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  1. Mohd Ngesom AM, Ahmad Razi A, Azizan NS, Wasi Ahmad N, Md Lasim A, Liang Y, et al.
    Parasit Vectors, 2021 Aug 18;14(1):413.
    PMID: 34407881 DOI: 10.1186/s13071-021-04918-9
    BACKGROUND: Dengue is a significant public health issue that is caused by Aedes spp. mosquitoes. The current vector control methods are unable to effectively reduce Aedes populations and thus fail to decrease dengue transmission. Hence, there is an urgent need for new tools and strategies to reduce dengue transmission in a wide range of settings. In this study, the Mosquito Home System (MHS) and Mosquito Home Aqua (MHAQ) formulations were assessed as commercial autodissemination traps in laboratory and small-scale field trials.

    METHOD: Multiple series of laboratory and small-scale field trials were performed to assess the efficacy of MHS and MHAQ exposed to Ae. aegypti. In the laboratory trials, various parameters such as fecundity, fertility, wing size, oviposition preferences, residual effects, and MHAQ transference to other containers through controlled experiments were tested. For small-scale field trials, the efficacy of the MHS and MHAQ approaches was determined to ascertain whether wild mosquitoes could transfer the MHAQ formulation from MHS stations to ovitraps.

    RESULTS: The data revealed that Ae. aegypti was highly susceptible to low concentrations of MHAQ formulations and had a residual effect of up to 3 months, with MHAQ exposure affecting fecundity, fertility, and mosquito wing size. In the oviposition studies, gravid females strongly preferred the hay infusion compared to tap water and MHAQ during egg-laying in the laboratory. Nevertheless, the use of commercial MHAQ by MHS was highly attractive in field settings compared to conventional ovitraps among local Aedes spp. mosquitoes. In addition, MHAQ horizontal transfer activities in the laboratory and small-scale field trials were demonstrated through larval bioassays. These findings demonstrated the potential of MHAQ to be transferred to new containers in each study site.

    CONCLUSION: This study provided proof of principle for the autodissemination of MHAQ. Through further refinement, this technique and device could become an effective oviposition trap and offer an alternative preventive tool for vector control management.

