Transcriptomic changes induced by Curcumin loaded solid nanoparticles and radiation in breast cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE118061 | GEO | 2019/08/20
REPOSITORIES: GEO
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Project description:Periodontitis (PD) as a chronic inflammatory disease instigated by periodontal pathogenic bacteria and mediated by the host immune response, resulting in the destruction of supporting periodontal tissue and tooth loss in adults. Constructing an injectable delivery system that allows for sustained drug release within periodontal pockets to continuously eliminate pathogenic bacteria, reduce periodontal inflammation, and promote periodontal tissue regeneration is an effective strategy for periodontitis treatment. Here, we explore the therapeutic potential and underlying mechanisms of curcumin-loaded Pickering emulsion (PE-CUR) in periodontitis treatment. The Pickering emulsion formulation offers an effective delivery system, enhancing curcumin's bioavailability and therapeutic efficacy. In vitro studies, we demonstrate that the PE-CUR exhibit excellent biocompatibility and anti-inflammatory property by elimination of reactive oxygen species (ROS). In addition, PE-CUR significantly eliminate key periodontal pathogens, including Porphyromonas gingivalis (P. gingivalis) and Staphylococcus aureus (S. aureus). In a rat model of periodontitis, PE-CUR significantly attenuates periodontal tissue inflammation and alveolar bone loss, indicating a protective effect against periodontal tissue destruction. Mechanistically, PE-CUR promotes the expression of anti-inflammatory factors and inhibits the release of pro-inflammatory factors by regulating macrophage polarization from M1 to M2 and modulating the MAPK and PI3K-AKT signaling pathway. Furthermore, PE-CUR decreases the formation of osteoclasts as well as stimulates the activation and differentiation of osteoblasts successively, thereby ameliorating the periodontal inflammation and promoting the alveolar bone regeneration. Overall, our findings elucidate the therapeutic mechanisms of PE-CUR in periodontitis, suggesting its potential as a promising treatment strategy warranting further clinical investigation.
2024-08-16 | GSE274645 | GEO
Project description:Although bladder-preserving trimodality therapy is recognized for patients with muscle-invasive bladder cancer (MIBC), chemotherapy can have toxic effects. Inhibitors to histone deacetylases (HDACis) have been identified as an effective strategy to enhance the radiotherapy (RT) effect, and several of them have clinical efficacy in BC. However, little is known about how a specific HDAC6 inhibitor (HDAC6i) acts in concert with RT. Knockdown of HDAC6 enhanced the radiosensitization of BC cells and increased γH2AX accumulation, similar to the effect of panobinostat, a pan-HDACi. Applying tubacin, a selective HDAC6i, to T24 cells induced H3K9ac and α-tubulin acetylation, and significantly decreased clonogenic cell survival when combined with RT. Further transcriptomic analysis of shHDAC6-transduced T24 cells under irradiation showed that genes that were highly downregulated compared to the levels in response to RT alone were significantly enriched in the inflammatory response. Moreover, HDAC6 knockdown counteracted the RT-induced mRNA expression of CXCL1, SERPINE1, SDC1 and SDC2. Importantly, tubacin suppressed RT-promoted invaded/migrated T24 cells, whereas panobinostat elevated RT-induced CXCL1 expression and invasion/migration abilities. This phenotype was significantly abrogated by the CXCL1 antibody, indicating that RT-induced CXCL1 is the key regulator contributing to BC malignancy. Immunohistochemical evaluation of tumours from BC patients supported the correlation between CXCL1 overexpression and poor prognosis. Unlike the pan-HDACi, the selective HDAC6i tubacin can enhance BC radiosensitization and suppress RT-induced oncogenic CXCL1-Snail signalling, thus further advancing the therapeutic potential of tubacin with RT.
