Displaying publications 221 - 240 of 897 in total

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  1. Optimization of L-asparaginase production from endophytic Fusarium proliferatum using OFAT and RSM and its cytotoxic evaluation
    Yap LS, Lee WL, Ting ASY
    J Microbiol Methods, 2021 12;191:106358.
    PMID: 34743930 DOI: 10.1016/j.mimet.2021.106358
    L-asparaginase from endophytic Fusarium proliferatum (isolate CCH, GenBank accession no. MK685139) isolated from the medicinal plant Cymbopogon citratus (Lemon grass), was optimized for its L-asparaginase production and its subsequent cytotoxicity towards Jurkat E6 cell line. The following factors were optimized; carbon source and concentration, nitrogen source and concentration, incubation period, temperature, pH and agitation rate. Optimization of L-asparaginase production was performed using One-Factor-At-A-Time (OFAT) and Response surface methodology (RSM) model. The cytotoxicity of the crude enzyme from isolate CCH was tested on leukemic Jurkat E6 cell line. The optimization exercise revealed that glucose concentration, nitrogen source, L-asparagine concentration and temperature influenced the L-asparaginase production of CCH. The optimum condition suggested using OFAT and RSM results were consistent. As such, the recommended conditions were 0.20% of glucose, 0.99% of L-asparagine and 5.34 days incubation at 30.50 °C. The L-asparaginase production of CCH increased from 16.75 ± 0.76 IU/mL to 22.42 ± 0.20 IU/mL after optimization. The cytotoxicity of the crude enzyme on leukemic Jurkat cell line recorded IC50 value at 33.89 ± 2.63% v/v. To conclude, the enzyme extract produced from Fusarium proliferatum under optimized conditions is a potential alternative resource for L-asparaginase.
    Matched MeSH terms: Asparaginase/biosynthesis*; Cytotoxins/biosynthesis*
  2. Clinicopathologic and immunohistochemical differences in complete and partial hydatidiform moles in a multiracial Malaysian population
    Hayati AR, Tan GC
    Int J Gynecol Pathol, 2005 Jul;24(3):277-85.
    PMID: 15968205
    Matched MeSH terms: Nuclear Proteins/biosynthesis*; Biomarkers, Tumor/biosynthesis*
  3. Fulltext Glypican-3 is useful but not superior to Hep Par 1 in differentiating hepatocellular carcinoma from other liver tumours
    Pour AM, Masir N, Rose IM
    Malays J Pathol, 2016 Dec;38(3):229-233.
    PMID: 28028292 MyJurnal
    To assess the diagnostic utility of glypican-3 (GPC-3) in comparison to Hep Par 1 in the diagnosis of liver tumours, a cross-sectional study involving 66 resected liver tumours were tested for the protein expression of these markers by immunohistochemistry using monoclonal antibodies. Of the 66 cases, 26 (39.4%) were hepatocellular carcinoma (HCC), 4 (6.1%) were intrahepatic cholangiocarcinoma and 36 (54.5%) were metastatic tumours. Hep Par 1 and GPC-3 expressions in HCC were 24/26 (92.3%) and 19/26 (73.1%) respectively. In contrast, of non-HCC cases, only 2/40 cases (5.0%) expressed Hep Par 1, including a metastatic colorectal adenocarcinoma and a metastatic gastric adenocarcinoma. GPC-3 was expressed in 3/40 cases (7.5%), i.e. a metastatic adenocarcinoma of unknown origin, a metastatic gastric adenocarcinoma and an intrahepatic cholangiocarcinoma. The sensitivity and specificity for Hep Par 1 were 92.3% and 95% respectively while that of GPC-3 was 73.1% and 92.5% respectively. GPC-3 is a useful marker in the diagnosis of HCC. However it is not superior to Hep Par 1 in its sensitivity and specificity. We recommend that it is utilized together with Hep Par 1 as a panel in the diagnosis of HCC.
    Matched MeSH terms: Antigens, Neoplasm/biosynthesis*; Glypicans/biosynthesis*
  4. Optimization of complex fermentation media for glucose oxidase production using statistical approach
    Gunny AA, Arbain D, Sithamparam L
    Pak J Biol Sci, 2013 Sep 15;16(18):960-4.
