at 12 and 16 weeks of age. Renal glutathione peroxidase (GPx) and glutathione s-transferase (GST) activities, levels of total glutathione and relative GPx-1 protein were significantly higher in Mel-SHR. GPx protein was however significantly higher in Mel-SHR. No significant differences were evident between the three groups in the activities of superoxide dismutase, catalase and glutathione reductase. In conclusion, it appears that while antenatal and postpartum melatonin supplementation decreases the rate of rise in blood pressure in SHR offspring, it however does not alter the tendency of offspring of SHR to develop hypertension.
Expression of oestrogen-α receptor in papillary thyroid carcinoma and its association with metastasis

Ab Halim SA, Lee SK, Mustangin M, Mohd Saleh MF, Shah SA, Md Isa N

Malays J Pathol, 2020 Dec;42(3):415-422.
PMID: 33361723

INTRODUCTION: Papillary thyroid carcinoma (PTC) is the ninth most common malignancy among women. Although the disease prognosis is good, less favourable outcomes are predicted in those with higher disease stages and nodal metastasis. Oestrogen- α (ER-α) expression has been associated with aggressive presentation and greater disease progression and has been proposed as a predictor for lymph node metastases. The objective of this study was to evaluate the association between ER expression and clinicopathological features i.e. lymph node metastasis, tumour size, extrathyroidal extension, histological variants of PTC , age groups , ethnic and gender.
METHODS: We studied ER-α expression in 84 cases of PTC obtained within an eight-year period (2011-2018) by immunohistochemical technique (IHC). Associations between ER-α expression and clinicopathological features were evaluated using Fisher's exact test. The statistical significance was set at p < 0.05.
RESULTS: ER-α was expressed in 13.1% of all the PTC cases examined (n=11/84). There were no associations observed between ER-α expression and lymph node metastasis (p=1.000), tumour size (p=0.970), extrathyroidal extension (p=0.677), variants of PTC (p=1.000), age groups (p=0.188), gender (p=0.725) or race (p=0.920).
CONCLUSION: There was no evidence in this study to support the application of ER-α as prediction marker for lymph node metastasis or disease aggressiveness in PTC. Given that the scope of this study was limited to the protein expression of ER- α, we also propose the inclusion of molecular analysis of ESR1 gene expression, as well as inclusion of detailed clinical and radiological findings in future research investigating the role of ER-α in prognostication of PTC.
Motivation structures of blood donation: a means-end chain approach

Tey YS, Arsil P, Brindal M, Lee SK, Teoh CT

Int J Health Econ Manag, 2020 Mar;20(1):41-54.
PMID: 31236797 DOI: 10.1007/s10754-019-09269-8

Understanding blood donation behaviours is pivotal to recruiting and retaining blood donors. Despite rich literature, this is the first study investigating the content and structure of motivations that underlie blood donation using a means-end chain approach. Based on soft laddering interviews with 227 respondents (31 first-time blood donors and 196 repeat blood donors) in the Klang Valley of Malaysia, we identified that their blood donation was primarily driven by the attribute 'help people', the consequences 'increase blood supply' (as perceived by first-time blood donors) and 'indirect downstream reciprocity' (as perceived by repeat blood donors) associated with the attribute and the belief that the consequences can lead to the fulfilment of the value 'humanitarianism'. Understanding of such hierarchical links between motivators is crucial in developing self-relevant communications. The resultant outcomes are likely to be more effective than the traditional approaches in behavioural change.
Fulltext Characterization of the mechanism of prolonged adaptation to osmotic stress of Jeotgalibacillus malaysiensis via genome and transcriptome sequencing analyses

Yaakop AS, Chan KG, Ee R, Lim YL, Lee SK, Manan FA, et al.