  2. Shafie SNA, Md Nordin NAH, Bilad MR, Misdan N, Sazali N, Putra ZA, et al.
    Membranes (Basel), 2021 May 19;11(5).
    PMID: 34069683 DOI: 10.3390/membranes11050371
    This study focuses on the effect of modified silica fillers by [EMIN][Tf2N] via physical adsorption on the CO2 separation performance of a mixed matrix membrane (MMM). The IL-modified silica was successfully synthesized as the presence of fluorine element was observed in both Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectrometer (XPS) analyses. The prepared MMMs with different loadings of the IL-modified silica were then compared with an unmodified silica counterpart and neat membrane. The morphology of IL-modified MMMs was observed to have insignificant changes, while polymer chains of were found to be slightly more flexible compared to their counterpart. At 2 bar of operating pressure, a significant increase in performance was observed with the incorporation of 3 wt% Sil-IL fillers compared to that of pure polycarbonate (PC). The permeability increased from 353 to 1151 Barrer while the CO2/CH4 selectivity increased from 20 to 76. The aforementioned increment also exceeded the Robeson upper bound. This indicates that the incorporation of fillers surface-modified with ionic liquid in an organic membrane is worth exploring for CO2 separation.
  3. Ernie Muneerah MA, Md Tamrin NA, Salisi MS, Zulkifly S, Ghazali SSM, Temuli JJ, et al.
    Animals (Basel), 2021 May 07;11(5).
    PMID: 34066910 DOI: 10.3390/ani11051328
    The Katjang goat is the only indigenous domestic goat breed in Malaysia. Following a national baseline survey from 2001 to 2002, this breed was reported to the FAO as being at risk of extinction. In this study, 36 microsatellite markers were screened, and 25 polymorphic markers were used to analyze the genetic structure of the Katjang goat breed in Peninsular Malaysia. A sample set of data derived from another 10 populations from three published research studies was used as an outgroup for an inter-population genetic study. The analysis showed that the mean value of the observed heterozygosity was 0.29 ± 0.14, and the expected heterozygosity was 0.72 ± 0.14, which indicated low genetic diversity. The inbreeding coefficient, FIS, was high, at 0.46. Significant (p < 0.01) deviations from the Hardy Weinberg equilibrium were noted for all loci. The bottleneck analysis using the Wilcoxon Rank test under the two-phase model of mutation was significant (p < 0.01) for heterozygosity excess, which suggested that the Katjang breed had undergone significant population reduction in the past. Through combined analysis of data from publicly available research, almost the entire population of Katjang goats represent the centroid and are grouped together on a multidimensional scaling plot, except for the Terengganu population. Network analysis revealed that the goat population from Pahang formed the centrality of the network.
  4. Mohd Abd Razak MR, Norahmad NA, Md Jelas NH, Afzan A, Mohmad Misnan N, Mat Ripen A, et al.
    Pathogens, 2021 Apr 21;10(5).
    PMID: 33919457 DOI: 10.3390/pathogens10050501
    The role of Carica papaya L. leaf juice in immune dysregulation caused by dengue virus infection remains unclear. This study aimed to investigate the immunomodulatory activities of the freeze-dried C. papaya leaf juice (FCPLJ) on AG129 mice infected with a clinical DENV-2 (DMOF015) isolate. The infected AG129 mice were orally treated with 500 and 1000 mg/kg/day of FCPLJ, for three days. Platelet, leukocyte, lymphocyte and neutrophil counts were microscopically determined. The level of plasma proinflammatory cytokines was measured by multiplex immunoassay. The levels of intracellular cytokines and viral RNA were determined by RT-qPCR technique. The results showed that the FCPLJ treatment increased the total white blood cell and neutrophil counts in the infected mice. The FCPLJ treatment decreased the level of GM-CSF, GRO-alpha, IL-1 beta, IL-6, MCP-1 and MIP-1 beta in the plasma of the infected mice. The intracellular IL-6 and viral RNA levels in the liver of infected mice were decreased by the FCPLJ treatment. In conclusion, this study supports the potential immunomodulatory role of the FCPLJ in a non-lethal, symptomatic dengue mouse model. Further studies on the action mechanism of the C. papaya leaf juice and its possible use as adjunctive dengue immunotherapy are warranted.
  5. Teh LK, Hamzah S, Hashim H, Bannur Z, Zakaria ZA, Hasbullani Z, et al.
    Ther Drug Monit, 2013 Oct;35(5):624-30.
    PMID: 23942539 DOI: 10.1097/FTD.0b013e318290acd2
    Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine catabolic enzyme involved in the initial and rate-limiting step of the catabolic pathway of toxic metabolites of 5-fluorouracil (5-FU). Several studies have reported that deficiency of DPD and polymorphisms of its gene are related to 5-FU toxicities and death. Association between serum concentration of 5-FU and its related toxicity has also been previously demonstrated. Hence, this study aims to understand the role of DPYD variants in serum level of 5-FU and the risk of developing toxicity to prevent adverse reactions and maximize therapy outcome for personalized medicine.
  6. Mohamad NA, Ramachandran V, Ismail P, Mohd Isa H, Chan YM, Ngah NF, et al.
    Bosn J Basic Med Sci, 2018 Aug 01;18(3):260-267.
    PMID: 29579408 DOI: 10.17305/bjbms.2018.2493
