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Fulltext Use of complementary and alternative medicine and adherence to antiepileptic drug therapy among epilepsy patients: a systematic review

Farrukh MJ, Makmor-Bakry M, Hatah E, Tan HJ

Patient Prefer Adherence, 2018;12:2111-2121.
PMID: 30349205 DOI: 10.2147/PPA.S179031

Purpose: To identify the use pattern of complementary and alternative medicine (CAM) and its impact on antiepileptic drug (AED) adherence among patients with epilepsy.
Method: Potential studies were identified through a systematic search of Scopus, Science Direct, Google Scholar, and PubMed. The keywords used to identify relevant articles were "adherence," "AED," "epilepsy," "non-adherence," and "complementary and alternative medicine." An article was included in the review if the study met the following criteria: 1) conducted in epilepsy patients, 2) conducted in patients aged 18 years and above, 3) conducted in patients prescribed AEDs, and 4) patients' adherence to AEDs.
Results: A total of 3,330 studies were identified and 30 were included in the final analysis. The review found that the AED non-adherence rate reported in the studies was between 25% and 66%. The percentage of CAM use was found to be between 7.5% and 73.3%. The most common reason for inadequate AED therapy and higher dependence on CAM was the patients' belief that epilepsy had a spiritual or psychological cause, rather than primarily being a disease of the brain. Other factors for AED non-adherence were forgetfulness, specific beliefs about medications, depression, uncontrolled recent seizures, and frequent medication dosage.
Conclusion: The review found a high prevalence of CAM use and non-adherence to AEDs among epilepsy patients. However, a limited number of studies have investigated the association between CAM usage and AED adherence. Future studies may wish to explore the influence of CAM use on AED medication adherence.
A colonic amoebic abscess mimicking colonic carcinoma

Tan LP, Foong KK, Yvonne Ai LL

Med J Malaysia, 2018 10;73(5):334-335.
PMID: 30350818 MyJurnal

Amebiasis is one of the major causes of diarrhea in the developing countries and it can present with a wide range of gastrointestinal symptoms depending on the phase of infection. We described a case of 50 year-old male patient who presented with abdominal pain, diarrhea and vomiting. After right hemicolectomy for appendicular abscess with tumour over the ileum, histopathological examinations revealed numerous trophozoites of Entamoeba histolytica in a background of inflammations (Figure 1). Following resection of the ameboma, he received intravenous metronidazole treatment for total of two weeks duration.
Fulltext Integrative machine learning analysis of multiple gene expression profiles in cervical cancer

Tan MS, Chang SW, Cheah PL, Yap HJ

PeerJ, 2018;6:e5285.
PMID: 30065881 DOI: 10.7717/peerj.5285

Although most of the cervical cancer cases are reported to be closely related to the Human Papillomavirus (HPV) infection, there is a need to study genes that stand up differentially in the final actualization of cervical cancers following HPV infection. In this study, we proposed an integrative machine learning approach to analyse multiple gene expression profiles in cervical cancer in order to identify a set of genetic markers that are associated with and may eventually aid in the diagnosis or prognosis of cervical cancers. The proposed integrative analysis is composed of three steps: namely, (i) gene expression analysis of individual dataset; (ii) meta-analysis of multiple datasets; and (iii) feature selection and machine learning analysis. As a result, 21 gene expressions were identified through the integrative machine learning analysis which including seven supervised and one unsupervised methods. A functional analysis with GSEA (Gene Set Enrichment Analysis) was performed on the selected 21-gene expression set and showed significant enrichment in a nine-potential gene expression signature, namely PEG3, SPON1, BTD and RPLP2 (upregulated genes) and PRDX3, COPB2, LSM3, SLC5A3 and AS1B (downregulated genes).
Effect of virgin avocado oil on diet-induced hypercholesterolemia in rats via 1 H NMR-based metabolomics approach