    PMID: 24502155
    Production cost of enzyme is largely determined by the type of the strain and raw material used to propagate the strain. Hence, selection of the strain and raw materials is crucial in enzyme production. For Glucose oxidase (GOx), previous studies showed Aspergillus terreus UniMAP AA-1 offers a better alternative to the existing sources. Thus, a lower production cost could be logically anticipated by growing the strain in a cheaper complex media such as molasses. In this work, sugar cane molasses, supplemented with urea and carbonate salt and a locally isolated strain Aspergillus terreus UniMAP AA-1 were used to produce a crude GOx enzyme in a small scale. A statistical optimization approach namely Response Surface Methodology (RSM) was used to optimize the media components for highest GOx activity. It was found that the highest GOx activity was achieved using a combination of molasses, carbonate salt and urea at concentration 32.51, 4.58 and 0.93% (w/v), respectively. This study provides an alternative optimized media conditions for GOx production using locally available raw materials.
    Matched MeSH terms: Bacterial Proteins/biosynthesis*; Glucose Oxidase/biosynthesis*
  5. Studies on extraction of mannanase enzyme by Aspergillus terreus SUK-1 from fermented palm kernel cake
    Rashid JI, Samat N, Yusoff WM
    Pak J Biol Sci, 2013 Sep 15;16(18):933-8.
    PMID: 24502150
    Microbial mannanases have become biotechnologically important in industry but their application is limited due to high production cost. In presents study, the extraction of mannanase from fermented Palm Kernel Cake (PKC) in the Solid State Fermentation (SSF) was optimized. Local isolate of Aspergillus terreus SUK-1 was grown on PKC in (SSF) using column bioreactor. The optimum condition were achieved after two washes of fermented PKC by adding of 10% glycerol (v/v) soaked for 10 h at the room temperature with solvent to ratio, 1:5 (w/v).
    Matched MeSH terms: Bacterial Proteins/biosynthesis; Mannosidases/biosynthesis
  6. Fulltext Enhanced anti-inflammatory potential of cinnamate-zinc layered hydroxide in lipopolysaccharide-stimulated RAW 264.7 macrophages
    Adewoyin M, Mohsin SM, Arulselvan P, Hussein MZ, Fakurazi S
    Drug Des Devel Ther, 2015;9:2475-84.
    PMID: 25995619 DOI: 10.2147/DDDT.S72716
    BACKGROUND: Cinnamic acid (CA) is a phytochemical originally derived from Cinnamomum cassia, a plant with numerous pharmacological properties. The intercalation of CA with a nanocarrier, zinc layered hydroxide, produces cinnamate-zinc layered hydroxide (ZCA), which has been previously characterized. Intercalation is expected to improve the solubility and cell specificity of CA. The nanocarrier will also protect CA from degradation and sustain its release. The aim of this study was to assess the effect of intercalation on the anti-inflammatory capacity of CA.

    METHODS: In this study, the anti-inflammatory activity of ZCA was investigated and compared with that of nonintercalated CA. Evaluations were based on the capacity of ZCA and CA to modulate the release of nitric oxide, prostaglandin E2, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β, and IL-10 in lipopolysaccharide-induced RAW 264.7 cells. Additionally, the expression of proinflammatory enzymes, ie, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor kappa B (NF-κB), were examined.

    RESULTS: Although both ZCA and CA downregulated nitric oxide, prostaglandin E2, tumor necrosis factor alpha, IL-1β, and IL-6, ZCA clearly displayed better activity. Similarly, expression of cyclooxygenase-2 and inducible nitric oxide synthase were inhibited in samples treated with ZCA and CA. The two compounds effectively inactivated the transcription factor NF-κB, but the anti-inflammatory cytokine, IL-10, was significantly upregulated by ZCA only.

    CONCLUSION: The present findings suggest that ZCA possesses better anti-inflammatory potential than CA, while zinc layered hydroxide had little or no effect, and these results were comparable with the positive control.

    Matched MeSH terms: Nitric Oxide/biosynthesis; Dinoprostone/biosynthesis
  7. Secretory expression in Escherichia coli and single-step purification of a heat-stable alkaline protease
    Fu Z, Hamid SB, Razak CN, Basri M, Salleh AB, Rahman RN
    Protein Expr Purif, 2003 Mar;28(1):63-8.