    Pharmacogenetic studies indicate that a variable response to anti-vascular endothelial growth factor (VEGF) therapy in patients with neovascular form of AMD (nAMD) may be due to polymorphisms in the complement factor H gene (CFH). This study is the first to investigate the association between CFH Y402H polymorphism and the response to ranibizumab therapy in Malaysian patients with nAMD. We included 134 patients with nAMD, examined between September 2014 and February 2016. The diagnosis of nAMD was confirmed by ophthalmologic examination, before ranibizumab therapy was started. Each patient received an intravitreal injection of 0.5 mg/0.05 ml ranibizumab following a treat-and-extend (TE) regimen. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded after 3 and 6 months following the first injection and compared with the baseline values. Genotyping of Y402H (rs1061170) polymorphism was performed using PCR-RFLP and the amplified product was digested with MluCI restriction enzyme. Association between the Y402H genotypes and response to treatment was determined by a logistic regression analysis of responder (n = 49) and non-responder (n = 84) group. Significantly worse mean BCVA was observed for the CC genotype compared to the TT + CT genotype in the total sample after 6-month follow-up (p = 0.018). Comparing the baseline and 6-month point measurements, improved mean BCVA was observed in responder group, while worse mean BCVA was recorded for non-responder group. However, our regression analysis, adjusted for confounding factors, showed no significant association between the Y402H genotypes and response to treatment in nAMD patients under the recessive model (p > 0.05). Overall, our results suggest that factors other than Y402H polymorphism may be involved in the progression of nAMD after treatment with anti-VEGF agents, in Malaysian population.
  7. Chuah SH, Md Sari NA, Chew BT, Tan LK, Chiam YK, Chan BT, et al.
    Phys Med, 2020 Oct;78:137-149.
    PMID: 33007738 DOI: 10.1016/j.ejmp.2020.08.022
    Differential diagnosis of hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) is clinically challenging but important for treatment management. This study aims to phenotype HHD and HCM in 3D + time domain by using a multiparametric motion-corrected personalized modeling algorithm and cardiac magnetic resonance (CMR). 44 CMR data, including 12 healthy, 16 HHD and 16 HCM cases, were examined. Multiple CMR phenotype data consisting of geometric and dynamic variables were extracted globally and regionally from the models over a full cardiac cycle for comparison against healthy models and clinical reports. Statistical classifications were used to identify the distinctive characteristics and disease subtypes with overlapping functional data, providing insights into the challenges for differential diagnosis of both types of disease. While HCM is characterized by localized extreme hypertrophy of the LV, wall thickening/contraction/strain was found to be normal and in sync, though it was occasionally exaggerated at normotrophic/less severely hypertrophic regions during systole to preserve the overall ejection fraction (EF) and systolic functionality. Additionally, we observed that hypertrophy in HHD could also be localized, although at less extreme conditions (i.e. more concentric). While fibrosis occurs mostly in those HCM cases with aortic obstruction, only minority of HHD patients were found affected by fibrosis. We demonstrate that subgroups of HHD (i.e. preserved and reduced EF: HHDpEF & HHDrEF) have different 3D + time CMR characteristics. While HHDpEF has cardiac functions in normal range, dilation and heart failure are indicated in HHDrEF as reflected by low LV wall thickening/contraction/strain and synchrony, as well as much reduced EF.
  8. Md Idris MH, Mohd Amin SN, Mohd Amin SN, Wibowo A, Zakaria ZA, Shaameri Z, et al.
    PMID: 34323638 DOI: 10.1080/10799893.2021.1951756
    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed to treat inflammatory-related diseases, pain and fever. However, the prolong use of traditional NSAIDs leads to undesirable side effects such as gastric, ulceration, and renal toxicity due to lack of selectivity toward respective targets for COX-2, 5-LOX, and PDE4B. Thus, targeting multiple sites can reduce these adverse effects of the drugs and increase its potency. A series of methoxyflavones (F1-F5) were synthesized and investigated for their anti-inflammatory properties through molecular docking and inhibition assays. Among these flavones, only F2 exhibited selectivity toward COX-2 (Selectivity Index, SI: 3.90, COX-2 inhibition: 98.96 ± 1.47%) in comparison with celecoxib (SI: 7.54, COX-2 inhibition: 98.20 ± 2.55%). For PDEs, F3 possessed better selectivity to PDE4B (SI: 4.67) than rolipram (SI: 0.78). F5 had the best 5-LOX inhibitory activity among the flavones (33.65 ± 4.74%) but less than zileuton (90.81 ± 0.19%). Docking analysis indicated that the position of methoxy group and the substitution of halogen play role in determining the bioactivities of flavones. Interestingly, F1-F5 displayed favorable pharmacokinetic profiles and acceptable range of toxicity (IC50>70 µM) in cell lines with the exception for F1 (IC50: 16.02 ± 1.165 µM). This study generated valuable insight in designing new anti-inflammatory drug based on flavone scaffold. The newly synthesized flavones can be further developed as future therapeutic agents against inflammation.
  9. Ghazali AR, Muralitharan RV, Soon CK, Salyam T, Ahmad Maulana NN, Mohamed Thaha UAB, et al.
    Asian Pac J Cancer Prev, 2020 Nov 01;21(11):3381-3386.
    PMID: 33247699 DOI: 10.31557/APJCP.2020.21.11.3381
    BACKGROUND: Traditional cooling rice powder (bedak sejuk) is a fermented rice-based cosmetic that is applied topically on one's skin, as an overnight facial mask. According to user testimonies, bedak sejuk beautifies and whitens skin, whereby these benefits could be utilised as a potential melanoma chemopreventive agent.

