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Upgradation of chemical, fuel, thermal, and structural properties of rice husk through microwave-assisted hydrothermal carbonization

Nizamuddin S, Siddiqui MTH, Baloch HA, Mubarak NM, Griffin G, Madapusi S, et al.

Environ Sci Pollut Res Int, 2018 Jun;25(18):17529-17539.
PMID: 29663294 DOI: 10.1007/s11356-018-1876-7

The process parameters of microwave hydrothermal carbonization (MHTC) have significant effect on yield of hydrochar. This study discusses the effect of process parameters on hydrochar yield produced from MHTC of rice husk. Results revealed that, over the ranges tested, a lower temperature, lower reaction time, lower biomass to water ratio, and higher particle size produce more hydrochar. Maximum hydrochar yield of 62.8% was obtained at 1000 W, 220 °C, and 5 min. The higher heating value (HHV) was improved significantly from 6.80 MJ/kg of rice husk to 16.10 MJ/kg of hydrochar. Elemental analysis results showed that the carbon content increased and oxygen content decreased in hydrochar from 25.9 to 47.2% and 68.5 to 47.0%, respectively, improving the energy and combustion properties. SEM analysis exhibited modification in structure of rice husk and improvement in porosity after MHTC, which was further confirmed from BET surface analysis. The BET surface area increased from 25.0656 m2/g (rice husk) to 92.6832 m2/g (hydrochar). Thermal stability of hydrochar was improved from 340 °C for rice husk to 370 °C for hydrochar.
Fulltext Teaching evidence based medicine to fourth year medical students at Cyberjaya University College of Medical Sciences, Malaysia

Ab Manan N, Jahan N, Mohamad Alwi MN, Qureshi AM, Abdul Rahman AR

Education in Medicine Journal, 2017;9(3):55-62.
MyJurnal

Background: Recently many medical schools have incorporated Evidence Based Medicine (EBM) as part of their undergraduate teaching. The aim is to provide a firm base of EBM to the medical students early on, so that they can understand the importance of EBM. Medical schools are encouraged to teach EBM to students but yet the education setting, learner level, modes of instruction, skills covered and teaching methods are not standardised and varies worldwide. In Cyberjaya University College of Medical Sciences (CUCMS), EBM was incorporated in the curriculum since 2009. EBM concepts was taught formally to the MBBS students during four weeks Research and Evidence Based Medicine Course (REBM). Students were exposed to the various thinking processes, formulation of clinical questions, searching evidence, intermediate biostatistics, research methodology and critical appraisal. Besides that, Good Clinical Practice (GCP) and research proposal development also include in the course. The objective of this paper is to describe
CUCMS experience of teaching EBM for undergraduate medical students.
Methods: This report analysed students feedback using a questionnaire which included a Likert scale and open-ended questions.
Result: Overall, three batches of students gave positive feedbacks regarding the course with constructive suggestions on room for improvement.
Conclusion: From our first three years’ experience in conducting the course, we concluded that the four-week EBM course offered was practical in instilling EBM principles.
Geographical distribution of persistent organic pollutants in the environment: A review

Batool S, Rashid SA, Moah MJ, Sarfraz M, Ashraf MA

J Environ Biol, 2016 09;37(5 Spec No):1125-1134.
PMID: 29989744

The sources, distribution, transformation, toxicity and accumulation of persistent organic pollutants (POPs) in aquatic and terrestrial ecosystems have attracted global concern and attention over the last several decades. Although, POPs are toxic, degrade slowly and have a tendency to accumulate in the food chain, they are still widely used worldwide in many fields, such as industrial and agricultural activities. In addition, discharge of POPs into waterways may lead to serious health-related and environmental problems. This review provides an overview of the continental distributions of many types of POPs and the health risks associated with the exposure to POPs in daily life. This review also discusses the distribution of POPs in Malaysia, and the future work that will be conducted in the Klang River, one of the basins subjected to pollution due to development and urbanization.
Fulltext A Systematic Review on Non-mammalian Models in Epilepsy Research

