Displaying publications 41 - 60 of 380 in total

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  1. Fulltext Vitamins D and E Stimulate the PI3K-AKT Signalling Pathway in Insulin-Resistant SK-N-SH Neuronal Cells
    Zaulkffali AS, Md Razip NN, Syed Alwi SS, Abd Jalil A, Abd Mutalib MS, Gopalsamy B, et al.
    Nutrients, 2019 Oct 19;11(10).
    PMID: 31635074 DOI: 10.3390/nu11102525
    This study investigated the effects of vitamins D and E on an insulin-resistant model and hypothesized that this treatment would reverse the effects of Alzheimer's disease (AD) and improves insulin signalling. An insulin-resistant model was induced in SK-N-SH neuronal cells with a treatment of 250 nM insulin and re-challenged with 100 nM at two different incubation time (16 h and 24 h). The effects of vitamin D (10 and 20 ng/mL), vitamin E in the form of tocotrienol-rich fraction (TRF) (200 ng/mL) and the combination of vitamins D and E on insulin signalling markers (IR, PI3K, GLUT3, GLUT4, and p-AKT), glucose uptake and AD markers (GSK3β and TAU) were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The results demonstrated an improvement of the insulin signalling pathway upon treatment with vitamin D alone, with significant increases in IR, PI3K, GLUT3, GLUT4 expression levels, as well as AKT phosphorylation and glucose uptake, while GSK3β and TAU expression levels was decreased significantly. On the contrary, vitamin E alone, increased p-AKT, reduced the ROS as well as GSK3β and TAU but had no effect on the insulin signalling expression levels. The combination of vitamins D and E only showed significant increase in GLUT4, p-AKT, reduced ROS as well as GSK3β and TAU. Thus, the universal role of vitamin D, E alone and in combinations could be the potential nutritional agents in restoring the sensitivity of neuronal cells towards insulin and delaying the pathophysiological progression of AD.
    Matched MeSH terms: Proto-Oncogene Proteins c-akt/genetics; Proto-Oncogene Proteins c-akt/metabolism*
  2. Increased SPRY1 expression activates NF-κB signaling and promotes pancreatic cancer progression by recruiting neutrophils and macrophages through CXCL12-CXCR4 axis
    Shi T, Li X, Zheng J, Duan Z, Ooi YY, Gao Y, et al.
    Cell Oncol (Dordr), 2023 Aug;46(4):969-985.
    PMID: 37014552 DOI: 10.1007/s13402-023-00791-z
    PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high mortality rate, in which about 90% of patients harbor somatic oncogenic point mutations in KRAS. SPRY family genes have been recognized as crucial negative regulators of Ras/Raf/ERK signaling. Here, we investigate the expression and role of SPRY proteins in PDAC.

    METHODS: Expression of SPRY genes in human and mice PDAC was analyzed using The Cancer Genome Atlas and Gene Expression Omnibus datasets, and by immunohistochemistry analysis. Gain-of-function, loss-of-function of Spry1 and orthotopic xenograft model were adopted to investigate the function of Spry1 in mice PDAC. Bioinformatics analysis, transwell and flowcytometry analysis were used to identify the effects of SPRY1 on immune cells. Co-immunoprecipitation and K-ras4B G12V overexpression were used to identify molecular mechanism.

    RESULTS: SPRY1 expression was remarkably increased in PDAC tissues and positively associated with poor prognosis of PDAC patients. SPRY1 knockdown suppressed tumor growth in mice. SPRY1 was found to promote CXCL12 expression and facilitate neutrophil and macrophage infiltration via CXCL12-CXCR4 axis. Pharmacological inhibition of CXCL12-CXCR4 largely abrogated the oncogenic functions of SPRY1 by suppressing neutrophil and macrophage infiltration. Mechanistically, SPRY1 interacted with ubiquitin carboxy-terminal hydrolase L1 to induce activation of nuclear factor κB signaling and ultimately increase CXCL12 expression. Moreover, SPRY1 transcription was dependent on KRAS mutation and was mediated by MAPK-ERK signaling.

