HSP70: a therapeutic biomarker for treatment of glioma

Gliomas are amongst the most malignant, invasive and recurrent forms of brain tumour with very short survival rate due to high chemoresistance. Recently, highly inducible molecular chaperones HSP70 and HSP90 are emerging as important anti-cancer targets. Previously, proteomic analysis had demonstrated that post-induction of HSP70 on HSP90 inhibition undermines the efficacy of treatment. The present study has quantified transcriptional levels and Akt/PKB activity of Hsp70 and Hsp90α in glioma cell lines. In order to evaluate the therapeutic value of both chaperones, HSP70 and HSP90 were targeted in glioma cells U87-MG using VER-155008 and 17-AAG, respectively. Improved efficacy of HSP70 and HSP90 inhibitors was evaluated using a chemosensitivity assay. MicroRNAs (miRNAs) are highly conserved small non-coding RNA molecules (21-24 nucleotides) that regulate simultaneously the expression of hundreds of mRNA targets, and are reported to be aberrantly expressed in glioma. Therefore, miRNA microarray technology was used to evaluate the efficacy of these inhibitory drugs compared with Temozolomide (TMZ) which is used as a standard treatment for glioma. Microarray data identified 154 miRNAs using either stringent or non-stringent parameters. 16 miRNAs were overlapped with treatments, 15 were upregulated, while 13 were overlapped between Temozolomide and VER-155008. In Temozolomide and VER-155008 treatment, Hsa-miR-194p was upregulated by 139 and 63 fold, respectively, Hsa-miR-215 was upregulated 165 and 61 fold, respectively, Hsa-miR-449a was upregulated by 62 and 77 fold, respectively and Hsa-miR-744-5p was upregulated by 63 and 43 fold, respectively. 17-AAG and VER-155008 treatment shown only one miRNA overlapping with 29 and 2 fold change, respectively. Hsa-miR-4636 was the only downregulated miRNA in TMZ and VER treatment with a 32 and 33 fold change, respectively. The miRNA target prediction software was used for the highly upregulated miRNAs: hsa-miR-194-5p, hsa-miR-215, hsa-miR-449a, hsa-miR-744-5p and hsa-miR-3161 correlating to Dnmt3a, Alcam, Cdk4, Dnajc16 (Hsp40) and R-Ras2 genes, respectively. Gene validation using qRT-PCR suggested no correlation between miRNA-mRNA levels, and thus, challenges the suitability of miRNAs technology as treatment predictors. In conclusion, the result for the protein data showed that HSP70 was inhibited on treatment with Temozolomide, 17-AAG and VER-155008 to 13, 0 and 20 %, respectively, while HSP90 inhibition was 84, 43 and 65 %, respectively, reflecting the affinities of these three compounds towards HSP90 compared to HSP70, and therefore infers that HSP70 could be a stronger therapeutic approach. In conclusion the result of the study has clearly demonstrated that HSP70 can be better therapeutic biomarker for treatment of glioma

Could the Anti-Chaperone VER155008 Replace Temozolomide for Glioma Treatment

Cancer inducible molecular chaperone HSP90 is of great importance as an anticancer target. Proteomic analysis showed that inhibiting HSP90 by the geldanamycin derivative, 17-AAG elevated the expression of the co-chaperone Hsp70. In this study we used HSP90 selective inhibitor 17-AAG and HSP70/90 dual inhibitor, VER155008 (VER) in U87-MG glioma cells. miRNAs microarray technology was used to evaluate the efficacy of these inhibitory drugs compared with temozolomide (TMZ), used as a standard treatment for glioma. Microarrays data identified 154 differentially expressed miRNAs using stringent or unstringent parameters. 16 miRNAs were overlapped between treatments, 13 upregulated and one downregulated miRNA were overlapped between TMZ and VER. The miRNA target prediction software was used for these overlapped miRNAs and identified 6 of the 13 upregulated miRNAs target methyltransferase genes. The IC50, together with Akt and HSP70 and 90 protein level data favour VER and TMZ to 17-AAG, however due to the selectivity of VER to cancer cells as a potent antichaperon, it may be more favourable to the standard TMZ

