Displaying publications 201 - 220 of 269 in total

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  1. Mohd Idrus FN, Ahmad NS, Hoe CH, Azlan M, Norfuad FA, Yusof Z, et al.
    BMC Immunol, 2021 03 24;22(1):21.
    PMID: 33761885 DOI: 10.1186/s12865-021-00410-2
    BACKGROUND: Differential polarization of macrophage into M1 and M2 mediates atherosclerotic plaque clearance through efferocytosis. Higher expression of Mer proto-oncogene tyrosine kinase (MerTK) on M2 macrophage helps in maintaining macrophage efferocytic efficiency. In healthy individuals, macrophage polarization into M1 and M2 occurs in tissues in concomitance with the acquisition of functional phenotypes depending on specific microenvironment stimuli. However, whether the macrophage differential polarization and MerTK expression vary in coronary artery disease (CAD) patients remain unknown.

    OBJECTIVE: This study aimed to elucidate the polarization of M1 and M2 macrophage from CAD patients as well as to investigate the expression of MerTK in these macrophage phenotypes.

    METHODS: A total of 14 (n) CAD patients were recruited and subsequently grouped into "no apparent CAD", "non-obstructive CAD" and "obstructive CAD" according to the degree of stenosis. Thirty ml of venous blood was withdrawn to obtain monocyte from the patients. The M1 macrophage was generated by treating the monocyte with GMCSF, LPS and IFN-γ while MCSF, IL-4 and IL-13 were employed to differentiate monocyte into M2 macrophage. After 7 days of polarization, analysis of cell surface differentiation markers (CD86+/CD80+ for M1 and CD206+/CD200R+ for M2) and measurement of MerTK expression were performed using flow cytometry.

    RESULTS: Both M1 and M2 macrophage expressed similar level of CD86, CD80 and CD206 in all groups of CAD patients. MerTK expression in no apparent CAD patients was significantly higher in M2 macrophage compared to M1 macrophage [12.58 ± 4.40 vs. 6.58 ± 1.37, p = 0.040].

    CONCLUSION: Differential polarization of macrophage into M1 and M2 was highly dynamic and can be varied due to the microenvironment stimuli in atherosclerotic plaque. Besides, higher expression of MerTK in patients with the least coronary obstructive suggest its vital involvement in efferocytosis.

    Matched MeSH terms: Up-Regulation
  2. Donald JA, Hamid NKA, McLeod JL
    Gen Comp Endocrinol, 2017 04 01;244:201-208.
    PMID: 27102941 DOI: 10.1016/j.ygcen.2016.04.015
    Water deprivation of the Spinifex hopping mouse, Notomys alexis, induced a biphasic pattern of food intake with an initial hypophagia that was followed by an increased, and then sustained food intake. The mice lost approximately 20% of their body mass and there was a loss of white adipose tissue. Stomach ghrelin mRNA was significantly higher at day 2 of water deprivation but then returned to the same levels as water-replete (day 0) mice for the duration of the experiment. Plasma ghrelin was unaffected by water deprivation except at day 10 where it was significantly increased. Plasma leptin levels decreased at day 2 and day 5 of water deprivation, and then increased significantly by the end of the water deprivation period. Water deprivation caused a significant decrease in skeletal muscle leptin mRNA expression at days 2 and 5, but then it returned to day 0 levels by day 29. In the hypothalamus, water deprivation caused a significant up-regulation in both ghrelin and neuropeptide Y mRNA expression, respectively. In contrast, hypothalamic GHSR1a mRNA expression was significantly down-regulated. A significant increase in LepRb mRNA expression was observed at days 17 and 29 of water deprivation. This study demonstrated that the sustained food intake in N. alexis during water deprivation was uncoupled from peripheral appetite-regulating signals, and that the hypothalamus appears to play an important role in regulating food intake; this may contribute to the maintenance of fluid balance in the absence of free water.
    Matched MeSH terms: Up-Regulation
  3. Mai CW, Chung FF, Leong CO
    Curr Drug Targets, 2017;18(11):1259-1268.
    PMID: 27993111 DOI: 10.2174/1389450117666161216125344
    BACKGROUND: Recent reports indicate that the tumor microenvironment plays a pivotal role in cancer development and progression, leading to a paradigm shift in the way cancer is studied and targeted. In contrast to traditional approaches, where only tumor cells are targeted for the treatment, an emerging approach is to develop therapeutics which target the tumor microenvironment while complementing or enhancing current treatments. Legumain (LGMN) is a newly identified target which is highly expressed in the tumor microenvironment and in tumor cells, and holds potential both as a biomarker and as a therapeutic target.