    CONCLUSION: High expression of SPRY1 can function as an oncogene in PDAC by promoting cancer-associated inflammation. Targeting SPRY1 might be an important approach for designing new strategy of tumor therapy.

  3. Effects of Alkoxy Chain Length and 1-Hydroxy Group on Anticolorectal Cancer Activity of 2-Bromoalkoxyanthraquinones
    Mekzali NW, Chee CW, Abdullah I, Lee YK, Rashid NN, Lee VS, et al.
    Med Chem, 2023;19(9):897-905.
    PMID: 37046198 DOI: 10.2174/1573406419666230410134213
    BACKGROUND: KRAS and p53 are two of the most common genetic alterations associated with colorectal cancer. New drug development targeting these mutated genes in colorectal cancer may serve as a potential treatment avenue to the current regimen.

    OBJECTIVE: The objective of the present study was to investigate the effects of alkoxy chain length and 1-hydroxy group on anticolorectal cancer activity of a series of 2-bromoalkoxyanthraquinones and corroborate it with their in silico properties.

    METHODS: In vitro anticancer activity of 2-bromoalkoxyanthraquinones was evaluated against HCT116, HT29, and CCD841 CoN cell lines, respectively. Molecular docking was performed to understand the interactions of these compounds with putative p53 and KRAS targets (7B4N and 6P0Z).

    RESULTS: 2-Bromoalkoxyanthraquinones with the 1-hydroxy group were proven to be more active than the corresponding counterparts in anticancer activity. Among the tested compounds, compound 6b with a C3 alkoxy chain exhibited the most promising antiproliferation activity against HCT116 cells (IC50 = 3.83 ± 0.05 μM) and showed high selectivity for HCT116 over CCD841 CoN cells (SI = 45.47). The molecular docking reveals additional hydrogen bonds between the 1-hydroxy group of 6b and the proteins. Compound 6b has adequate lipophilicity (cLogP = 3.27) and ligand efficiency metrics (LE = 0.34; LLE = 2.15) close to the proposed acceptable range for an initial hit.

    CONCLUSION: This work highlights the potential of the 1-hydroxy group and short alkoxy chain on anticolorectal cancer activity of 2-bromoalkoxyanthraquinones. Further optimisation may be warranted for compound 6b as a therapeutic agent against colorectal cancer.

