Displaying publications 81 - 100 of 1563 in total

Abstract:
Sort:
  1. Fulltext Hydrogen Sulphide Treatment Prevents Renal Ischemia-Reperfusion Injury by Inhibiting the Expression of ICAM-1 and NF-kB Concentration in Normotensive and Hypertensive Rats
    Hashmi SF, Rathore HA, Sattar MA, Johns EJ, Gan CY, Chia TY, et al.
    Biomolecules, 2021 Oct 19;11(10).
    PMID: 34680182 DOI: 10.3390/biom11101549
    Our main objective was to investigate the effect of chronic administration of hydrogen sulphide donor (sodium hydrosulphide) on the expression of intercellular adhesion molecule-1 (ICAM-1) and concentration of nuclear factor-kappa B (NF-kB) in a renal ischemia-reperfusion injury (IRI) model of WKY and L-nitro-arginine-methyl-ester (L-NAME)-induced hypertensive rats. Sodium hydrosulphide (NaHS) was administered intraperitoneally (i.p.) for 35 days while cystathionine gamma lyase (CSE) inhibitor dL-propargylglycine (PAG) was administered at a single dose of 50 mg/kg. Animals were anesthetised using sodium pentobarbitone (60 mg/kg) and then prepared to induce renal ischemia by clamping the left renal artery for 30 min followed by 3 h of reperfusion. Pre-treatment with NaHS improved the renal functional parameters in both WKY and L-NAME-induced hypertensive rats along with reduction of blood pressure in hypertensive groups. Oxidative stress markers like malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione (GSH) were also improved by NaHS treatment following renal IRI. Levels of ICAM-1 and NF-kB concentration were reduced by chronic treatment with NaHS and increased by PAG administration after renal IRI in plasma and kidney. Treatment with NaHS improved tubular morphology and glomerulus hypertrophy. Pre-treatment with NaHS reduced the degree of renal IRI by potentiating its antioxidant and anti-inflammatory mechanism, as evidenced by decreased NF-kB concentration and downregulation of ICAM-1 expression.
    Matched MeSH terms: Gene Expression Regulation/drug effects
  2. Real time monitoring of dopamine release evoked by mitragynine (Kratom): An insight through electrochemical sensor
    Effendy MA, Yunusa S, Zain ZM, Hassan Z
    Neurosci Lett, 2021 10 15;763:136183.
    PMID: 34418508 DOI: 10.1016/j.neulet.2021.136183
    BACKGROUND: Mitragynine, the major indole alkaloid from Mitragyna speciosa has been reported previously to possess abuse liability. However, there are insufficient data suggesting the mechanism through which this pharmacological agent causes addiction.

    AIMS: In this study, we investigated the effects of mitragynine on dopamine (DA) level and dopamine transporter (DAT) expression from the rat's frontal cortex.

    METHODS: DA level was recorded in the brain samples of animals treated with acute or repeated exposure for 4 consecutive days with either vehicle or mitragynine (1 and 30 mg/kg) using electrochemical sensor. Animals were then decapitated and the brain regions were removed, snap-frozen in liquid nitrogen and immediately stored at -80 °C. DA level was quantified using Enzyme linked immunosorbent assay (ELISA) kits and DAT gene expression was determined using quantitative real time polymerase chain reaction (RT-qPCR).

    RESULTS/OUTCOME: Mitragynine (1 and 30 mg/kg) did not increase DA release following acute treatment, however, after repeated exposure at day 4, mitragynine significantly and dose dependently increased DA release in the frontal cortex. In this study, we also observed a significant increase in DAT mRNA expression at day 4 in group treated with mitragynine (30 mg/kg).

    CONCLUSION/INTERPRETATION: Data from this study indicates that mitragynine significantly increased DA release when administered repeatedly, increased in DAT mRNA expression with the highest tested dose (30 mg/kg). Therefore, the rewarding effects observed after mitragynine administration could be due to its ability to increase DA content in certain areas of the brain especially the frontal cortex.

    Matched MeSH terms: Gene Expression Profiling
  3. Fulltext Comparative genome-wide analysis of WRKY, MADS-box and MYB transcription factor families in Arabidopsis and rice
    Abdullah-Zawawi MR, Ahmad-Nizammuddin NF, Govender N, Harun S, Mohd-Assaad N, Mohamed-Hussein ZA
    Sci Rep, 2021 10 04;11(1):19678.