    PMID: 12651108
    Bacteriocin release proteins (BRPs) can be used for the release of heterologous proteins from the Escherichia coli cytoplasm into the culture medium. The gene for a highly thermostable alkaline protease was cloned from Bacillus stearothermophilus F1 by the polymerase chain reaction. The recombinant F1 protease was efficiently excreted into the culture medium using E. coli XL1-Blue harboring two vectors: pTrcHis bearing the protease gene and pJL3 containing the BRPs. Both vectors contain the E. coli lac promoter-operator system. In the presence of 40 microM IPTG, the recombinant F1 protease and the BRP were expressed and mature F1 protease was released into the culture medium. This opens the way for the large-scale production of this protease in E. coli. The recombinant enzyme was purified through a one-step heat treatment at 70 degrees C for 3h and this method purified the protease to near homogeneity. The purified enzyme showed a pH optimum of 9.0, temperature optimum of 80 degrees C, and was stable at 70 degrees C for 24h in the pH range from 8.0 to 10.0. The enzyme exhibited a high degree of thermostability with a half-life of 4 h at 85 degrees C, 25 min at 90 degrees C, and was inhibited by the serine protease inhibitor phenylmethylsulfonyl fluoride (PMSF).
    Matched MeSH terms: Recombinant Proteins/biosynthesis; Serine Endopeptidases/biosynthesis*
  8. Fulltext Differential expression of basal microRNAs' patterns in human dental pulp stem cells
    Vasanthan P, Govindasamy V, Gnanasegaran N, Kunasekaran W, Musa S, Abu Kasim NH
    J Cell Mol Med, 2015 Mar;19(3):566-80.
    PMID: 25475098 DOI: 10.1111/jcmm.12381
    MicroRNAs (miRNAs) are small non-coding RNAs that regulate translation of mRNA into protein and play a crucial role for almost all biological activities. However, the identification of miRNAs from mesenchymal stem cells (MSCs), especially from dental pulp, is poorly understood. In this study, dental pulp stem cells (DPSCs) were characterized in terms of their proliferation and differentiation capacity. Furthermore, 104 known mature miRNAs were profiled by using real-time PCR. Notably, we observed 19 up-regulated miRNAs and 29 significantly down-regulated miRNAs in DPSCs in comparison with bone marrow MSCs (BM-MSCs). The 19 up-regulated miRNAs were subjected to ingenuity analysis, which were composed into 25 functional networks. We have chosen top 2 functional networks, which comprised 10 miRNA (hsa-miR-516a-3p, hsa-miR-125b-1-3p, hsa-miR-221-5p, hsa-miR-7, hsa-miR-584-5p, hsa-miR-190a, hsa-miR-106a-5p, hsa-mir-376a-5p, hsa-mir-377-5p and hsa-let-7f-2-3p). Prediction of target mRNAs and associated biological pathways regulated by each of this miRNA was carried out. We paid special attention to hsa-miR-516a-3p and hsa-miR-7-5p as these miRNAs were highly expressed upon validation with qRT-PCR analysis. We further proceeded with loss-of-function analysis with these miRNAs and we observed that hsa-miR-516a-3p knockdown induced a significant increase in the expression of WNT5A. Likewise, the knockdown of hsa-miR-7-5p increased the expression of EGFR. Nevertheless, further validation revealed the role of WNT5A as an indirect target of hsa-miR-516a-3p. These results provide new insights into the dynamic role of miRNA expression in DPSCs. In conclusion, using miRNA signatures in human as a prediction tool will enable us to elucidate the biological processes occurring in DPSCs.
    Matched MeSH terms: Proto-Oncogene Proteins/biosynthesis*; MicroRNAs/biosynthesis*; Wnt Proteins/biosynthesis*
  9. Luteolin, a bioflavonoid inhibits colorectal cancer through modulation of multiple signaling pathways: a review
    Pandurangan AK, Esa NM
    Asian Pac J Cancer Prev, 2014;15(14):5501-8.