Johan Arief MF, Choo BKM, Yap JL, Kumari Y, Shaikh MF

Front Pharmacol, 2018;9:655.
PMID: 29997502 DOI: 10.3389/fphar.2018.00655

Epilepsy is a common neurological disorder characterized by seizures which result in distinctive neurobiological and behavioral impairments. Not much is known about the causes of epilepsy, making it difficult to devise an effective cure for epilepsy. Moreover, clinical studies involving epileptogenesis and ictogenesis cannot be conducted in humans due to ethical reasons. As a result, animal models play a crucial role in the replication of epileptic seizures. In recent years, non-mammalian models have been given a primary focus in epilepsy research due to their advantages. This systematic review aims to summarize the importance of non-mammalian models in epilepsy research, such as in the screening of anti-convulsive compounds. The reason for this review is to integrate currently available information on the use and importance of non-mammalian models in epilepsy testing to aid in the planning of future studies as well as to provide an overview of the current state of this field. A PRISMA model was utilized and PubMed, Springer, ScienceDirect and SCOPUS were searched for articles published between January 2007 and November 2017. Fifty-one articles were finalized based on the inclusion/exclusion criteria and were discussed in this review. The results of this review demonstrated the current use of non-mammalian models in epilepsy research and reaffirmed their potential to supplement the typical rodent models of epilepsy in future research into both epileptogenesis and the treatment of epilepsy. This review also revealed a preference for zebrafish and fruit flies in lieu of other non-mammalian models, which is a shortcoming that should be corrected in future studies due to the great potential of these underutilized animal models.
Fabrication of calixarene-grafted bio-polymeric magnetic composites for magnetic solid phase extraction of non-steroidal anti-inflammatory drugs in water samples

Syed Yaacob SFF, Mohd Jamil AK, Kamboh MA, Wan Ibrahim WA, Mohamad S

PeerJ, 2018;6:e5108.
PMID: 30002963 DOI: 10.7717/peerj.5108

Calixarene framework functionalized bio-polymeric magnetic composites (MSp-TDI-calix) were synthesized and utilized as magnetic solid-phase extraction (MSPE) sorbent for the extraction of non-steroidal anti-inflammatory drugs (NSAIDs), namely indoprofen (INP), ketoprofen (KTP), ibuprofen (IBP) and fenoprofen (FNP), from environmental water samples. MSp-TDI-calix was characterized by FT-IR, XRD, FESEM, EDX, VSM and BET analysis, and the results were compared with Sp-TDI and Sp-TDI-calix. To maximize the extraction performance of MSp-TDI-calix decisive MSPE affective parameters such as sorbent amount, extraction time, sample volume, type of organic eluent, volume of organic eluent, desorption time and pH were comprehensively optimized prior to HPLC-DAD determination. The analytical validity of the proposed MSPE method was evaluated under optimized conditions and the following figures of merit were acquired: linearity with good determination coefficient (R2 ≥ 0.991) over the concentration range of 0.5-500 µg/L, limits of detection (LODs) ranged from 0.06-0.26 µg/L and limits of quantitation (LOQ) between 0.20-0.89 µg/L. Excellent reproducibility and repeatability under harsh environment with inter-day and intra-day relative standard deviations were obtained in the range of 2.5-3.2% and 2.4-3.9% respectively. The proposed method was successfully applied for analysis of NSAIDs in tap water, drinking water and river water with recovery efficiency ranging from 88.1-115.8% with %RSD of 1.6-4.6%.
Synthesis, characterization, monoamine oxidase inhibition, molecular docking and dynamic simulations of novel 2,1-benzothiazine-2,2-dioxide derivatives

Ahmad S, Zaib S, Jalil S, Shafiq M, Ahmad M, Sultan S, et al.

Bioorg Chem, 2018 10;80:498-510.
PMID: 29996111 DOI: 10.1016/j.bioorg.2018.04.012

In this research work, we report the synthesis and biological evaluation of two new series of 1-benzyl-4-(benzylidenehydrazono)-3,4-dihydro-1H-benzo[c] [1,2]thiazine 2,2-dioxides and 1-benzyl-4-((1-phenylethylidene)hydrazono)-3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxides. The synthetic plan involves the mesylation of methyl anthranilate with subsequent N-benzylation of the product. The methyl 2-(N-benzylmethylsulfonamido)benzoate was subjected to cyclization reaction in the presence of sodium hydride to obtain 1-benzyl-1H-benzo[c][1,2]thiazin-4(3H)-one 2,2-dioxide which was treated with hydrazine hydrate to get corresponding hydrazone precursor. Finally, the titled compounds were obtained by reaction of hydrazone with various substituted aldehydes and ketones. The synthesized derivatives were subjected to carry out their inhibition activities against monoamine oxidases along with modelling investigations to evaluate their binding interactions and dynamic stability during the docking studies. The inhibition profile of potent compounds was found as competitive for both the isozymes. The compounds were more selective inhibitors of MAO-A as compared to MAO-B. Moreover, drug likeness profile of the derivatives was evaluated to have an additional insight into the physicochemical properties. The molecular dynamic simulations predicted the behaviour of amino acids with the active site residues.
Efficacy and tolerability of micronized purified flavonoid fractions (MPFF) for haemorrhoids: A systematic review and meta-analysis

