29 research outputs found
Epithelial to mesenchymal transition influences fibroblast phenotype in colorectal cancer by altering miR-200 levels in extracellular vesicles
No full textColorectal cancer (CRC) with a mesenchymal gene expression signature has the greatest propensity for distant metastasis and is characterised by the accumulation of cancer-associated fibroblasts in the stroma. We investigated whether the epithelial to mesenchymal transition status of CRC cells influences fibroblast phenotype, with a focus on the transfer of extracellular vesicles (EVs), as a controlled means of cell–cell communication. Epithelial CRC EVs suppressed TGF-β-driven myofibroblast differentiation, whereas mesenchymal CRC EVs did not. This was driven by miR-200 (miR-200a/b/c, -141), which was enriched in epithelial CRC EVs and transferred to recipient fibroblasts. Ectopic miR-200 expression or ZEB1 knockdown, in fibroblasts, similarly suppressed myofibroblast differentiation. Supporting these findings, there was a strong negative correlation between miR-200 and myofibroblastic markers in a cohort of CRC patients in the TCGA dataset. This was replicated in mice, by co-injecting epithelial or mesenchymal CRC cells with fibroblasts and analysing stromal markers of myofibroblastic phenotype. Fibroblasts from epithelial tumours contained more miR-200 and expressed less ACTA2 and FN1 than those from mesenchymal tumours. As such, these data provide a new mechanism for the development of fibroblast heterogeneity in CRC, through EV-mediated transfer of miRNAs, and provide an explanation as to why CRC tumours with greater metastatic potential are CAF rich
Multiple intracellular signal transduction pathways mediating inward current produced by the neuropeptide, achatin-I
No full text博士論文 (Doctoral dissertation
Lineweaver-burk analysis for the blocking effects of mammalian dopamine receptor antagonists on dopamine-induced currents in Achatina giant neurones
No full textMultiple intracellular signal transduction pathways mediating inward current produced by the neuropeptide, achatin-I
No full text博士論文 (Doctoral dissertation)doctoral thesi
HDMX-L is expressed from a functional P53-responsive promoter in the first intron of the HDMX gene, and participates in an auto-regulatory feedback loop to control P53 activity.
No full textThe p53 regulatory network is critically involved in preventing the initiation of cancer. In unstressed cells p53 is maintained at low levels and is largely inactive, mainly through the action of its two essential negative regulators, HDM2 and HDMX. p53 abundance and activity are upregulated in response to various stresses including DNA damage and oncogene activation. Active p53 initiates transcriptional and transcription-independent programs that result in cell cycle arrest, cellular senescence or apoptosis. p53 also activates transcription of HDM2, which initially leads to the degradation of HDMX, creating a positive feedback loop to obtain maximal activation of p53. Subsequently, when stress-induced post-translational modifications start to decline, HDM2 becomes effective in targeting p53 for degradation, thus attenuating the p53 response. To date, no clear function for HDMX in this critical attenuation phase has been demonstrated experimentally. Like HDM2, the HDMX gene contains a promoter (P2) in its first intron that is potentially inducible by p53. We show that p53 activation in response to a plethora of p53-activating agents induces the transcription of a novel HDMX mRNA transcript from the HDMX-P2 promoter. This mRNA is more efficiently translated than that expressed from the constitutive HDMX-P1 promoter, and it encodes a long form of HDMX protein, HDMX-L. Importantly, we demonstrate that HDMX-L cooperates with HDM2 to promote the ubiquitination of p53, and that p53-induced HDMX transcription from the P2 promoter can play a key role in the attenuation phase of the p53-response, to effectively diminish p53 abundance as cells recover from stress
مفهوم الأدب بين الأدباء العرب والأدباء الملايويين بماليزيا دراسة تقابلية = The concept of Islamic literature between Arab and Malay writers: a comparative study
No full textThis article focuses on the idea of Islamic Literature which began in the Arab world through the
writings of Muhammad Qutb, Syed Qutb, Naj
ib al
-
Kilani, Emaduddin Khalil and a few others who
came after them, influenced by their ideas. Later, concepts or theories of Islamic Literature began
to take shape among the writers. In Malaysia, the concept was presented by Syed Muhammad
Naquib Al
-
‘Atta
s who said that a writer must have a balanced views in the soul, body and mind.
After him, there was Affandi Hassan who came up with something unconventional on the theory of
Islamic literature. A number of other writers also tried to conceptualize the Isl
amic literature such
as Shafie Abu Bakar, Kamala, ‘Ali Ahmad, Uthman el
-
Muhammady and Muhammad Kamal Hasan
who tried to come up with the realistic view on Islamic literature based on what was suggested by
another writer, Shahnon Ahmad. Another scholar, Kas
ssim
Ahmad tried to dwell on the issue of
methodology in Islamic literature. Ismail Ibrahim, another scholar, suggested that Islamic literature
must stand on the principle of the unity of God (tawheed). This paper intends to study the concept
of Islamic Li
terature and its development among the Arab and Malay writers. A comparative study
on the similarities and differences of these concepts will also be a focus.
Keywords: Islamic Literature, concept, differences, similaritie
Use of steroids in COVID-19 patients: What is known?
No full textCOVID-19 pandemic has exaggerated the role of steroids in the standard of care despite minimum direct evidence of their efficacy in COVID-19 patients and their well-known adverse effects. The literature abounds on the side effects of steroids affecting different organ systems of the body. COVID-19 patients, who are on long-term steroids, are more susceptible to their adverse effects. We, herein, briefly review the potential uses and the adverse effects of steroids on different organ systems of the body. Key Words: Steroids, COVID-19, Adverse effects
Optimization of Bug Reporting System (BRS): Artificial Intelligence Based Method to Handle Duplicate Bug Report
No full text