Tan CX, Chong GH, Hamzah H, Ghazali HM

Phytother Res, 2018 Nov;32(11):2264-2274.
PMID: 30051518 DOI: 10.1002/ptr.6164

Hypercholesterolemia is a major risk factor for the initiation and development of nonalcoholic fatty liver disease and atherosclerosis. The present study evaluated the hypocholesterolemic effect of virgin avocado oil (VAO) using urinary metabolomic method. Male Sprague-Dawley rats were fed high-cholesterol diet for four weeks to induce hypercholesterolemia. After confirming the establishment of hypercholesterolemia model, the VAO (450 and 900 mg·kg-1 ·day-1 ) and simvastatin (10 mg·kg-1 ·day-1 ) were given orally while maintaining the high-cholesterol diet for another four weeks. Assessment of urinary metabolomics using NMR revealed that VAO treatment could partially recover the metabolism dysfunction induced by hypercholesterolemia mainly via lipid, energy, amino acid, and gut microbiota metabolism.
Fulltext Crown damage and the mortality of tropical trees

Arellano G, Medina NG, Tan S, Mohamad M, Davies SJ

New Phytol, 2019 01;221(1):169-179.
PMID: 30067290 DOI: 10.1111/nph.15381

What causes individual tree death in tropical forests remains a major gap in our understanding of the biology of tropical trees and leads to significant uncertainty in predicting global carbon cycle dynamics. We measured individual characteristics (diameter at breast height, wood density, growth rate, crown illumination and crown form) and environmental conditions (soil fertility and habitat suitability) for 26 425 trees ≥ 10 cm diameter at breast height belonging to 416 species in a 52-ha plot in Lambir Hills National Park, Malaysia. We used structural equation models to investigate the relationships among the different factors and tree mortality. Crown form (a proxy for mechanical damage and other stresses) and prior growth were the two most important factors related to mortality. The effect of all variables on mortality (except habitat suitability) was substantially greater than expected by chance. Tree death is the result of interactions between factors, including direct and indirect effects. Crown form/damage and prior growth mediated most of the effect of tree size, wood density, fertility and habitat suitability on mortality. Large-scale assessment of crown form or status may result in improved prediction of individual tree death at the landscape scale.
Andrographolide prevented toluene diisocyanate-induced occupational asthma and aberrant airway E-cadherin distribution via p38 MAPK-dependent Nrf2 induction

Sulaiman I, Tan K, Mohtarrudin N, Lim JCW, Stanslas J

Pulm Pharmacol Ther, 2018 12;53:39-51.
PMID: 30244166 DOI: 10.1016/j.pupt.2018.09.008

Toluene diisocyanate (TDI) is a major cause of chemical-induced occupational asthma, which contributes about 15% of global asthma burden. Resistance and compounded side effects associated with the use of corticosteroid in asthma necessitate the search for alternative drugs. Andrographolide (AGP), a naturally occurring diterpene lactone is known to exhibit various bioactivities. Its ability to ameliorate cardinal features of allergic asthma was previously suggested in an eosinophilic asthma endotype. However, its potential antiasthma activity and mechanism of action in a neutrophilic occupational asthma model, as well as its effect on epithelial dysfunction remain unknown. BALB/c mice were dermally sensitised with 0.3% TDI or acetone olive oil (AOO) vehicle on day 1 and 8, followed by 0.1% TDI intranasal challenge on days 15, 18 and 21. Endpoints were evaluated via bronchoalveolar lavage fluid (BALF) cell analysis, 2',7'-dichlorofluorescein diacetate (DCFDA) assays, immunoblotting, immunohistochemistry and methacholine challenge test. Decreases in total and differential leukocyte counts of BALF were recorded in AGP-treated animals. The compound dose-dependently reduced intracellular de-esterification of DCFDA, thus suggesting AGP's potential to inhibit intracellular reactive oxygen species (ROS). Mechanistically, the treatment prevented TDI-induced aberrant E-cadherin distribution and restored airway epithelial β-catenin at cell to cell contact site. Furthermore, AGP ameliorated TDI induced pulmonary collagen deposition. In addition, the treatment significantly upregulated pulmonary HO-1, Nrf2 and phospho-p38 levels. Airway hyperresponsiveness was markedly suppressed among AGP-treated animals. Collectively, these findings suggest AGP's protective function against TDI-induced airway epithelial barrier dysfunction and oxidative lung damage possibly through the upregulation of adherence junction proteins and the activation of p38/Nrf2 signalling. This study elucidates the therapeutic potential of AGP in the control and management of chemical-induced allergic asthma. To the best of our knowledge, the potential anti-asthma activity of AGP in TDI-induced occupational asthma has not been reported previously.
Fulltext Changes in 3-MCPD esters, glycidyl esters, bioactive compounds and oxidation indexes during kenaf seed oil refining