2023-04-07 | GSE197659 | GEO
Project description:Purpose: The goals of this study are to compare NGS-derived gingiva transcriptome profiling (RNA-seq) of rats with or without experimental periodontitis and to explore the effect of curcumin/ZNPs hydrogel on the transcription of gingiva in rats with periodontitis. Methods: Six-week-old male Sprague-Dawley rats weighing 250–300 g (Dashuo company, China) were randomly divided into five groups (n = 5 per group): i) healthy control (Sham); ii) experimental periodontitis (EP); iii) experimental periodontitis treated by curcumin hydrogel (EP+Cur); iv) experimental periodontitis treated by ZNPs hydrogel (EP+ZNPs); v) experimental periodontitis treated by curcumin/ZNPs hydrogel (EP+Cur/ZNPs). Animals were anesthetized with isoflurane (5% induction, 2% maintenance, sealed until euthanized) and intramuscularly administered 0.1 mL penicillin (40,000 U/mL) for 7 days. EP was established by ligature with 4–0 silk thread around the bilateral maxillary first molars. Three days after ligature, P. gingivalis ATCC 33277 (107 CFU/mL) was smeared onto silk twice. Rats in the EP+Cur group were treated by curcumin hydrogel (Dalian Meilun Biotech Co., Ltd), EP+ZNPs group were treated by ZNPs hydrogel (Shanghai aladdin Biochemical Technology Co., Ltd), and EP+Cur/ZNPs group were treated by curcumin/ZNPs hydrogel. Total RNA was extracted with TRIzol® reagent (Thermo Fisher Scientific, Inc.). The TruSeq Stranded total RNA with RiboZero Plus kit (IIlumina, San Diego, CA) was used to obtain a sequencing library from 1μg of total RNA. Eukaryotic mRNA sequencing was performed on Illumina Novaseq 6000 by Shanghai Majorbio Bio-pharm Technology Co., Ltd. Raw gene counts with a minimum of two counts per million in at least one sample were used for downstream analyses. Differentially expressed genes were determined by the DESeq2 Bioconductor/R package. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: Transcriptome analysis of 25 samples was completed in this project, and a total of 184.45 Gb Clean Data was obtained. The Clean Data of each sample reached 5.92 Gb and above, and the Q30 base percentage was above 92.75%. The Clean Reads of each sample were compared with the designated reference genome, and the comparison rate ranged from 93.38% to 95.1%. A total of 26188 expressed genes were detected in this analysis, including 22736 known genes and 3452 new genes; 57,961 expressed transcripts, including 29332 known transcripts and 28629 new transcripts. Conclusions: Our study represents the first detailed analysis of gingival transcriptomes of rats treated by Cur/ZnO gel, with biologic replicates, generated by RNA-seq technology.
2022-01-01 | GSE185147 | GEO
Project description:Colorectal cancer (CRC) remains the leading cause of cancer-related death in the world. Aspirin (ASA) and curcumin (CUR) are widely investigated chemopreventive candidates for CRC. However, the precise mechanisms of their action and their combinatorial effects have not been evaluated. The purpose of the present study was to determine the effect of ASA, CUR, and their combination in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-accelerated colorectal cancer (CAC). We also aimed to characterize the differential gene expression profiles in AOM/DSS-induced tumors as well as in tumors modulated by ASA and CUR using RNA-seq. Diets supplemented with 0.02% ASA, 2% CUR or 0.01% ASA + 1% CUR were given to mice from 1 week prior to the AOM injection until the experiment was terminated 22 weeks after AOM initiation. Our results showed that CUR had a superior inhibitory effect in colon tumorigenesis compared to that of ASA. The combination of ASA and CUR at a lower dose exhibited similar efficacy to that of a higher dose of CUR at 2%. RNA isolated from colonic tissue from the control group and from tumor samples from the experimental groups was subjected to RNA-seq. Transcriptomic analysis suggested that the low-dose combination of ASA and CUR modulated larger gene sets than the single treatment. These differentially expressed genes were situated in several canonical pathways important in the inflammatory network and liver metastasis in CAC. We identified a small subset of genes as potential molecular targets involved in the preventive action of the combination of ASA and CUR. Taken together, the current results provide the first evidence in support of the chemopreventive effect of a low-dose combination of ASA and CUR in CAC. Moreover, the transcriptional profile obtained in our study may provide a framework for identifying the mechanisms underlying the carcinogenesis process from normal colonic tissue to tumor development as well as the cancer inhibitory effects and potential molecular targets of ASA and CUR.