Impact of heat stress on expression pattern of nine rice heat shock factor genes and its traits related to tolerance

65-75Global warming is unusually increasing the earth temperature over the past century at an average rate of 0.07 per decade since 1880. The increased temperature exhibit greater impact on grain yield, approximately 5.18 million tons of rice yields due to heat wave. Heat shock factors (HSF) has major role in regulating heat shock proteins which in turn responsible for survival of plants in heat stress by refolding proteins, maintaining functional confirmation, aiding in host defence mechanism. The aim of this research was to analyse phenological, biochemical changes and key genes highly expressed during heat stress at flowering stage in rice. Expression analysis of nine HSF genes had given a differential expression under heat stress as compared to controlled traits. This study suggested OsHSP26.7 as most responsive gene under heat stress and rice line 159, RRF-127, GP-145-103 and Annada with heat tolerant adaptive mechanisms and better performance under high temperatures and was found to be in correlation with the estimated biochemical traits. This can be taken as a base for heat tolerance response of the crop, which may be useful for further validation studies of the candidate genes for heat tolerance in the rice as well as other crop plants

Awareness about the concept of Green Corridor among medical student and doctors in a Rural Medical College of Maharashtra, India

Background: India\u27s traffic problem over the years has been the root cause of many deaths. During an medical emergency like organ transplantation over long distances, the unsuitability of roads and highways hamper in the worst way possible. In a developing unplanned country like India, where lane discipline is an alien concept, emergency lanes won\u27t sustain as of now. Thus, for provision of better health services, a temporary emergency lane has been implemented in organ transplantation cases known as a Green Corridor. It is a special route with manual operation of street signals and traffic to avoid any hindrances that could come in the way of an ambulance. Aims and Objectives: To learn about the awareness, strategies and possibilities of Green Corridor in India. Material and Method: This was an interventional study by the undergraduate students of Rural Medical College, Pravara Institute of Medical Sciences, Loni, Maharashtra. The study also included 350 Students and 150 Faculty members of Pravara Institute of Medical Sciences (Deemed University) and Practicing Doctors of Central Maharashtra were included in the survey. The survey conducted was in a pre and post-test format. Results: The study involved 500 participants out of which 135 were medical faculty and practicing doctor and 350 were students of Rural Medical College. The awareness among medical students about green corridor increased from 14% to 61%, while it went up to 71% from 26% in medical faculty after intervention. Willingness to donate organs increased from 57% to 66% and 78% to 85% among medical students and medical faculty, respectively. The participants gave suggestions to make available air ambulance & emergency roads and increase awareness regarding green corridor. Conclusion: From the survey conducted, it can be perceived that there is a massive lack of awareness about Green Corridor as well as reluctance for organ donation. Therefore, awareness should be created on a large scale so that no person is left oblivious. Even on a smaller scale, an implementation of the suggested strategies could make a massive difference in the present scenario regarding medical emergencies

Plasma etching and surface characteristics depending on the crystallinity of the BaTiO3 thin film

Due to its high dielectric constant (κ), the BaTiO3 (BTO) thin film has significant potential as a next-generation dielectric material for metal oxide semiconductor field-effect transistors (MOSFETs). Hence, the evaluation of the BTO thin film etching process is required for such nanoscale device applications. Herein, the etching characteristics and surface properties are examined according to the crystallinity of the BTO thin film. The results demonstrate that the etching rate is low in the high-crystallinity thin film, and the surface residues are much lower than in the low-crystallinity thin film. In particular, the accelerated Cl radicals in the plasma are shown to penetrate more easily into the low-crystallinity thin film than the high-crystallinity thin film. After the etching process, the surface roughness is significantly lower in the high-crystallinity thin film than in the low-crystallinity thin film. This result is expected to provide useful information for the process design of high-performance electronic devices

Role of Drug Repurposing in Cancer Treatment and Liposomal Approach of Drug Targeting