Aziz Z, Huin WK, Badrul Hisham MD, Tang WL, Yaacob S

Complement Ther Med, 2018 Aug;39:49-55.
PMID: 30012392 DOI: 10.1016/j.ctim.2018.05.011

OBJECTIVE: To present a systematic review of randomised controlled trials (RCTs) examining the effects of MPFF in the management of haemorrhoid symptoms.
METHODS: Electronic databases including CENTRAL, CINAHL, EMBASE, MEDLINE were searched up to April 2018 for relevant RCTs. Journal and conference proceedings were also searched. Two review authors independently selected trials, extracted data, assessed the risks of bias in included trials and graded the quality of evidence. Meta-analyses were conducted for studies presenting similar outcomes.
RESULTS: Ten RCTs involving 1164 participants were included. These RCTs varied in terms of patients' grade of haemorrhoids, length of trials, and outcome assessed. Most of the studies did not describe adequately the process of randomisation and allocation concealment. The pooled analysis of data from three studies indicated that there was significant difference between groups for the bleeding outcome, favoring the MPFF group (RR 1.46; 95% CI 1.10-1.93; p = 0.008). Except for bleeding, the current evidence did not show MPFF has significant effects on all the other outcomes examined when compared with placebo. Even then, the quality of evidence for bleeding was judged as low due to the small number and inconsistent results among the included studies.
CONCLUSION: This review highlights the need for further rigorous research if MPFF was to be routinely used for the treatment of haemorrhoid symptoms.
Efficacy and Safety of Polymer-Free Ultrathin Strut Sirolimus-Probucol Coated Drug-Eluting Stents for Chronic Total Occlusions: Insights from the Coroflex ISAR 2000 Worldwide Registry

Mahmood Zuhdi AS, Krackhardt F, Waliszewski MW, Ismail MD, Boxberger M, Wan Ahmad WA

Cardiol Res Pract, 2018;2018:8053168.
PMID: 29686890 DOI: 10.1155/2018/8053168

Objective: Coronary revascularization in chronic total occlusion (CTO) is associated with improved clinical outcomes. The choice of the coronary stent is crucial in maintaining long-term vessel patency after CTO revascularization. We investigated the efficacy and safety of polymer-free ultrathin strut sirolimus-probucol coated drug-eluting stents (PF-SES) for CTO lesions.
Methods: Patients with CTO lesions treated with PF-SES were identified from the prospective multicenter international ISAR 2000 registry. The primary endpoint was clinically driven target lesion revascularization (TLR) at 9 months. Secondary endpoints were 9-month major adverse cardiac events (death, myocardial infarction, or TLR) (MACE) and the occurrence of stent thrombosis.
Results: A total of 111 patients with CTO lesions (n=127) were available for analysis. The 9-month clinical follow-up rate was 91%. The mean reference vessel diameter and lesion length were 2.76 mm ± 0.40 and 26.8 mm ± 13.1, respectively. The overall DAPT duration was 9.7 ± 2.8 months. Only one (1%) in-hospital MI was reported. The TLR and MACE rates at 9 months were 2% (2/101) and 5.9% (6/101), respectively. The 9-month accumulated rates of definite or probable stent thrombosis was 0% (0/101).
Conclusion: Revascularizations for CTO with PF-SES are associated with low rates of TLR and MACE at 9 months with no stent thrombosis. These initial findings need to be compared with results of other new generation DES of larger studies.
Overexpression of acetyl-CoA carboxylase in Aspergillus terreus to increase lovastatin production

Hasan H, Abd Rahim MH, Campbell L, Carter D, Abbas A, Montoya A

N Biotechnol, 2018 Sep 25;44:64-71.
PMID: 29727712 DOI: 10.1016/j.nbt.2018.04.008

