Nano-biotechnology in tumour and cancerous disease: A perspective review

In recent years, drug manufacturers and researchers have begun to consider the nanobiotechnology approach to improve the drug delivery system for tumour and cancer diseases. In this article, we review current strategies to improve tumour and cancer drug delivery, which mainly focuses on sustaining biocompatibility, biodistribution, and active targeting. The conventional therapy using cornerstone drugs such as fludarabine, cisplatin etoposide, and paclitaxel has its own challenges especially not being able to discriminate between tumour versus normal cells which eventually led to toxicity and side effects in the patients. In contrast to the conventional approach, nanoparticle-based drug delivery provides target-specific delivery and controlled release of the drug, which provides a better therapeutic window for treatment options by focusing on the eradication of diseased cells via active targeting and sparing normal cells via passive targeting. Additionally, treatment of tumours associated with the brain is hampered by the impermeability of the blood–brain barriers to the drugs, which eventually led to poor survival in the patients. Nanoparticle-based therapy offers superior delivery of drugs to the target by breaching the blood–brain barriers. Herein, we provide an overview of the properties of nanoparticles that are crucial for nanotechnology applications. We address the potential future applications of nanobiotechnology targeting specific or desired areas. In particular, the use of nanomaterials, biostructures, and drug delivery methods for the targeted treatment of tumours and cancer are explored.     

The effect of population density of parasitePerisierola nephantidis [Hym.: Bethylidae] on the mortality of coconut caterpillar,Nephantis serinops [Lep.: Cryptophagidae]

The population density ofPerisierola nephantidis Mues. acts as key mortality factor in the biological control ofNephantis serinopa Meyrick. The mortality ofN. serinopa was directly proportional to the density of parasiteP. nephantidis and recorded a maximum of 96% at 1∶8 ratio of host to parasite at constant population of host. A significant inverse density-dependent action ofP. nephantidis was observed under various density ofNephantis larvae at a constant population of the parasite.     

Lose and gain: impacts of ERK5 and JNK cascades on each other

Kinase cascades in ERK5 (Extracellular signal-regulated kinases) and JNK (c-Jun N-terminal kinases) signaling pathways mediate the sensing and processing of stimuli. Cross-talks between signaling cascades is a likely phenomenon that can cause apparently different biological responses from a single pathway, on its activation. Feedback loops have the potential to greatly alter the properties of a pathway and its response to stimuli. Based on enzyme kinetic reactions, mathematical models have been developed to predict and analyze the impacts of cross-talks and feedback loops in ERK5 and JNK cascades. It has been observed that, there is no significant impact on neither ERK5 activation nor JNKs’ activation due to cross-talks between them. But it is due to cross-talks and feedback loops in ERK5 and JNK cascade, ERK5 gets activated in a transient manner in the absence of input signals. Planning to obtain the parameter values from the experimentalist and the result should be validated by experimental verification.     

Strategies to target SARS-CoV-2 entry and infection using dual mechanisms of inhibition by acidification inhibitors

Many viruses utilize the host endo-lysosomal network for infection. Tracing the endocytic itinerary of SARS-CoV-2 can provide insights into viral trafficking and aid in designing new therapeutic strategies. Here, we demonstrate that the receptor binding domain (RBD) of SARS-CoV-2 spike protein is internalized via the pH-dependent CLIC/GEEC (CG) endocytic pathway in human gastric-adenocarcinoma (AGS) cells expressing undetectable levels of ACE2. Ectopic expression of ACE2 (AGS-ACE2) results in RBD traffic via both CG and clathrin-mediated endocytosis. Endosomal acidification inhibitors like BafilomycinA1 and NH₄Cl, which inhibit the CG pathway, reduce the uptake of RBD and impede Spike-pseudoviral infection in both AGS and AGS-ACE2 cells. The inhibition by BafilomycinA1 was found to be distinct from Chloroquine which neither affects RBD uptake nor alters endosomal pH, yet attenuates Spike-pseudovirus entry. By screening a subset of FDA-approved inhibitors for functionality similar to BafilomycinA1, we identified Niclosamide as a SARS-CoV-2 entry inhibitor. Further validation using a clinical isolate of SARS-CoV-2 in AGS-ACE2 and Vero cells confirmed its antiviral effect. We propose that Niclosamide, and other drugs which neutralize endosomal pH as well as inhibit the endocytic uptake, could provide broader applicability in subverting infection of viruses entering host cells via a pH-dependent endocytic pathway.     

Evaluation of resistance of wild rices,Oryza spp., to the whitebacked planthopper,Sogatella furcifera (Horvath) (Homoptera: Delphacidae)

Evaluation of wild rice species for resistance against major insect pests of rice was carried out in both field and greenhouse conditions. A total of 219 wild rice lines were evaluated under field conditions against yellow stem borer, Scirpophaga incertulas (Walker) and leaf folder, Cnaphalocrocis medinalis (Guenee). Of the selected 185 lines tested by “standard seed box screening technique” against whitebacked planthopper, Sogatella furcifera (Horvath), 20 were found to be resistant, 54 moderately resistant, 88 moderately susceptible, and 23 susceptible. Out of the 185 wild rice lines tested against all the three major pests, 17 lines had multiple resistance. Out of these 17 lines, 14 lines were evaluated for mechanisms of resistance against S. furcifera; they showed antixenosis for feeding, as fewer nymphs settled on them compared to the susceptible O. sativa cultivar TN1. However, the eggs were observed to be randomly distributed on them. Antibiosis was exhibited as the nymphal period was prolonged, while there was a decrease in survival and growth index. Thus, besides possessing multiple resistance against all the three major pests during the present investigation, all these 14 wild rice lines belonging to different Oryza spp. exhibited good antixenotic and antibiotic effects.     

Structural and biophysical characterization of Mycobacterium tuberculosis dodecin Rv1498A

Dodecins (assembly of twelve monomers) are the smallest known flavoprotein with only 65-73 amino acids and are involved in binding and storage of flavins in archaea. Here we report the crystal structure of Rv1498A, a Mycobacterium tuberculosis dodecin. This bacterial dodecin structure is similar to that of other reported dodecins. Each monomer has a 3 stranded β-sheet and an α-helix perpendicular to it. This protein has polyextreme (halophilic and thermophilic) properties. Interestingly, positively and negatively charged residues aggregate separately and do not seem to contribute to thermophilic and halophilic stability. We have examined the interactions that stabilize the Rv1498A dodecamer by preparing selected point mutants that break salt bridges and hydrophobic contacts, thereby leading to collapse of the assembly.     

Analysis of the impact of ERK5, JNK,and P38 kinase cascades on each other: A systems approach

The classical concept of linear pathways is being increasingly challenged by network representations, which emphasize the importance of interactions between components of a biological system, and motivates for adopting a system‐level approach in biology. We have developed a dynamical system that integrates quantitative, dynamic and topological representation of network of ERK5 (Extracellular signal‐regulated kinases 5), JNK(c‐Jun N‐terminal kinases) and P38 kinase cascades. We have observered that, the transient activation of ERK5, JNK1 and P38β kinase, and the persistent activation of JNK2, JNK3 and P38 δ kinase does not get affected due to the cross‐talks between ERK5, JNK and P38 kinase cascades. But it is due to the cross ‐ talks, the transiently activated P38α kinase become inactivated, and the transiently activated P38γ kinase become persistently activated. The impacts of one‐way cross‐talks between the cascades are insignificant and differ from the impact of two‐way cross‐talks. We generate a hypothesis that, signaling pathways should be studied as a system by considering the cross‐talks between the two adjacent cascades.