Chew SC, Tan CP, Lai OM, Nyam KL

Food Sci Biotechnol, 2018 Jun;27(3):905-914.
PMID: 30263818 DOI: 10.1007/s10068-017-0295-8

An optimized refining process for kenaf seed oil was conducted. The 3-monochloro-1,2-propanediol (3-MCPD) contents, triacylglycerol composition, fatty acids composition, bioactive compounds, phosphorus contents, and oxidation indexes of the kenaf seed oil during each stage of the refining process were determined. The results showed that there was no detected 3-MCPD ester in kenaf seed oil throughout the refining process. Deodorization had slightly increased the 2-MCPD ester (9.0 μg/kg) and glycidyl ester (54.8 μg/kg). Oleic (36.53%) and linoleic acids (36.52%) were presented in the largest amount in the refined kenaf seed oil, and triacylglycerols contributed to 99.96% in the oil. There was a removal of 31.6% of phytosterol content and 17.1% of tocopherol and tocotrienol contents in kenaf seed oil after refining. The refining process was totally removed the hydroperoxides, 93% of free fatty acids and 98.8% of phosphorus content in kenaf seed oil.
Arrhythmia detection using deep convolutional neural network with long duration ECG signals

Yıldırım Ö, Pławiak P, Tan RS, Acharya UR

Comput Biol Med, 2018 11 01;102:411-420.
PMID: 30245122 DOI: 10.1016/j.compbiomed.2018.09.009

This article presents a new deep learning approach for cardiac arrhythmia (17 classes) detection based on long-duration electrocardiography (ECG) signal analysis. Cardiovascular disease prevention is one of the most important tasks of any health care system as about 50 million people are at risk of heart disease in the world. Although automatic analysis of ECG signal is very popular, current methods are not satisfactory. The goal of our research was to design a new method based on deep learning to efficiently and quickly classify cardiac arrhythmias. Described research are based on 1000 ECG signal fragments from the MIT - BIH Arrhythmia database for one lead (MLII) from 45 persons. Approach based on the analysis of 10-s ECG signal fragments (not a single QRS complex) is applied (on average, 13 times less classifications/analysis). A complete end-to-end structure was designed instead of the hand-crafted feature extraction and selection used in traditional methods. Our main contribution is to design a new 1D-Convolutional Neural Network model (1D-CNN). The proposed method is 1) efficient, 2) fast (real-time classification) 3) non-complex and 4) simple to use (combined feature extraction and selection, and classification in one stage). Deep 1D-CNN achieved a recognition overall accuracy of 17 cardiac arrhythmia disorders (classes) at a level of 91.33% and classification time per single sample of 0.015 s. Compared to the current research, our results are one of the best results to date, and our solution can be implemented in mobile devices and cloud computing.
Ramadan fasting alters sleep behavior in type 2 diabetes patients

Lee JY, Tan CSS, Lee SWH

J Diabetes, 2019 Jan;11(1):93-94.
PMID: 30094944 DOI: 10.1111/1753-0407.12838
Withaferin A Protects Against High-Fat Diet-Induced Obesity Via Attenuation of Oxidative Stress, Inflammation, and Insulin Resistance

Abu Bakar MH, Azmi MN, Shariff KA, Tan JS

Appl Biochem Biotechnol, 2019 May;188(1):241-259.
PMID: 30417321 DOI: 10.1007/s12010-018-2920-2