    OBJECTIVE: Hence, this study aimed to determine the effects of bedak sejuk made from Oryza sativa ssp. indica (Indica) and Oryza sativa ssp. japonica (Japonica) on UVB-induced B164A5 melanoma cells, and also identify the antioxidant capacities of both types of bedak sejuk.

    METHODS: The optimum dose of Indica and Japonica bedak sejuk to treat the cells was determined via the MTT assay. Then, the antioxidant capacities of both types of bedak sejuk were determined using the FRAP assay.

    RESULTS: From the MTT assay, it was found that Indica and Japonica bedak sejuk showed no cytotoxic effects towards the cells. Hence, no IC50 can be obtained and two of the higher doses, 50 and 100 g/L were chosen for treatment. In the FRAP assay, Indica bedak sejuk at 50 and 100 g/L showed FRAP values of 0.003 ± 0.001 μg AA (ascorbic acid)/g of bedak sejuk and 0.004 ± 0.0003 μg AA/g of bedak sejuk. Whereas Japonica bedak sejuk at 50 g/L had the same FRAP value as Indica bedak sejuk at 100 g/L. As for Japonica bedak sejuk at 100 g/L, it showed the highest antioxidant capacity with the FRAP value of 0.01 ± 0.0007 μg AA/g of bedak sejuk which was statistically significant (p < 0.05) when compared to other tested concentrations.

    CONCLUSION: In conclusion, Japonica bedak sejuk has a higher antioxidant capacity compared to Indica bedak sejuk despite both being not cytotoxic towards the cells. Regardless, further investigations need to be done before bedak sejuk could be developed as potential melanoma chemoprevention agents.

  10. Bujang NN, Lee YJ, Mohd-Zain SA, Aris JH, Md-Yusoff FA, Suli Z, et al.
    JCO Glob Oncol, 2021 02;7:333-341.
    PMID: 33625866 DOI: 10.1200/GO.20.00460
    PURPOSE: The Malaysian Ministry of Health had launched free opportunistic screening for colorectal cancer using immunochemical fecal occult blood test (iFOBT) targeting the average-risk individuals since 2014. This study aims to determine factors associated with colorectal cancer screening using iFOBT among the average-risk Malaysian population.

    METHODS: A cross-sectional study was conducted at five government-run health clinics in the state of Selangor. Adults with an average risk of colorectal cancer (age > 50 years, asymptomatic, and no family history of colorectal cancer) were recruited using systematic random sampling. An interviewer-administered questionnaire adapted from the Cancer Awareness Measure and Health Belief Model was used.

    RESULTS: The median age of participants was 61 years (interquartile range, 56 to 66). Almost 60% of participants indicated their willingness to be screened. However, only 7.5% had undergone iFOBT. Good knowledge of risk factors of colorectal cancer, perceived susceptibility to the disease, and the doctor's recommendation were associated with increased willingness to be screened: adjusted odds ratio (aOR), 1.66 (95% CI, 1.12 to 2.46); aOR, 1.70 (95% CI, 1.08 to 2.70); and aOR, 5.76 (95% CI, 2.13 to 15.57), respectively. Nevertheless, being elderly (aOR, 0.67; 95% CI, 0.45 to 0.99) and high negative perception toward the testing method (iFOBT) (aOR, 0.12; 95% CI, 0.05 to 0.30) were independently associated with lower willingness to be screened. Multivariable analysis within the average-risk individuals who were willing to be screened for colorectal cancer showed that the doctor's recommendations remained as an important cue for positive action, whereas negative perception toward the test was a significant barrier to the actual uptake of iFOBT.

    CONCLUSION: The present findings must be factored in when tailoring colorectal cancer screening promotion activities in multiethnic, middle-income settings.