    PMID: 25081655
    Luteolin, 3', 4', 5,7-tetrahydroxyflavone, belongs to a group of naturally occurring compounds called flavonoids that are found widely in the plant kingdom. It possesses many beneficial properties including antioxidant, anti- inflammatory, anti-bacterial, anti-diabetic and anti-proliferative actions. Colorectal cancer (CRC) is a leading cause of cancer related deaths worldwide. Many signaling pathways are deregulated during the progression of colon cancer. In this review we aimed to analyze the protection offered by luteolin on colon cancer. During colon cancer genesis, luteolin known to reduce oxidative stress thereby protects the cell to undergo damage in vivo. Wnt/β-catenin signaling, deregulated during neoplastic development, is modified by luteolin. Hence, luteolin can be considered as a potential drug to treat CRC.
    Matched MeSH terms: Wnt Proteins/biosynthesis; beta Catenin/biosynthesis; Nitric Oxide Synthase Type II/biosynthesis
  10. Fulltext Immunomodulatory effect of an isolated fraction from Tinospora crispa on intracellular expression of INF-γ, IL-6 and IL-8
    Abood WN, Fahmi I, Abdulla MA, Ismail S
    BMC Complement Altern Med, 2014;14:205.
    PMID: 24969238 DOI: 10.1186/1472-6882-14-205
    Immunomodulators are substances that modify immune system response to a threat. Immunomodulators modulate and potentiate the immune system, keeping it highly prepared for any threat. The immunomodulatory effect of the traditional medicine Tinospora crispa is investigated in this work.
    Matched MeSH terms: Interferon-gamma/biosynthesis*; Interleukin-6/biosynthesis*; Interleukin-8/biosynthesis*
  11. Fulltext Variable characteristics of bacteriocin-producing Streptococcus salivarius strains isolated from Malaysian subjects
    Barbour A, Philip K
    PLoS One, 2014;9(6):e100541.
    PMID: 24941127 DOI: 10.1371/journal.pone.0100541
    Salivaricins are bacteriocins produced by Streptococcus salivarius, some strains of which can have significant probiotic effects. S. salivarius strains were isolated from Malaysian subjects showing variable antimicrobial activity, metabolic profile, antibiotic susceptibility and lantibiotic production.
    Matched MeSH terms: Bacterial Proteins/biosynthesis; Bacteriocins/biosynthesis; Hexosyltransferases/biosynthesis
  12. Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxy-4-methylvalerate) by recombinant Escherichia coli expressing leucine metabolism-related enzymes derived from Clostridium difficile
    Saika A, Watanabe Y, Sudesh K, Tsuge T
    J Biosci Bioeng, 2014 Jun;117(6):670-5.
    PMID: 24484910 DOI: 10.1016/j.jbiosc.2013.12.006
    An obligate anaerobic bacterium Clostridium difficile has a unique metabolic pathway to convert leucine to 4-methylvalerate, in which 4-methyl-2-pentenoyl-CoA (4M2PE-CoA) is an intermediate of this pathway. 4M2PE-CoA is also able to be converted to 3-hydroxy-4-methylvalerate (3H4MV), a branched side chain monomer unit, for synthesis of polyhydroxyalkanoate (PHA) copolymer. In this study, to synthesize 3H4MV-containing PHA copolymer from leucine, the leucine metabolism-related enzymes (LdhA and HadAIBC) derived from C. difficile and PHA biosynthesis enzymes (PhaPCJAc and PhaABRe) derived from Aeromonas caviae and Ralstonia eutropha were co-expressed in the codon usage-improved Escherichia coli. Under microaerobic culture conditions, this E. coli was able to synthesize P(3HB-co-12.2 mol% 3H4MV) from glucose with the supplementation of 1 g/L leucine. This strain also produced P(3HB-co-12.6 mol% 3H4MV) using the culture supernatant of leucine overproducer E. coli strain NS1391 as the medium for PHA production, achieving 3H4MV copolymer synthesis only from glucose. Furthermore, we tested the feasibility of the 3H4MV copolymer synthesis in E. coli strain NS1391 from glucose. The recombinant E. coli NS1391 was able to synthesize P(3HB-co-3.0 mol% 3H4MV) from glucose without any leucine supplementation. This study demonstrates the potential of the new metabolic pathway for 3H4MV synthesis using leucine metabolism-related enzymes from C. difficile.