Withaferin A (WA), a bioactive constituent derived from Withania somnifera plant, has been shown to exhibit many qualifying properties in attenuating several metabolic diseases. The current investigation sought to elucidate the protective mechanisms of WA (1.25 mg/kg/day) on pre-existing obese mice mediated by high-fat diet (HFD) for 12 weeks. Following dietary administration of WA, significant metabolic improvements in hepatic insulin sensitivity, adipocytokines with enhanced glucose tolerance were observed. The hepatic oxidative functions of obese mice treated with WA were improved via augmented antioxidant enzyme activities. The levels of serum pro-inflammatory cytokines and hepatic mRNA expressions of toll-like receptor (TLR4), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand-receptor, and cyclooxygenase 2 (COX2) in HFD-induced obese mice were reduced. Mechanistically, WA increased hepatic mRNA expression of peroxisome proliferator-activated receptors (PPARs), cluster of differentiation 36 (CD36), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), glucokinase (GCK), phosphofructokinase (PFK), and phosphoenolpyruvate carboxykinase (PCK1) that were associated with enhanced lipid and glucose metabolism. Taken together, these results indicate that WA exhibits protective effects against HFD-induced obesity through attenuation of hepatic inflammation, oxidative stress, and insulin resistance in mice.
Choline-Chloride-Based Eutectic Solvent for the Efficient Production of Docosahexaenoyl and Eicosapentaenoyl Ethanolamides via an Enzymatic Process

Liang H, Qin X, Tan CP, Li D, Wang Y

J Agric Food Chem, 2018 Nov 21;66(46):12361-12367.
PMID: 30394748 DOI: 10.1021/acs.jafc.8b04804

Docosahexaenoyl and eicosapentaenoyl ethanolamides (DHEA and EPEA) have physiological functions, including immunomodulation, brain development, and anti-inflammation, but their efficient production is still unresolved. In this study, choline-chloride-based natural deep eutectic solvents are used as media to improve the production of DHEA and EPEA. The water content showed a key effect on the reactant conversion. Adding water to choline chloride-glucose (CG, molar ratio of 5:2) led to a significant increase (13.03% for EPEA and 27.95% for DHEA) in the yields after 1 h. The high yields of EPEA (96.84%) and DHEA (90.06%) were obtained under the optimized conditions [fish oil ethyl esters/ethanolamine molar ratio of 1:2, temperature of 60 °C, 1 h, enzyme loading of 2195 units, and CG containing 8.50% water of 43.30% (w/w, relative to total reactants)]. The products could be easily separated using centrifugation. In summary, the research has the potential to produce fatty acyl ethanolamides.
Fulltext Matrix association region/scaffold attachment region (MAR/SAR) sequence: its vital role in mediating chromosome breakages in nasopharyngeal epithelial cells via oxidative stress-induced apoptosis

Tan SN, Sim SP, Khoo ASB

BMC Mol. Biol., 2018 12 04;19(1):15.
PMID: 30514321 DOI: 10.1186/s12867-018-0116-5

BACKGROUND: Oxidative stress is known to be involved in most of the aetiological factors of nasopharyngeal carcinoma (NPC). Cells that are under oxidative stress may undergo apoptosis. We have previously demonstrated that oxidative stress-induced apoptosis could be a potential mechanism mediating chromosome breakages in nasopharyngeal epithelial cells. Additionally, caspase-activated DNase (CAD) may be the vital player in mediating the chromosomal breakages during oxidative stress-induced apoptosis. Chromosomal breakage occurs during apoptosis and chromosome rearrangement. Chromosomal breakages tend to cluster in certain regions, such as matrix association region/scaffold attachment region (MAR/SAR). We hypothesised that oxidative stress-induced apoptosis may result in chromosome breaks preferentially at the MAR/SAR sites. The AF9 gene at 9p22 was targeted in this study because 9p22 is a deletion site commonly found in NPC.
RESULTS: By using MAR/SAR recognition signature (MRS), potential MAR/SAR sites were predicted in the AF9 gene. The predicted MAR/SAR sites precisely match to the experimentally determined MAR/SARs. Hydrogen peroxide (H2O2) was used to induce apoptosis in normal nasopharyngeal epithelial cells (NP69) and NPC cells (HK1). Nested inverse polymerase chain reaction was employed to identify the AF9 gene cleavages. In the SAR region, the gene cleavage frequency of H2O2-treated cells was significantly higher than that of the non-treated cells. A few chromosomal breakages were detected within the AF9 region which was previously found to be involved in the mixed lineage leukaemia (MLL)-AF9 translocation in an acute lymphoblastic leukaemia patient. As for the non-SAR region, no significant difference in the gene cleavage frequency was found between the untreated control and H2O2-treated cells. Furthermore, H2O2-induced cleavages within the SAR region were reduced by caspase-3 inhibitor, which indirectly inhibits CAD.
CONCLUSIONS: These results reaffirm our previous findings that oxidative stress-induced apoptosis could be one of the potential mechanisms underlying chromosome breakages in nasopharyngeal epithelial cells. MAR/SAR may play a vital role in defining the location of chromosomal breakages mediated by oxidative stress-induced apoptosis, where CAD is the major nuclease.
Methylmalonic Aciduria: A Treatable Disorder of Which Adult Neurologists Need to Be Aware

