The purpose of this study was to determine if therapeutic efficacy of a Cetuximab based near-infrared (NIR) targeted photo therapy (TPT) was dependent on light delivery strategies. We examined the cytotoxic effects of TPT in a pancreatic cancer mouse model, when administered to tumors interstitially and superficially.

A subcutaneous mouse model of pancreatic cancer using BXPC-3 - GFP cells was established in male athymic (nu/nu) mice. The mice received intravenous (IV) injection of Cetuximab-IR700DX, 24 hours prior to near-infrared light irradiation. Interstitial illumination was administered at a 400mW/cm fixed power output, at a light dose of 100 J/cm to half the mice and at 300 J/cm to the remaining mice. Superficial illumination was administered at a 150mw/cm² fixed power density at a dose of 50 J/cm² to half the mice, and at 250 J/cm² to the other half. Cellular damage and decrease in cell viability were determined by the decrease in GFP fluorescence intensity levels in whole animal images and in relative intensity measurements.

Interstitially administered TPT resulted in greater long-term permanent damage (72 hours post treatment) to tumor cells (0% recovery at low dose, and 11% recovery at high dose) compared to superficially administered TPT (1% recovery at low dose, and 44% recovery at high dose). While these results demonstrated that near-infrared targeted photo therapy efficacy was dependent on the type of light delivery strategy, overall, both superficial and interstitial Cet-IR700DX based near-infrared targeted photo therapy can affect significant long-term damage (less signal recovery) to pancreatic cancer cells in vivo at lower doses regimens, compared to higher dose regimens (higher signal recovery).

Patanjali Research Institute,  University of Patanjali, University of Science and Technology,  Saveetha Institute of Medical and Technical Sciences - INDIA, and Albert Einstein College of Medicine, New York, USA.

SARS-CoV-2 causes COVID-19, a life-threatening respiratory illness with high rates of morbidity and mortality. As of date, there is no specific medicine to treat COVID-19. Therefore, there is an acute need to identify evidence-based holistic and safe mitigators. The present study aims to screen phytochemicals based on bioprospection analysis and subsequently predicting their binding potential to SARS-CoV-2 proteins in silico. The drug likeliness and ADMETox descriptors of 24 phytoligands were computationally predicted. Docking studies were further conducted with those phytoligands that qualified the drug likeliness parameters. Docking studies suggested that the herbal moiety, namely, gamma-glutamyl-S-allylcysteine demonstrated highly significant binding energies with viral spike glycoprotein, endoribonuclease, and main protease (binding energy ≥ -490 kcal/mol for all the tested target viral proteins). Gamma-glutamyl-S-allylcysteine demonstrated more significant binding potential as compared to the known chemical analog, i.e., hydroxychloroquine, as observed in the computational docking studies. This study serves to present pre-eminent information for further clinical studies highlighting the utility of herbal ligands as probable lead molecules for mitigating novel Coronavirus infection.

The circadian clock regulates vital cellular processes by adjusting the physiology of the organism to daily changes in the environment. Rhythmic transcription of core Clock Genes (CGs) and their targets regulate these processes at the cellular level. Circadian clock disruption has been observed in people with neurodegenerative disorders like Alzheimer’s and Parkinson’s. Also, ablation of CGs during development has been shown to affect neurogenesis in both in vivo and in vitro models. Previous studies on the function of CGs in the brain have used knock-out models of a few CGs. However, a complete catalogue of CGs in different cell types of the developing brain is not available and it is also tedious to obtain. Recent advancements in single-cell RNA sequencing (scRNA-seq) have revealed novel cell types and elusive dynamic cell states of the developing brain. In this study, by using publicly available single-cell transcriptome datasets we systematically explored CGs co-expressing networks (CGs-CNs) during embryonic and adult neurogenesis. Our meta-analysis reveals CGs-CNs in human embryonic radial glia, neurons, and other lesser studied non-neuronal cell types of the developing brain.

We have previously published in detail our methodology of developing the novel tumor spheroid-based shell-less chicken embryo Chorioallantoic Membrane (CAM) model, and its applications in biomedical research. In this article, we will present methods of drug delivery to expand the utility of this model, and also to provide researchers with useful techniques to investigate therapeutic efficacy, drug delivery, and selectivity on this model.

Biochemistry, University of Otago, PO Box 56, Dunedin, Otago, 9054, New Zealand.

Biochemistry and Molecular Biology, Michigan State University, 603 Wilson Road, East Lansing, Michigan, 48824, USA

Crystallography was used to characterize the cesium-binding sites in the sacrificial sulfur transferase LarE from Lactobacillus plantarum. Cs⁺ binding was unique when compared to a large range of other previously investigated metals. Database searches reveal that Cs⁺ preferentially binds to protein backbone carbonyl groups, often at crystal contacts and that the use of Cs⁺ in protein crystallography is an underutilized approach.