Sci Rep, 2016 09 19;6:33660.
PMID: 27641516 DOI: 10.1038/srep33660

Jeotgalibacillus malaysiensis, a moderate halophilic bacterium isolated from a pelagic area, can endure higher concentrations of sodium chloride (NaCl) than other Jeotgalibacillus type strains. In this study, we therefore chose to sequence and assemble the entire J. malaysiensis genome. This is the first report to provide a detailed analysis of the genomic features of J. malaysiensis, and to perform genetic comparisons between this microorganism and other halophiles. J. malaysiensis encodes a native megaplasmid (pJeoMA), which is greater than 600 kilobases in size, that is absent from other sequenced species of Jeotgalibacillus. Subsequently, RNA-Seq-based transcriptome analysis was utilised to examine adaptations of J. malaysiensis to osmotic stress. Specifically, the eggNOG (evolutionary genealogy of genes: Non-supervised Orthologous Groups) and KEGG (Kyoto Encyclopaedia of Genes and Genomes) databases were used to elucidate the overall effects of osmotic stress on the organism. Generally, saline stress significantly affected carbohydrate, energy, and amino acid metabolism, as well as fatty acid biosynthesis. Our findings also indicate that J. malaysiensis adopted a combination of approaches, including the uptake or synthesis of osmoprotectants, for surviving salt stress. Among these, proline synthesis appeared to be the preferred method for withstanding prolonged osmotic stress in J. malaysiensis.
Endovascular management of axillosubclavian artery injuries: report of three cases

Leong BD, Naresh G, Hanif H, Lee SK, Zainal AA, Sara CM

Surg Today, 2013 Aug;43(8):918-22.
PMID: 22987278 DOI: 10.1007/s00595-012-0330-6

Open surgical repair of axillosubclavian artery injuries is technically demanding and associated with significant morbidity and mortality. Endovascular intervention has emerged as a valuable alternative to open surgical repair. This report presents three cases with axillosubclavian artery injuries managed with endovascular intervention. All three cases had a pseudoaneurysm of the axillosubclavian artery with one case associated with an arteriovenous fistula. They were successfully treated with endovascular stenting and balloon angioplasty. There were no observed acute complications. No complications or recurrence have occurred, with a mean follow-up of 26 months. Endovascular intervention for axillosubclavian artery injuries is less invasive, safe and effective; however, data concerning the long-term effects and complications associated with this technique are lacking.
Chronic Administration of Red Yeast Rice Mitigates Endothelial Dysfunction in Spontaneously Hypertensive Rats by Inhibiting Oxidative Stress and Endothelial Nitric Oxide Synthase Uncoupling

Tan JJ, Murugan DD, Ling WC, Lee SK, Kang WH

Curr Vasc Pharmacol, 2024 Jun 06.
PMID: 38847159 DOI: 10.2174/0115701611295900240529104225

BACKGROUND: Hypertension is associated with endothelial dysfunction. An imbalance in the production of Nitric Oxide (NO) and Reactive Oxygen Species (ROS), leading to impaired NO-cyclic Guanosine Monophosphate (cGMP) pathway, contributes to this disorder. Red Yeast Rice (RYR), produced from the fermentation of rice with Monascus purpureus, is a traditional functional food originating from China. Although recognized for its anti-dyslipidemia properties, there has been growing evidence regarding the anti-hypertensive effects of RYR. However, these studies only focused on its direct and short-term effects.
AIM: This study aims to investigate the vasoprotective effects of chronic oral RYR administration using Spontaneously Hypertensive Rats (SHR).
MATERIALS AND METHODS: SHR were randomly divided into 3 groups: SHR - Control; SHR - RYR extract (100 mg/kg/day); SHR - lovastatin (10 mg/kg/day). Wistar-Kyoto Rats (WKY) were used as normotensive controls. All animals were treated for 12 weeks by oral gavage. Systolic Blood Pressure (SBP) was measured weekly (tail-cuff method). Vascular reactivity was determined using isolated rat aortic rings in an organ bath. Aortic ROS, NO, tetrahydrobiopterin (BH4 ), and cGMP levels were evaluated.
RESULTS: Administration of RYR attenuated SBP elevation and enhanced endothelium-dependent vasodilation in aortic rings. In addition, RYR decreased ROS production and significantly improved the level of vascular NO, BH4, and cGMP.
CONCLUSION: In an SHR model, treatment with RYR for 12 weeks exerts an SBP lowering effect that can be attributed to improved vascular function via reduction of oxidative stress, decreased endothelial NO Synthase (eNOS) uncoupling and enhanced NO-cGMP pathway.
Fulltext Complete genome sequencing of Pandoraea pnomenusa RB38 and Molecular Characterization of Its N-acyl homoserine lactone synthase gene ppnI

Lim YL, Ee R, How KY, Lee SK, Yong D, Tee KK, et al.