    PMID: 34608238 DOI: 10.1038/s41598-021-99206-y
    Transcription factors (TFs) form the major class of regulatory genes and play key roles in multiple plant stress responses. In most eukaryotic plants, transcription factor (TF) families (WRKY, MADS-box and MYB) activate unique cellular-level abiotic and biotic stress-responsive strategies, which are considered as key determinants for defense and developmental processes. Arabidopsis and rice are two important representative model systems for dicot and monocot plants, respectively. A comprehensive comparative study on 101 OsWRKY, 34 OsMADS box and 122 OsMYB genes (rice genome) and, 71 AtWRKY, 66 AtMADS box and 144 AtMYB genes (Arabidopsis genome) showed various relationships among TFs across species. The phylogenetic analysis clustered WRKY, MADS-box and MYB TF family members into 10, 7 and 14 clades, respectively. All clades in WRKY and MYB TF families and almost half of the total number of clades in the MADS-box TF family are shared between both species. Chromosomal and gene structure analysis showed that the Arabidopsis-rice orthologous TF gene pairs were unevenly localized within their chromosomes whilst the distribution of exon-intron gene structure and motif conservation indicated plausible functional similarity in both species. The abiotic and biotic stress-responsive cis-regulatory element type and distribution patterns in the promoter regions of Arabidopsis and rice WRKY, MADS-box and MYB orthologous gene pairs provide better knowledge on their role as conserved regulators in both species. Co-expression network analysis showed the correlation between WRKY, MADs-box and MYB genes in each independent rice and Arabidopsis network indicating their role in stress responsiveness and developmental processes.
    Matched MeSH terms: Gene Expression Regulation; Gene Expression Regulation, Plant
  4. Comparative transcriptome profiling of horseshoe crab Tachypleus gigas hemocytes in response to lipopolysaccharides
    Sarmiento ME, Chin KL, Lau NS, Aziah I, Ismail N, Norazmi MN, et al.
    Fish Shellfish Immunol, 2021 Oct;117:148-156.
    PMID: 34358702 DOI: 10.1016/j.fsi.2021.08.001
    Horseshoe crabs (HSCs) are living fossil species of marine arthropods with a long evolutionary history spanning approximately 500 million years. Their survival is helped by their innate immune system that comprises cellular and humoral immune components to protect them against invading pathogens. To help understand the genetic mechanisms involved, the present study utilised the Illumina HiSeq platform to perform transcriptomic analysis of hemocytes from the HSC, Tachypleus gigas, that were challenged with lipopolysaccharides (LPS). The high-throughput sequencing resulted in 352,077,208 and 386,749,136 raw reads corresponding to 282,490,910 and 305,709,830 high-quality mappable reads for the control and LPS-treated hemocyte samples, respectively. Based on the log-fold change of > 0.3 or genes were significantly upregulated and 215 genes were significantly downregulated following LPS stimulation. The differentially expressed genes (DEGs) were further identified to be associated with multiple pathways such as those related to immune defence, stress response, cytoskeleton function and signal transduction. This study provides insights into the underlying molecular and regulatory mechanisms in hemocytes exposed to LPS, which has relevance for the study of the immune response of HSCs to infection.
    Matched MeSH terms: Gene Expression Profiling
  5. Intracellular and exosomal microRNAome profiling of human vascular smooth muscle cells during replicative senescence
    Nguyen DDN, Zain SM, Kamarulzaman MH, Low TY, Chilian WM, Pan Y, et al.
    Am J Physiol Heart Circ Physiol, 2021 10 01;321(4):H770-H783.
    PMID: 34506226 DOI: 10.1152/ajpheart.00058.2021
    Vascular aging is highly associated with cardiovascular morbidity and mortality. Although the senescence of vascular smooth muscle cells (VSMCs) has been well established as a major contributor to vascular aging, intracellular and exosomal microRNA (miRNA) signaling pathways in senescent VSMCs have not been fully elucidated. This study aimed to identify the differential expression of intracellular and exosomal miRNA in human VSMCs (hVSMCs) during replicative senescence. To achieve this aim, intracellular and exosomal miRNAs were isolated from hVSMCs and subsequently subjected to whole genome small RNA next-generation sequencing, bioinformatics analyses, and qPCR validation. Three significant findings were obtained. First, senescent hVSMC-derived exosomes tended to cluster together during replicative senescence and the molecular weight of the exosomal protein tumor susceptibility gene 101 (TSG-101) increased relative to the intracellular TSG-101, suggesting potential posttranslational modifications of exosomal TSG-101. Second, there was a significant decrease in both intracellular and exosomal hsa-miR-155-5p expression [n = 3, false discovery rate (FDR) < 0.05], potentially being a cell type-specific biomarker of hVSMCs during replicative senescence. Importantly, hsa-miR-155-5p was found to associate with cell-cycle arrest and elevated oxidative stress. Lastly, miRNAs from the intracellular pool, that is, hsa-miR-664a-3p, hsa-miR-664a-5p, hsa-miR-664b-3p, hsa-miR-4485-3p, hsa-miR-10527-5p, and hsa-miR-12136, and that from the exosomal pool, that is, hsa-miR-7704, were upregulated in hVSMCs during replicative senescence (n = 3, FDR < 0.05). Interestingly, these novel upregulated miRNAs were not functionally well annotated in hVSMCs to date. In conclusion, hVSMC-specific miRNA expression profiles during replicative senescence potentially provide valuable insights into the signaling pathways leading to vascular aging.NEW & NOTEWORTHY This is the first study on intracellular and exosomal miRNA profiling on human vascular smooth muscle cells during replicative senescence. Specific dysregulated sets of miRNAs were identified from human vascular smooth muscle cells. Hsa-miR-155-5p was significantly downregulated in both intracellular and exosomal hVSMCs, suggesting its crucial role in cellular senescence. Hsa-miR-155-5p might be the mediator in linking cellular senescence to vascular aging and atherosclerosis.