2017-03-24 | GSE97013 | GEO
Project description:Aflatoxin B1 (AFB1) is extremely carcinogenic and can cause liver cancer in humans and animals with continued ingestion. As a natural compound, curcumin (Cur) exhibits excellent anti-inflammatory, and anti-cancer properties with few side effects. In this study, a total of 60 male mice (6-week-olds, 15 per group). After one week of acclimatization feeding, the mice were divided into control group (Con), AFB1 group, curcumin group (Cur), and AF+Cur group. The mice were gavaged with curcumin (Cur, 100 mg/kg) and/or AFB1 (0.75 mg/kg). To identify a new therapeutic target for AFB1-induced pyroptosis, we performed proteomic profiling for curcumin alleviating liver injury caused by AFB1 to further validate the targets through volcano plot analysis, Venn analysis, heatmap analysis, correlation, cluster analysis, GO and KEGG enrichment. AFB1 exposure resulted in the loss of hepatocyte membrane, swelling of the endoplasmic reticulum, and a significant increase in transaminase (ALT and AST) contents, while curcumin greatly improved these changes. We found that differentially expressed proteins are enriched in the endoplasmic reticulum membrane and identified ITPR2 as a target of curcumin that alleviates AFB1-induced liver injury by proteomics. Furthermore, ITPR2 expression was detected by immunofluorescence, and qRT-PCR for mRNA expression of genes downstream of ITPR2 (calpain1, calpain2, caspase-12, caspase-3). ITPR2-activated endoplasmic reticulum stress-related proteins (calpain1, calpaini2, bcl-2, BAX, cl-caspase-12, cl-caspase-3), apoptosis (PARP) and pyroptosis (DFNA5) related proteins were examined by western blotting. The analysis showed that it effectively prevents AFB1-induced pyroptosis by lowering endoplasmic reticulum stress via interfering with ITPR2 and its downstream proteins (calpain1, calpain2, bcl-2, Bax) and inhibiting caspase-12/caspase-3 pathway. Conclusively, this study applied proteomic profiling to elucidate ITPR2 as a new target, which might give a new perspective on the mechanism of curcumin alleviating AFB1-induced pyroptosis.
2023-05-21 | PXD042376 |
Project description:Radiation therapy (RT) remains a vital component of the curative multimodality therapy for many types of cancer including breast cancer (BC) disease. Thus, many efforts from research teams are needed to help clinicians in understanding the molecular portrait of a specific cancer type. Moreover, technological advances in RT are evolving with the use of hadrons, such as protons. However, cell and molecular changes induced by proton exposure are poorly characterized as well as molecular differences induced by high and low Linear Energy Transfer (LET) irradiation modalities, representing a topic of radiobiological interest. We analyze and compare molecular responses, in term of gene expression profile (GEP) changes, induced by conventional and non conventional radiation treatment modalities characterized by different LET values (using electron and proton beams respectively), delivering the same dose of IR, in tumorigenic and non-tumorigenic breast cell lines. We trust that this study could have a role in driving RT towards personalised treatments, evaluating possible combined treatments, based also on the molecular characterization in BC.
2018-12-26 | GSE103472 | GEO
Project description:Expression analysis was performed with human SUP-T1 cell line infected with HIV alone, treated with curcumin alone and infected with HIV in presence of curcumin. The control untreated sample was compared with all the three types of treatments to calculate the fold change. The purpose of the experiment was to identify set of genes that are dys-regulated during HIV infection and shows normal expression when treated with curcumin. This experiment is useful in identifying the mechanism of anti-HIV activity of curcumin at genetic level.
2015-10-29 | E-MTAB-3977 | biostudies-arrayexpress
Project description:Sarcolipin (SLN) is a key regulator of SERCA pump in atria. To determine the role of SLN in atrial Ca2+ homeostasis, we have generated a SLN null (sln-/-) mouse model. Ablation of SLN results in increased SR Ca2+ load and Ca2+ transients in atria. Further, loss of SLN results in electrophysiological and strcutural remodeling of atria. The SLN knockout and C57/BL6 wildtype mice (each n=3) were selected for RNA extraction. The cRNA probes were hybridized to Affymetrix gene array.
2010-11-01 | E-GEOD-23403 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of human blood samples. The Illumina Infinium EPIC DNA methylation Beadchip was used to obtain DNA methylation profiles Survival has increased in early stage breast cancer (BC), and the late effects of cancer treatment can persist for decades. The molecular mechanisms underlying acceleration of age-related diseases after chemotherapy and radiotherapy are poorly understood. We examined epigenetic changes in peripheral blood in early stage BC patients undergoing either adjuvant radiotherapy, or adjuvant chemotherapy and radiotherapy. DNA methylation experiments were performed on peripheral blood samples from women collected prior to and following completion of adjuvant therapy. Methylation profiles were used to estimate three measures of epigenetic age acceleration - intrinsic, extrinsic, and phenotypic - as well as estimated cell counts.
2020-06-23 | GSE140038 | GEO
Project description:Sarcolipin (SLN) is a key regulator of SERCA pump in atria. To determine the role of SLN in atrial Ca2+ homeostasis, we have generated a SLN null (sln-/-) mouse model. Ablation of SLN results in increased SR Ca2+ load and Ca2+ transients in atria. Further, loss of SLN results in electrophysiological and strcutural remodeling of atria.
2010-11-01 | GSE23403 | GEO