Extirpating the cancer stem cell hydra: Differentiation therapy and Hyperthermia therapy for targeting the cancer stem cell hierarchy.

Ever since the discovery of cancer stem cells (CSCs), they have progressively attracted more attention as a therapeutic target. Like the mythical hydra, this subpopulation of cells seems to contribute to cancer immortality, spawning more cells each time that some components of the cancer cell hierarchy are destroyed. Traditional modalities focusing on cancer treatment have emphasized apoptosis as a route to eliminate the tumor burden. A major problem is that cancer cells are often in varying degrees of dedifferentiation contributing to what is known as the CSCs hierarchy and cells which are known to be resistant to conventional therapy. Differentiation therapy is an experimental therapeutic modality aimed at the conversion of malignant phenotype to a more benign one. Hyperthermia therapy (HT) is a modality exploiting the changes induced in cells by the application of heat produced to aid in cancer therapy. While differentiation therapy has been successfully employed in the treatment of acute myeloid leukemia, it has not been hugely successful for other cancer types. Mounting evidence suggests that hyperthermia therapy may greatly augment the effects of differentiation therapy while simultaneously overcoming many of the hard-to-treat facets of recurrent tumors. This review summarizes the progress made so far in integrating hyperthermia therapy with existing modules of differentiation therapy. The focus is on studies related to the successful application of both hyperthermia and differentiation therapy when used alone or in conjunction for hard-to-treat cancer cell niche with emphasis on combined approaches to target the CSCs hierarchy.

Comprehensive study of high pressure annealing on the ferroelectric properties of Hf0.5Zr0.5O2 thin films.

Thin films of ferroelectric materials are potential candidates to be implemented in the unfolding of a new paradigm in high-density memory devices. As the thickness of these films reaches the sub-10 nm level, the interface properties between the electrode and ferroelectric material undergo significant changes that play a crucial role in governing the ferroelectric behavior. The present state-of-the-art approach presents a detailed investigation of different high pressure annealing (HPA) conditions through simulation studies. The simulation studies were performed using Landau-Khalatnikov equations, with Landau's parameters calculated using the least regression method as described in the Method S1. The extracted coefficients were used to determine various relationships (free energy, ferroelectric potential and negative capacitance) with which to observe the impact of HPA on the negative capacitance (NC) effect on account of the majority ferroelectric phase. To verify the simulation results, pulse transient switching measurements were conducted using Pt/Ti/TiN/Hf0.5Zr0.5O2/TiN-based metal-ferroelectric-metal (MFM) devices to study the coercive field, interfacial capacitance and load resistance behavior. The results suggest that the non-ferroelectric portion (t-phase) coexists with the ferroelectric (o-phase) within the thin layer of the MFM capacitor adjacent to TiN electrode, which undergoes a phase transformation from the t-phase to the o-phase when exposed to different HPA conditions as well as electric field cycling during PS measurements. The simulation and experimental results confirm that the 550 °C at 50 atm N2 environment provides the best possibility of achieving the highest ferroelectric characteristics with the lowest proportion of the non-ferroelectric phase and thus the maximum NC effect as well.

Highly Exfoliated MWNT-rGO Ink-Wrapped Polyurethane Foam for Piezoresistive Pressure Sensor Applications.

The fabrication of pressure sensors based on reduced graphene oxide (rGO) as the sensing material is challenging due to the intrinsic hydrophobic behavior of graphene oxide inks as well as the agglomeration of graphene oxide flakes after reduction. Hydrazine (a reducing agent) and a dual-component additive comprising benzisothiazolinone and methylisothiazolinone in appropriate proportion were used to synthesize a rGO ink with a hydrophilic nature. Utilizing this hydrophilic rGO ink mixed with multiwalled carbon nanotubes (MWNTs), a very simple, low-cost approach is demonstrated for the fabrication of a pressure sensor based on polyurethane (PU) foam coated with the MWNT-rGO ink (MWNT-rGO@PU foam). The MWNT-rGO@PU foam-based devices are shown to be versatile pressure sensors with the potential to detect both small-scale and large-scale movements. At low pressure (below 2.7 kPa, 50% strain), the formation of microcracks that scatter electrical charges results in a detectable increase in resistance suitable for detecting small-scale motion. At a higher pressure, the compressive contact of the coated faces of the PU foam results in a sharp decrease in resistance suitable for monitoring of large-scale motion. Moreover, these sensors exhibit good flexibility and reproducibility over 5000 cycles. The versatility of this sensor has been demonstrated in a wide range of applications, such as speech recognition, health monitoring, and body motion detection. The significant advantages of this sensor are that its cost is low, it is easy to fabricate, and it has a versatility that renders it favorable to health-monitoring applications.

Longevity effect of a polysaccharide from Chlorophytum borivilianum on Caenorhabditis elegans and Saccharomyces cerevisiae.

The traditional Indian medicine, Ayurveda, provides insights and practical solutions towards a healthy life style. Rasayana is a branch of Ayurveda known for preserving and promoting health, enhancing the quality of life and delaying the aging process. In the traditional knowledge, the Rasayana herb, Chlorophytum borivilianum (C. borivilanum) is regarded as a general health promoting tonic that delays aging and increases lifespan, cognitive function and physical strength. Aging is a complex and multifactorial physiological phenomenon that manifests itself over a wide range of biological systems, tissues, and functions. Longevity is an obvious marker of physiological aging. Simple model systems such as the single-cell budding yeast Saccharomyces cerevisiae (S. cerevisiae) and the nematode, Caenorhabditis elegans (C. elegans) are widely used to study the aging process and longevity. Here, we show that a polysaccharide fraction obtained from C. borivilianum increases the lifespan of S. cerevisiae and C. elegans, using an automated screening platform (ChronoscreenTM). Chemical analysis of this extract revealed a low molecular weight polysaccharide of 1000 Da, predominantly comprising Glu1→6Glu linkage. This polysaccharide showed significant dose-dependent extension of the median lifespan of S. cerevisiae by up to 41% and of the median lifespan of C. elegans by up to 10%. Taking cue from these results and the traditionally described benefits of Rasayanas on skin rejuvenation, we tested in vitro the polysaccharide for potential skin benefits. In a keratinocyte culture, we observed that this polysaccharide increased cell proliferation significantly, and induced synthesis of hyaluronic acid (HA), a well-known extracellular matrix component. Furthermore, when added to culture medium of human reconstructed epidermis, we observed an enhanced production of epidermal markers, e.g. CD44 and HA that are otherwise diminished in aged skin. Together, these results suggest that in addition to life-span extension of S. cerevisiae and C. elegans, a polysaccharide from the Rasayana herb, C. borivilianum may have beneficial effects on skin aging parameters.