Advancement in precision diagnosis and therapeutic for triple-negative breast cancer: Harnessing diagnostic potential of CRISPR-cas & engineered CAR T-cells mediated therapeutics.

Cancer is characterized by uncontrolled cell growth, disrupted regulatory pathways, and the accumulation of genetic mutations. These mutations across different types of cancer lead to disruptions in signaling pathways and alterations in protein expression related to cellular growth and proliferation. This review highlights the AKT signaling cascade and the retinoblastoma protein (pRb) regulating cascade as promising for novel nanotheranostic interventions. Through synergizing state-of-the-art gene editing tools like the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas system with nanomaterials and targeting AKT, there is potential to enhance cancer diagnostics significantly. Furthermore, the integration of modified CAR-T cells into multifunctional nanodelivery systems offers a promising approach for targeted cancer inhibition, including the eradication of cancer stem cells (CSCs). Within the context of highly aggressive and metastatic Triple-negative Breast Cancer (TNBC), this review specifically focuses on devising innovative nanotheranostics. For both pre-clinical and post-clinical TNBC detection, the utilization of the CRISPR-Cas system, guided by RNA (gRNA) and coupled with a fluorescent reporter specifically designed to detect TNBC's mutated sequence, could be promising. Additionally, a cutting-edge approach involving the engineering of TNBC-specific iCAR and syn-Notch CAR T-cells, combined with the co-delivery of a hybrid polymeric nano-liposome encapsulating a conditionally replicative adenoviral vector (CRAdV) against CSCs, could present an intriguing intervention strategy. This review thus paves the way for exciting advancements in the field of nanotheranostics for the treatment of TNBC and beyond.

An overview of remote monitoring methods in biodiversity conservation.

Conservation of biodiversity is critical for the coexistence of humans and the sustenance of other living organisms within the ecosystem. Identification and prioritization of specific regions to be conserved are impossible without proper information about the sites. Advanced monitoring agencies like the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) had accredited that the sum total of species that are now threatened with extinction is higher than ever before in the past and are progressing toward extinct at an alarming rate. Besides this, the conceptualized global responses to these crises are still inadequate and entail drastic changes. Therefore, more sophisticated monitoring and conservation techniques are required which can simultaneously cover a larger surface area within a stipulated time frame and gather a large pool of data. Hence, this study is an overview of remote monitoring methods in biodiversity conservation via a survey of evidence-based reviews and related studies, wherein the description of the application of some technology for biodiversity conservation and monitoring is highlighted. Finally, the paper also describes various transformative smart technologies like artificial intelligence (AI) and/or machine learning algorithms for enhanced working efficiency of currently available techniques that will aid remote monitoring methods in biodiversity conservation.

A comprehensive review on the applications of nano-biosensor-based approaches for non-communicable and communicable disease detection.

The outstretched applications of biosensors in diverse domains has become the reason for their attraction for scientific communities. Because they are analytical devices, they can detect both quantitative and qualitative biological components through the generation of detectable signals. In the recent past, biosensors witnessed significant changes and developments in their design as well as features. Nanotechnology has revolutionized sensing phenomena by increasing biodiagnostic capacity in terms of specificity, size, and cost, resulting in exceptional sensitivity and flexibility. The steep increase of non-communicable diseases across the world has emerged as a matter of concern. In parallel, the abrupt outbreak of communicable diseases poses a serious threat to mankind. For decreasing the morbidity and mortality associated with various communicable and non-communicable diseases, early detection and subsequent treatment are indispensable. Detection of different biological markers generates quantifiable signals that can be electrochemical, mass-based, optical, thermal, or piezoelectric. Speculating on the incumbent applicability and versatility of nano-biosensors in large disciplines, this review highlights different types of biosensors along with their components and detection mechanisms. Moreover, it deals with the current advancements made in biosensors and the applications of nano-biosensors in detection of various non-communicable and communicable diseases, as well as future prospects of nano-biosensors for diagnostics.

Molecular prospect of type-2 diabetes: Nanotechnology based diagnostics and therapeutic intervention.

About ninety percent of all diabetic conditions account for T2D caused due to abnormal insulin secretion/ action or increased hepatic glucose production. Factors that contribute towards the aetiology of T2D could be well explained through biochemical, molecular, and cellular aspects. In this review, we attempt to explain the recent evolving molecular and cellular advancement associated with T2D pathophysiology. Current progress fabricated in T2D research concerning intracellular signaling cascade, inflammasome, autophagy, genetic and epigenetics changes is discretely explained in simple terms. Present available anti-diabetic therapeutic strategies commercialized and their limitations which are needed to be acknowledged are addressed in the current review. In particular, the pre-eminence of nanotechnology-based approaches to nullify the inadequacy of conventional anti-diabetic therapeutics and heterogeneous nanoparticulated systems exploited in diabetic researches are also discretely mentioned and are also listed in a tabular format in the review. Additionally, as a future prospect of nanotechnology, the review presents several strategic hypotheses to ameliorate the austerity of T2D by an engineered smart targeted nano-delivery system. In detail, an effort has been made to hypothesize novel nanotechnological based therapeutic strategies, which exploits previously described inflammasome, autophagic target points. Utilizing graphical description it is explained how a smart targeted nano-delivery system could promote ß-cell growth and development by inducing the Wnt signaling pathway (inhibiting Gsk3ß), inhibiting inflammasome (inhibiting NLRP3), and activating autophagic target points (protecting Atg3/Atg7 complex from oxidative stress) thereby might ameliorate the severity of T2D. Additionally, several targeting molecules associated with autophagic and epigenetic factors are also highlighted, which can be exploited in future diabetic research.

