Statins as anti-tumor agents: A paradigm for repurposed drugs.

BACKGROUND: Statins, frequently prescribed medications, work by inhibiting the rate-limiting enzyme HMG-CoA reductase (HMGCR) in the mevalonate pathway to reduce cholesterol levels. Due to their multifaceted benefits, statins are being adapted for use as cost-efficient, safe and effective anti-cancer treatments. Several studies have shown that specific types of cancer are responsive to statin medications since they rely on the mevalonate pathway for their growth and survival. RECENT FINDINGS: Statin are a class of drugs known for their potent inhibition of cholesterol production and are typically prescribed to treat high cholesterol levels. Nevertheless, there is growing interest in repurposing statins for the treatment of malignant neoplastic diseases, often in conjunction with chemotherapy and radiotherapy. The mechanism behind statin treatment includes targeting apoptosis through the BCL2 signaling pathway, regulating the cell cycle via the p53-YAP axis, and imparting epigenetic modulations by altering methylation patterns on CpG islands and histone acetylation by downregulating DNMTs and HDACs respectively. Notably, some studies have suggested a potential chemo-preventive effect, as decreased occurrence of tumor relapse and enhanced survival rate were reported in patients undergoing long-term statin therapy. However, the definitive endorsement of statin usage in cancer therapy hinges on population based clinical studies with larger patient cohorts and extended follow-up periods. CONCLUSIONS: The potential of anti-cancer properties of statins seems to reach beyond their influence on cholesterol production. Further investigations are necessary to uncover their effects on cancer promoting signaling pathways. Given their distinct attributes, statins might emerge as promising contenders in the fight against tumorigenesis, as they appear to enhance the efficacy and address the limitations of conventional cancer treatments.

A Prebiotic Genetic Nucleotide as an Early Darwinian Ancestor for Pre-RNA Evolution.

Prebiotic genetic nucleotides (PGNs) often outcompete canonical alphabets in the formation of nucleotides and subsequent RNA oligomerization under early Earth conditions. This indicates that the early genetic code might have been dominated by pre-RNA that contained PGNs for information transfer and catalysis. Despite this, deciphering pre-RNAs' capacity to acquire function and delineating their evolutionary transition to a canonical RNA World has remained under-researched in the origins of life (OoL) field. We report the synthesis of a prebiotically relevant nucleotide (BaTP) containing the noncanonical nucleobase barbituric acid. We demonstrate the first instance of its enzymatic incorporation into an RNA, using a T7 RNA polymerase. BaTP's incorporation into baby spinach aptamer allowed it to retain its overall secondary structure and function. Finally, we also demonstrate faithful transfer of information from the pre-RNA-containing BaTP to DNA, using a high-fidelity RNA-dependent DNA polymerase, alluding to how selection pressures and complexities could have ensued during the molecular evolution of the early genetic code.

Encapsulated nanopesticides application in plant protection: Quo vadis?

The increased global food insecurity due to the growing population can be addressed with precision and sustainable agricultural practices. To tackle the issues regarding food insecurity, farmers used different agrochemicals that improved plant growth and protection. Among these agrochemicals, synthetic pesticides used for plant protection in the agricultural field have various disadvantages. Conventional applications of synthetic pesticides have drawbacks such as rapid degradation, poor solubility, and non-target effects, as well as increased pesticide runoff that pollutes the environment. Nanotechnology has evolved as a potential solution to increase agricultural productivity through the development of different nanoforms of agrochemicals such as nanopesticides, nano-fabricated fertilizers, nanocapsules, nanospheres, nanogels, nanofibers, nanomicelles, and nano-based growth promoters. Encapsulation of these pesticides inside the nanomaterials has provided good biocompatibility over conventional application by inhibiting the early degradation of active ingredients (AI), increasing the uptake and adhesion of pesticides, improving the stability, solubility, and permeability of the pesticides, and decreasing the environmental impacts due to the pesticide runoff. In this review, different nanoforms of encapsulated pesticides and their smart delivery systems; nanocarriers in RNA interference (RNAi) based pesticides; environmental fate, practical implications, management of nanopesticides; and future perspectives are discussed.

Ameliorative effects of Si-SNP synergy to mitigate chromium induced stress in Brassica juncea.

Hyperaccumulation of heavy metal in agricultural land has hampered yield of important crops globally. It has consequently deepened concerns regarding the burning issue of food security in the world. Among heavy metals, Chromium (Cr) is not needed for plant growth and found to pose detrimental effects on plants. Present study highlights the role of exogenous application of sodium nitroprusside (SNP, exogenous donor of NO) and silicon (Si) in alleviating detrimental ramification of Cr toxicity in Brassica juncea. The exposure of B. juncea to Cr (100 µM) under hydroponic system hampered the morphological parameters of plant growth like length and biomass and physiological parameters like carotenoid and chlorophyll contents. It also resulted in oxidative stress by disrupting the equilibrium between ROS production and antioxidant quenching leading to accumulation of ROS such as hydrogen peroxide (H2O2) and superoxide (O2•‾) radicle which causes lipid peroxidation. However, application of Si and SNP both individually and in combination counteracted oxidative stress due to Cr by regulating ROS accumulation and enhancing antioxidant metabolism by upregulation of antioxidant genes of DHAR, MDHAR, APX and GR. As the alleviatory effects were more pronounced in plants treated with combined application of Si and SNP; therefore, our findings suggest that dual application of these two alleviators can be used to mitigate Cr stress.

Recent Advances and Perspectives of Nanomaterials in Agricultural Management and Associated Environmental Risk: A Review.

The advancement in nanotechnology has enabled a significant expansion in agricultural production. Agri-nanotechnology is an emerging discipline where nanotechnological methods provide diverse nanomaterials (NMs) such as nanopesticides, nanoherbicides, nanofertilizers and different nanoforms of agrochemicals for agricultural management. Applications of nanofabricated products can potentially improve the shelf life, stability, bioavailability, safety and environmental sustainability of active ingredients for sustained release. Nanoscale modification of bulk or surface properties bears tremendous potential for effective enhancement of agricultural productivity. As NMs improve the tolerance mechanisms of the plants under stressful conditions, they are considered as effective and promising tools to overcome the constraints in sustainable agricultural production. For their exceptional qualities and usages, nano-enabled products are developed and enforced, along with agriculture, in diverse sectors. The rampant usage of NMs increases their release into the environment. Once incorporated into the environment, NMs may threaten the stability and function of biological systems. Nanotechnology is a newly emerging technology, so the evaluation of the associated environmental risk is pivotal. This review emphasizes the current approach to NMs synthesis, their application in agriculture, interaction with plant-soil microbes and environmental challenges to address future applications in maintaining a sustainable environment.