    Matched MeSH terms: Acyltransferases/biosynthesis; Bacterial Proteins/biosynthesis; Oxidoreductases/biosynthesis
  13. Organotypic culture of human amnion cells in air-liquid interface as a potential substitute for skin regeneration
    Fatimah SS, Chua K, Tan GC, Azmi TI, Tan AE, Abdul Rahman H
    Cytotherapy, 2013 Aug;15(8):1030-41.
    PMID: 23830235 DOI: 10.1016/j.jcyt.2013.05.003
    The aim of the present study was to evaluate the effects of air-liquid interface on the differentiation potential of human amnion epithelial cells (HAECs) to skin-like substitute in organotypic culture.
    Matched MeSH terms: Protein Precursors/biosynthesis; Cell Adhesion Molecules/biosynthesis; Collagen Type IV/biosynthesis
  14. Fulltext An analysis of predictive biomarkers in routine histopathological reporting of infiltrating ductal breast carcinoma in a tertiary hospital in Malaysia with a focus on limitations and directions for future development
    Teoh KH, Looi LM, Sabaratnam S, Cheah PL, Nazarina AR, Mun KS
    Malays J Pathol, 2011 Jun;33(1):35-42.
    PMID: 21874750 MyJurnal
    Predictive biomarkers such as oestrogen (ER) and progesterone (PR) receptors and c-erbB-2 oncoprotein have become a staple in breast cancer reports in the country as they increasingly play an important role in the treatment and prognosis of women with breast cancers. This study reviews the practice of histopathology reporting of these biomarkers in a Malaysian tertiary hospital setting. Retrospective data on demographic, pathological and biomarker profiles of patients with invasive ductal carcinoma who had undergone mastectomy or lumpectomy with axillary node clearance from 2005 to 2006 were retrieved from the Department of Pathology, Penang Hospital and analysed. The prevalence of ER positivity (55.8%), PR positivity (52.5%), c-erbB-2 oncoprotein overexpression (24%) and triple negativity (ER negative, PR negative, c-erbB-2 negative) (15%) by immunohistochemistry were comparable with other studies. Notably, c-erbB-2 overexpression was equivocal (2+) in 15% of cases. Since about a quarter of equivocal (2+) cases usually show amplification by FISH, a small but certain percentage of patients would miss the benefit of anti-c-erbB-2 antibody therapy if FISH is not performed. New ASCO/CAP guidelines on the quantitation of ER and PR will probably increase the prevalence of ER/PR positivity, invariably leading to significant ramifications on the management of patients as more patients would be deemed eligible for endocrine therapy, as well as categorisation of triple negative breast cancers.
    Matched MeSH terms: Receptors, Estrogen/biosynthesis; Receptors, Progesterone/biosynthesis; Receptor, ErbB-2/biosynthesis
  15. Fulltext Neonatal feed restriction modulates circulating levels of corticosterone and expression of glucocorticoid receptor and heat shock protein 70 in aged Japanese quail exposed to acute heat stress
    Soleimani AF, Zulkifli I, Omar AR, Raha AR
    Poult Sci, 2011 Jul;90(7):1427-34.
    PMID: 21673157 DOI: 10.3382/ps.2011-01403
    This study aimed to determine the effect of neonatal feed restriction on plasma corticosterone concentration (CORT), hippocampal glucocorticoid receptor (GR) expression, and heat shock protein (Hsp) 70 expression in aged male Japanese quail subjected to acute heat stress. Equal numbers of chicks were subjected to either ad libitum feeding (AL) or 60% feed restriction on d 4, 5, and 6 (FR). At 21 (young) and 270 (aged) d of age, birds were exposed to 43 ± 1°C for 1 h. Blood and hippocampus samples were collected to determine CORT and Hsp 70 and GR expressions before heat stress and following 1 h of heat stress, 1 h of post-heat stress recovery, and 2 h of post-heat stress recovery. With the use of real-time PCR and enzyme immunoassay, we examined the hippocampal expression of GR and Hsp 70 and CORT. The GR expression of the young birds increased following heat stress and remained consistent throughout the period of recovery. Conversely, no significant changes were noted on GR expression of aged birds. Although both young and aged birds had similar CORT before and during heat stress, the latter exhibited greater values following 1 and 2 h of recovery. Within the young group, feeding regimens had no significant effect on Hsp 70 expression. However, neonatal feed restriction improved Hsp 70 expression in aged birds. Neonatal feed restriction, compared with the AL group, resulted in higher CORT on d 21 but the converse was noted on d 270. Neonatal feed restriction appears to set a robust reactive hypothalamo-pituitary-adrenal response allowing the development of adaptive, healthy, and resilient phenotypes in aged quail as measured by a higher hippocampal Hsp 70 expression along with lower CORT.