  11. Ghazalli MN, Md Sah MS, Mat M, Awang K, Jaafar MA, Mirad R, et al.
    Trop Life Sci Res, 2021 Mar;32(1):107-117.
    PMID: 33936554 DOI: 10.21315/tlsr2021.32.1.7
    Mitragyna speciosa (Korth.) Havil. or locally known as ketum/daun sebiak/biak-biak belongs to Rubiaceae family and generally occurs in secondary forest or disturbed areas in tropical and subtropical region. This research enumerated the characterisation of Mitragyna speciosa leaf anatomy and micromorphology features which is still not well documented. This medium to large sized tree species characterised with opposite arrangement, ovate-acuminate leaf and with 12-17 pairs of veins. Transverse sections of petioles showed that this species has petiole outlines with slightly convex at the middle of the adaxial part and 'U'-shaped on abaxial side. Results also showed that this species has paracytic and hypostomatic stomata, combination of non-glandular (majority) and glandular trichomes (minority), with observation on the secretory cells present in petiole and midrib parenchyma cells. Cuticle on the abaxial and adaxial epidermal surfaces showed the presence granule and wax films with periclinal and anticlinal walls can be differentiated clearly. The results obtained in this study can be used to providing additional systematics information of Mitragyna speciosa with the documentation of the leaf anatomy and micromorphology characters.
  12. Salem SA, Rashidbenam Z, Jasman MH, Ho CCK, Sagap I, Singh R, et al.
    Tissue Eng Regen Med, 2020 08;17(4):553-563.
    PMID: 32583275 DOI: 10.1007/s13770-020-00271-7
    BACKGROUND: The urinary tract can be affected by both congenital abnormalities as well as acquired disorders, such as cancer, trauma, infection, inflammation, and iatrogenic injuries, all of which may lead to organ damage requiring eventual reconstruction. As a gold standard, gastrointestinal segment is used for urinary bladder reconstruction. However, one major problem is that while bladder tissue prevents reabsorption of specific solutes, gastrointestinal tissue actually absorbs them. Therefore, tissue engineering approach had been attempted to provide an alternative tissue graft for urinary bladder reconstruction.

    METHODS: Human adipose-derived stem cells isolated from fat tissues were differentiated into smooth muscle cells and then seeded onto a triple-layered PLGA sheet to form a bladder construct. Adult athymic rats underwent subtotal urinary bladder resection and were divided into three treatment groups (n = 3): Group 1 ("sham") underwent anastomosis of the remaining basal region, Group 2 underwent reconstruction with the cell-free scaffold, and Group 3 underwent reconstruction with the tissue-engineered bladder construct. Animals were monitored on a daily basis and euthanisation was performed whenever a decline in animal health was detected.

    RESULTS: All animals in Groups 1, 2 and 3 survived for at least 7 days and were followed up to a maximum of 12 weeks post-operation. It was found that by Day 14, substantial ingrowth of smooth muscle and urothelial cells had occurred in Group 2 and 3. In the long-term follow up of group 3 (tissue-engineered bladder construct group), it was found that the urinary bladder wall was completely regenerated and bladder function was fully restored. Urodynamic and radiological evaluations of the reconstructed bladder showed a return to normal bladder volume and function.Histological analysis revealed the presence of three muscular layers and a urothelium similar to that of a normal bladder. Immunohistochemical staining using human-specific myocyte markers (myosin heavy chain and smoothelin) confirmed the incorporation of the seeded cells in the newly regenerated muscular layers.

    CONCLUSION: Implantation of PLGA construct seeded with smooth muscle cells derived from human adipose stem cells can lead to regeneration of the muscular layers and urothelial ingrowth, leading to formation of a completely functional urinary bladder.