PeerJ, 2015;3:e1225.
PMID: 26336650 DOI: 10.7717/peerj.1225

In this study, we sequenced the genome of Pandoraea pnomenusa RB38 using Pacific Biosciences RSII (PacBio) Single Molecule Real Time (SMRT) sequencing technology. A pair of cognate luxI/R homologs was identified where the luxI homolog, ppnI, was found adjacent to a luxR homolog, ppnR1. An additional orphan luxR homolog, ppnR2, was also discovered. Multiple sequence alignment and phylogenetic analysis revealed that ppnI is an N-acyl homoserine lactone (AHL) synthase gene that is distinct from those of the nearest phylogenetic neighbor viz. Burkholderia spp. High resolution tandem mass spectrometry (LC-MS/MS) analysis showed that Escherichia coli BL21 harboring ppnI produced a similar AHL profile (N-octanoylhomoserine lactone, C8-HSL) as P. pnomenusa RB38, the wild-type donor strain, confirming that PpnI directed the synthesis of AHL in P. pnomenusa RB38. To our knowledge, this is the first documentation of the luxI/R homologs of the genus Pandoraea.
Fulltext In vitro invasion inhibition assay using antibodies against Plasmodium knowlesi Duffy binding protein alpha and apical membrane antigen protein 1 in human erythrocyte-adapted P. knowlesi A1-H.1 strain

Muh F, Lee SK, Hoque MR, Han JH, Park JH, Firdaus ER, et al.

Malar J, 2018 Jul 27;17(1):272.
PMID: 30049277 DOI: 10.1186/s12936-018-2420-4

BACKGROUND: The rapid process of malaria erythrocyte invasion involves ligand-receptor interactions. Inducing antibodies against specific ligands or receptors that abrogate the invasion process is a key challenge for blood stage vaccine development. However, few candidates were reported and remain to be validated for the discovery of new vaccine candidates in Plasmodium knowlesi.
METHODS: In order to investigate the efficacy of pre-clinical vaccine candidates in P. knowlesi-infected human cases, this study describes an in vitro invasion inhibition assay, using a P. knowlesi strain adapted to in vitro growth in human erythrocytes, PkA1-H.1. Recombinant proteins of P. knowlesi Duffy binding protein alpha (PkDBPα) and apical membrane antigen 1 (PkAMA1) were produced in Escherichia coli system and rabbit antibodies were generated from immune animals.
RESULTS: PkDBPα and PkAMA1 recombinant proteins were expressed as insoluble and produced as a functional refolded form for this study. Antibodies against PkDBPα and PkAMA1 specifically recognized recombinant proteins and native parasite proteins in schizont-stage parasites on the merozoite organelles. Single and combination of anti-PkDBPα and anti-PkAMA1 antibodies elicited strong growth inhibitory effects on the parasite in concentration-dependent manner. Meanwhile, IgG prevalence of PkDBPα and PkAMA1 were observed in 13.0 and 46.7% in human clinical patients, respectively.
CONCLUSION: These data provide support for the validation of in vitro growth inhibition assay using antibodies of DBPα and AMA1 in human-adapted P. knowlesi parasite PkA1-H.1 strain.
Natural alternatives from your garden for hair care: Revisiting the benefits of tropical herbs

Sang SH, Akowuah GA, Liew KB, Lee SK, Keng JW, Lee SK, et al.

Heliyon, 2023 Nov;9(11):e21876.
PMID: 38034771 DOI: 10.1016/j.heliyon.2023.e21876

Hair shampoos containing botanical ingredients without synthetic additives, such as parabens, petrochemicals, sulfates and silicones are more skin- and environmentally friendly. In recent years, there is a growing demand for shampoo products with botanical extracts. Shampoos with botanical extracts are well-known for their perceived health benefits. They are also generally milder, non-toxic, natural, and less likely to disrupt the hair and scalp's natural pH and oil balance. Many also believe that shampoos with botanical origins have higher standards of quality. Numerous botanical extracts had been used as natural active ingredients in cosmetic formulations to meet consumer demands. In this review, we have revisited six tropical plants commonly added as natural active ingredients in shampoo formulations: Acacia concinna, Camellia oleifera, Azadirachta indica, Emblica officinalis, Sapindus mukorossi, and Garcinia mangostana. These plants have been traditionally used for hair care, and scientific research has shown that they exhibit relevant physicochemical properties and biological activities that are beneficial for hair care and scalp maintenance.
Development of a Novel Co-processed Excipitient Comprising of Xylitol, Mannitol, Microcrystalline Cellulose, and Crospovidone for the Compounding of Memantine Hydrochloride Orally Disintegrating Tablet

Hazdi SN, Phang HC, Ng ZQ, Chew YL, Uddin AH, Sarker ZI, et al.

