Rational screening approaches for HCC in NAFLD patients

AKT1 is emerging as a useful target for treating cancer. Herein, we discovered a new set of ligands that inhibit the AKT1, as shown by in vitro binding and cell line studies, using a newly designed virtual screening protocol that combines structure-based pharmacophore and docking screens. Taking together with the biological data, the combination of structure based pharamcophore and docking methods demonstrated reasonable success rate in identifying new inhibitors (60-70%) proving the success of aforementioned approach. A detail analysis of the ligand-protein interactions was performed explaining observed activities.<br>

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Progress and Challenges in Laboratory-Based Diagnostic and Screening Approaches for Aneuploidy Detection during Pregnancy

SLAS TECHNOLOGY Translating Life Sciences Innovation ◽

10.1177/24726303211021787 ◽

2021 ◽

pp. 247263032110217

Author(s):

Lindsay Schneider ◽

Anubhav Tripathi

Keyword(s):

Sample Collection ◽

Aneuploidy Screening ◽

Preimplantation Genetic Testing ◽

Cellular Division ◽

Vitro Fertilization ◽

Genetic Abnormalities ◽

The Social ◽

Diagnostic Technologies ◽

Screening Approaches

Aneuploidy is caused by problems during cellular division and segregation errors during meiosis that lead to an abnormal number of chromosomes and initiate significant genetic abnormalities during pregnancy or the loss of a fetus due to miscarriage. Screening and diagnostic technologies have been developed to detect this genetic condition and provide parents with critical information about their unborn child. In this review, we highlight the complexities of aneuploidy as a disease as well as multiple technological advancements in testing that help to identify aneuploidy at various time points throughout pregnancy. We focus on aneuploidy diagnosis during preimplantation genetic testing that is performed during in vitro fertilization as well as prenatal screening and diagnosis during pregnancy. This review focuses on DNA-based analysis and laboratory techniques for aneuploidy detection through reviewing molecular- and engineering-based technical advancements. We also present key challenges in aneuploidy detection during pregnancy, including sample collection, mosaic embryos, economic factors, and the social implications of this testing. The goal of this review is to synthesize broad information about aneuploidy screening and diagnostic sample collection and analysis during pregnancy and discuss major challenges the field is still facing despite decades of advancements.

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Correction: ER-mitochondria contact sites in neurodegeneration: genetic screening approaches to investigate novel disease mechanisms

Cell Death and Differentiation ◽

10.1038/s41418-020-00723-6 ◽

2021 ◽

Author(s):

Emma Louise Wilson ◽

Emmanouil Metzakopian

Keyword(s):

Genetic Screening ◽

Contact Sites ◽

Disease Mechanisms ◽

Screening Approaches

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Multiple screening approaches reveal HDAC6 as a novel regulator of glycolytic metabolism in triple-negative breast cancer

Science Advances ◽

10.1126/sciadv.abc4897 ◽

2021 ◽

Vol 7 (3) ◽

pp. eabc4897

Author(s):

Catríona M. Dowling ◽

Kate E. R. Hollinshead ◽

Alessandra Di Grande ◽

Justin Pritchard ◽

Hua Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Histone Deacetylase Inhibitors ◽

Triple Negative ◽

Mitochondrial Apoptosis ◽

Glycolytic Metabolism ◽

Set Up ◽

Screening Approaches

Triple-negative breast cancer (TNBC) is a subtype of breast cancer without a targeted form of therapy. Unfortunately, up to 70% of patients with TNBC develop resistance to treatment. A known contributor to chemoresistance is dysfunctional mitochondrial apoptosis signaling. We set up a phenotypic small-molecule screen to reveal vulnerabilities in TNBC cells that were independent of mitochondrial apoptosis. Using a functional genetic approach, we identified that a “hit” compound, BAS-2, had a potentially similar mechanism of action to histone deacetylase inhibitors (HDAC). An in vitro HDAC inhibitor assay confirmed that the compound selectively inhibited HDAC6. Using state-of-the-art acetylome mass spectrometry, we identified glycolytic substrates of HDAC6 in TNBC cells. We confirmed that inhibition or knockout of HDAC6 reduced glycolytic metabolism both in vitro and in vivo. Through a series of unbiased screening approaches, we have identified a previously unidentified role for HDAC6 in regulating glycolytic metabolism.

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