  13. Mustafa MF, Saliluddin SM, Fakurazi S, Tizen Laim NMS, Md Pauzi SH, Nik Yahya NH, et al.
    Front Oncol, 2021;11:612009.
    PMID: 34490076 DOI: 10.3389/fonc.2021.612009
    Mitochondria play important roles in regulating cell bioenergetics status and reactive oxygen species (ROS) generation. ROS-induced mitochondrial damage is among the main intracellular signal inducers of autophagy. Autophagy is a cellular catabolic process that regulates protein and organelle turnover, while a selective form of autophagy, mitophagy, specifically targets dysfunctional mitochondrial degradation. This study aims to measure the levels of autophagy, mitophagy, oxidative stress, and apoptosis in invasive breast carcinoma tissues using immunohistochemistry (IHC). Tissue microarrays of 76 patients with breast cancer were stained with six IHC markers (MnSOD, Beclin-1, LC3, BNIP3, Parkin, and cleaved caspase 3). The expression intensity was determined for each tumor tissue and the adjacent tumor-matched control tissues. Intermediate and strong staining scores of MnSOD, Beclin-1, LC-3, BNIP-3, and Parkin were significantly higher in tumor tissues compared to the adjacent matched control. The scoring intensity was further classified into tissues with negative staining and positive staining, which showed that positive scores of Beclin-1 and Parkin were significantly high in tumor tissues compared to other markers. Positive association was also noted between BNIP-3 and Beclin-1 as well as LC-3 and cleaved caspase-3 immunostaining. To our knowledge, this is one of the first studies that measure both mitophagy and autophagy in the same breast cancer tissues and the adjacent matched control. The findings from this study will be of great potential in identifying new cancer biomarkers and inspire significant interest in applying anti-autophagy therapies as a possible treatment for breast cancer.
  14. Low SC, Md Sari NA, Tan CY, Ahmad-Annuar A, Wong KT, Law WC, et al.
    Neuromuscul Disord, 2021 07;31(7):642-650.
    PMID: 34059423 DOI: 10.1016/j.nmd.2021.03.008
    We report the clinical and genetic characteristics of hereditary transthyretin amyloidosis in the multi-ethnic Malaysian population. Subjects with genetically confirmed transthyretin amyloidosis seen between 2001 till August 2020 were included. There were 30 patients and 14 asymptomatic carriers, of which 26 (59.1%) were men. The majority (86.7%) were ethnic Chinese while two (6.7%) each were Malay and Sri Lankan Tamil ethnicity respectively. Among patients, mean age of symptom-onset was 55.9 ± 9.8 years with mean duration from symptom-onset to diagnosis of 3.2 ± 2.5 years. Common presenting symptoms were sensory symptoms of upper limbs (43.3%), symmetric sensory symptoms of both lower limbs (16.7%) and autonomic symptoms (16.7%). Nerve conduction studies showed sensorimotor polyneuropathy in 25 (83.3%) patients (22, axonal). Abnormal echocardiograms were seen in 24 (80%) patients, although 15 were asymptomatic. Of six different TTR mutations found, Ala97Ser was the commonest, and found exclusively in 84.6% of Chinese patients. Other mutations among Chinese patients were Val30Met, Ala25Thr and Asp39Val. Our Malay and Tamil patients had Glu54Lys and Gly47Val mutations respectively. In conclusion, TTR Ala97Ser is the commonest mutation among ethnic Chinese Malaysians which presented with late-onset progressive sensorimotor polyneuropathy, autonomic dysfunction and subclinical cardiac involvement.
  15. Shahzad N, Khan W, Md S, Ali A, Saluja SS, Sharma S, et al.
    Biomed Pharmacother, 2017 Apr;88:786-794.
    PMID: 28157655 DOI: 10.1016/j.biopha.2017.01.068
    Phytosterols are naturally occurring compounds in plants, structurally similar to cholesterol. The human diet is quite abundant in sitosterol and campesterol. Phytosterols are known to have various bioactive properties including reducing intestinal cholesterol absorption which alleviates blood LDL-cholesterol and cardiovascular problems. It is indicated that phytosterol rich diets may reduce cancer risk by 20%. Phytosterols may also affect host systems, enabling antitumor responses by improving immune response recognition of cancer, affecting the hormone dependent endocrine tumor growth, and by sterol biosynthesis modulation. Moreover, phytosterols have also exhibited properties that directly inhibit tumor growth, including reduced cell cycle progression, apoptosis induction, and tumor metastasis inhibition. The objective of this review is to summarize the current knowledge on occurrences, chemistry, pharmacokinetics and potential anticancer properties of phytosterols in vitro and in vivo. In conclusion, anticancer effects of phytosterols have strongly been suggested and support their dietary inclusion to prevent and treat cancers.
  16. Bharudin I, Abu Bakar MF, Hashim NHF, Mat Isa MN, Alias H, Firdaus-Raih M, et al.
    Mar Environ Res, 2018 Jun;137:169-176.
    PMID: 29598997 DOI: 10.1016/j.marenvres.2018.03.007
    Glaciozyma antarctica PI12, is a psychrophilic yeast isolated from Antarctic sea. In this work, Expressed Sequence Tags (EST) from cells exposed to three different temperatures; 15 °C, 0 °C and -12 °C were generated to identify genes associated with cold adaptation. A total of 5376 clones from each library were randomly picked and sequenced. Comparative analyses from the resulting ESTs in each condition identified several groups of genes required for cold adaptation. Additionally, 319 unique transcripts that encoded uncharacterised functions were identified in the -12 °C library and are currently unique to G. antarctica. Gene expression analysis using RT-qPCR revealed two of the unknown genes to be up-regulated at -12 °C compared to 0 °C and 15 °C. These findings further contribute to the collective knowledge into G. antarctica cold adaptation and as a resource for understanding the ecological and physiological tolerance of psychrophilic microbes in general.
  17. Zulkawi N, Ng KH, Zamberi NR, Yeap SK, Satharasinghe DA, Tan SW, et al.
    Drug Des Devel Ther, 2018;12:1373-1383.
    PMID: 29872261 DOI: 10.2147/DDDT.S157803
    Background: Fermented food has been widely consumed as health food to ameliorate or prevent several chronic diseases including diabetes. Xeniji™, a fermented food paste (FFP), has been previously reported with various bioactivities, which may be caused by the presence of several metabolites including polyphenolic acids, flavonoids, and vitamins. In this study, the anti-hyperglycemic and anti-inflammatory effects of FFP were assessed.