  4. Fulltext Gene Therapy Targeting p53 and KRAS for Colorectal Cancer Treatment: A Myth or the Way Forward?
    Hasbullah HH, Musa M
    Int J Mol Sci, 2021 Nov 03;22(21).
    PMID: 34769370 DOI: 10.3390/ijms222111941
    Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and is responsible as one of the main causes of mortality in both men and women. Despite massive efforts to raise public awareness on early screening and significant advancements in the treatment for CRC, the majority of cases are still being diagnosed at the advanced stage. This contributes to low survivability due to this cancer. CRC patients present various genetic changes and epigenetic modifications. The most common genetic alterations associated with CRC are p53 and KRAS mutations. Gene therapy targeting defect genes such as TP53 (tumor suppressor gene encodes for p53) and KRAS (oncogene) in CRC potentially serves as an alternative treatment avenue for the disease in addition to the standard therapy. For the last decade, significant developments have been seen in gene therapy for translational purposes in treating various cancers. This includes the development of vectors as delivery vehicles. Despite the optimism revolving around targeted gene therapy for cancer treatment, it also has various limitations, such as a lack of availability of related technology, high cost of the involved procedures, and ethical issues. This article will provide a review on the potentials and challenges of gene therapy targeting p53 and KRAS for the treatment of CRC.
  5. Fulltext In-Vitro and In-Silico Evaluations of Heterocyclic-Containing Diarylpentanoids as Bcl-2 Inhibitors Against LoVo Colorectal Cancer Cells
    Leong SW, Chia SL, Abas F, Yusoff K
    Molecules, 2020 Aug 26;25(17).
    PMID: 32858795 DOI: 10.3390/molecules25173877
    In the present study, we investigated the in-vitro anti-cancer potential of six diarylpentanoids against a panel of BRAF- and KRAS-mutated colorectal cancer cell lines including T84, SW620, LoVo, HT29, NCI-H508, RKO, and LS411N cells. Structure-activity relationship study suggested that the insertions of tetrahydro-4H-thiopyran-4-one and brominated phenyl moieties are essential for better cytotoxicity. Among the evaluated analogs, 2e has been identified as the lead compound due to its low IC50 values of approximately 1 µM across all cancer cell lines and high chemotherapeutic index of 7.1. Anti-proliferative studies on LoVo cells showed that 2e could inhibit cell proliferation and colony formations by inducing G2/M cell cycle arrest. Subsequent cell apoptosis assay confirmed that 2e is a Bcl-2 inhibitor that could induce intrinsic cell apoptosis by creating a cellular redox imbalance through its direct inhibition on the Bcl-2 protein. Further molecular docking studies revealed that the bromophenyl moieties of 2e could interact with the Bcl-2 surface pocket through hydrophobic interaction, while the tetrahydro-4H-thiopyran-4-one fragment could form additional Pi-sulfur and Pi-alkyl interactions in the same binding site. In all, the present results suggest that 2e could be a potent lead that deserves further modification and investigation in the development of a new Bcl-2 inhibitor.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors*; Proto-Oncogene Proteins c-bcl-2/metabolism
  6. Fulltext The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease
    Fu YP, Kohaar I, Moore LE, Lenz P, Figueroa JD, Tang W, et al.
    Cancer Res, 2014 Oct 15;74(20):5808-18.
    PMID: 25320178 DOI: 10.1158/0008-5472.CAN-14-1531
    A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) ≥ 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 × 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P(trend) = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.
    Matched MeSH terms: Oncogene Proteins/genetics*; Oncogene Proteins/metabolism
  7. Fulltext The Effects of Pre-emptive Administration of Ketamine and norBNI on Pain Behavior, c-Fos, and Prodynorphin Protein Expression in the Rat Spinal Cord after Formalin-induced Pain Is Modulated by the DREAM Protein
    Long I, Suppian R, Ismail Z
