Endocrinology Division, CSIR-Central Drug Research Institute, Jankipuram Extension, sitapur road, Lucknow, India. 

Cancer heterogeneity and development of resistance is the main limiting factor for the management and treatment of the disease. However, major technological innovations in precision medicine and immune-based therapies have renewed faith in having a cure for different types of cancers. Classical cancer treatment options include chemotherapy, radiotherapy, and immunotherapy. Emergence of novel tumor targeting bacteria could open up new therapeutic avenues. Bacteriotherapy alone or in conjunction with classical cancer therapies has given promising results on local tumor regression and distant metastasis. Moreover, bacteria exhibit direct anti-cancer effects that subsequently aid in the activation of innate and adaptive anti-tumor immune responses. Overall, genetically reprogrammed bacterial vectors holds great potential for the specific targeting of cancers as delivery vehicles. In this review article, we have reviewed the therapeutic potential of bacteriotherapy as monotherapy or combination therapy and discussed its benefits, challenges, and future directions.

Mitochondria are increasingly recognized as key factors in cancer, affecting a multitude of tumor hallmarks. Likewise, sirtuin 3, a master regulator of mitochondrial function, has gained attention as a therapeutic target in cancer. As a main mediator of calorie restriction, sirtuin 3 inhibits anabolic reactions and cell proliferation, acting as a tumor suppressor. At the same time, sirtuin 3 protects the cell during nutrient stress by regulating cell death and DNA repair, thereby acting as an oncogene. Here we discuss this conflicting role of sirtuin 3 in cancer and evaluate the therapeutic potential of sirtuin 3 activators and inhibitors in different cancers.

Reactive oxygen species is one of the most common cellular RNA damaging agents in living organisms. A growing number of studies show a strong correlation between oxidatively damaged RNA and human diseases, predominantly age-related neurodegenerative disorders. Oxidized RNAs impair the fundamental cellular processes including gene regulatory activities and protein synthesis. Molecular characterization of oxidized RNA such as understanding the sources of RNA oxidation, their mechanism of action, and cellular consequences may help to unravel their involvement in the pathogenesis of human diseases. Several proteins and factors with potential function to control RNA oxidation have been identified. Here, we will discuss the role of oxidized RNA binding protein polynucleotide phosphorylase (PNPase) in the quality control of oxidized RNA. PNPase is an evolutionarily conserved 3’-5’ exoribonuclease having multifaceted RNA regulatory roles. Apart from binding to oxidized RNA, PNPase reduces the level of RNA oxidation and protects cells during oxidative stress. In this review, we discuss RNA oxidation and its quality control process with a specific focus on PNPase in regulating oxidized RNA.

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.