    Matched MeSH terms: Gene Expression Profiling*
  6. Fulltext Local ablation of gastric cancer by reconstituted apolipoprotein B lipoparticles carrying epigenetic drugs
    Yang CL, Chao YJ, Wang HC, Hou YC, Chen CG, Chang CC, et al.
    Nanomedicine, 2021 10;37:102450.
    PMID: 34332115 DOI: 10.1016/j.nano.2021.102450
    Epigenetic inhibitors have shown anticancer effects. Combination chemotherapy with epigenetic inhibitors has shown high effectiveness in gastric cancer clinical trials, but severe side effect and local progression are the causes of treatment failure. Therefore, we sought to develop an acidity-sensitive drug delivery system to release drugs locally to diminish unfavorable outcome of gastric cancer. In this study, we showed that, as compared with single agents, combination treatment with the demethylating agent 5'-aza-2'-deoxycytidine and HDAC inhibitors Trichostatin A or LBH589 decreased cell survival, blocked cell cycle by reducing number of S-phase cells and expression of cyclins, increased cell apoptosis by inducing expression of Bim and cleaved Caspase 3, and reexpressed tumor suppressor genes more effectively in MGCC3I cells. As a carrier, reconstituted apolipoprotein B lipoparticles (rABLs) could release drugs in acidic environments. Orally administrated embedded drugs not only showed inhibitory effects on gastric tumor growth in a syngeneic orthotopic mouse model, but also reduced the hepatic and renal toxicity. In conclusion, we have established rABL-based nanoparticles embedded epigenetic inhibitors for local treatment of gastric cancer, which have good therapeutic effects but do not cause severe side effects.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/genetics
  7. Fulltext Nanoparticle-Encapsulated Camptothecin: Epigenetic Modulation in DNA Repair Mechanisms in Colon Cancer Cells
    Farhana A, Koh AE, Tong JB, Alsrhani A, Kumar Subbiah S, Mok PL
    Molecules, 2021 Sep 06;26(17).
    PMID: 34500845 DOI: 10.3390/molecules26175414
    Molecular crosstalk between the cellular epigenome and genome converge as a synergistic driver of oncogenic transformations. Besides other pathways, epigenetic regulatory circuits exert their effect towards cancer progression through the induction of DNA repair deficiencies. We explored this mechanism using a camptothecin encapsulated in β-cyclodextrin-EDTA-Fe3O4 nanoparticles (CPT-CEF)-treated HT29 cells model. We previously demonstrated that CPT-CEF treatment of HT29 cells effectively induces apoptosis and cell cycle arrest, stalling cancer progression. A comparative transcriptome analysis of CPT-CEF-treated versus untreated HT29 cells indicated that genes controlling mismatch repair, base excision repair, and homologues recombination were downregulated in these cancer cells. Our study demonstrated that treatment with CPT-CEF alleviated this repression. We observed that CPT-CEF exerts its effect by possibly affecting the DNA repair mechanism through epigenetic modulation involving genes of HMGB1, APEX1, and POLE3. Hence, we propose that CPT-CEF could be a DNA repair modulator that harnesses the cell's epigenomic plasticity to amend DNA repair deficiencies in cancer cells.
    Matched MeSH terms: Gene Expression Regulation
  8. Differentiated sap (4-6) gene expression of Candida albicans isolates from HIV-positive patients with oral candidiasis and commensals in healthy individuals
    Meylani V, Sembiring L, Fudholi A, Wibawa T
    Microb Pathog, 2021 Sep;158:105075.