Tan AH, Mah JSY, Thong MK, Lim SY

Mov Disord Clin Pract, 2015 09 16;3(1):104-105.
PMID: 30713905 DOI: 10.1002/mdc3.12237
Automated beat-wise arrhythmia diagnosis using modified U-net on extended electrocardiographic recordings with heterogeneous arrhythmia types

Oh SL, Ng EYK, Tan RS, Acharya UR

Comput Biol Med, 2019 Feb;105:92-101.
PMID: 30599317 DOI: 10.1016/j.compbiomed.2018.12.012

Abnormality of the cardiac conduction system can induce arrhythmia - abnormal heart rhythm - that can frequently lead to other cardiac diseases and complications, and are sometimes life-threatening. These conduction system perturbations can manifest as morphological changes on the surface electrocardiographic (ECG) signal. Assessment of these morphological changes can be challenging and time-consuming, as ECG signal features are often low in amplitude and subtle. The main aim of this study is to develop an automated computer aided diagnostic (CAD) system that can expedite the process of arrhythmia diagnosis, as an aid to clinicians to provide appropriate and timely intervention to patients. We propose an autoencoder of ECG signals that can diagnose normal sinus beats, atrial premature beats (APB), premature ventricular contractions (PVC), left bundle branch block (LBBB) and right bundle branch block (RBBB). Apart from the first, the rest are morphological beat-to-beat elements that characterize and constitute complex arrhythmia. The novelty of this work lies in how we modified the U-net model to perform beat-wise analysis on heterogeneously segmented ECGs of variable lengths derived from the MIT-BIH arrhythmia database. The proposed system has demonstrated self-learning ability in generating class activations maps, and these generated maps faithfully reflect the cardiac conditions in each ECG cardiac cycle. It has attained a high classification accuracy of 97.32% in diagnosing cardiac conditions, and 99.3% for R peak detection using a ten-fold cross validation strategy. Our developed model can help physicians to screen ECG accurately, potentially resulting in timely intervention of patients with arrhythmia.
Intravaginal treatment with Marantodes pumilum (Kacip Fatimah) ameliorates vaginal atrophy in rats with post-menopausal condition

Tan NAS, Giribabu N, Karim K, Nyamathulla S, Salleh N

J Ethnopharmacol, 2019 May 23;236:9-20.
PMID: 30771519 DOI: 10.1016/j.jep.2019.02.027

ETHNOPHARMACOLOGICAL RELEVANCE: Marantodes pumilum (MP) (Kacip Fatimah) is used to maintain the well-being of post-menopausal women. However, its role in ameliorating post menopause-related vaginal atrophy (VA) is unknown.
AIMS: To investigate the ability of intravaginal MP gel treatment to ameliorate VA in sex-steroid deficient condition, mimicking post-menopause.
METHODS: Ovariectomized female Sprague-Dawley rats received MP (100 μg/ml, 250 μg/ml and 500 μg/ml) and estriol (E) gels intravaginally for seven consecutive days. Rats were then euthanized and vagina was harvested and subjected for histological and protein expression and distribution analyses. Vaginal ultrastructure was observed by transmission electron microscopy (TEM).
RESULTS: Thickness of vaginal epithelium increased with increasing intravaginal MP doses. Additionally, increased in expression and distribution of proliferative protein i.e. PCNA, tight junction protein i.e. occludin, water channel proteins i.e. AQP-1 and AQP-2 and proton extruder protein i.e. V-ATPase A1 were observed in the vagina following intravaginal MP and E gels treatment. Intravaginal MP and E gels also induced desmosome formation and approximation of the intercellular spaces between the vaginal epithelium.
CONCLUSIONS: Intravaginal MP was able to ameliorate features associated with VA; thus, it has potential to be used as an agent to treat this condition.
Fulltext Kombiglyze (metformin and saxagliptin)-induced hepatotoxicity in a patient with non-alcoholic fatty liver disease