    CONCLUSION: This review will be the first to summarize the expression of LGMN in common cancers, as well as its roles in tumorigenesis and metastasis. This review also discusses the current developments and future prospects of targeting LGMN through the development of DNA vaccines, azopeptides, small molecule inhibitors and LGMN activated prodrugs, highlighting the potential of LGMN as a target for cancer therapeutics.

    Matched MeSH terms: Up-Regulation
  4. See JX, Chandramathi S, Abdulla MA, Vadivelu J, Shankar EM
    PLoS Negl Trop Dis, 2017 Aug;11(8):e0005702.
    PMID: 28820897 DOI: 10.1371/journal.pntd.0005702
    BACKGROUND: Melioidosis is a neglected tropical disease endemic across South East Asia and Northern Australia. The etiological agent, Burkholderia pseudomallei (B.pseudomallei), is a Gram-negative, rod-shaped, motile bacterium residing in the soil and muddy water across endemic regions of the tropical world. The bacterium is known to cause persistent infections by remaining latent within host cells for prolonged duration. Reactivation of the recrudescent disease often occurs in elders whose immunity wanes. Moreover, recurrence rates in melioidosis patients can be up to ~13% despite appropriate antibiotic therapy, suggestive of bacterial persistence and inefficacy of antibiotic regimens. The mechanisms behind bacterial persistence in the host remain unclear, and hence understanding host immunity during persistent B. pseudomallei infections may help designing potential immunotherapy.

    METHODOLOGY/PRINCIPAL FINDINGS: A persistent infection was generated using a small-colony variant (SCV) and a wild-type (WT) B. pseudomallei in BALB/c mice via intranasal administration. Infected mice that survived for >60 days were sacrificed. Lungs, livers, spleens, and peripheral blood mononuclear cells were harvested for experimental investigations. Histopathological changes of organs were observed in the infected mice, suggestive of successful establishment of persistent infections. Moreover, natural killer (NK) cell frequency was increased in SCV- and WT-infected mice. We observed programmed death-1 (PD-1) upregulation on B cells of SCV- and WT-infected mice. Interestingly, PD-1 upregulation was only observed on NK cells and monocytes of SCV-infected mice. In contrast, cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) downregulation was seen on NK cells of WT-infected mice, and on monocytes of SCV- and WT-infected mice.

    CONCLUSIONS/SIGNIFICANCE: The SCV and the WT of B. pseudomallei distinctly upregulated PD-1 expression on B cells, NK cells, and monocytes to dampen host immunity, which likely facilitates bacterial persistence. PD-1/PD-L1 pathway appears to play an important role in the persistence of B. pseudomallei in the host.

    Matched MeSH terms: Up-Regulation
  5. Bakri MM, Yahya F, Munawar KMM, Kitagawa J, Hossain MZ
    Arch Oral Biol, 2018 May;89:94-98.
    PMID: 29499561 DOI: 10.1016/j.archoralbio.2018.02.011
    OBJECTIVE: Transient receptor potential vanilloid 4 (TRPV4) has been considered as a mechano-, thermo- and osmo-receptor. Under inflammatory conditions in dental pulp, teeth can become sensitive upon exposure to a variety of innocuous stimuli. The objective of the present study was to investigate the expression of the TRPV4 channel on nerve fibers in human dental pulp of non-symptomatic and symptomatic teeth associated with inflammatory conditions.