    Matched MeSH terms: Receptors, Glucocorticoid/biosynthesis*; RNA, Messenger/biosynthesis; HSP70 Heat-Shock Proteins/biosynthesis*
  16. Generation and characterization of a high-affinity monoclonal antibody for MUC1 measurement in breast cancer
    Hamid SS, Cheah SH
    Hybridoma (Larchmt), 2011 Apr;30(2):137-43.
    PMID: 21529286 DOI: 10.1089/hyb.2010.0091
    Breast mucin is secreted by breast tumor cells and serves as a marker for breast cancer. Thus, antibodies against breast mucin will be valuable in the development of immunotherapy and laboratory diagnostic tests. Monoclonal antibodies (MAbs) against breast cancer-associated antigen were generated and characterized. Balb/c mice were immunized with breast cancer-associated antigen CA15-3, and subsequently splenocytes from immunized mice were fused with myeloma cells. After fusion, culture supernatants from hybridomas surviving HAT medium were screened by enzyme-linked immunosorbent assay (ELISA). A total of eight hybridomas producing MAbs against breast cancer showed significant levels of antibody activity against CA15-3. Two selected stable hybridomas were adapted into CELLine CL 350 bioreactors, and the MAbs produced were characterized for their subclass, specificity, and affinity. The MAbs were of high specificity and affinity as shown by ELISA. The MAbs produced may represent a powerful tool and are considered promising reagents for use in diagnosis and detection of early stage of the disease.
    Matched MeSH terms: Antibodies, Monoclonal/biosynthesis; Biomarkers, Tumor/biosynthesis; Mucin-1/biosynthesis
  17. Correlations in survivin expression with the expression of p53 and bcl-2 in invasive ductal carcinoma of the breast
    Al-Joudi FS, Iskandar ZA, Imran AK
    Southeast Asian J. Trop. Med. Public Health, 2007 Sep;38(5):904-10.
    PMID: 18041310
    This work studied the correlations between survivin, bcl-2 and p53 in infiltrating ductal carcinoma of the breast. A total number of 382 cases were collected from 3 hospitals in northeastern Malaysia. Survivin, bcl-2 and p53 were detected by immunohistochemistry on samples prepared from tissue blocks. Significant correlations were found between tumor histological grades and tumor size and lymph node involvement. Highly significant statistical correlations (p<0.001) were found in expression of the markers under study. It is concluded that such significant correlations may imply that the alterations in the expression take place in a concerted fashion, implying that many of these cases may share common abnormalities.
    Matched MeSH terms: Microtubule-Associated Proteins/biosynthesis*; Neoplasm Proteins/biosynthesis*; Tumor Suppressor Protein p53/biosynthesis*
  18. Fulltext The pattern of CD15, CD30 and Bcl-2 expression in diffuse large B-cell lymphoma
    Eow GI, Kim LH, Peh SC
    Med J Malaysia, 2006 Oct;61(4):416-21.
    PMID: 17243518 MyJurnal
    Diffuse large B-cell lymphoma (DLBCL) is a heterogenous entity. The pattern of CD15, CD30 and Bcl-2 expression is not well documented, especially in local population. We investigated 67 consecutive cases of DLBCL by immunohistochemistry on paraffin-embedded tissue. The male to female ratio was 1.2:1 with median age of 55 years, and more common nodal than extranodal in presentation. Only 3 of 67 cases expressed CD15. In addition, three cases showed weak membrane staining for CD30. Only one of these three cases was noted to have co-expression of CD15 and with occasional tumour cells showing weak CD30 expression. Bcl-2 protein was expressed in 43 of 67 (64%), more frequently in nodal than in extranodal tumours. In conclusion, CD15 and CD30 expressions are infrequent in DLBCL, and co-expression is rare. Bcl-2 protein expression is common in DLBCL.