    PMID: 34224845 DOI: 10.1016/j.micpath.2021.105075
    Gene expression of SAP 4-6 based on the detection of mRNA was observed in Candida albicans isolates from HIV-positive patients with oral candidiasis and commensal from healthy individuals. The species of C. albicans strains were selectively isolated from both sources using CHROMagar Chromogenic Media. The obtained isolates were then induced to express SAP 4-6 using SAP 4-6 gene inducer media. Analysis of gene expression was performed on a molecular basis using the RT-PCR method. Molecular analysis of gene expression showed that the isolates CH3 from HIV-positive patients with oral candidiasis could express SAP 4-6 gene, while commensal isolates from healthy people could not. Based on the results of this study, it could be concluded that, in terms of molecular detection, only isolates from HIV-positive patients (CH3) could express their SAP 4-6 gene.
    Matched MeSH terms: Gene Expression
  9. Hot water extract of Pleurotus pulmonarius stalk waste enhances innate immune response and immune-related gene expression in red hybrid tilapia Oreochromis sp. following challenge with pathogen-associated molecular patterns
    Ching JJ, Shuib AS, Abdullah N, Majid NA, Taufek NM, Sutra J, et al.
    Fish Shellfish Immunol, 2021 Sep;116:61-73.
    PMID: 34157396 DOI: 10.1016/j.fsi.2021.06.005
    In aquaculture, commercial fish such as red hybrid tilapia are usually raised at high density to boost the production within a short period of time. This overcrowded environment, however, may cause stress to the cultured fish and increase susceptibility to infectious diseases. Antibiotics and chemotherapeutics are used by fish farmers to overcome these challenges, but this may increase the production cost. Studies have reported on the potential of mushroom polysaccharides that can act as immunostimulants to enhance the immune response and disease resistance in fish. In the current study, hot water extract (HWE) from mushroom stalk waste (MSW) was used to formulate fish feed and hence administered to red hybrid tilapia to observe the activation of immune system. Upon 30 days of feeding, the fish were challenged with pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides (LPS) and polyinosinic:polycytidylic acid (poly (I:C)) to mimic bacterial and viral infection, respectively. HWE supplementation promoted better feed utilisation in red hybrid tilapia although it did not increase the body weight gain and specific growth rate compared to the control diet. The innate immunological parameters such as phagocytic activity and respiratory burst activity were significantly higher in HWE-supplemented group than that of the control group following PAMPs challenges. HWE-supplemented diet also resulted in higher mRNA transcription of il1b and tnfa in midgut, spleen and head kidney at 1-day post PAMPs injection. Tlr3 exhibited the highest upregulation in the HWE fed fish injected with poly (I:C). At 3-days post PAMPs injection, both ighm and tcrb expression were upregulated significantly in the spleen and head kidney. Results showed that HWE supplementation enhances the immune responses of red hybrid tilapia and induced a higher serum bactericidal activity against S. agalactiae.
    Matched MeSH terms: Gene Expression Regulation/drug effects; Gene Expression Regulation/immunology
  10. Quercetin against MCF7 and CAL51 breast cancer cell lines: apoptosis, gene expression and cytotoxicity of nano-quercetin
    Mohammed HA, Sulaiman GM, Anwar SS, Tawfeeq AT, Khan RA, Mohammed SAA, et al.
    Nanomedicine (Lond), 2021 09;16(22):1937-1961.
    PMID: 34431317 DOI: 10.2217/nnm-2021-0070
    Aims: To evaluate the anti breast-cancer activity, biocompatibility and toxicity of poly(d,l)-lactic-co-glycolic acid (PLGA)-encapsulated quercetin nanoparticles (Q-PLGA-NPs). Materials & methods: Quercetin was nano-encapsulated by an emulsion-diffusion process, and the nanoparticles were fully characterized through Fourier transform infrared spectroscopy, x-ray diffractions, FESEM and zeta-sizer analysis. Activity against CAL51 and MCF7 cell lines were assessed by DNA fragmentation assays, fluorescence microscopy, and acridine-orange, and propidium-iodide double-stainings. Biocompatibility towards red blood cells and toxicity towards mice were also explored. Results: The Q-PLGA-NPs exhibited apoptotic activity against the cell lines. The murine in vivo studies showed no significant alterations in the liver and kidney's functional biomarkers, and no apparent abnormalities, or tissue damages were observed in the histological images of the liver, spleen, lungs, heart and kidneys. Conclusion: The study established the preliminary in vitro efficacy and in vivo safety of Q-PLGA-NPs as a potential anti-breast cancer formulation.
    Matched MeSH terms: Gene Expression
  11. Benchtop Isolation and Characterisation of Small Extracellular Vesicles from Human Mesenchymal Stem Cells
    Tan KL, Chia WC, How CW, Tor YS, Show PL, Looi QHD, et al.