    DESIGN: Dental pulp from extracted human permanent teeth was processed for fluorescence immunohistochemistry. Ten asymptomatic (normal) and 10 symptomatic (symptoms associated with pulpitis) teeth were used in this study. Nerve fibers were identified by immunostaining for a marker, protein gene product 9.5, and the cells were counterstained with 4',6-diamidino-2-phenylindole. An anti-TRPV4 antibody was used to trace TRPV4 expression.

    RESULTS: TRPV4 expression was co-localized with the nerve fiber marker. Immunoreactivity for TRPV4 was more intense (p 

    Matched MeSH terms: Up-Regulation
  6. Lan YW, Theng SM, Huang TT, Choo KB, Chen CM, Kuo HP, et al.
    Stem Cells Transl Med, 2017 03;6(3):1006-1017.
    PMID: 28297588 DOI: 10.5966/sctm.2016-0054
    Mesenchymal stem cells (MSCs) are widely considered for treatment of pulmonary fibrosis based on the anti-inflammatory, antifibrotic, antiapoptotic, and regenerative properties of the cells. Recently, elevated levels of oncostatin M (OSM) have been reported in the bronchoalveolar lavage fluid of a pulmonary fibrosis animal model and in patients. In this work, we aimed to prolong engrafted MSC survival and to enhance the effectiveness of pulmonary fibrosis transplantation therapy by using OSM-preconditioned MSCs. OSM-preconditioned MSCs were shown to overexpress type 2 OSM receptor (gp130/OSMRβ) and exhibited high susceptibility to OSM, resulting in upregulation of the paracrine factor, hepatocyte growth factor (HGF). Moreover, OSM-preconditioned MSCs enhanced cell proliferation and migration, attenuated transforming growth factor-β1- or OSM-induced extracellular matrix production in MRC-5 fibroblasts through paracrine effects. In bleomycin-induced lung fibrotic mice, transplantation of OSM-preconditioned MSCs significantly improved pulmonary respiratory functions and downregulated expression of inflammatory factors and fibrotic factors in the lung tissues. Histopathologic examination indicated remarkable amelioration of the lung fibrosis. LacZ-tagged MSCs were detected in the lung tissues of the OSM-preconditioned MSC-treated mice 18 days after post-transplantation. Taken together, our data further demonstrated that HGF upregulation played an important role in mediating the therapeutic effects of transplanted OSM-preconditioned MSCs in alleviating lung fibrosis in the mice. Stem Cells Translational Medicine 2017;6:1006-1017.
    Matched MeSH terms: Up-Regulation
  7. Yong WK, Abd Malek SN
    PMID: 25949267 DOI: 10.1155/2015/921306
    We investigate induction of apoptosis by xanthohumol on Ca Ski cervical cancer cell line. Xanthohumol is a prenylated chalcone naturally found in hop plants, previously reported to be an effective anticancer agent in various cancer cell lines. The present study showed that xanthohumol was effective to inhibit proliferation of Ca Ski cells based on IC50 values using sulforhodamine B (SRB) assay. Furthermore, cellular and nuclear morphological changes were observed in the cells using phase contrast microscopy and Hoechst/PI fluorescent staining. In addition, 48-hour long treatment with xanthohumol triggered externalization of phosphatidylserine, changes in mitochondrial membrane potential, and DNA fragmentation in the cells. Additionally, xanthohumol mediated S phase arrest in cell cycle analysis and increased activities of caspase-3, caspase-8, and caspase-9. On the other hand, Western blot analysis showed that the expression levels of cleaved PARP, p53, and AIF increased, while Bcl-2 and XIAP decreased in a dose-dependent manner. Taken together, these findings indicate that xanthohumol-induced cell death might involve intrinsic and extrinsic apoptotic pathways, as well as downregulation of XIAP, upregulation of p53 proteins, and S phase cell cycle arrest in Ca Ski cervical cancer cells. This work suggests that xanthohumol is a potent chemotherapeutic candidate for cervical cancer.