The present work describes the application of homologous recombination techniques in a wild-type Aspergillus terreus (ATCC 20542) strain to increase the flow of precursors towards the lovastatin biosynthesis pathway. A new strain was generated to overexpress acetyl-CoA carboxylase (ACCase) by replacing the native ACCase promoter with a strong constitutive PadhA promoter from Aspergillus nidulans. Glycerol and a mixture of lactose and glycerol were used independently as the carbon feedstock to determine the degree of response by the A. terreus strains towards the production of acetyl-CoA, and malonyl-CoA. The new strain increased the levels of malonyl-CoA and acetyl-CoA by 240% and 14%, respectively, compared to the wild-type strain. As a result, lovastatin production was increased by 40% and (+)-geodin was decreased by 31% using the new strain. This study shows for the first time that the metabolism of Aspergillus terreus can be manipulated to attain higher levels of precursors and valuable secondary metabolites.
Hyaluronic acid, an efficient biomacromolecule for treatment of inflammatory skin and joint diseases: A review of recent developments and critical appraisal of preclinical and clinical investigations

Chen LH, Xue JF, Zheng ZY, Shuhaidi M, Thu HE, Hussain Z

Int J Biol Macromol, 2018 Sep;116:572-584.
PMID: 29772338 DOI: 10.1016/j.ijbiomac.2018.05.068

Hyaluronic acid (HA) plays multifaceted role in regulating various biological processes and maintaining homeostasis into the body. Numerous researches evidenced the biomedical implications of HA in skin repairmen, cancer prognosis, wound healing, tissue regeneration, anti-inflammatory, immunomodulation. The present review was aimed to summarize and critically appraise the recent developments and efficacy of HA for treatment of inflammatory skin and joint diseases. A thorough analysis of the literature revealed that HA based formulations (i.e., gels, creams, autologous graft, thin sheets, soaked gauze, gauze pad, tincture, injection) have shown remarkable efficacy in treating a wide range of inflammatory skin diseases. The safety, tolerability, and efficacy of HA (as intra-articular injection) have also been well-documented for treatment of various types of joint disease including knee osteoarthritic, joint osteoarthritis, canine osteoarthritis, and meniscal swelling. Intra-articular injection of HA produces remarkable reduction in joint pain, synovial inflammation, and articular swelling. A remarkable improvement in chondrocyte density, territorial matrix appearance, reconstitution of superficial amorphous layer of the cartilage, collagen remodelling, and regeneration of meniscus have also been evident in patients treated with HA. Conclusively, we validate that the application/administration of HA is a promising pharmacotherapeutic regimen for treatment of inflammatory skin and joint diseases.
Ionic-Liquid-Based Paclitaxel Preparation: A New Potential Formulation for Cancer Treatment

Chowdhury MR, Moshikur RM, Wakabayashi R, Tahara Y, Kamiya N, Moniruzzaman M, et al.

Mol Pharm, 2018 06 04;15(6):2484-2488.
PMID: 29762034 DOI: 10.1021/acs.molpharmaceut.8b00305

Paclitaxel (PTX) injection (i.e., Taxol) has been used as an effective chemotherapeutic treatment for various cancers. However, the current Taxol formulation contains Cremophor EL, which causes hypersensitivity reactions during intravenous administration and precipitation by aqueous dilution. This communication reports the preliminary results on the ionic liquid (IL)-based PTX formulations developed to address the aforementioned issues. The formulations were composed of PTX/cholinium amino acid ILs/ethanol/Tween-80/water. A significant enhancement in the solubility of PTX was observed with considerable correlation with the density and viscosity of the ILs, and with the side chain of the amino acids used as anions in the ILs. Moreover, the formulations were stable for up to 3 months. The driving force for the stability of the formulation was hypothesized to be the involvement of different types of interactions between the IL and PTX. In vitro cytotoxicity and antitumor activity of the IL-based formulations were evaluated on HeLa cells. The IL vehicles without PTX were found to be less cytotoxic than Taxol, while both the IL-based PTX formulation and Taxol exhibited similar antitumor activity. Finally, in vitro hypersensitivity reactions were evaluated on THP-1 cells and found to be significantly lower with the IL-based formulation than Taxol. This study demonstrated that specially designed ILs could provide a potentially safer alternative to Cremophor EL as an effective PTX formulation for cancer treatment giving fewer hypersensitivity reactions.
Preliminary assessment of the diagnostic performances of a new rapid diagnostic test for the serodiagnosis of human cystic echinococcosis

Vola A, Tamarozzi F, Noordin R, Yunus MH, Khanbabaie S, De Silvestri A, et al.