Cancer is the leading cause of death, and incidences are increasing significantly and patients suffering from it desperately need a complete cure from it. The science of using an already-invented drug that has been approved by the FDA for a new application is known as “drug repurposing.” Currently, scientists are drawn to drug repositioning science in order to investigate existing drugs for newer therapeutic uses and cancer treatment. Because of their unique ability to target cancer cells, recently repurposed drugs and the liposomal approach are effective in the treatment of cancer. Liposomes are nanovesicles that are drastically flexible, rapidly penetrate deeper layers of cells, and enhance intracellular uptake. More importantly, liposomes are biocompatible, biodegradable; entrap both hydrophobic and hydrophilic drugs. This chapter summarizes various approaches to drug repurposing, as well as drug repurposing methods, advantages and limitations of drug repurposing, and a liposomal approach to using repurposed drugs in cancer targeting. This chapter also summarizes liposomal structure, drug loading, and the mechanism of liposomes in targeted cancer treatment. The lipid-based liposomal approach is emerging as a powerful technique for improving drug solubility, bioavailability, reducing side effects, and improving the therapeutic efficacy of repurposed drugs for cancer treatment

ANALYSIS OF PAPR IN IFDMA SYSTEMS USING NORM TECHNIQUE

Interleaved Frequency Domain multiple access (IFDMA) utilizes single carrier modulation and frequency domain equalization and has similar performance as of orthogonal frequency division multiple access (OFDMA) and has been adopted for the uplink communications in release 8 LTE. But it is sensitive to non-linear effects duo to the high peak-toaverage power ratio (PAPR) of the transmitted signal .The reduction in PAPR is required in order to achieve better BER performance and more power efficiency. This paper presents an Reduced maximum complexity Max Norm algorithm [1] for reducing the PAPR in IFDMA signals .This method does not require the transmission of the side information to the receiver, which improves the utilization of bandwidth. The result has been shown using complementary cumulative distribution function (CCDF) plot and also have been compared with PAPR of IFDMA signals without implementing RCMN technique and which shows that the PAPR of IFDMA signals with RCMN technique have lower PAPR compared to IFDMA signals without using RCMN technique

Stable and Multilevel Data Storage Resistive Switching of Organic Bulk Heterojunction

Organic nonvolatile memory devices have a vital role for the next generation of electrical memory units, due to their large scalability and low-cost fabrication techniques. Here, we show bipolar resistive switching based on an Ag/ZnO/P3HT-PCBM/ITO device in which P3HT-PCBM acts as an organic heterojunction with inorganic ZnO protective layer. The prepared memory device has consistent DC endurance (500 cycles), retention properties (104 s), high ON/OFF ratio (105), and environmental stability. The observation of bipolar resistive switching is attributed to creation and rupture of the Ag filament. In addition, our conductive bridge random access memory (CBRAM) device has adequate regulation of the current compliance leads to multilevel resistive switching of a high data density storage

Two-dimensional materials memory devices with floating metal gate for neuromorphic applications

Emerging technologies such as neuromorphic computing and nonvolatile memories based on floating gate field-effect transistors (FETs) hold promise for addressing a wide range of artificial intelligence tasks. For example, neuromorphic computing seeks to emulate the human brain's functionality and employs a device that mimics the role of a synapse in the brain. However, achieving a high current ON/OFF ratio for the program and erase states of nonvolatile memory and neuromorphic computing device with a metal gate is necessary. This study demonstrates a multi-functional device based on heterostructures of transition metal dichalcogenides (TMDCs) with a metal floating gate. Five different channel materials (SnS2, WSe2, MoS2, WS2, and MoTe2) were employed, and hexagonal boron nitride (h-BN) was used as a tunneling layer. The study found that n-type SnS2 exhibits high endurance (15,000 cycles), good retention (2.4 × 105 s), and the highest current ON/OFF ratio (∼2.58 × 108) among the materials for the program and erase states. Moreover, the SnS2 device exhibits synaptic behavior and offers highly stable operation at room temperature. Furthermore, the device shows high linearity in both potentiation and depression, with good retention time and repeatable results with low cycle-to-cycle variations. Additionally, the study used an artificial neural network (ANN) for MNIST simulation of image recognition and achieved the highest accuracy of ∼92 % based on the SnS2 synaptic device experimental results. These findings pave the way for developing nonvolatile memory devices and their applications in brain-inspired neuromorphic computing and artificial intelligence systems