The rapid development of engineered nanomaterials (ENMs) for use in food, consumer products, medicine, and the environment has raised considerable concern about their potential health effects. Conventional toxicological frameworks may inadequately capture the dynamic dose- and time-dependent behaviour of engineered nanomaterials. Increasing evidence is showing that both the magnitude of the dose and duration of the exposure are key determinants of toxicity; however, these elements are not always taken into consideration while assessing safety. This review paper will present the current state of knowledge regarding the dose and time dependent toxicity of the four major classes of ENMs - metals, metal oxides, polymers, and carbon-based materials - with a particular focus on how the physicochemical properties of each type of ENM (size, surface charge, coating, and agglomeration state) can modulate biological responses. Mechanistic explanations will be provided for classes of chemicals related to oxidative stress, inflammation, mitochondrial dysfunction, and genotoxicity, in terms of cumulative and delayed actions. Finally, the implications for human risk assessment will be discussed, with an emphasis on the need for standardized dosing metrics, chronic exposure studies and toxicokinetic integration to provide a basis for evidence-based regulatory decisions and the protection of public health.
Although plants are exposed to many environmental stressors (heat, drought, salinity, and pathogen), they survive by rapidly reprogramming their gene expression. Recent findings show that many regulatory mechanisms are maintained within liquid-liquid phase separation (LLPS) formed biomolecular condensates, instead of maintaining these mechanisms within membrane-bound organelles. LLPS has been shown to exist in plant cells; however, the integration of LLPS with functional stress adaptations and gene regulations is still unclear from the studies that have been published thus far. In this review, we discuss recent research that demonstrates how these biomolecular condensates act as dynamic regulatory centers by linking environmental stress perception to transcriptional and post-transcriptional regulation of genes in plants. We describe the biophysical principles that govern the occurrence of LLPS in a plant cellular environment and provide an overview of how both abiotic (e.g., drought, heat) and biotic (i.e., pathogens) stressors initiate the LLPS and remodel nuclear and cytosolic condensate structures. The focus of this work will be on the effects of stress-induced changes (both qualitatively and quantitatively) in the condensate composition and material properties on transcription factor activity (either as an activator or repressor) and the organization of chromatin, RNA stability, and selective translation. We will also discuss post-translational modifications (PTMs) that modulate condensate dynamics and allow for reversibility. Collectively, these findings suggest that LLPS likely contributes significantly to gene regulation and stress adaptation in plants, although the degree of mechanistic validation varies among different condensate systems.
Sonia Mahi, B. Rathod, Sachin Puri· Plant, Cell and Environment· 0 citations
This review highlights key engineering strategies enabling in vivo CAR T-cell generation, summarizes emerging clinical research and development, and discusses future opportunities for expanding in vivo CAR T-cell therapies as scalable immunotherapy platforms.
Janani Gopalakrishnan, B. Rathod, Sachin Puri· International Immunopharmaco...· 0 citations
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