Diagn Microbiol Infect Dis, 2018 Sep;92(1):31-33.
PMID: 29776711 DOI: 10.1016/j.diagmicrobio.2018.04.007

Rapid diagnostic tests for cystic echinococcosis (CE) are convenient to support ultrasound diagnosis in uncertain cases, especially in resource-limited settings. We found comparable diagnostic performances of the experimental Hyd Rapid Test and the commercial VIRapid HYDATIDOSIS Test, used in our diagnostic laboratory, using samples from well-characterized hepatic CE cases.
Serotonin Selective Reuptake Inhibitors (SSRIs) and Female Sexual Dysfunction (FSD): Hypothesis on its Association and Options of Treatment

Rappek NAM, Sidi H, Kumar J, Kamarazaman S, Das S, Masiran R, et al.

Curr Drug Targets, 2018;19(12):1352-1358.
PMID: 28025939 DOI: 10.2174/1389450117666161227142947

Sexual dysfunctions are commonly seen in women on selective serotonin reuptake inhibitors (SSRIs). The complexities of female sexual functioning are reflected through modulation of inter- playing factors like the neuropsychophysiological factors, inter-personal and relationship issue, psychiatric co-morbidities and physical disorder. The incidence of SSRIs-induced FSD is difficult to estimate because of the potential confounding effects of SSRIs, presence of polypharmacy, marital effect, socio-cultural factors and due to the design and assessment problems in majority of the studies. The exact mechanism of FSD-induced SSRIs is unknown. It has been postulated that although SSRIs may modulate other neurotransmitter system such as nitric oxide (NO), noradrenergic and dopamine in inducing FSD. In the present review, we highlight current evidence regarding potential mechanism of SSRIs in causing FSD, which include low sexual desire (low libido), arousal difficulties (lack of lubrication), and anorgasmia. The specific association of FSD to SSRI use, has not been ellucidated. The relationship is dose-dependent, and may vary among the groups with respect to mechanism of serotonin and dopamine reuptake, induction of release of prolactin from the pituitary gland, anticholinergic side-effects, inhibition of NO synthesis and emotional-memory circuit encryption for sexual experiences. Various interventional strategies exist regarding the treatment of SSRI-induced FSD and this includes tolerance, titration dosage, substitution to another antidepressant drug and psychotherapy. There is a need of better understanding of SSRIs-induced FSD for better treatment outcome.
Polyphenolic profiling of Ipomoea carnea Jacq. by HPLC-DAD and its implications in oxidative stress and cancer

Khan MZI, Zahra SS, Ahmed M, Fatima H, Mirza B, Haq IU, et al.

Nat Prod Res, 2019 Jul;33(14):2099-2104.
PMID: 29873254 DOI: 10.1080/14786419.2018.1482551

Ipomoea carnea Jacq. is an important folklore medicinal plant, assessed for its underexplored biological potential. Antioxidant, cytotoxic, antiproliferative and polyphenolic profile of whole plant was evaluated using various techniques. Maximum extract recovery (29% w/w), phenolic [13.54 ± 0.27 μg GAE/mg dry weight (DW)] and flavonoid (2.11 ± 0.10 μg QE /mg DW) content were recorded in methanol-distilled water (1:1) flower extract. HPLC-DAD analysis quantified substantial amount of six different polyphenols ranging from 0.081 to 37.95 μg/mg extract. Maximum total antioxidant and reducing potential were documented in methanol-distilled water and acetone-distilled water flower extracts (42.62 ± 0.47 and 24.38 ± 0.39 μg AAE/mg DW) respectively. Ethanol-chloroform root extract manifested highest free radical scavenging (IC50 of 61.22 μg/mL) while 94.64% of the extracts showed cytotoxicity against brine shrimps. Ethanol leaf extract exhibited remarkable activity against THP-1 cell line (IC50 = 8 ± 0.05 μg/mL) and protein kinases (31 mm phenotype bald zone).
Fulltext Induction of Apoptosis and Cytotoxicity by Isothiocyanate Sulforaphene in Human Hepatocarcinoma HepG2 Cells

