Certain excitable cells, such as those in cardiac and smooth muscle, are known to form electrical syncytia. Cells within a syncytium are coupled to adjacent cells by means of structures known as gap junctions, which provide electrical continuity between cells. This results in the spread and propagation of electrical activity, such as action potentials (APs), from the originating cell to other cells in its syncytium. We propose that this ability of APs to propagate through an electrical syncytium depends on various syncytial features, and also the AP profile. The current study attempts to investigate these various factors using a computational approach. Simulations were conducted on a model of a three-dimensional syncytium using the NEURON simulation platform. The results confirm that the capacity of action potentials to propagate in a syncytium is influenced by the features of the action potential, and also the arrangement of cells within the syncytium. The excitability of biophysically identical cells was found to differ based on the size of the syncytium, their location within it, and the extent of gap junctional coupling between neighboring cells. Only a window of gap junctional coupling levels allowed both the initiation and propagation of action potentials. The results clearly exhibit the role of AP diversity and syncytial features in determining the spread of action potentials. This has significant implications for understanding the functioning of syncytial tissues, such as the detrusor smooth muscle, both in physiology and in disease.

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Although human and murine Endothelial Progenitor Cells (EPCs) are routinely used for research, the results can only be imperfectly analyzed due to our limited understanding of source-specific differential responses to stress. Although the routinely used cellular and functional assays are effective for detection of EPC dysfunction (EPD) in single source test systems, there is lack of a universal detection system capable of detecting high glucose (HG) and/or Diabetes mellitus (DM)-induced EPD irrespective of source or site. To remedy this lacuna we compared the test systems from both cell sources. Comparison of sensitivity of various cellular assays revealed that of all the assays performed, only colony formation assays (CFU) showed comparable responses to diabetes/high glucose in both test systems, while cell adhesion assay (CAA), proliferation potential and viability differed in their responses to HG. On the other hand, the functional assays i.e. tubule formation, chemotactic migration assay and CXCR4 and VEGFR2 mRNA expression were uniformly affected by HG in vitro and DM in vivo. Interestingly, other parameters studied i.e. nitric oxide, reactive oxygen species (ROS) and manganese superoxide dismutase (MnSOD) showed dissimilar responses to HG and DM exposure. On this basis, we propose a panel of assays comprising CFU, tubule formation, chemotactic-migration and CXCR4 and VEGFR2 mRNA expression that can accurately detect HG-/DM-induced EPD irrespective of various systemic factors. These assays will also enhance uniformity across data sets and increase accuracy of EPD detection in human and murine systems.

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Iron oxide nanoparticles (IONPs) have attracted extensive applications in biomedical fields such as drug delivery, magnetic resonance imaging (MRI) for medical diagnosis and cancer therapeutics. Designing efficient IONPs for cancer treatment requires their surface modification with suitable biocompatible organic and inorganic molecules having multifunctional groups. This review focuses on recent developments in the area of surface engineering of IONPs and their potential applications in cancer therapy. The imaging and targeting potential of IONPs in conjugation with luminescent markers and receptor molecules are briefly discussed.

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Abrin is a highly lethal ribosome-inactivating protein of high relevance in bio-warfare. Neutralizing antibodies to abrin reported so far afford protection in a very small window with no rescue observed post-abrin exposure. The utility of the most specific mode of defense against abrin poisoning is thus undermined. We proposed that intracellular delivery of antibodies which otherwise lack the ability to enter cells would increase the therapeutic potential. Towards this, we analyzed the use of silica nanoparticles and chimeric Sesbania mosaic virus-like particles in delivering antibodies inside cells. The antibody-nanocarrier conjugate was found to be effective in protecting cells from abrin-mediated toxicity when administered as long as 9 h prior and up to 1 h post abrin exposure. These results highlight the potential of nanocarrier-based intracellular delivery of neutralizing antibodies in widening the therapeutic window for prophylaxis and to some extent post-exposure treatment of abrin poisoning.

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Leukemia is a common cancer in the paediatric group with good prognosis and the overall survival rate for leukemia has improved over the years. However, despite the chemopreventive agents and better diagnostic and therapeutic strategies, novel strategies and approaches shows better prognosis and overall survival, particularly if detected early. The common modality of haematological malignancy management is chemotherapy. Although good response is noted early on treatment, resistance to the chemotherapy is observed later due to the drug resistance, may be due to increased expression of P-glycoprotein (Pgp) and multidrug resistance protein (MRP1), which may be reversed by inhibitors of the proteins. However, adverse side effects of the chemotherapeutic agents are a cause of concern in several patients. Hence, plant derived molecules (phytochemicals) may be considered as an alternative to the synthetic inhibitors. Phytochemicals possess not only chemopreventive and chemotherapeutic potential, but also can be used for prevention and reversal of drug resistance. Phytochemicals are generally nontoxic, economic and minimal adverse effects are observed. Potential phytochemicals may be used as stand-alone or in combination for cancer treatment.

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Senescence is a phenomenon of ‘end of cells replicative capacity’, characterized by irreversible cell cycle arrest which in the context of cancer, will contain the growth of tumour. Hence possibility of using pro-senescence therapies for cancer therapeutics has generated substantial interest. In this regards there are several reports showing that senescence can be induced in cancer cells by genotoxic agents used in anti-neoplastic therapy, such senescence is called ‘therapy induced senescence’ (TIS). Therapy induced senescent cells undergo cell death or eventual immune-mediated clearance. However, recent reports also show the existence of ‘therapy induced senescence reversal’ mechanisms in some cancers, wherein after a definite period of time, senescent cells overcome the arrest and re-enter the cell cycle, eventually repopulating the tumour which will limit the use of senescence for cancer therapeutics. The data also highlighs that TIS is complex and we do not fully understand many aspects of this phenomenon. Therefore to harness senescence for cancer therapeutics, a deeper understanding of the underlying molecular mechanisms governing establishment and reversal of senescence is required. In the current review, we have discussed current knowledge of the therapeutic agents inducing senescence, their mechanism of induction and the implication of senescence reversal in cancers.

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