    Korean J Pain, 2013 Jul;26(3):255-64.
    PMID: 23861999 DOI: 10.3344/kjp.2013.26.3.255
    We investigated the effects of pre-emptive administration of ketamine and norBNI on pain behavior and the expression of DREAM, c-Fos, and prodynorphin proteins on the ipsilateral side of the rat spinal cord at 2 and 4 hours after formalin injection.
    Matched MeSH terms: Proto-Oncogene Proteins c-fos
  8. Fulltext Molecular detection, quantification, and isolation of Streptococcus gallolyticus bacteria colonizing colorectal tumors: inflammation-driven potential of carcinogenesis via IL-1, COX-2, and IL-8
    Abdulamir AS, Hafidh RR, Bakar FA
    Mol. Cancer, 2010;9:249.
    PMID: 20846456 DOI: 10.1186/1476-4598-9-249
    Colorectal cancer (CRC) has long been associated with bacteremia and/or endocarditis by Streptococcus gallolyticus member bacteria (SGMB) but the direct colonization of SGMB along with its molecular carcinogenic role, if any, has not been investigated. We assessed the colonization of SGMB in CRC patients with history of bacteremia (CRC-w/bac) and without history of bacteremia (CRC-wo/bac) by isolating SGMB from feces, mucosal surfaces of colorectum, and colorectal tissues and detecting SGMB DNA, via PCR and in situ hybridization (ISH) assays targeting SodA gene in colorectal tissues. Moreover, mRNA of IL1, IL-8, COX-2, IFN-γ, c-Myc, and Bcl-2 in colorectal tissues of studied groups was assessed via ISH and RT-PCR.
    Matched MeSH terms: Proto-Oncogene Proteins c-myc/genetics; Proto-Oncogene Proteins c-bcl-2/genetics
  9. Styrylpyrone derivative induces apoptosis through the up-regulation of Bax in the human breast cancer cell line MCF-7
    Chien AL, Pihie AH
    J. Biochem. Mol. Biol., 2003 May 31;36(3):269-74.
    PMID: 12787481
    In the fight against cancer, novel chemotherapeutic agents are constantly being sought to complement existing drugs. Various studies have presented evidence that the apoptosis that is induced by these anticancer agents is implicated in tumor regression, and Bcl-2 family genes play a part in apoptosis following treatment with various stimuli. Here, we present data that a styrylpyrone derivative (SPD) that is extracted from the plant Goniothalamus sp. showed cytotoxic effects on the human breast cancer cell line MCF-7. SPD significantly increased apoptosis in MCF-7 cells, as visualized by phase contrast microscopy and evaluated by the Tdt-mediated dUTP nick end-labeling assay and nuclear morphology. Western blotting and immunostaining revealed up-regulation of the proapoptotic Bax protein expression. SPD, however, did not affect the expression of the anti-apoptotic protein, Bcl-2. These results, therefore, suggest SPD as a potent cytotoxic agent on MCF-7 cells by inducing apoptosis through the modulation of Bax levels.
    Matched MeSH terms: Proto-Oncogene Proteins/metabolism*; Proto-Oncogene Proteins c-bcl-2*
  10. Protein expression and molecular analysis of c-myc gene in primary breast carcinomas using immunohistochemistry and differential polymerase chain reaction
    Naidu R, Wahab NA, Yadav M, Kutty MK
    Int J Mol Med, 2002 Feb;9(2):189-96.
    PMID: 11786932
    Overexpression of c-myc protein and amplification of c-myc were investigated by immunohistochemistry and differential polymerase chain reaction (dPCR) in 440 formalin-fixed primary breast carcinoma tissues, respectively. Overexpression of c-myc was detected in 45% (199/440) and amplification of c-myc was observed in 25% (112/440) of the primary breast carcinomas. Immunolocalization of c-myc oncoprotein was demonstrated in 35% (8/23) of the comedo subtype, 17% (3/18) of the non-comedo subtype, 37% (15/41) of the comedo DCIS and 49% (20/41) of the adjacent invasive ductal carcinomas, 21% (4/19) of the non-comedo DCIS and 37% (7/19) of the adjacent invasive lesions, 49% (133/270) of the invasive ductal carcinomas, 33% (11/33) of the invasive lobular carcinomas, 29% (6/21) of the colloid carcinomas and 47% (7/15) of the medullary carcinomas. C-myc was amplified in 13% (3/23) of the comedo DCIS, 17% (7/41) of the comedo DCIS and 24% (10/41) of the adjacent invasive ductal carcinomas, 