Kntayya SB, Ibrahim MD, Mohd Ain N, Iori R, Ioannides C, Abdull Razis AF

Nutrients, 2018 Jun 04;10(6).
PMID: 29866995 DOI: 10.3390/nu10060718

Glucoraphenin, a glucosinolate present in large quantities in radish is hydrolysed by myrosinase to form the isothiocyanate sulforaphene, which is believed to be responsible for its chemopreventive activity; however, the underlying mechanisms of action have not been investigated, particularly in human cell lines. The aim of the study is to assess the cytotoxicity of sulforaphene in HepG2 cells and evaluate its potential to enhance apoptosis. The cytotoxicity of sulforaphene in HepG2 cells was carried out ensuing an initial screening with two other cell lines, MFC-7 and HT-29, where sulforaphene displayed highest toxicity in HepG2 cells following incubation at 24, 48 and 72 h. In contrast, the intact glucosinolate showed no cytotoxicity. Morphological studies indicated that sulforaphene stimulated apoptosis as exemplified by cell shrinkage, blebbing, chromatin condensation, and nuclear fragmentation. The Annexin V assay revealed significant increases in apoptosis and the same treatment increased the activity of caspases -3/7 and -9, whereas a decline in caspase-8 was observed. Impairment of cell proliferation was indicated by cell cycle arrest at the Sub G₀/G₁ phase as compared to the other phases. It may be concluded that sulforaphene, but not its parent glucosinolate, glucoraphenin, causes cytotoxicity and stimulates apoptosis in HepG2 cells.
Fulltext Vitamin D non-sufficiency is prevalent in children with chronic liver disease in a tropical country

Lee WS, Jalaludin MY, Wong SY, Ong SY, Foo HW, Ng RT

Pediatr Neonatol, 2019 02;60(1):12-18.
PMID: 29680189 DOI: 10.1016/j.pedneo.2018.03.011

BACKGROUND: To determine vitamin D status in children with chronic liver disease (CLD) in a tropical country.
METHODS: Cross-sectional study in Malaysian children with CLD. Factors affecting serum vitamin D level (definition: deficient
Fulltext 16S rRNA Gene Sequencing for Deciphering the Colorectal Cancer Gut Microbiome: Current Protocols and Workflows

Osman MA, Neoh HM, Ab Mutalib NS, Chin SF, Jamal R

Front Microbiol, 2018;9:767.
PMID: 29755427 DOI: 10.3389/fmicb.2018.00767

The human gut holds the densest microbiome ecosystem essential in maintaining a healthy host physiology, whereby disruption of this ecosystem has been linked to the development of colorectal cancer (CRC). The advent of next-generation sequencing technologies such as the 16S rRNA gene sequencing has enabled characterization of the CRC gut microbiome architecture in an affordable and culture-free approach. Nevertheless, the lack of standardization in handling and storage of biospecimens, nucleic acid extraction, 16S rRNA gene primer selection, length, and depth of sequencing and bioinformatics analyses have contributed to discrepancies found in various published studies of this field. Accurate characterization of the CRC microbiome found in different stages of CRC has the potential to be developed into a screening tool in the clinical setting. This mini review aims to concisely compile all available CRC microbiome studies performed till end of 2016 and to suggest standardized protocols that are crucial in developing a gut microbiome screening panel for CRC.
Fulltext Non-Synonymous Single-Nucleotide Polymorphisms and Physical Activity Interactions on Adiposity Parameters in Malaysian Adolescents

Zaharan NL, Muhamad NH, Jalaludin MY, Su TT, Mohamed Z, Mohamed MNA, et al.

Front Endocrinol (Lausanne), 2018;9:209.
PMID: 29755414 DOI: 10.3389/fendo.2018.00209