Int J Pharm Compd, 2023;27(6):522-527.
PMID: 38100670

Orally disintegrating tablets, which were originally developed in the pharmaceutical field to improve the compliance of patients who had difficulty swallowing tablets, have become a preferable choice in solid dosage forms since it brings advantages to the patients and consumers in the healthcare system. Among the advantages of this novel dosage form are a faster onset of action, improved bioavailability, and the ease of administration as it can be taken without water. However, there are still some limitations of orally disintegrating tablets that need to be overcome, including a lack of mechanical strength, an unpleasant taste of the drug in the mouth, and a stability issue due to its hygroscopicity nature. This objective of this study was to identify the composition of co-processed excipients comprising of mannitol, microcrystalline cellulose, xylitol, and crospovidone or croscarmellose sodium in order to formulate orally disintegrating tablets containing memantine hydrochloride. This study was carried out in two stages. Firstly, orally disintegrating tablets containing memantine hydrochloride with 6 different formulations, which differed in the percentage of crospovidone or croscarmellose sodium, were formulated and manufactured. Secondly, the orally disintegrating tablets obtained were evaluated through pre- and post-compression tests based on the standard for orally disintegrating tablets. Formulation 3, which consisted of 10% xylitol, 10% mannitol, 72% microcrystalline cellulose, and 8% crospovidone, was chosen as the optimum formulation for the co-processed excipient since it was the fastest disintegration process among all the formulations in the study. In addition, Formulation 3 also showed the acceptable and satisfying results in other evaluation tests such as - weight variation test, hardness test, and friability test. The co-processed excipient comprising of 10% xylitol, 10% mannitol, 72% microcrystalline cellulose, and 8% crospovidone, which is characterized by improved functionalities such as a fast disintegration process, plays a crucial role in the application of orally disintegrating tablets.
Fulltext Cross-species analysis of apical asparagine-rich protein of Plasmodium vivax and Plasmodium knowlesi

Muh F, Ahmed MA, Han JH, Nyunt MH, Lee SK, Lau YL, et al.

Sci Rep, 2018 04 10;8(1):5781.
PMID: 29636493 DOI: 10.1038/s41598-018-23728-1

The Plasmodium falciparum apical asparagine (Asn)-rich protein (AARP) is one of malarial proteins, and it has been studied as a candidate of malaria subunit vaccine. Basic characterization of PvAARP has been performed with a focus on its immunogenicity and localization. In this study, we further analyzed the immunogenicity of PvAARP, focusing on the longevity of the antibody response, cross-species immunity and invasion inhibitory activity by using the primate malaria parasite Plasmodium knowlesi. We found that vivax malaria patient sera retained anti-PvAARP antibodies for at least one year without re-infection. Recombinant PvAARP protein was strongly recognized by knowlesi malaria patients. Antibody raised against the P. vivax and P. knowlesi AARP N-termini reacted with the apical side of the P. knowlesi merozoites and inhibited erythrocyte invasion by P. knowlesi in a concentration-dependent manner, thereby suggesting a cross-species nature of anti-PvAARP antibody against PkAARP. These results can be explained by B cell epitopes predicted in conserved surface-exposed regions of the AARP N-terminus in both species. The long-lived anti-PvAARP antibody response, cross-reactivity, and invasion inhibitory activity of anti-PvAARP support a critical role of AARP during the erythrocyte invasion and suggest that PvAARP induces long-lived cross-species protective immunity against P. vivax and P. knowlesi.
Fulltext Cocoa Butter: Evolution from Natural Food Ingredient to Pharmaceutical Excipient and Drug Delivery System

Loke YH, Phang HC, Mohamad N, Kee PE, Chew YL, Lee SK, et al.