30% (82/270) of the invasive ductal carcinomas, 21% (7/33) of the invasive lobular carcinomas, 14% (3/21) of the colloid carcinomas and 24% (4/15) of the medullary carcinomas. Amplification of c-myc was noted in 16% (3/9) of the invasive ductal carcinomas but not in the adjacent non-comedo DCIS lesions. A significant association (P<0.05) was observed between in situ components and adjacent invasive lesions for c-myc expression and amplification. Overexpression of c-myc protein was significantly correlated with poorly differentiated (P<0.05) and high proliferation index (Ki-67) (P<0.05) tumors but not with lymph node metastases (P>0.05), patient age (P>0.05) and estrogen receptor status (P>0.05). Significant relationship was also noted between amplification of c-myc and absence of estrogen receptor (P<0.05), high histological grade (P<0.05) and high proliferation index (Ki-67) (P<0.05). No relationship was seen with nodal status (P>0.05) and patient age (P>0.05). Majority of the Malaysian female patients are from younger age group (<50 years old) but overexpression and amplification of c-myc was not statistically associated with patient age (P>0.05) indicating that these alterations may be independent events of patient age. The above observations suggest that overexpression and amplification of c-myc could play an important role in tumor progression from non-invasive to invasive and, also, it may have the potential as a marker of poor prognosis of breast cancer.
    Matched MeSH terms: Proto-Oncogene Proteins c-myc/analysis*; Proto-Oncogene Proteins c-myc/genetics; Proto-Oncogene Proteins c-myc/immunology
  11. A comprehensive review of techniques for natural fibers as reinforcement in composites: Preparation, processing and characterization
    M R S, Siengchin S, Parameswaranpillai J, Jawaid M, Pruncu CI, Khan A
    Carbohydr Polym, 2019 Mar 01;207:108-121.
    PMID: 30599990 DOI: 10.1016/j.carbpol.2018.11.083
    Designing environmentally friendly materials from natural resources represents a great challenge in the last decade. However, the lack of fundamental knowledge in the processing of the raw materials to fabricate the composites structure is still a major challenge for potential applications. Natural fibers extracted from plants are receiving more attention from researchers, scientists and academics due to their use in polymer composites and also their environmentally friendly nature and sustainability. The natural fiber features depend on the preparation and processing of the fibers. Natural plant fibers are extracted either by mechanical retting, dew retting and/or water retting processes. The natural fibers characteristics could be improved by suitable chemicals and surface treatments. This survey proposes a detailed review of the different types of retting processes, chemical and surface treatments and characterization techniques for natural fibers. We summarize major findings from the literature and the treatment effects on the properties of the natural fibers are being highlighted.
    Matched MeSH terms: Proto-Oncogene Proteins c-ret
  12. Fulltext P53/MDM2 co-expression correlates with the tumour differentiation in oral squamous cell carcinoma - a retrospective study and a systematic review
    Choon, Y.F., Ramanathan, A., Ali, H., Ghani, W.M.N., Cheong, S.C., Zain, R.B.
    Ann Dent, 2011;18(1):8-17.
    MyJurnal
    Background: MDM2 and p53 are involved in a negative feedback loop where p53 regulates MDM2 at the transcriptional level. MDM2, in turn, downregulates p53. This co-ordinated interaction between these proteins is set to play an important role in the regulation of cell cycle progression following DNA damage to cells. The over-expression of both p53 and MDM2 has been reported in various cancers. However there are only few studies discussing the co-expression of MDM2 with p53 in oral squamous cell carcinoma Aim: The purpose of this study was to determine the correlation of co-expression of p53, MDM2, and Ki-67 proteins with clinico-pathological factors in oral squamous cell carcinoma (OSCC) and to conduct a systematic review of the co-expression of p53/MDM2.