    Matched MeSH terms: Up-Regulation
  8. Huat TJ, Khan AA, Abdullah JM, Idris FM, Jaafar H
    Int J Mol Sci, 2015;16(5):9693-718.
    PMID: 25938966 DOI: 10.3390/ijms16059693
    Insulin-like growth factor 1 (IGF-1) enhances cellular proliferation and reduces apoptosis during the early differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into neural progenitor-like cells (NPCs) in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). BMSCs were differentiated in three groups of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, and (C) without growth factor. To unravel the molecular mechanisms of the NPCs derivation, microarray analysis using GeneChip miRNA arrays was performed. The profiles were compared among the groups. Annotated microRNA fingerprints (GSE60060) delineated 46 microRNAs temporally up-regulated or down-regulated compared to group C. The expressions of selected microRNAs were validated by real-time PCR. Among the 46 microRNAs, 30 were consistently expressed for minimum of two consecutive time intervals. In Group B, only miR-496 was up-regulated and 12 microRNAs, including the let-7 family, miR-1224, miR-125a-3p, miR-214, miR-22, miR-320, miR-708, and miR-93, were down-regulated. Bioinformatics analysis reveals that some of these microRNAs (miR-22, miR-214, miR-125a-3p, miR-320 and let-7 family) are associated with reduction of apoptosis. Here, we summarize the roles of key microRNAs associated with IGF-1 in the differentiation of BMSCs into NPCs. These findings may provide clues to further our understanding of the mechanisms and roles of microRNAs as key regulators of BMSC-derived NPC maintenance.
    Matched MeSH terms: Up-Regulation/drug effects; Up-Regulation/genetics
  9. Surien O, Ghazali AR, Masre SF
    Sci Rep, 2021 Jul 21;11(1):14862.
    PMID: 34290382 DOI: 10.1038/s41598-021-94508-7
    Cell proliferation and cell death abnormalities are strongly linked to the development of cancer, including lung cancer. The purpose of this study was to investigate the effect of pterostilbene on cell proliferation and cell death via cell cycle arrest during the transition from G1 to S phase and the p53 pathway. A total of 24 female Balb/C mice were randomly categorized into four groups (n = 6): N-nitroso-tris-chloroethyl urea (NTCU) induced SCC of the lungs, vehicle control, low dose of 10 mg/kg PS + NTCU (PS10), and high dose of 50 mg/kg PS + NTCU (PS50). At week 26, all lungs were harvested for immunohistochemistry and Western blotting analysis. Ki-67 expression is significantly lower, while caspase-3 expression is significantly higher in PS10 and PS50 as compared to the NTCU (p 
    Matched MeSH terms: Up-Regulation/drug effects; Up-Regulation/genetics
  10. Hanafi NI, Mohamed AS, Md Noor J, Abdu N, Hasani H, Siran R, et al.
    Genet. Mol. Res., 2016 Jun 17;15(2).
    PMID: 27323195 DOI: 10.4238/gmr.15028150
    Ursodeoxycholic acid (UDCA) is used to treat liver diseases and demonstrates cardioprotective effects. Accumulation of the plasma membrane sphingolipid sphingomyelin in the heart can lead to atherosclerosis and coronary artery disease. Sphingomyelinases (SMases) break down sphingomyelin, producing ceramide, and inhibition of SMases activity can promote cell survival. We hypothesized that UDCA regulates activation of ERK and Akt survival signaling pathways and SMases in protecting cardiac cells against hypoxia. Neonatal cardiomyocytes were isolated from 0- to 2-day-old Sprague Dawley rats, and given 100 μM CoCl2, 150 μM H2O2, or placed in a hypoxia chamber for 24 h. The ameliorative effects of 100-μM UDCA treatment for 12 h were then assessed using MTS, QuantiGene Plex (for Smpd1 and Smpd2), and SMase assays, beating rate assessment, and western blotting (for ERK and Akt). Data were analyzed by the paired Student t-tests and one-way analyses of variance. Cell viability decreased significantly after H2O2 (85%), CoCl2 (50%), and hypoxia chamber (52%) treatments