Planta Med, 2024 Sep;90(11):824-833.
PMID: 39043195 DOI: 10.1055/a-2359-8097

For decades, cocoa butter has been extensively used in food industries, particularly in the production of chocolate confectioneries. The composition of fats within cocoa butter, such as stearic acid, palmitic acid, and oleic acid, determines its properties. Studies have indicated the existence of at least six polymorphic forms of cocoa butter, each possessing distinct characteristics and melting points. Recently, cocoa butter has garnered attention for its potential as a delivery system for pharmaceutical products. This review thoroughly explores cocoa butter, encompassing its production process, composition, properties, and polymorphism. It delves into its diverse applications across various industries including food, cosmetics, and pharmaceuticals. Additionally, the review investigates cocoa butter alternatives aiming to substitute cocoa butter and their roles in different drug delivery systems. The unique properties of cocoa butter have sparked interest in pharmaceutical industries, particularly since its introduction as a drug delivery system and excipient. This has prompted researchers and industry stakeholders to explore novel formulations and delivery methods, thereby expanding the range of options available to consumers in the pharmaceutical market.
Fulltext Lack of clinical manifestations in asymptomatic dengue infection is attributed to broad down-regulation and selective up-regulation of host defence response genes

Yeo AS, Azhar NA, Yeow W, Talbot CC, Khan MA, Shankar EM, et al.

PLoS One, 2014;9(4):e92240.
PMID: 24727912 DOI: 10.1371/journal.pone.0092240

Dengue represents one of the most serious life-threatening vector-borne infectious diseases that afflicts approximately 50 million people across the globe annually. Whilst symptomatic infections are frequently reported, asymptomatic dengue remains largely unnoticed. Therefore, we sought to investigate the immune correlates conferring protection to individuals that remain clinically asymptomatic.
Fulltext Cross-species reactivity of antibodies against Plasmodium vivax blood-stage antigens to Plasmodium knowlesi

Muh F, Kim N, Nyunt MH, Firdaus ER, Han JH, Hoque MR, et al.

PLoS Negl Trop Dis, 2020 06;14(6):e0008323.
PMID: 32559186 DOI: 10.1371/journal.pntd.0008323

Malaria is caused by multiple different species of protozoan parasites, and interventions in the pre-elimination phase can lead to drastic changes in the proportion of each species causing malaria. In endemic areas, cross-reactivity may play an important role in the protection and blocking transmission. Thus, successful control of one species could lead to an increase in other parasite species. A few studies have reported cross-reactivity producing cross-immunity, but the extent of cross-reactive, particularly between closely related species, is poorly understood. P. vivax and P. knowlesi are particularly closely related species causing malaria infections in SE Asia, and whilst P. vivax cases are in decline, zoonotic P. knowlesi infections are rising in some areas. In this study, the cross-species reactivity and growth inhibition activity of P. vivax blood-stage antigen-specific antibodies against P. knowlesi parasites were investigated. Bioinformatics analysis, immunofluorescence assay, western blotting, protein microarray, and growth inhibition assay were performed to investigate the cross-reactivity. P. vivax blood-stage antigen-specific antibodies recognized the molecules located on the surface or released from apical organelles of P. knowlesi merozoites. Recombinant P. vivax and P. knowlesi proteins were also recognized by P. knowlesi- and P. vivax-infected patient antibodies, respectively. Immunoglobulin G against P. vivax antigens from both immune animals and human malaria patients inhibited the erythrocyte invasion by P. knowlesi. This study demonstrates that there is extensive cross-reactivity between antibodies against P. vivax to P. knowlesi in the blood stage, and these antibodies can potently inhibit in vitro invasion, highlighting the potential cross-protective immunity in endemic areas.
Fulltext Optimization of a Luteolin-Loaded TPGS/Poloxamer 407 Nanomicelle: The Effects of Copolymers, Hydration Temperature and Duration, and Freezing Temperature on Encapsulation Efficiency, Particle Size, and Solubility

Mod Razif MRF, Chan SY, Widodo RT, Chew YL, Hassan M, Hisham SA, et al.