Emerging Molecular Prospective of SARS-CoV-2: Feasible Nanotechnology Based Detection and Inhibition.

The rapid dissemination of SARS-CoV-2 demonstrates how vulnerable it can make communities and is why it has attained the status of global pandemic. According to the estimation from Worldometer, the SARS-CoV-2 affected cases and deaths are exponentially increasing worldwide, marking the mortality rate as ∼3.8% with no probability of its cessation till now. Despite massive attempts and races among scientific communities in search of proper therapeutic options, the termination of this breakneck outbreak of COVID-19 has still not been made possible. Therefore, this review highlights the diverse molecular events induced by a viral infection, such as autophagy, unfolded protein response (UPR), and inflammasome, illustrating the intracellular cascades regulating viral replication inside the host cell. The SARS-CoV-2-mediated endoplasmic reticulum stress and apoptosis are also emphasized in the review. Additionally, host's immune response associated with SARS-CoV-2 infection, as well as the genetic and epigenetic changes, have been demonstrated, which altogether impart a better understanding of its epidemiology. Considering the drawbacks of available diagnostics and medications, herein we have presented the most sensitive nano-based biosensors for the rapid detection of viral components. Moreover, conceptualizing the viral-induced molecular changes inside its target cells, nano-based antiviral systems have also been proposed in this review.

DrRecQ regulates guanine quadruplex DNA structure dynamics and its impact on radioresistance in Deinococcus radiodurans.

The GC-rich genome of Deinococcus radiodurans contains a very high density of putative guanine quadruplex (G4) DNA motifs and its RecQ (drRecQ) was earlier characterized as a 3'→5' dsDNA helicase. We saw that N-Methyl mesoporphyrin IX (NMM), a G4 DNA binding drug affected normal growth as well as the gamma radiation resistance of the wild-type bacterium. Interestingly, NMM treatment and recQ deletion showed additive effect on normal growth but there was no effect of NMM on gamma radiation resistance of recQ mutant. The recombinant drRecQ showed ~400 times higher affinity to G4 DNA (Kd  = 11.74 ± 1.77 nM) as compared to dsDNA (Kd  = 4.88 ± 1.30 µM). drRecQ showed ATP independent helicase function on G4 DNA, which was higher than ATP-dependent helicase activity on dsDNA. Unlike wild-type cells that sparingly stained for G4 structure with Thioflavin T (ThT), recQ mutant showed very high-density of ThT fluorescence foci on DNA indicating an important role of drRecQ in regulation of G4 DNA structure dynamics in vivo. These results together suggested that drRecQ is an ATP independent G4 DNA helicase that plays an important role in the regulation of G4 DNA structure dynamics and its impact on radioresistance in D. radiodurans.

Maintenance of multipartite genome system and its functional significance in bacteria.

Bacteria are unicellular organisms that do not show compartmentalization of the genetic material and other cellular organelles as seen in higher organisms. Earlier, bacterial genomes were defined as single circular chromosome and extrachromosomal plasmids. Recently, many bacteria were found harbouringmultipartite genome system and the numbers of copies of genome elements including chromosomes vary from one to several per cell. Interestingly, it is noticed that majority of multipartite genome-harbouring bacteria are either stress tolerant or pathogens. Further, it is observed that the secondary genomes in these bacteria encode proteins that are involved in bacterial genome maintenance and also contribute to higher stress tolerance, and pathogenicity in pathogenic bacteria. Surprisingly, in some bacteria the genes encoding the proteins of classical homologous recombination pathways are present only on the secondary chromosomes, and some do not have either of the classical homologous recombination pathways. This review highlights the presence of ploidy and multipartite genomes in bacterial system, the underlying mechanisms of genome maintenance and the possibilities of these features contributing to higher abiotic and biotic stress tolerance in these bacteria.

Studies of protein-protein interactions in Fanconi anemia pathway to unravel the DNA interstrand crosslink repair mechanism.

Fanconi anemia (FA), a cancer predisposition syndrome exhibits hallmark feature of radial chromosome formation, and hypersensitivity to DNA crosslinking agents. A set of FA pathway proteins mainly FANCI, FANCD2 and BRCA2 are expressed to repair the covalent crosslink between the dsDNA. However, FA, BRCA pathways play an important role in DNA ICL repair as well as in homologous recombination repair, but the presumptive role of FA-BRCA proteins has not clearly explored particularly in context to function associated protein-protein interactions (PPIs). Here, in-vivo, in-vitro and in-silico studies have been performed for functionally relevant domains of FANCI, FANCD2 and BRCA2. To our conclusion, FANCI ARM repeat interacts with FANCD2 CUE domain and BRCA2 C-terminal region. Interestingly, FANCD2 CUE domain also interacts strongly with BRCA2 C-terminal region. Interactions between BRCA2 CTR and functionally relevant mutations Ser222Ala (cell cycle checkpoint mutant) and Leu231Arg (DNA ICL repair mutant) present in FANCD2 CUE domain have been analysed. To our finding, these mutations abrogate the binding between FANCD2 CUE domain and BRCA2 CTR. Furthermore, (1) different domain of FANCI, FANCD2 and BRCA2 are playing important role in PPIs, (2) mutations cause the impairment in the PPIs which in turn may disrupt the DNA ICL repair mechanism.