compared to the untreated control (100%). UDCA significantly counteracted the effects of chamber- and CoCl2- induced hypoxia on viability and beating rate. However, no significant differences were observed in acid SMase gene and protein expression between the untreated, CoCl2, and UDCA-CoCl2 groups. In contrast, neutral SMase gene and protein expression did significantly differ between the latter two groups. ERK and Akt phosphorylation was higher in hypoxic cardiomyocytes treated with UDCA than those given CoCl2 alone. In conclusion, UDCA regulates the activation of survival signaling proteins and SMases in neonatal rat cardiomyocytes during hypoxia.
    Matched MeSH terms: Up-Regulation
  11. Karimian H, Mohan S, Moghadamtousi SZ, Fadaeinasab M, Razavi M, Arya A, et al.
    Molecules, 2014 Jul 03;19(7):9478-501.
    PMID: 24995928 DOI: 10.3390/molecules19079478
    Tanacetum polycephalum (L.) Schultz-Bip (Mokhaleseh) has been traditionally used in the treatment of headaches, migraines, hyperlipidemia and diabetes. The present study aimed to evaluate its anticancer properties and possible mechanism of action using MCF7 as an in vitro model. T. polycephalum leaves were extracted using hexane, chloroform and methanol solvents and the cytotoxicity was evaluated using the MTT assay. Detection of the early apoptotic cells was investigated using acridine orange/propidium iodide staining. An Annexin-V-FITC assay was carried out to observe the phosphatidylserine externalization as a marker for apoptotic cells. High content screening was applied to analyze the cell membrane permeability, nuclear condensation, mitochondrial membrane potential (MMP) and cytochrome c release. Apoptosis was confirmed by using caspase-8, caspase-9 and DNA laddering assays. In addition, Bax/Bcl-2 expressions and cell cycle arrest also have been investigated. MTT assay revealed significant cytotoxicity of T. Polycephalum hexane extract (TPHE) on MCF7 cells with the IC50 value of 6.42±0.35 µg/mL. Significant increase in chromatin condensation was also observed via fluorescence analysis. Treatment of MCF7 cells with TPHE encouraged apoptosis through reduction of MMP by down-regulation of Bcl-2 and up-regulation of Bax, triggering the cytochrome c leakage from mitochondria to the cytosol. The treated MCF7 cells significantly arrested at G1 phase. The chromatographic analysis elicited that the major active compound in this extract is 8β-hydroxy-4β,15-dihydrozaluzanin C. Taken together, the results presented in this study demonstrated that the hexane extract of T. Polycephalum inhibits the proliferation of MCF7 cells, resulting in the cell cycle arrest and apoptosis, which was explained to be through the mitochondrial pathway.
    Matched MeSH terms: Up-Regulation
  12. Gupta ED, Sakthiswary R
    Asian Cardiovasc Thorac Ann, 2014 May;22(4):397-401.
    PMID: 24771726 DOI: 10.1177/0218492313484917
    The objectives of this study were to determine the incidence of a myocardial infarction "false alarm" and evaluate the efficacy of the initial electrocardiogram and cardiac enzymes in diagnosing myocardial infarction in Malaysia.
    Matched MeSH terms: Up-Regulation
  13. Sabanayagam C, Shankar A, Lee J, Wong TY, Tai ES
    J Hum Hypertens, 2013 Apr;27(4):231-6.
    PMID: 22418747 DOI: 10.1038/jhh.2011.117
    Few previous studies in Western populations have reported an association between C-reactive protein (CRP) and prehypertension. However, no previous study has examined this association in Asians. We examined individuals who were free of hypertension from two independent population-based studies in Singapore: the Singapore Prospective Study Programme (SP2, n=2843 Chinese, Malay and Indians aged 24 years) and the Singapore Malay Eye Study (SiMES, n=957 Malays, aged 40-80 years). Prehypertension was defined as systolic blood pressure (BP) 120-139 mm Hg or diastolic BP 80-89 mm Hg. CRP was analyzed as categories (<1, 1-3, >3 