Cancers (Basel), 2023 Jul 24;15(14).
PMID: 37509402 DOI: 10.3390/cancers15143741

BACKGROUND: Luteolin is a flavonoid compound that has been widely studied for its various anti-cancer properties and sensitization to multidrug-resistant cells. However, the limited solubility and bioavailability of Lut hindered its potential clinical use. Theoretically, the combination of this compound with vitamin E TPGS and poloxamer 407 can produce a synergistic effect to enhance tumor apoptosis and P-glycoprotein inhibition. This study aimed to develop and optimize vitamin E TPGS/Poloxamer 407 micelles loaded with luteolin through investigating certain factors that can affect the encapsulation efficiency and particle size of the micelle.
METHODS: A micelle was prepared using the film hydration method, and the micellar solution was lyophilized. The cake formed was analyzed. The factors investigated include the concentrations of the surfactants, ratio of vitamin E TPGS/Poloxamer 407, temperature of the hydrating solution, duration of hydration, and freezing temperature before lyophilization. The effects of these factors on the encapsulation efficiency and particle size of the micelle were also studied. The encapsulation efficiency was measured using a UV-Vis spectrophotometer, while particle size was measured using dynamic light scattering.
RESULTS: The optimized micelle was found to have 90% encapsulation efficiency with a particle size of less than 40 nm, which was achieved using a 10% concentration of surfactants at a vitamin E TPGS/Poloxamer 407 ratio of 3:1. The optimized temperature for hydrating the micellar film was 40 °C, the optimized mixing time was 1 h, and the optimized freezing temperature was -80 °C. The solubility of the luteolin-loaded micelles increased 459-fold compared to pure Lut in water. The critical micelle concentration of the vitamin E TPGS/Poloxamer 407 micelle was 0.001 mg/mL, and the release study showed that luteolin-loaded micelles exhibited sustained release behavior. The release of luteolin from a micelle was found to be higher in pH 6.8 compared to pH 7.4, which signified that luteolin could be accumulated more in a tumor microenvironment compared to blood.
CONCLUSION: This study demonstrated that several factors need to be considered when developing such nanoparticles in order to obtain a well-optimized micelle.
Development of a novel direct compressible co-processed excipient and its application for formulation of Mirtazapine orally disintegrating tablets

Loke YH, Chew YL, Janakiraman AK, Lee SK, Uddin ABMH, Goh CF, et al.

Drug Dev Ind Pharm, 2024 Jan;50(1):36-44.
PMID: 38149637 DOI: 10.1080/03639045.2023.2294095

INTRODUCTION: Orally disintegrating tablets (ODTs) are designed to dissolve in the oral cavity within 3 min, providing a convenient option for patients as they can be taken without water. Direct compression is the most common method used for ODTs formulations. However, the availability of single composite excipients with desirable characteristics such as good compressibility, fast disintegration, and a good mouthfeel suitable for direct compression is limited.
OBJECTIVE: This research was proposed to develop a co-processed excipient composed of xylitol, mannitol, and microcrystalline cellulose for the formulation of ODTs.
METHODS: A total of 11 formulations of co-processed excipients with different ratios of ingredients were prepared, which were then compressed into ODTs, and their characteristics were thoroughly examined. The primary focus was on evaluating the disintegration time and hardness of the tablets, as these factors are important in ensuring the ODTs meet the desired criteria. The model drug, Mirtazapine was then incorporated into the chosen optimized formulation.
RESULTS: The results showed that the formulation comprised of 10% xylitol, 10% mannitol and 80% microcrystalline cellulose demonstrated the fastest disintegration time (1.77 ± 0.119 min) and sufficient hardness (3.521 ± 0.143 kg) compared to the other formulations. Furthermore, the drug was uniformly distributed within the tablets and fully released within 15 min.
CONCLUSION: Therefore, the developed co-processed excipients show great potential in enhancing the functionalities of ODTs, offering a promising solution to improve the overall performance and usability of ODTs in various therapeutic applications.
Fulltext Clinical Significance of BCL2, C-MYC, and BCL6 Genetic Abnormalities, Epstein-Barr Virus Infection, CD5 Protein Expression, Germinal Center B Cell/Non-Germinal Center B-Cell Subtypes, Co-expression of MYC/BCL2 Proteins and Co-expression of MYC/BCL2/BCL6 Proteins in Diffuse Large B-Cell Lymphoma: A Clinical and Pathological Correlation Study of 120 Patients

Ting CY, Chang KM, Kuan JW, Sathar J, Chew LP, Wong OJ, et al.