    Mol Biotechnol, 2021 Sep;63(9):780-791.
    PMID: 34061307 DOI: 10.1007/s12033-021-00339-2
    The objective of this study is to develop a simple protocol to isolate and characterise small extracellular vesicles (sEVs) from human umbilical cord-derived MSCs (hUC-MSCs). hUC-MSCs were characterised through analysis of morphology, immunophenotyping and multidifferentiation ability. SEVs were successfully isolated by ultrafiltration from the conditioned medium of hUC-MSCs. The sEVs' size distribution, intensity within a specific surface marker population were measured with zetasizer or nanoparticle tracking analysis. The expression of surface and internal markers of sEVs was also assessed by western blotting. Morphology of hUC-MSCs displayed as spindle-shaped, fibroblast-like adherent cells. Phenotypic analysis by flow cytometry revealed that hUC-MSCs expressed MSC surface marker, including CD90, CD73, CD105, CD44 and exhibited the capacity for osteogenic, adipogenic and chondrogenic differentiation. Populations of sEVs with CD9, CD63 and CD81 positive were detected with size distribution in the diameter of 63.2 to 162.5 nm. Typical sEVs biomarkers such as CD9, CD63, CD81, HSP70 and TSG101 were also detected with western blotting. Our study showed that sEVs from hUC-MSCs conditioned medium were successfully isolated and characterised. Downstream application of hUC-MSCs-sEVs will be further explored.
    Matched MeSH terms: Gene Expression
  12. Seasonal expression and distribution of kisspeptin1 (kiss1) in the ovary and testis of freshwater catfish, Clarias batrachus: A putative role in steroidogenesis
    Singh A, Lal B, Parhar IS, Millar RP
    Acta Histochem, 2021 Sep;123(6):151766.
    PMID: 34384940 DOI: 10.1016/j.acthis.2021.151766
    The central role of kisspeptin (kiss) in mammalian reproduction is well established; however, its intra-gonadal role is poorly addressed. Moreover, studies investigating intra-gonadal role of kiss in fish reproduction are scanty, contradictory and inconclusive. The expression of kiss1 mRNA has been detected in the fish brain, and functionally attributed to the regulation of reproduction, feeding and behavior. The kiss1 mRNA has also been demonstrated in tissues other than the brain in some studies, but its cellular distribution and role at the tissue level have not been adequately addressed in fish. Therefore, an attempt was made in the present study to localize kiss1 in gonadal cells of the freshwater catfish, Clarias batrachus. This study reports the presence of kiss1 in the theca cells and granulosa cells of the ovarian oocytes and interstitial cells in the testis of the catfish. The role of kiss1 in the ovary and testis of the catfish was also investigated using kiss1 receptor (kiss1r) antagonist (p234). The p234 treatment decreased the production of 17β-estradiol in ovary and testosterone in the testis by lowering the activities of 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase under both, in vivo as well as in vitro conditions. The p234 treatment also arrested the progression of oogenesis, as evident from the low number of advancing/advanced oocytes in the treated ovary in comparison to the control ovary. It also reduced the area and perimeter of the seminiferous tubules in the treated catfish testis. Thus, our findings suggest that kiss is involved in the regulation of gonadal steroidogenesis, independent of known endocrine/ autocrine/ paracine regulators, and thereby it accelerates gametogenic processes in the freshwater catfish.
    Matched MeSH terms: Gene Expression Regulation*
  13. Fulltext Effect of organic and inorganic dietary selenium supplementation on gene expression in oviduct tissues and Selenoproteins gene expression in Lohman Brown-classic laying hens
    Muhammad AI, Dalia AM, Loh TC, Akit H, Samsudin AA
    BMC Vet Res, 2021 Aug 21;17(1):281.
    PMID: 34419016 DOI: 10.1186/s12917-021-02964-0
    BACKGROUND: The oviduct of a hen provides a conducive environment for egg formation, which needs a large amount of mineral elements from the blood via trans-epithelial permeability. Eggshell is the calcified layer on the outside of an egg that provides protection and is critical for egg quality. However, little is known about the genes or proteins involved in eggshell formation, and their relationship to dietary microminerals. We hypothesized that dietary selenium supplementation in chickens will influence genes involved in eggshell biomineralization, and improve laying hen antioxidant capacity. The objective of this research was to investigate how organic and inorganic dietary selenium supplementation affected mRNA expression of shell gland genes involved in eggshell biomineralization, and selenoproteins gene expression in Lohman Brown-Classic laying hens.