mg l(-1)). The prevalence of prehypertension increased with increasing categories of CRP in both cohorts (P for trend <0.05 in both cohorts). After adjusting for potential confounders including body mass index (BMI), smoking and diabetes, persons with higher levels of CRP were more likely to have prehypertension in both SP2 (compared with CRP <1 mg l(-1), odds ratio (OR) 1.23, 95% confidence interval (CI) 1.03-1.48 for CRP 1-3 and OR 1.67, 95% CI 1.32-2.10 for >3 mg l(-1)) and SiMES (OR 1.45, 95% CI 1.04-2.01 and OR 1.56, 95% CI 1.07-2.27) respectively. In conclusion, data from two population-based Asian cohorts suggest that elevated serum CRP levels are associated with prehypertension.
    Matched MeSH terms: Up-Regulation
  14. Lokman FE, Seman NA, Ismail AA, Yaacob NA, Mustafa N, Khir AS, et al.
    J Nephrol, 2011;24(6):778-89.
    PMID: 21360476 DOI: 10.5301/JN.2011.6382
    BACKGROUND: Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD) among type 2 diabetes mellitus patients (DM) in Malaysia. This study used microarray analysis to determine the gene expression profiling in ethnic Malay patients with type 2 DM.
    METHODS: A total of 312 patients were recruited; 25 were on dialysis due to ESRD, 128 were classified as normoalbuminuric, 93 as microalbuminuric and 66 as macroalbuminuric, based on urine albumin to creatinine ratio of <3.5, between 3.5 and 35 and =35 mg/mmol, respectively.
    RESULTS: Microalbuminuria was associated with up- and down-regulation of 2,694 and 2,538 genes, respectively, while macroalbuminuria was associated with up-regulation of 2,520 genes and down-regulation of 2,920 genes. There was significant up-regulation of 1,135 genes and down-regulation of 908 genes in the ESRD samples. Thirty-seven significantly up-regulated genes and 40 down-regulated genes were commonly expressed in all 3 groups of patients with worsening of renal functions. Up-regulated genes included major histocompatibility complex (HLA-C), complement component 3a receptor 1 (C3AR1), solute carrier family 16, member 3 (SLC16A3) and solute carrier family 9 (sodium/hydrogen exchanger) (SLC9A8). Consistently down-regulated genes included were bone morphogenetic phosphatase kinase (BMP2K), solute carrier family 12, member 1 (SLC12A1), solute carrier family 7 (SLC7A2), paternally expressed 10 (PEG10) and protein phosphatase 1 regulatory (inhibitor unit) (PPP1R1C).
    CONCLUSION: This study has identified several genes of interest, such as HLA-C, SLC16A3, SLC9A8, SLC12A1 and SLC7A2, that require verification of their roles as susceptibility genes for diabetic nephropathy in ethnic Malays with type 2 DM.
    Matched MeSH terms: Up-Regulation
  15. Erejuwa OO, Omotayo EO, Gurtu S, Sulaiman SA, Ab Wahab MS, Sirajudeen KN, et al.
    Int J Vitam Nutr Res, 2010 Jan;80(1):74-82.
    PMID: 20533247 DOI: 10.1024/0300-9831/a000008
    Oxidative stress plays a crucial role in the development of diabetic complications. The aims of this study were to investigate whether honey could reduce hyperglycemia and ameliorate oxidative stress in kidneys of streptozotocin-induced diabetic rats.
    Matched MeSH terms: Up-Regulation
  16. Ramdas P, Rajihuzzaman M, Veerasenan SD, Selvaduray KR, Nesaretnam K, Radhakrishnan AK
    Cancer Genomics Proteomics, 2011 Jan-Feb;8(1):19-31.
    PMID: 21289334
    Tocotrienols belong to the vitamin E family and have multiple anticancer effects, such as antiproliferative, antioxidant, pro-apoptosis and antimetastatic. This study aimed to identify the genes that are regulated in human breast cancer cells following exposure to various isomers of vitamin E as these may be potential targets for the treatment of breast cancer.
    Matched MeSH terms: Up-Regulation
  17. Chang LY, Ali AR, Hassan SS, AbuBakar S
    Virol J, 2007;4:54.
    PMID: 17553172