Thalha AM, Mahadeva S, Boon Tan AT, Mun KS

JGH Open, 2018 Oct;2(5):242-245.
PMID: 30483596 DOI: 10.1002/jgh3.12083

A 33-year-old man was referred with hyperosmotic symptoms of 4 weeks. Clinical examination showed palpable hepatomegaly and no stigmata of liver disease. Findings were random glucose 16.6 mmol/L, HbA1c 12.4%, triglyceride 6.2 mmol/L, normal LFTs and ultrasound liver: increased echogenicity. Management consisted of dietician referral and commencement of metformin 500 mg bd, diamicron MR 60 mg od, and fenofibrate 145 mg od. He was non-compliant, complaining of "heaviness of head" after consuming oral diabetic agents, without symptoms of hypoglycemia. Treatment was switched to Kombiglyze XR (saxaglipitin 5 mg + metformin 1000 mg) and empagliflozin 25 mg od. He presented 1 week later with generalised pruritus with ALT 307 IU/L and serum GGT 808 IU/L. Following this, a percutaneous liver biopsy was performed, revealing steatohepatitis and marked intra-hepatic cholestasis. Kombiglyze XR was withheld, with resolution of LFTs to baseline. Phenotypes of liver injury are categorised according to R value, defined as ratio ALT/ULN:ALP/ULN. R value of ≥5:hepatocellular injury, ≤2:cholestatic injury, 2-5:mixed-type injury. Here, R value points toward mixed type (R = 3.203). Hepatotoxicity in patients with NASH is difficult to diagnose, based on laboratory parameters. Liver histology was useful in indicating additional changes apart from NASH, causing liver derangement. The Rousal Uclaf Causality Assessment Method is a scoring method to determine the probability of drug induced liver injury. RUCAM score for this case was 6 (probable adverse drug reaction). Hepatotoxicity from saxagliptin not been reported prior. Clinicians need to be more vigilant, particularly in patients with NASH.
Comprehensive studies on optimization of cellulase and xylanase production by a local indigenous fungus strain via solid state fermentation using oil palm frond as substrate

Tai WY, Tan JS, Lim V, Lee CK

Biotechnol Prog, 2019 05;35(3):e2781.
PMID: 30701709 DOI: 10.1002/btpr.2781

The high cost of cellulases remains the most significant barrier to the economical production of bio-ethanol from lignocellulosic biomass. The goal of this study was to optimize cellulases and xylanase production by a local indigenous fungus strain (Aspergillus niger DWA8) using agricultural waste (oil palm frond [OPF]) as substrate. The enzyme production profile before optimization indicated that the highest carboxymethyl cellulose (CMCase), filter paper (FPase), and xylanase activities of 1.06 U/g, 2.55 U/g, and 2.93 U/g were obtained on day 5, day 4, and day 5 of fermentation, respectively. Response surface methodology was used to study the effects of several key process parameters in order to optimize cellulase production. Of the five physical and two chemical factors tested, only moisture content of 75% (w/w) and substrate amount of 2.5 g had statistically significant effect on enzymes production. Under optimized conditions of 2.5 g of substrate, 75% (w/w) moisture content, initial medium of pH 4.5, 1 × 106 spores/mL of inoculum, and incubation at ambient temperature (±30°C) without additional carbon and nitrogen, the highest CMCase, FPase, and xylanase activities obtained were 2.38 U/g, 2.47 U/g, and 5.23 U/g, respectively. Thus, the optimization process increased CMCase and xylanase production by 124.5 and 78.5%, respectively. Moreover, A. niger DWA8 produced reasonably good cellulase and xylanase titers using OPF as the substrate when compared with previous researcher finding. The enzymes produced by this process could be further use to hydrolyze biomass to generate reducing sugars, which are the feedstock for bioethanol production.
Gardnerella vaginalis in perinatology: An overview of the clinicopathological correlation