Background: Several non-synonymous single-nucleotide polymorphisms (nsSNPs) have been shown to be associated with obesity. Little is known about their associations and interactions with physical activity (PA) in relation to adiposity parameters among adolescents in Malaysia.
Methods: We examined whether (a) PA and (b) selected nsSNPs are associated with adiposity parameters and whether PA interacts with these nsSNPs on these outcomes in adolescents from the Malaysian Health and Adolescents Longitudinal Research Team study (n = 1,151). Body mass indices, waist-hip ratio, and percentage body fat (% BF) were obtained. PA was assessed using Physical Activity Questionnaire for Older Children (PAQ-C). Five nsSNPs were included: beta-3 adrenergic receptor (ADRB3) rs4994, FABP2 rs1799883, GHRL rs696217, MC3R rs3827103, and vitamin D receptor rs2228570, individually and as combined genetic risk score (GRS). Associations and interactions between nsSNPs and PAQ-C scores were examined using generalized linear model.
Results: PAQ-C scores were associated with % BF (β = -0.44 [95% confidence interval -0.72, -0.16], p = 0.002). The CC genotype of ADRB3 rs4994 (β = -0.16 [-0.28, -0.05], corrected p = 0.01) and AA genotype of MC3R rs3827103 (β = -0.06 [-0.12, -0.00], p = 0.02) were significantly associated with % BF compared to TT and GG genotypes, respectively. Significant interactions with PA were found between ADRB3 rs4994 (β = -0.05 [-0.10, -0.01], p = 0.02) and combined GRS (β = -0.03 [-0.04, -0.01], p = 0.01) for % BF.
Conclusion: Higher PA score was associated with reduced % BF in Malaysian adolescents. Of the nsSNPs, ADRB3 rs4994 and MC3R rs3827103 were associated with % BF. Significant interactions with PA were found for ADRB3 rs4994 and combined GRS on % BF but not on measurements of weight or circumferences. Targeting body fat represent prospects for molecular studies and lifestyle intervention in this population.
Fulltext Chemical and structural changes of pretreated empty fruit bunch (EFB) in ionic liquid-cellulase compatible system for fermentability to bioethanol

Elgharbawy AA, Alam MZ, Moniruzzaman M, Kabbashi NA, Jamal P

3 Biotech, 2018 May;8(5):236.
PMID: 29744268 DOI: 10.1007/s13205-018-1253-8

The pretreatment of empty fruit bunch (EFB) was conducted using an integrated system of IL and cellulases (IL-E), with simultaneous fermentation in one vessel. The cellulase mixture (PKC-Cel) was derived from Trichoderma reesei by solid-state fermentation. Choline acetate [Cho]OAc was utilized for the pretreatment due to its biocompatibility and biodegradability. The treated EFB and its hydrolysate were characterized by the Fourier transform infrared spectroscopy, scanning electron microscopy, and chemical analysis. The results showed that there were significant structural changes in EFB after the treatment in IL-E system. The sugar yield after enzymatic hydrolysis by the PKC-Cel was increased from 0.058 g/g of EFB in the crude sample (untreated) to 0.283 and 0.62 ± 06 g/g in IL-E system after 24 and 48 h of treatment, respectively. The EFB hydrolysate showed the eligibility for ethanol production without any supplements where ethanol yield was 0.275 g ethanol/g EFB in the presence of the IL, while lower yield obtained without IL-pretreatment. Moreover, it was demonstrated that furfural and phenolic compounds were not at the level of suppressing the fermentation process.
Characterization and cytotoxicity evaluation of biocompatible amino acid esters used to convert salicylic acid into ionic liquids

Moshikur RM, Chowdhury MR, Wakabayashi R, Tahara Y, Moniruzzaman M, Goto M

Int J Pharm, 2018 Jul 30;546(1-2):31-38.
PMID: 29751143 DOI: 10.1016/j.ijpharm.2018.05.021

The technological utility of active pharmaceutical ingredients (APIs) is greatly enhanced when they are transformed into ionic liquids (ILs). API-ILs have better solubility, thermal stability, and the efficacy in topical delivery than solid or crystalline drugs. However, toxicological issue of API-ILs is the main challenge for their application in drug delivery. To address this issue, 11 amino acid esters (AAEs) were synthesized and investigated as biocompatible counter cations for the poorly water-soluble drug salicylic acid (Sal) to form Sal-ILs. The AAEs were characterized using 1H and 13C NMR, FTIR, elemental, and thermogravimetric analyses. The cytotoxicities of the AAE cations, Sal-ILs, and free Sal were investigated using mammalian cell lines (L929 and HeLa). The toxicities of the AAE cations greatly increased with inclusion of long alkyl chains, sulfur, and aromatic rings in the side groups of the cations. Ethyl esters of alanine, aspartic acid, and proline were selected as a low cytotoxic AAE. The cytotoxicities of the Sal-ILs drastically increased compared with the AAEs on incorporation of Sal into the cations, and were comparable to that of free Sal. Interestingly, the water miscibilities of the Sal-ILs were higher than that of free Sal, and the Sal-ILs were miscible with water at any ratio. A skin permeation study showed that the Sal-ILs penetrated through skin faster than the Sal sodium salt. These results suggest that AAEs could be used in biomedical applications to eliminate the use of traditional toxic solvents for transdermal delivery of poorly water-soluble drugs.

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