Protein synthesis is often regulated at the level of initiation of translation, making it a critical step. This regulation occurs by both the cis‐regulatory elements, which are located in the 5′‐ and 3′‐UTRs (untranslated regions), and trans‐acting factors. A breakdown in this regulation machinery can perturb cellular metabolism, leading to various physiological abnormalities. The highly structured UTRs, along with features such as GC‐richness, upstream open reading frames and internal ribosome entry sites, significantly influence the rate of translation of mRNAs. In this review, we discuss how changes in the cis‐regulatory sequences of the UTRs, for example, point mutations and truncations, influence expression of specific genes at the level of translation. Such modifications may tilt the physiological balance from healthy to diseased states, resulting in conditions such as hereditary thrombocythaemia, breast cancer, fragile X syndrome, bipolar affective disorder and Alzheimer's disease. This information tends to establish the crucial role of UTRs, perhaps as much as that of coding sequences, in health and disease.

We have cloned the cDNA of the heme-regulated eIF-2 alpha kinase (HRI) of rabbit reticulocytes. In vitro translation of mRNA transcribed from the HRI cDNA yields a 90-kDa polypeptide that exhibits eIF-2 alpha kinase activity and is recognized by a monoclonal antibody directed against authentic HRI. The open reading frame sequence of the HRI cDNA contains all 11 catalytic domains of protein kinases with consensus sequences of protein-serine/threonine kinases in conserved catalytic domains VI and VIII. The HRI cDNA also contains an insert of approximately 140 amino acids between catalytic domains V and VI. The HRI cDNA coding sequence has extensive homology to GCN2 protein kinase of Saccharomyces cerevisiae and to human double-stranded-RNA-dependent eIF-2 alpha kinase. This observation suggests that GCN2 protein kinase may be an eIF-2 alpha kinase in yeast. In addition, HRI has an unusually high degree of homology to three protein kinases (NimA, Wee1, and CDC2) that are involved in the regulation of the cell cycle.

The microenvironment in which cancer resides plays an important role in regulating cancer survival, progression, malignancy and drug resistance. Tumor microenvironment (TME) consists of heterogeneous number and types of cellular and non-cellular components that vary in relation to tumor phenotype and genotype. In recent, non-cellular secreted components of microenvironmental heterogeneity have been suggested to contain various growth factors, cytokines, RNA, DNA, metabolites, structural matrix and matricellular proteins. These non-cellular components have been indicated to orchestrate numerous ways to support cancer survival and progression by providing metabolites, energy, growth signals, evading immune surveillance, drug resistance environment, metastatic and angiogenesis cues. Thus, switching action from pro-cancer to anti-cancer activities of these secreted components of TME has been considered as a new avenue in cancer therapeutics and drug resistance. In this report, we summarize the recent pre-clinical and clinical evidences to emphasize the importance of non-cellular components of TME in achieving precision therapeutics and biomarker study.

Dioscorea bulbifera is a potent medicinal plant used in both Indian and Chinese traditional medicine owing to its rich phytochemical diversity. Herein, we report the rapid synthesis of novel Au_coreAg_shell nanoparticles by D. bulbifera tuber extract (DBTE). Au_coreAg_shell NPs synthesis was completed within 5 h showing a prominent peak at 540 nm. HRTEM analysis revealed 9 nm inner core of elemental gold covered by a silver shell giving a total particle diameter upto 15 nm. Au_coreAg_shellNPs were comprised of 57.34 ± 1.01% gold and 42.66 ± 0.97% silver of the total mass. Au_coreAg_shellNPs showed highest biofilm inhibition upto 83.68 ± 0.09% against A. baumannii. Biofilms of P. aeruginosa, E. coli, and S. aureus were inhibited up to 18.93 ± 1.94%, 22.33 ± 0.56%, and 30.70 ± 1.33%, respectively. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) confirmed unregulated cellular efflux through pore formation leading to cell death. Potent antileishmanial activity of Au_coreAg_shellNPs (MIC = 32 µg/mL) was confirmed by MTT assay. Further SEM micrographs showed pronounced deformity in the spindle shaped cellular morphology changing to spherical. This is the first report of synthesis, characterization, antibiofilm, and antileishmanial activity of Au_coreAg_shellNPs synthesized by D. bulbifera.

How tumour suppressor p53 bifurcates cell cycle arrest and apoptosis and executes these distinct pathways is not clearly understood. We show that BAX and PUMA promoters harbour an identical MAR element and are transcriptional targets of SMAR1. On mild DNA damage, SMAR1 selectively represses BAX and PUMA through binding to the MAR independently of inducing p53 deacetylation through HDAC1. This generates an anti‐apoptotic response leading to cell cycle arrest. Importantly, knockdown of SMAR1 induces apoptosis, which is abrogated in the absence of p53. Conversely, apoptotic DNA damage results in increased size and number of promyelocytic leukaemia (PML) nuclear bodies with consequent sequestration of SMAR1. This facilitates p53 acetylation and restricts SMAR1 binding to BAX and PUMA MAR leading to apoptosis. Thus, our study establishes MAR as a damage responsive cis element and SMAR1–PML crosstalk as a switch that modulates the decision between cell cycle arrest and apoptosis in response to DNA damage.