Wong YP, Tan GC, Wong KK, Anushia S, Cheah FC

Malays J Pathol, 2018 Dec;40(3):267-286.
PMID: 30580358

Gardnerella vaginalis (GV) is a facultatively anaerobic gram-variable bacillus and is the major organism involved in bacterial vaginosis. GV-associated bacterial vaginosis has been associated with adverse pregnancy outcomes include preterm parturition and subclinical chorioamnionitis. Inflammatory response induced by GV presents paediatric problems as well. Studies had shown that increased levels of proinflammatory cytokines include TNF-α, IL-1β and IL-6 following fetal inflammatory response syndrome secondary to GV-induced intrauterine infection may result in the development of periventricular leukomalacia and bronchopulmonary dysplasia in the infected fetus. There is increasing evidence that GV-associated BV infection serves as a risk factor for long-term neurological complications, such as cerebral palsy and learning disability. GV is fastidious and could elude conventional detection methods such as bacterial cultures. With current more sophisticated molecular biology detection methods, its role and pathogenic effects have been shown to have a greater impact on intrauterine inflammation and fetal/neonatal infection. This review gives an overview on the characteristics of GV and its virulence properties. Its detrimental role in causing unfavourable GV-related perinatal outcomes, with emphasis on the possible mechanistic pathways is discussed. The discovery of disease mechanisms allows the building of a strong platform where further research on innovative therapies can be based on, for instance, an anti-TLR monoclonal antibody as therapeutic agent to halt inflammation-precipitate adverse perinatal outcomes.
Immobilized Talaromyces thermophilus lipase as an efficient catalyst for the production of LML-type structured lipids

Lian W, Wang W, Tan CP, Wang J, Wang Y

Bioprocess Biosyst Eng, 2019 Feb;42(2):321-329.
PMID: 30421172 DOI: 10.1007/s00449-018-2036-7

LML-type structured lipids are one type of medium- and long-chain triacylglycerols. LML was synthesized using immobilized Talaromyces thermophilus lipase (TTL)-catalyzed interesterification of tricaprylin and ethyl linoleate. The resin AB-8 was chosen, and the lipase/support ratio was determined to be 60 mg/g. Subsequently, the immobilized TTL with strict sn-1,3 regiospecificity was applied to synthesize LML. Under the optimized conditions (60 °C, reaction time 6 h, enzyme loading of 6% of the total weight of substrates, substrate of molar ratio of ethyl linoleate to tricaprylin of 6:1), Triacylglycerols with two long- and one medium-chain FAs (DL-TAG) content as high as 52.86 mol% was obtained. Scale-up reaction further verified the industrial potential of the established process. The final product contained 85.24 mol% DL-TAG of which 97 mol% was LML after purification. The final product obtained with the high LML content would have substantial potential to be used as functional oils.
Cardiovascular therapies utilizing targeted delivery of nanomedicines and aptamers

Tan KX, Pan S, Jeevanandam J, Danquah MK

Int J Pharm, 2019 Mar 10;558:413-425.
PMID: 30660748 DOI: 10.1016/j.ijpharm.2019.01.023

Cardiovascular ailments are the foremost trigger of death in the world today, including myocardial infarction and ischemic heart diseases. To date, extraordinary measures have been prescribed, from the perspectives of both conventional medical therapies and surgeries, to enforce cardiac cell regeneration post cardiac traumas, albeit with limited long-term success. The prospects of successful heart transplants are also grim, considering exorbitant costs and unavailability of suitable donors in most cases. From the perspective of cardiac revascularization, use of nanoparticles and nanoparticle mediated targeted drug delivery have garnered substantial attention, attributing to both active and passive heart targeting, with enhanced target specificity and sensitivity. This review focuses on this aspect, while outlining the progress in targeted delivery of nanomedicines in the prognosis and subsequent therapy of cardiovascular disorders, and recapitulating the benefits and intrinsic challenges associated with the incorporation of nanoparticles. This article categorically provides an overview of nanoparticle-mediated targeted delivery systems and their implications in handling cardiovascular diseases, including their intrinsic benefits and encountered procedural trials and challenges. Additionally, the solicitations of aptamers in targeted drug delivery with identical objectives, are presented. This includes a detailed appraisal on various aptamer-navigated nanoparticle targeted delivery platforms in the diagnosis and treatment of cardiovascular maladies. Despite a few impending challenges, subject to additional investigations, both nanoparticles as well as aptamers show a high degree of promise, and pose as the next generation of drug delivery vehicles, in targeted cardiovascular therapy.

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