    Methods: In this study, type 2 diabetes model mice were induced by streptozotocin and high-fat diet (HFD) and used to evaluate the antihyperglycemic and anti-inflammatory effects of FFP. Mice were fed with HFD and challenged with 30 mg/kg body weight (BW) of streptozotocin for 1 month followed by 6 weeks of supplementation with 0.1 and 1.0 g/kg BW of FFP. Metformin was used as positive control treatment.

    Results: Xeniji™-supplemented hyperglycemic mice were recorded with lower glucose level after 6 weeks of duration. This effect was contributed by the improvement of insulin sensitivity in the hyperglycemic mice indicated by the oral glucose tolerance test, insulin tolerance test, and end point insulin level. In addition, gene expression study has shown that the antihyperglycemic effect of FFP is related to the improvement of lipid and glucose metabolism in the mice. Furthermore, both 0.1 and 1 g/kg BW of FFP was able to reduce hyperglycemia-related inflammation indicated by the reduction of proinflammatory cytokines, NF-kB and iNOS gene expression and nitric oxide level.

    Conclusion: FFP potentially demonstrated in vivo antihyperglycemic and anti-inflammatory effects on HFD and streptozotocin-induced diabetic mice.

  18. Ibrahim M, Mikail MA, Ahmed IA, Hazali N, Abdul Rasad MSB, Abdul Ghani R, et al.
    Eur J Nutr, 2018 Aug;57(5):1817-1828.
    PMID: 28516253 DOI: 10.1007/s00394-017-1466-3
    PURPOSE: Baccaurea angulata (common names: belimbing dayak or belimbing hutan) is a Malaysian underutilized fruit. The preliminary work on B. angulata fruit juice showed that it possesses antioxidant properties. Therefore, further work is needed to confirm the efficacy and proper dosage of B. angulata as a potential natural antioxidant. The present study was thus carried out to compare the effects of three different B. angulata whole fruit (WF) juice doses administered at nutritional doses of 0.50, 1.00 and 1.50 ml/kg/day on plasma, aorta and liver malondialdehyde (MDA) levels, antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase) as well as total antioxidant capacity in rabbits fed high-cholesterol diet.

    METHODS: Thirty-five male rabbits of New Zealand strain were randomly assigned to seven groups. For 12 weeks, group CH was fed 1% cholesterol diet only; group C1 was fed 1% cholesterol diet and 0.50 ml/kg/day B. angulata WF juice; group C2 was fed 1% cholesterol diet and 1.00 ml/kg/day B. angulata WF juice; group C3 was fed 1% cholesterol diet and 1.50 ml/kg/day B. angulata WF juice; group N was fed standard pellet only; group N1 was fed standard pellet and 0.50 ml/kg/day B. angulata WF juice; and group N2 was fed standard pellet and 1.00 ml/kg/day B. angulata WF juice.

