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Differences in Therapeutic Efficacy in Pancreatic Cancer Between Interstitial and Superficial Light Delivery Strategies in Targeted Photo Therapy
Nzola De Magalhães
In silico screening for investigating the potential activity of phytoligands against SARS-CoV-2
Acharya Balkrishna, Pallavi Thakur, Shivam Singh, Namita Singh, Ankit Tanwar, and Rakesh Kumar Sharma
Cell type resolved co-expression networks of core clock genes in brain development
Surbhi Sharma, Asgar Hussain Ansari, Soundhar Ramasamy
Drug testing and delivery techniques for the in vivo tumor spheroid based shell-less chorioallantoic membrane model
Nzola De Magalhães
The role of wild-type tau in Alzheimer’s disease and related tauopathies
Chih Hung Lo and Jonathan N. Sachs
Integration of spatial and non-spatial information by heterogeneous dentate gyrus granule cells
Xiaomin Zhang and Peter Jonas
T cell receptor sequencing in autoimmunity
Angela M. Mitchell and Aaron W. Michels
Modulating lysosomal pH: a molecular and nanoscale materials design perspective
Jialiu Zeng, Orian S. Shirihai and Mark W. Grinstaff
Snapshot of miRNA biology - progress from 1993 to 2020
Vinny Negi and Balaram Ghosh
Understanding the complexity of Multiple Sclerosis: A short communication
Rashmi Wardhan, Ankit Tanwar Anil K Gupta, and Ruby Sharma
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Author(s)
Nzola De Magalhães

Institute
University of California Irvine
Address
Department of Surgery, School of Medicine, University of California Irvine, Irvine, California, USA
Abstract:

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).


Author(s)
Acharya Balkrishna, Pallavi Thakur, Shivam Singh, Namita Singh, Ankit Tanwar, and Rakesh Kumar Sharma

Institute
Multiple Institutions across India, and Albert Einstein College of Medicine, New York, USA
Address

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.

Abstract:

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.


Author(s)
Surbhi Sharma, Asgar Hussain Ansari, Soundhar Ramasamy

Institute
CSIR Institute of Genomics and Integrative Biology and Academy of Scientific and Innovative Research
Address
(IGIB), Mathura Road, New Delhi 110025, India
(AcSIR), CSIR Human Resource Development Centre (CSIR-HRDC), Campus Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh 201 002, India

Abstract:

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.


Author(s)
Nzola De Magalhães

Institute
University of California Irvine
Address
Department of Surgery, School of Medicine, University of California Irvine, Irvine, California, USA
Abstract:

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.


Author(s)
Chih Hung Lo and Jonathan N. Sachs

Institute
University of Minnesota, Harvard Medical School
Address

Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455

Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115

Abstract:

Tau oligomers have recently emerged as the principal toxic species in Alzheimer’s disease (AD) and tauopathies. Tau oligomers are spontaneously self-assembled soluble tau proteins that are formed prior to fibrils, and they have been shown to play a central role in neuronal cell death and in the induction of neurodegeneration in animal models. As the therapeutic paradigm shifts to targeting toxic tau oligomers, this suggests the focus to study tau oligomerization in species that are less susceptible to fibrillization. While truncated and mutation containing tau as well as the isolated repeat domains are particularly prone to fibrillization, the wild-type (WT) tau proteins have been shown to be resistant to fibril formation in the absence of aggregation inducers. In this review, we will summarize and discuss the toxicity of WT tau both in vitro and in vivo, as well as its involvement in tau oligomerization and cell-to-cell propagation of pathology. Understanding the role of WT tau will enable more effective biomarker development and therapeutic discovery for treatment of AD and tauopathies.

 
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