The authors address the current molecular biological features for understanding the multifactorial function of PARP-1 in pancreatic cancer related to the aforementioned roles, along with the summary of recent approaches with PARP-1 inhibition in clinical studies targeting pancreatic cancer.
[International Journal of Molecular Sciences]
Researchers suggested that accumulation of endogenous mtdsRNA following degradosome knockdown depended on the proliferative capacity of the cells and was not a mediator of the type I interferon response in human pancreatic beta cells.
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Coomans de Brachène, A., Castela, A., Musuaya, A. E., Marselli, L., Marchetti, P., & Eizirik, D. L. (2021). Endogenous mitochondrial double‐stranded RNA is not an activator of the type I interferon response in human pancreatic beta cells. Autoimmunity Highlights, 12(1), 6. https://doi.org/10.1186/s13317-021-00148-2 Cite
Scientists showed that hydrophobic components of bitter melon fruit extract increased ATP production and augmented insulin secretion from β-cells, consequently decreasing blood glucose levels.
[British Journal of Nutrition]
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Bitter melon fruit extract enhances intracellular ATP production and insulin secretion from rat pancreatic β-cells | British Journal of Nutrition | Cambridge Core. (n.d.). Retrieved March 30, 2021, from https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/bitter-melon-fruit-extract-enhances-intracellular-atp-production-and-insulin-secretion-from-rat-pancreatic-cells/B388E6AC085C0B1DB936801BDC00EF61 Cite
The effects of fetuin-A were assessed during in vitro maturation of porcine neonatal islet cell clusters and in adult human islets. Expression alterations were examined via microarray, RNA sequencing and reverse transcription quantitative real-time PCR, proteins were analyzed by western blotting and immunostaining, and insulin secretion was quantified in static incubations.
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The hepatokine fetuin-A disrupts functional maturation of pancreatic beta cells | SpringerLink. (n.d.). Retrieved March 30, 2021, from https://link.springer.com/article/10.1007%2Fs00125-021-05435-1 Cite
Most PDAC cells showed similar pleomorphic morphologies in 2D culture. Under 3D culture, PDAC cells with high E-cadherin and low vimentin expression levels formed small round spheres encircled with flat lining cells, whereas those with high vimentin and low E-cadherin expression levels formed large grape-like spheres without lining cells and were highly proliferative.
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Minami, F., Sasaki, N., Shichi, Y., Gomi, F., Michishita, M., Ohkusu-Tsukada, K., Toyoda, M., Takahashi, K., & Ishiwata, T. (2021). Morphofunctional analysis of human pancreatic cancer cell lines in 2- and 3-dimensional cultures. Scientific Reports, 11. https://doi.org/10.1038/s41598-021-86028-1 Cite
While much has been learned about type 1 diabetes (T1D), it is now clear that there is considerable heterogeneity in T1D with regards to genetics, pathology, response to immune-based therapies, clinical course, and susceptibility to diabetes-related complications. This review highlights knowledge gaps and opportunities to improve the understanding of T1D pathogenesis and outlines emerging therapies to treat or prevent T1D and reduce the burden of T1D.
[Journal of Clinical Investigation]
Fractyl Laboratories Inc. announced the enrollment of the first patient in a pivotal clinical trial of Revita® DMR for patients with type 2 diabetes. The trial, called REVITA-T2Di, will evaluate the ability of a single Revita DMR treatment to allow patients currently on insulin therapy but with inadequate glycemic control to achieve durable insulin-free glycemic control.
[Fractyl Laboratories Inc.]
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The authors investigated the potential role and mechanisms of activating transcription factor 4 (ATF4) in cancer-associated fibroblasts-induced malignancy and gemcitabine resistance. They demonstrated that ATF4 was overexpressed in PDAC and associated with a poor prognosis.
[Cell Death & Disease]
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Wei, L., Lin, Q., Lu, Y., Li, G., Huang, L., Fu, Z., Chen, R., & Zhou, Q. (2021). Cancer-associated fibroblasts-mediated ATF4 expression promotes malignancy and gemcitabine resistance in pancreatic cancer via the TGF-β1/SMAD2/3 pathway and ABCC1 transactivation. Cell Death & Disease, 12(4), 1–14. https://doi.org/10.1038/s41419-021-03574-2 Cite
It was initially confirmed that escin, at concentrations >10 µM, significantly inhibited the proliferation of several pancreatic cancer cell lines.
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Omi, K., Matsuo, Y., Ueda, G., Aoyama, Y., Kato, T., Hayashi, Y., Imafuji, H., Saito, K., Tsuboi, K., Morimoto, M., Ogawa, R., Takahashi, H., & Takiguchi, S. (2021). Escin inhibits angiogenesis by suppressing interleukin‑8 and vascular endothelial growth factor production by blocking nuclear factor‑κB activation in pancreatic cancer cell lines. Oncology Reports, 45(5), 1–9. https://doi.org/10.3892/or.2021.8006 Cite
Investigators showed that gestational vitamin B6 deficiency decreased serotonin levels in maternal pancreatic islets and reduced β-cell proliferation in an serotonin receptor 2B-dependent manner.
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The authors applied a non-genetic lineage tracing method of human pancreatic exocrine acinar and duct cells that allowed cell-type-specific gene expression profiling by RNA sequencing.
[Cell Death & Differentiation]
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Backx, E., Wauters, E., Baldan, J., Van Bulck, M., Michiels, E., Heremans, Y., De Paep, D. L., Kurokawa, M., Goyama, S., Bouwens, L., Jacquemin, P., Houbracken, I., & Rooman, I. (2021). MECOM permits pancreatic acinar cell dedifferentiation avoiding cell death under stress conditions. Cell Death & Differentiation, 1–15. https://doi.org/10.1038/s41418-021-00771-6 Cite