    RESULTS: The three doses reduced the formation of MDA and enhanced the expression of endogenous antioxidant enzymes. The highest dose used (1.50 ml/kg/day) was, however, seen as the most potent.

    CONCLUSION: Higher doses of B. angulata juice exerted better antioxidant activity.

  19. Yeow TP, Pacini G, Tura A, Hor CP, Lim SL, Tan FH, et al.
    BMJ Open Diabetes Res Care, 2017;5(1):e000352.
    PMID: 28321312 DOI: 10.1136/bmjdrc-2016-000352
    OBJECTIVE: Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect are scarce. We examined the insulin resistance, β-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM.

    RESEARCH DESIGN AND METHODS: This case-control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index. Serum glucose, insulin, C peptide and GLP-1 were sampled during 2-hour oral glucose tolerance tests (OGTTs) and 1-hour intravenous glucose tolerance tests (IVGTTs). Insulin sensitivity was derived from the Quantitative Insulin Sensitivity Check Index (QUICKI), Oral Glucose Insulin Sensitivity Index (OGIS) in OGTT and surrogate index of SI from the minimal model (calculated SI, CSI). Acute insulin response (AIR) was obtained from IVGTT. Total BC was computed as incremental area under the curve of insulin/incremental area under the curve of glucose, during OGTT (BCOG) and IVGTT (BCIV), respectively. Disposition index (DI) was calculated using the product of insulin sensitivity and insulin secretion. GLP-1 response to oral glucose was calculated as incremental area under the curve of GLP-1 (ΔAUCGLP-1). Per cent incretin effect was estimated as 100×(BCOG-BCIV)/BCOG).

    RESULTS: The YT2DM had marked impairment in BC (>80% reduction in AIR and BCOG, p<0.001) and lower QUICKI (p<0.001), OGIS (p<0.001) and CSI (p=0.015) compared with controls. There was no difference in GLP-1 at all time points and ΔAUCGLP-1 but the per cent incretin effect was reduced in the YT2DM compared with controls (12.1±8.93 vs 70.0±4.03, p<0.001).

    CONCLUSIONS: Asian YT2DM showed similar GLP-1 response to oral glucose as controls but reduced incretin effect, BC and insulin sensitivity. The lack of compensatory mechanisms, as shown by the DI may be partly ascribed to the impaired incretin effect, similar to that of adult T2DM.

    TRIAL REGISTRATION NUMBER: NMRR-12-1042-13254.
  20. Low YM, Chong CW, Yap IKS, Chai LC, Clarke SC, Ponnampalavanar S, et al.
    Pathog Glob Health, 2018 10;112(7):378-386.
    PMID: 30380366 DOI: 10.1080/20477724.2018.1538281
    The increasing prevalence of antibiotic resistant pathogens poses a serious threat to global health. However, less emphasis has been placed to co-relate the gene expression and metabolism of antibiotic resistant pathogens. This study aims to elucidate gene expression and variations in metabolism of multidrug resistant Klebsiella pneumoniae after exposure to antibiotics. Phenotypic responses of three genotypically distinct carbapenem resistant Klebsiella pneumoniae (CRKP) strains untreated and treated with sub-lethal concentrations of imipenem were investigated via phenotype microarrays (PM). The gene expression and metabolism of the strain harboring blaNDM-1 before and after exposure to sub-lethal concentration of imipenem were further investigated by RNA-sequencing (RNA-Seq) and 1H NMR spectroscopy respectively. Most genes related to cell division, central carbon metabolism and nucleotide metabolism were downregulated after imipenem treatment. Similarly, 1H NMR spectra obtained from treated CRKP showed decrease in levels of bacterial end products (acetate, pyruvate, succinate, formate) and metabolites involved in nucleotide metabolism (uracil, xanthine, hypoxanthine) but elevated levels of glycerophosphocholine. The presence of anserine was also observed for the treated CRKP while FAPγ-adenine and methyladenine were only present in untreated bacterial cells. As a conclusion, the studied CRKP strain exhibited decrease in central carbon metabolism, cell division and nucleotide metabolism after exposure to sub-lethal concentrations of imipenem. The understanding of the complex biological system of this multidrug resistant bacterium may help in the development of novel strategies and potential targets for the management of the infections.
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