    Matched MeSH terms: Antigens, CD15/biosynthesis*; Antigens, CD30/biosynthesis*; bcl-2-Associated X Protein/biosynthesis*
  19. Fulltext Hypoglycemic effect of Octomeles sumatrana aqueous extract in streptozotocin-induced diabetic rats and its molecular mechanisms
    Azahar MA, Al-Naqeb G, Hasan M, Adam A
    Asian Pac J Trop Med, 2012 Nov;5(11):875-81.
    PMID: 23146801 DOI: 10.1016/S1995-7645(12)60163-1
    OBJECTIVE: To investigate the hypoglycemic effect of the aqueous extract of Octomeles sumatrana (O. sumatrana) (OS) in streptozotocin-induced diabetic rats (STZ) and its molecular mechanisms.

    METHODS: Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg) in to male Sprague-Dawley rats. Rats were divided into six different groups; normal control rats were not induced with STZ and served as reference, STZ diabetic control rats were given normal saline. Three groups were treated with OS aqueous extract at 0.2, 0.3 and 0.5 g/kg, orally twice daily continuously for 21 d. The fifth group was treated with glibenclamide (6 mg/kg) in aqueous solution orally continuously for 21 d. After completion of the treatment period, biochemical parameters and expression levels of glucose transporter 2 (Slc2a2), glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PCK1) were determined in liver by quantitative real time PCR.

    RESULTS: Administration of OS at different doses to STZ induced diabetic rats, resulted in significant decrease (P<0.05) in blood glucose level in a dose dependent manner by 36%, 48%, and 64% at doses of 0.2, 0.3 and 0.5 g/kg, respectively, in comparison to the STZ control values. Treatment with OS elicited an increase in the expression level of Slc2a2 gene but reduced the expression of G6Pase and PCK1 genes. Morefore, OS treated rats, showed significantly lower levels of serum alanine transaminase (ALT), aspartate aminotransferase (AST) and urea levels compared to STZ untreated rats. The extract at different doses elicited signs of recovery in body weight gain when compared to STZ diabetic controls although food and water consumption were significantly lower in treated groups compared to STZ diabetic control group.

    CONCLUSIONS: O. sumatrana aqueous extract is beneficial for improvement of hyperglycemia by increasing gene expression of liver Slc2a2 and reducing expression of G6Pase and PCK1 genes in streptozotocin-induced diabetic rats.

    Matched MeSH terms: Glucose-6-Phosphatase/biosynthesis; Phosphoenolpyruvate Carboxykinase (GTP)/biosynthesis; Glucose Transporter Type 2/biosynthesis
  20. Fulltext Overexpressing 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) in the lactococcal mevalonate pathway for heterologous plant sesquiterpene production
    Song AA, Abdullah JO, Abdullah MP, Shafee N, Othman R, Tan EF, et al.
    PLoS One, 2012;7(12):e52444.
    PMID: 23300671 DOI: 10.1371/journal.pone.0052444
    Isoprenoids are a large and diverse group of metabolites with interesting properties such as flavour, fragrance and therapeutic properties. They are produced via two pathways, the mevalonate pathway or the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway. While plants are the richest source of isoprenoids, they are not the most efficient producers. Escherichia coli and yeasts have been extensively studied as heterologous hosts for plant isoprenoids production. In the current study, we describe the usage of the food grade Lactococcus lactis as a potential heterologous host for the production of sesquiterpenes from a local herbaceous Malaysian plant, Persicaria minor (synonym Polygonum minus). A sesquiterpene synthase gene from P. minor was successfully cloned and expressed in L. lactis. The expressed protein was identified to be a β-sesquiphellandrene synthase as it was demonstrated to be functional in producing β-sesquiphellandrene at 85.4% of the total sesquiterpenes produced based on in vitro enzymatic assays. The recombinant L. lactis strain developed in this study was also capable of producing β-sesquiphellandrene in vivo without exogenous substrates supplementation. In addition, overexpression of the strain's endogenous 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR), an established rate-limiting enzyme in the eukaryotic mevalonate pathway, increased the production level of β-sesquiphellandrene by 1.25-1.60 fold. The highest amount achieved was 33 nM at 2 h post-induction.
    Matched MeSH terms: Hydroxymethylglutaryl CoA Reductases/biosynthesis; Recombinant Proteins/biosynthesis; Alkyl and Aryl Transferases/biosynthesis
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