Identification of Compounds Protecting Pancreatic Islets against Oxidative Stress Using a 3D Pseudoislet Screening Platform

Oxidative stress leads to a lower success rate of clinical islet transplantation

Rademakers, T.; Sthijns, M. M. J. P. E.; Paulino da Silva Filho, O.; Joris, V.; Oosterveer, J.; Lam, T. W.; van Doornmalen, E.; van Helden, S.; LaPointe, V. L. S.
Advanced Biology 7 (12), 2300264 (2023)

Here, FDA-approved compounds are screened for their potential to decrease oxidative stress and to protect or enhance pancreatic islet viability and function. Studies are performed on in vitro “pseudoislet” spheroids, which are pre-incubated with 1280 different compounds and subjected to oxidative stress.

pyHeart4Fish: Chamber-Specific Heart Phenotype Quantification of Zebrafish in High-Content Screens

Vedder, V. L.; Reinberger, T.; Haider, S. M. I.; Eichelmann, L.; Odenthal, N.; Abdelilah-Seyfried, S.; Aherrahrou, Z.; Breuer, M.; Erdmann, J.
Frontiers in Cell and Developmental Biology (2023)

The Action of Physiological and Synthetic Steroids on the Calcium Channel CatSper in Human Sperm

The sperm-specific channel CatSper (cation channel of sperm) controls the intracellular Ca2+ concentration ([Ca2+]i) and plays an essential role in sperm function

Wehrli, L.; Galdadas, I.; Voirol, L.; Smieško, M.; Cambet, Y.; Jaquet, V.; Guerrier, S.; Gervasio, F. L.; Nef, S.; Rahban, R.
Front Cell Dev Biol 11, 1221578 (2023)

It is mainly activated by the steroid progesterone (P4) but is also promiscuously activated by a wide range of synthetic and physiological compounds. These compounds include diverse steroids whose action on the channel is so far still controversial. To investigate the effect of these compounds on CatSper and sperm function, we developed a high-throughput screening […]

Non-Steroidal Estrogens Inhibit Influenza Virus by Interacting with Hemagglutinin and Preventing Viral Fusion

Influenza virus is one of the main causes of respiratory infections worldwide

Franzi, E.; Mathez, G.; Dinant, S.; Deloizy, C.; Kaiser, L.; Tapparel, C.; Le Goffic, R.; Cagno, V.
International Journal of Molecular Sciences 24 (20), 15382 (2023)

Despite the availability of seasonal vaccines and antivirals, influenza virus infections cause an important health and economic burden. Therefore, the need to identify alternative antiviral strategies persists. In this study, we identified non-steroidal estrogens as potent inhibitors of influenza virus due to their interaction with the hemagglutinin protein, preventing viral entry. This activity is maintained […]

Phenotypic Screening Platform Identifies Statins as Enhancers of Immune Cell-Induced Cancer Cell Death

High-throughput screening (HTS) of small molecule drug libraries has greatly facilitated the discovery of new cancer drugs

Selvin, T.; Berglund, M.; Lenhammar, L.; Jarvius, M.; Nygren, P.; Fryknäs, M.; Larsson, R.; Andersson, C. R.
BMC Cancer 23 (1), 164 (2023)

However, most phenotypic screening platforms used in the field of oncology are based solely on cancer cell populations and do not allow for the identification of immunomodulatory agents.

Novel Therapeutic Strategies Targeting UCP2 in Uterine Leiomyosarcoma

Uterine leiomyosarcoma (ULMS) is a malignant stromal tumor arising from the myometrium with a poor prognosis and very limited response to current chemotherapy

Nagao, Y.; Yokoi, A.; Yoshida, K.; Sugiyama, M.; Watanabe, E.; Nakamura, K.; Kitagawa, M.; Asano-Inami, E.; Koya, Y.; Yoshihara, M.; Tamauchi, S.; Shimizu, Y.; Ikeda, Y.; Yoshikawa, N.; Kato, T.; Yamamoto, Y.; Kajiyama, H.
Pharmacological Research 189, 106693 (2023)

This study aimed to identify novel targets for ULMS through a three-step screening process using a chemical library consisting of 1271 Food and Drug Administration-approved drugs. First, we evaluated their inhibitory effects on ULMS cells and identified four candidates: proscillaridin A, lanatoside C, floxuridine, and digoxin. Then, we subcutaneously or orthotopically transplanted SK-UT-1 cells into […]

Preclinical Validation of Repurposable Candidate Drug Compound for Cystic Nephropathies

Clanget, T.; Heigwer, J.; Pandey, G.; Kraft, P.; Rodenbeck, B.; Mayer, T.; Tabatabaeifar, M.; Gehrig, J.; Westhoff, J.; Korkmaz-Icöz, S.; Schaefer, F.
Nephrology Dialysis Transplantation 38 (Supplement_1), gfad063c_6189 (2023)

Early-onset cystic kidney disease is a clinically and genetically heterogeneous and overlapping group of rare and often severe disorders with limited, mostly symptomatic treatment options. We developed and utilized inherited polycystic cystic kidney disease (PKD) models to search for pharmacological agents that can rescue or mitigate the disease phenotype.

Evolution of antibiotic resistance is a world health crisis, fueled by new mutations

Drugs to slow mutagenesis could, as cotherapies, prolong the shelf-life of antibiotics, yet evolution-slowing drugs and drug targets have been underexplored and ineffective

Zhai, Y.; Pribis, J. P.; Dooling, S. W.; Garcia-Villada, L.; Minnick, P. J.; Xia, J.; Liu, J.; Mei, Q.; Fitzgerald, D. M.; Herman, C.; Hastings, P. J.; (8) Costa-Mattioli, M.; Rosenberg, S. M.
Science Advances 9 (25), eadg0188 (2023)

Here, we used a network-based strategy to identify drugs that block hubs of fluoroquinolone antibiotic-induced mutagenesis. We identify a U.S. Food and Drug Administration– and European Medicines Agency–approved drug, dequalinium chloride (DEQ), that inhibits activation of the Escherichia coli general stress response, which promotes ciprofloxacin-induced (stress-induced) mutagenic DNA break repair. We uncover the step in […]

CRISPR/Cas9-Based Screening of FDA-Approved Drugs for NRF2 Activation: A Novel Approach to Discover Therapeutics for Non-Alcoholic Fatty Liver Disease

With the rising prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) now affects 20–25% of the global population

Li, J.; Arest, S.; Olszowy, B.; Gordon, J.; Barrero, C. A.; Perez-Leal, O.
Antioxidants 12 (7), 1363 (2023)

NAFLD, a progressive condition associated with oxidative stress, can result in cirrhosis and liver cancer in 10% and 3% of patients suffering NAFLD, respectively. Therapeutic options are currently limited, emphasizing the need for novel treatments. In this study, we examined the potential of activating the transcription factor NRF2, a crucial player in combating oxidative stress, […]

Oxiconazole Potentiates Gentamicin against Gentamicin-Resistant Staphylococcus Aureus In Vitro and In Vivo

Kaul, G.; Akhir, A.; Shukla, M.; Shafi, H.; Akunuri, R.; Pawar, G.; Ghouse, M.; Srinivas, N.; Chopra, S.
Microbiology Spectrum e05031-22 (2023)