Int J Med Sci, 2019;16(4):556-566.
PMID: 31171907 DOI: 10.7150/ijms.27610

Background: Clinical significance of germinal center B-cell (GCB) and non-GCB sub-categorization, expression of MYC, BCL2, BCL6, CD5 proteins and Epstein Barr virus encoded RNA (EBER) positivity in diffuse large B-cell lymphoma (DLBCL) remain controversial. Could these biomarkers accurately identify high risk DLBCL patients? Are MYC, BCL2 and BCL6 proteins expression feasible as baseline testing to predict c-Myc, BCL2 or BCL6 gene rearrangements? Aims: To investigate prognostic values of GCB/non-GCB sub-categorization, Double Protein Expression Lymphoma (DPL), Triple Protein Expression Lymphoma (TPL), positivity of CD5 protein and EBER in patients with DLBCL disease. To evaluate correlation between BCL2 , c-Myc and BCL6 gene rearrangements with BCL2, MYC and BCL6 proteins expression. Methods: Diagnostic tissue samples of 120 DLBCL patients between January 2012 to December 2013 from four major hospitals in Malaysia were selected. Samples were subjected to immunohistochemical staining, fluorescent in-situ hybridization (FISH) testing, and central pathological review. Pathological data were correlated with clinical characteristics and treatment outcome. Results: A total of 120 cases were analysed. Mean age of diagnosis was 54.1 years ± 14.6, 64 were males, 56 were females, mean follow up period was 25 months (ranged from 1 to 36 months). Of the 120 cases, 74.2% were non-GCB whereas 25.8% were GCB, 6.7% were EBER positive, 6.7% expressed CD5 protein, 13.3% were DPL and 40% were TPL. The prevalence of c-Myc, BCL2, BCL6 gene rearrangements were 5.8%, 5.8%, and 14.2%, respectively; and 1.6% were Double Hit Lymphoma (DHL). EBER positivity, DPL, TPL, c-Myc gene rearrangement, BCL2 gene rearrangement, extra copies of BCL2 gene and BCL6 gene rearrangement were associated with shorter median overall survival (P<0.05). IPI score was the significant determinants of median overall survival in DPL and TPL (P<0.05). CD5 protein expression and GCB/non-GCB sub-categorization did not affect treatment outcome (P>0.05). Overall, c-Myc, BCL2 and BCL6 gene rearrangements showed weak correlation with expression of MYC, BCL2 and BCL6 proteins (P>0.05). Fluorescent in situ hybridization is the preferred technique for prediction of treatment outcome in DLBCL patients. Conclusion:c-Myc, BCL2, and BCL6 gene rearrangements, EBER expression, DHL, TPL and IPI score are reliable risk stratification tools. MYC, BCL2 and BCL6 proteins expression are not applicable as baseline biomarkers to predict c-Myc, BCL2, and BCL6 gene rearrangements.
Fulltext Coming down from the trees: is terrestrial activity in Bornean orangutans natural or disturbance driven?

Ancrenaz M, Sollmann R, Meijaard E, Hearn AJ, Ross J, Samejima H, et al.

Sci Rep, 2014;4:4024.
PMID: 24526001 DOI: 10.1038/srep04024

The orangutan is the world's largest arboreal mammal, and images of the red ape moving through the tropical forest canopy symbolise its typical arboreal behaviour. Records of terrestrial behaviour are scarce and often associated with habitat disturbance. We conducted a large-scale species-level analysis of ground-based camera-trapping data to evaluate the extent to which Bornean orangutans Pongo pygmaeus come down from the trees to travel terrestrially, and whether they are indeed forced to the ground primarily by anthropogenic forest disturbances. Although the degree of forest disturbance and canopy gap size influenced terrestriality, orangutans were recorded on the ground as frequently in heavily degraded habitats as in primary forests. Furthermore, all age-sex classes were recorded on the ground (flanged males more often). This suggests that terrestrial locomotion is part of the Bornean orangutan's natural behavioural repertoire to a much greater extent than previously thought, and is only modified by habitat disturbance. The capacity of orangutans to come down from the trees may increase their ability to cope with at least smaller-scale forest fragmentation, and to cross moderately open spaces in mosaic landscapes, although the extent of this versatility remains to be investigated.

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