    Nipah virus (NiV), a recently discovered zoonotic virus infects and replicates in several human cell types. Its replication in human neuronal cells, however, is less efficient in comparison to other fully susceptible cells. In the present study, the SK-N-MC human neuronal cell protein response to NiV infection is examined using proteomic approaches.
    Matched MeSH terms: Up-Regulation
  18. Tan ML, Muhammad TS, Najimudin N, Sulaiman SF
    J Ethnopharmacol, 2005 Jan 15;96(3):375-83.
    PMID: 15619555
    Epipremnum pinnatum (L.) Engl. hexane extract produced a significant growth inhibition against T-47D breast carcinoma cells and analysis of cell death mechanisms indicated that the extract elicited a non-apoptotic programmed cell death. T-47D cells exposed to the extract at EC(50) concentration (72 h) for 24 h failed to demonstrate typical DNA fragmentation associated with apoptosis, as carried out using a modified TUNEL assay. In addition, acute exposure to the extract produced an insignificant regulation of caspase-3 and p53 mRNA expression but increased in the c-myc mRNA expression. Ultrastructural analysis using transmission electron microscope demonstrated distinct vacuolated cells, which strongly indicated a Type II non-apoptotic cell death although the changes in chromatin were also detected. The presence of non-apoptotic programmed cell death was then reconfirmed with annexin-V and propidium iodide staining. These findings suggested that up-regulation of c-myc mRNA expression may have contributed to the growth arrest and Type II non-apoptotic programmed cell death in the Epipremnum pinnatum (L.) Engl. hexane extract-treated T-47D cells.
    Matched MeSH terms: Up-Regulation
  19. Teo AE, Garg S, Shaikh LH, Zhou J, Karet Frankl FE, Gurnell M, et al.
    N Engl J Med, 2015 Oct 08;373(15):1429-36.
    PMID: 26397949 DOI: 10.1056/NEJMoa1504869
    Recent discoveries of somatic mutations permit the recognition of subtypes of aldosterone-producing adenomas with distinct clinical presentations and pathological features. Here we describe three women with hyperaldosteronism, two who presented in pregnancy and one who presented after menopause. Their aldosterone-producing adenomas harbored activating mutations of CTNNB1, encoding β-catenin in the Wnt cell-differentiation pathway, and expressed LHCGR and GNRHR, encoding gonadal receptors, at levels that were more than 100 times as high as the levels in other aldosterone-producing adenomas. The mutations stimulate Wnt activation and cause adrenocortical cells to de-differentiate toward their common adrenal-gonadal precursor cell type. (Funded by grants from the National Institute for Health Research Cambridge Biomedical Research Centre and others.).
    Matched MeSH terms: Up-Regulation
  20. Tan HK, Muhammad TST, Tan ML
    Toxicol Appl Pharmacol, 2016 06 01;300:55-69.
    PMID: 27049118 DOI: 10.1016/j.taap.2016.03.017
    14-Deoxy-11,12-didehydroandrographolide (14-DDA), a major diterpenoid isolated from Andrographis paniculata (Burm.f.) Nees, is known to be cytotoxic and elicits a non-apoptotic cell death in T-47D breast carcinoma cells. In this study, the mechanistic toxicology properties of 14-DDA in T-47D cells were further investigated. 14-DDA is found to induce the formation of endoplasmic reticulum (ER) vacuoles and autophagosomes, with concurrent upregulation of LC3-II in the breast carcinoma cells. It stimulated an increase in cytosolic calcium concentration and caused a collapse in mitochondrial membrane potential in these cells. In addition, both DDIT3 and GADD45A, molecules implicated in ER stress pathway, were significantly upregulated. DDIT3 knockdown suppressed the formation of both ER vacuoles and autophagosomes, indicating that 14-DDA-induced ER stress and autophagy is dependent on this transcription factor. Collectively, it is possible that GADD45A/p38 MAPK/DDIT3 pathway is involved in the 14-DDA-induced ER-stress-mediated autophagy in T-47D cells.
    Matched MeSH terms: Up-Regulation
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