    Method: This is a retrospective descriptive study and a systematic review. Formalin-fixed paraffinembedded tissues from 45 OSCC cases were stained by immunohistochemistry (IHC) for p53, MDM2, and Ki-67 proteins.

    Results: Immuno-reactivity for p53, MDM2, and Ki-67 was seen in 75.6%, 97.8%, and 62.2% cases of OSCC respectively. The co-expression of p53 and MDM2 (p53/MDM2) was detected in 97.1%, however there was no significant correlation between p53 and MDM2 expression. Notably, p53/MDM2 coexpression was significantly associated with tumour differentiation (p-value = 0.045). The Ki-67LI was not significantly associated with neither MDM2 nor p53/MDM2 co-expression (p-value = 0.268, 0.916 respectively).

    Conclusion: The expression of MDM2 was not signif icantly associated with p53 expression suggesting that MDM2 expression is mediated by p53-independent pathways or mutated p53 could not induce the expression of MDM2 in this set of OSCCs. The only clinico-pathological parameter that correlates significantly with co-expression of p53/MDM2 is tumour differentiation where it is suggestive that the co-expression of these 2 proteins is indicative of aggressive tumour behavior.
    Matched MeSH terms: Proto-Oncogene Proteins c-mdm2
  13. Fulltext Oncogenic Signaling in Tumorigenesis and Applications of siRNA Nanotherapeutics in Breast Cancer
    Kamaruzman NI, Aziz NA, Poh CL, Chowdhury EH
    Cancers (Basel), 2019 May 06;11(5).
    PMID: 31064156 DOI: 10.3390/cancers11050632
    Overexpression of oncogenes and cross-talks of the oncoproteins-regulated signaling cascades with other intracellular pathways in breast cancer could lead to massive abnormal signaling with the consequence of tumorigenesis. The ability to identify the genes having vital roles in cancer development would give a promising therapeutics strategy in combating the disease. Genetic manipulations through siRNAs targeting the complementary sequence of the oncogenic mRNA in breast cancer is one of the promising approaches that can be harnessed to develop more efficient treatments for breast cancer. In this review, we highlighted the effects of major signaling pathways stimulated by oncogene products on breast tumorigenesis and discussed the potential therapeutic strategies for targeted delivery of siRNAs with nanoparticles in suppressing the stimulated signaling pathways.
    Matched MeSH terms: Oncogene Proteins
  14. Analysis of variants of AKT1 in schizophrenia multiplex families
    Chow TJ, Tee SF, Loh SY, Yong HS, Abu Bakar AK, Tang PY
    Asian J Psychiatr, 2020 Mar;49:101957.
    PMID: 32078952 DOI: 10.1016/j.ajp.2020.101957
    Matched MeSH terms: Proto-Oncogene Proteins c-akt
  15. Fulltext Papillary Thyroid Cancer: Genetic Alterations and Molecular Biomarker Investigations
    Abdullah MI, Junit SM, Ng KL, Jayapalan JJ, Karikalan B, Hashim OH
    Int J Med Sci, 2019;16(3):450-460.
    PMID: 30911279 DOI: 10.7150/ijms.29935
    Papillary thyroid cancer (PTC) is the most prevalent form of malignancy among all cancers of the thyroid. It is also one of the few cancers with a rapidly increasing incidence. PTC is usually contained within the thyroid gland and generally biologically indolent. Prognosis of the cancer is excellent, with less than 2% mortality at 5 years. However, more than 25% of patients with PTC developed a recurrence during a long term follow-up. The present article provides an updated condensed overview of PTC, which focuses mainly on the molecular alterations involved and recent biomarker investigations.
    Matched MeSH terms: Proto-Oncogene Proteins B-raf/genetics; Proto-Oncogene Proteins c-ret/genetics
  16. Fulltext Molecular modeling, dynamics simulations, and binding efficiency of berberine derivatives: A new group of RAF inhibitors for cancer treatment
    Jabbarzadeh Kaboli P, Ismail P, Ling KH
    PLoS One, 2018;13(3):e0193941.
    PMID: 29565994 DOI: 10.1371/journal.pone.0193941
    RAF kinases are a family of enzymes in the MAP kinase pathway that contribute to the development of different types of cancer. BRAF is the most important member of RAF kinases. BRAF mutations have been detected in 7% of all cancers and 66% of melanomas; as such, the FDA has approved a few BRAF inhibitor drugs to date. However, BRAF can activate CRAF leading to resistance to BRAF inhibitors. Berberine (BBR) is an alkaloid that is widely distributed in different plant species. Several studies have been carried out on the anti-cancer effects of BBR but direct targets of BBR are unknown. In this study, interactions of BBR derivatives against BRAF and CRAF kinases were modeled and predicted using an in silico-based approach. To analyze and identify the residues important in BRAF docking, we modeled interactions of ATP, the universal substrate of BRAF, and found that Lys483 and Asp594 are the most important residues involved in both ATP and BBR binding [(The average score = -11.5 kcal/mol (ATP); Range of scores = -7.78 to -9.55 kcal/mol (BBR)]. In addition to these polar residues, Trp530 and Phe583 are also applicable to the molecular docking of BRAF. We also observed that Asp593 was excluded from the enzyme cavity, while Phe594 was included inside the cavity, making the enzyme inactive. Finally, three alternatives for BBR were identified with dual RAF inhibition effects [The best scores against BRAF = -11.62 kcal/mol (BBR-7), -10.64 kcal/mol (BBR-9), and -11.01 kcal/mol (BBR-10); the best scores against CRAF = -9.68 kcal/mol (BBR-7), -9.60 kcal/mol (BBR-9), and -9.20 kcal/mol (BBR-10)]. Direct effects of BBR derivatives against BRAF and CRAF kinases had not yet been reported previously, and, thus, for the first time, we report three cycloprotoberberines as lead compounds against RAF kinases.