    RESULTS: Shell gland (Uterus) and liver tissue samples were collected from hens during the active growth phase of calcification (15-20 h post-ovulation) for RT-PCR analysis. In the oviduct (shell gland and magnum) and liver of laying hens, the relative expression of functional eggshell and hepatic selenoproteins genes was investigated. Results of qPCR confirmed the higher (p gene expression in laying hens, indicating that it could be used as a viable alternative source of Se in laying hens. The findings could suggest that organic Se upregulation of shell gland genes and hepatic selenoproteins in laying hens is efficient.

    Matched MeSH terms: Gene Expression
  14. Microarray-based identification of differentially expressed genes associated with andrographolide derivatives-induced resistance in colon and prostate cancer cell lines
    Quah SY, Wong CC, Wong HC, Ho KL, Abdul Manan N, Deb PK, et al.
    Toxicol Appl Pharmacol, 2021 08 15;425:115605.
    PMID: 34087331 DOI: 10.1016/j.taap.2021.115605
    Chemoresistance poses a major hurdle to cancer treatments. Andrographolide-derived SRJ09 and SRJ23 were reported to exhibit potent, selective inhibitory activities against colon and prostate cancer cells, respectively. In this study, previously developed resistant colon (HCT-116rst09) and prostate (PC-3rst23) cancer cell lines were used to elucidate the molecular mechanisms contributing to chemoresistance. Cytotoxic effects of SRJ09 and SRJ23 on both parental and resistant cells were investigated. Cell cycle distributions in HCT-116rst09 cells following SRJ09 treatment were analysed using flow cytometry. Whole-genome microarray analysis was performed on both parental and resistant cells to obtain differential gene expression profiles. Microarray data were subjected to protein-protein interaction network, functional enrichment, and pathway analyses. Reverse transcription-polymerase chain reaction (RT-PCR) was used to validate the changes in expression levels of selected genes. Besides morphological changes, HCT-116rst09 cells showed 7.0-fold resistance to SRJ09 while PC-3rst23 cells displayed a 5.5-fold resistance to SRJ23, as compared with their respective parental cells. G0/G1-phase cell cycle arrest was observed in HCT-116rst09 cells upon SRJ09 treatment. Collectively, 77 and 21 genes were found differentially modulated in HCT-116rst09 and PC-3rst23 cells, respectively. Subsequent bioinformatics analysis revealed several genes associated with FGFR4 and PI3K pathways, and cancer stemness, were chemoresistance mediators in HCT-116rst09 cells. RT-PCR confirmed the HMOX1 upregulation and ATG12 downregulation protected the PC-3rst23 cells from SRJ23 cytotoxicity. In conclusion, acquired chemoresistance to SRJ09 and SRJ23 in colon and prostate cancer cells, respectively, could be attributed to the alterations in the expression of genes such as those related to PI3K and autophagy pathways.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
  15. Fulltext Regulation of Proteolytic Activity to Improve the Recovery of Macrobrachium rosenbergii Nodavirus Capsid Protein
    Selvaraj BA, Mariatulqabtiah AR, Ho KL, Ng CL, Yong CY, Tan WS
    Int J Mol Sci, 2021 Aug 13;22(16).
    PMID: 34445426 DOI: 10.3390/ijms22168725
    The causative agent of white tail disease (WTD) in the giant freshwater prawn is Macrobrachium rosenbergii nodavirus (MrNV). The recombinant capsid protein (CP) of MrNV was previously expressed in Escherichia coli, and it self-assembled into icosahedral virus-like particles (VLPs) with a diameter of approximately 30 nm. Extensive studies on the MrNV CP VLPs have attracted widespread attention in their potential applications as biological nano-containers for targeted drug delivery and antigen display scaffolds for vaccine developments. Despite their advantageous features, the recombinant MrNV CP VLPs produced in E. coli are seriously affected by protease degradations, which significantly affect the yield and stability of the VLPs. Therefore, the aim of this study is to enhance the stability of MrNV CP by modulating the protease degradation activity. Edman degradation amino acid sequencing revealed that the proteolytic cleavage occurred at arginine 26 of the MrNV CP. The potential proteases responsible for the degradation were predicted in silico using the Peptidecutter, Expasy. To circumvent proteolysis, specific protease inhibitors (PMSF, AEBSF and E-64) were tested to reduce the degradation rates. Modulation of proteolytic activity demonstrated that a cysteine protease was responsible for the MrNV CP degradation. The addition of E-64, a cysteine protease inhibitor, remarkably improved the yield of MrNV CP by 2.3-fold compared to the control. This innovative approach generates an economical method to improve the scalability of MrNV CP VLPs using individual protease inhibitors, enabling the protein to retain their structural integrity and stability for prominent downstream applications including drug delivery and vaccine development.