    Matched MeSH terms: Proto-Oncogene Proteins c-raf/antagonists & inhibitors; Proto-Oncogene Proteins B-raf/antagonists & inhibitors
  17. Fulltext Holistic and featural processing's link to face recognition varies by individual and task
    Leong BQZ, Estudillo AJ, Hussain Ismail AM
    Sci Rep, 2023 Oct 06;13(1):16869.
    PMID: 37803085 DOI: 10.1038/s41598-023-44164-w
    While it is generally accepted that holistic processing facilitates face recognition, recent studies suggest that poor recognition might also arise from imprecise perception of local features in the face. This study aimed to examine to what extent holistic and featural processing relates to individual differences in face recognition ability (FRA), during face learning (Experiment 1) and face recognition (Experiment 2). Participants performed two tasks: (1) The "Cambridge Face Memory Test-Chinese" which measured participants' FRAs, and (2) an "old/new recognition memory test" encompassing whole faces (preserving holistic and featural processing) and faces revealed through a dynamic aperture (impairing holistic processing but preserving featural processing). Our results showed that participants recognised faces more accurately in conditions when holistic information was preserved, than when it is impaired. We also show that the better use of holistic processing during face learning and face recognition was associated with better FRAs. However, enhanced featural processing during recognition, but not during learning, was related to better FRAs. Together, our findings demonstrate that good face recognition depends on distinct roles played by holistic and featural processing at different stages of face recognition.
    Matched MeSH terms: Proto-Oncogene Proteins c-fos
  18. No association between AKT1 gene variants and schizophrenia: a Malaysian case-control study and meta-analysis
    Loh HC, Chow TJ, Tang PY, Yong HS
    Psychiatry Res, 2013 Oct 30;209(3):732-3.
    PMID: 23747160 DOI: 10.1016/j.psychres.2013.05.017
    We aim to replicate AKT1 gene variants studies using Malaysian samples. Seven AKT1 single nucleotide polymorphisms (SNPs) were studied in 417 patients and 429 controls. Haplotype showed significant association (p=0.036) with schizophrenia, especially in Malays and Indians. Meta-analysis of rs2494732 showed significant association worldwide (p=0.018) and in Asians (p=0.023).
    Matched MeSH terms: Proto-Oncogene Proteins c-akt/genetics*
  19. Xanthorrhizol induced DNA fragmentation in HepG2 cells involving Bcl-2 family proteins
    Tee TT, Cheah YH, Meenakshii N, Mohd Sharom MY, Azimahtol Hawariah LP
    Biochem Biophys Res Commun, 2012 Apr 20;420(4):834-8.
    PMID: 22465013 DOI: 10.1016/j.bbrc.2012.03.083
    Xanthorrhizol is a plant-derived pharmacologically active sesquiterpenoid compound isolated from Curcuma xanthorrhiza. Previously, we have reported that xanthorrhizol inhibited the proliferation of HepG2 human hepatoma cells by inducing apoptotic cell death via caspase activation. Here, we attempt to further elucidate the mode of action of xanthorrhizol. Apoptosis in xanthorrhizol-treated HepG2 cells as observed by scanning electron microscopy was accompanied by truncation of BID; reduction of both anti-apoptotic Bcl-2 and Bcl-X(L) expression; cleavage of PARP and DFF45/ICAD proteins and DNA fragmentation. Taken together, these results suggest xanthorrhizol as a potent antiproliferative agent on HepG2 cells by inducing apoptosis via Bcl-2 family members. Hence we proposed that xanthorrhizol could be used as an anti-liver cancer drug for future studies.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/metabolism*
  20. A Dimeric sesquiterpenoid from a Malaysian Meiogyne as a new inhibitor of Bcl-xL/BakBH3 domain peptide interaction
    Litaudon M, Bousserouel H, Awang K, Nosjean O, Martin MT, Dau ME, et al.
    J Nat Prod, 2009 Mar 27;72(3):480-3.
    PMID: 19161318 DOI: 10.1021/np8006292
    In an effort to find potent inhibitors of the antiapoptotic protein Bcl-xL, a systematic in vitro evaluation was undertaken on 1470 Malaysian plant extracts. The ethyl acetate extract obtained from the bark of Meiogyne cylindrocarpa was selected for its interaction with the Bcl-xL/Bak association. Bioassay-guided purification of this species led to the isolation of two new dimeric sesquiterpenoids (1 and 2) possessing an unprecedented substituted cis-decalin carbon skeleton. Meiogynin A (1) showed the strongest activity with a K(i) of 10.8 +/- 3.1 microM.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors*
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