    Matched MeSH terms: Gene Expression Regulation, Viral
  16. Fulltext Harnessing the Potential of CRISPR/Cas in Atherosclerosis: Disease Modeling and Therapeutic Applications
    Siew WS, Tang YQ, Kong CK, Goh BH, Zacchigna S, Dua K, et al.
    Int J Mol Sci, 2021 Aug 05;22(16).
    PMID: 34445123 DOI: 10.3390/ijms22168422
    Atherosclerosis represents one of the major causes of death globally. The high mortality rates and limitations of current therapeutic modalities have urged researchers to explore potential alternative therapies. The clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system is commonly deployed for investigating the genetic aspects of Atherosclerosis. Besides, advances in CRISPR/Cas system has led to extensive options for researchers to study the pathogenesis of this disease. The recent discovery of Cas9 variants, such as dCas9, Cas9n, and xCas9 have been established for various applications, including single base editing, regulation of gene expression, live-cell imaging, epigenetic modification, and genome landscaping. Meanwhile, other Cas proteins, such as Cas12 and Cas13, are gaining popularity for their applications in nucleic acid detection and single-base DNA/RNA modifications. To date, many studies have utilized the CRISPR/Cas9 system to generate disease models of atherosclerosis and identify potential molecular targets that are associated with atherosclerosis. These studies provided proof-of-concept evidence which have established the feasibility of implementing the CRISPR/Cas system in correcting disease-causing alleles. The CRISPR/Cas system holds great potential to be developed as a targeted treatment for patients who are suffering from atherosclerosis. This review highlights the advances in CRISPR/Cas systems and their applications in establishing pathogenetic and therapeutic role of specific genes in atherosclerosis.
    Matched MeSH terms: Gene Expression/genetics
  17. Fulltext PIP4Ks impact on PI3K, FOXP3, and UHRF1 signaling and modulate human regulatory T cell proliferation and immunosuppressive activity
    Poli A, Abdul-Hamid S, Zaurito AE, Campagnoli F, Bevilacqua V, Sheth B, et al.
    Proc Natl Acad Sci U S A, 2021 08 03;118(31).
    PMID: 34312224 DOI: 10.1073/pnas.2010053118
    Regulatory T cells (Tregs) play fundamental roles in maintaining peripheral tolerance to prevent autoimmunity and limit legitimate immune responses, a feature hijacked in tumor microenvironments in which the recruitment of Tregs often extinguishes immune surveillance through suppression of T-effector cell signaling and tumor cell killing. The pharmacological tuning of Treg activity without impacting on T conventional (Tconv) cell activity would likely be beneficial in the treatment of various human pathologies. PIP4K2A, 2B, and 2C constitute a family of lipid kinases that phosphorylate PtdIns5P to PtdIns(4,5)P 2 They are involved in stress signaling, act as synthetic lethal targets in p53-null tumors, and in mice, the loss of PIP4K2C leads to late onset hyperinflammation. Accordingly, a human single nucleotide polymorphism (SNP) near the PIP4K2C gene is linked with susceptibility to autoimmune diseases. How PIP4Ks impact on human T cell signaling is not known. Using ex vivo human primary T cells, we found that PIP4K activity is required for Treg cell signaling and immunosuppressive activity. Genetic and pharmacological inhibition of PIP4K in Tregs reduces signaling through the PI3K, mTORC1/S6, and MAPK pathways, impairs cell proliferation, and increases activation-induced cell death while sparing Tconv. PIP4K and PI3K signaling regulate the expression of the Treg master transcriptional activator FOXP3 and the epigenetic signaling protein Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1). Our studies suggest that the pharmacological inhibition of PIP4K can reprogram human Treg identity while leaving Tconv cell signaling and T-helper differentiation to largely intact potentially enhancing overall immunological activity.
    Matched MeSH terms: Gene Expression Regulation, Enzymologic/drug effects; Gene Expression Regulation, Enzymologic/immunology; Gene Expression Regulation, Enzymologic/physiology
  18. Protein profile of MCF-7 breast cancer cell line treated with lectin delivered by CaCO3NPs revealed changes in molecular chaperones, cytoskeleton, and membrane-associated proteins
    Mahmood RI, Abbass AK, Razali N, Al-Saffar AZ, Al-Obaidi JR
    Int J Biol Macromol, 2021 Aug 01;184:636-647.
    PMID: 34174302 DOI: 10.1016/j.ijbiomac.2021.06.144
    The second most predominant cancer in the world and the first among women is breast cancer. We aimed to study the protein abundance profiles induced by lectin purified from the Agaricus bisporus mushroom (ABL) and conjugated with CaCO3NPs in the MCF-7 breast cancer cell line. Two-dimensional electrophoresis (2-DE) and orbitrap mass spectrometry techniques were used to reveal the protein abundance pattern induced by lectin. Flow cytometric analysis showed the accumulation of ABL-CaCO3NPs treated cells in the G1 phase than the positive control. Thirteen proteins were found different in their abundance in breast cancer cells after 24 h exposure to lectin conjugated with CaCO3NPs. Most of the identified proteins were showing a low abundance in ABL-CaCO3NPs treated cells in comparison to the positive and negative controls, including V-set and immunoglobulin domain, serum albumin, actin cytoplasmic 1, triosephosphate isomerase, tropomyosin alpha-4 chain, and endoplasmic reticulum chaperone BiP. Hornerin, tropomyosin alpha-1 chain, annexin A2, and protein disulfide-isomerase were up-regulated in comparison to the positive. Bioinformatic analyses revealed the regulation changes of these proteins mainly affected the pathways of 'Bcl-2-associated athanogene 2 signalling pathway', 'Unfolded protein response', 'Caveolar-mediated endocytosis signalling', 'Clathrin-mediated endocytosis signalling', 'Calcium signalling' and 'Sucrose degradation V', which are associated with breast cancer. We concluded that lectin altered the abundance in molecular chaperones/heat shock proteins, cytoskeletal, and metabolic proteins. Additionally, lectin induced a low abundance of MCF-7 cancer cell proteins in comparison to the positive and negative controls, including; V-set and immunoglobulin domain, serum albumin, actin cytoplasmic 1, triosephosphate isomerase, tropomyosin alpha-4 chain, and endoplasmic reticulum chaperone BiP.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
  19. The effects of Naja sumatrana venom cytotoxin, sumaCTX on alteration of the secretome in MCF-7 breast cancer cells following membrane permeabilization
    Hiu JJ, Yap MKK
    Int J Biol Macromol, 2021 Aug 01;184:776-786.
    PMID: 34174307 DOI: 10.1016/j.ijbiomac.2021.06.145
    Naja sumatrana venom cytotoxin (sumaCTX) is a basic protein which belongs to three-finger toxin family. It has been shown to induce caspase-dependent, mitochondrial-mediated apoptosis in MCF-7 cells at lower concentrations. This study aimed to investigate the alteration of secretome in MCF-7 cells following membrane permeabilization by high concentrations of sumaCTX, using label-free quantitative (LFQ) approach. The degree of membrane permeabilization of sumaCTX was determined by lactate dehydrogenase (LDH) assay and calcein-propidium iodide (PI) assays. LDH and calcein-PI assays revealed time-dependent membrane permeabilization within a narrow concentration range. However, as toxin concentrations increased, prolonged exposure of MCF-7 cells to sumaCTX did not promote the progression of membrane permeabilization. The secretome analyses showed that membrane permeabilization was an event preceding the release of intracellular proteins. Bioinformatics analyses of the LFQ secretome revealed the presence of 105 significantly distinguished proteins involved in metabolism, structural supports, inflammatory responses, and necroptosis in MCF-7 cells treated with 29.8 μg/mL of sumaCTX. Necroptosis was presumably an initial stress response in MCF-7 cells when exposed to high sumaCTX concentration. Collectively, sumaCTX-induced the loss of membrane integrity in a concentration-dependent manner, whereby the cell death pattern of MCF-7 cells transformed from apoptosis to necroptosis with increasing toxin concentrations.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
  20. Emerging strategies for sensitization of therapy resistant tumors toward cancer therapeutics by targeting the Bcl-2 family, TGF-β, Wnt/β-Catenin, RASSF and miRNA regulated signaling pathways
    Veerasamy T, Eugin Simon S, Tan KO
    Int J Biochem Cell Biol, 2021 08;137:106016.
    PMID: 34082133 DOI: 10.1016/j.biocel.2021.106016
    Conventional chemotherapy relies on the cytotoxicity of chemo-drugs to inflict destructive effects on tumor cells. However, as most tumor cells develop resistance to chemo-drugs, small doses of chemo-drugs are unlikely to provide significant clinical benefits in cancer treatment while high doses of chemo-drugs have been shown to impact normal human cells negatively due to the non-specific nature and cytotoxicity associated with chemo-drugs. To overcome this challenge, sensitizations of tumor cells with bioactive molecules that specifically target the pro-survival and pro-apoptosis signaling pathways of the tumor cells are likely to increase the therapeutic impacts and improve the clinical outcomes by reducing the dependency and adverse effects associated with using high doses of chemo-drugs in cancer treatment. This review focuses on emerging strategies to enhance the sensitization of tumor cells toward cancer therapies based on our understanding of tumor cell biology and underlying signaling pathways.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects*
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links