Novel RC oscillators using the current-feedback operationalamplifier

Novel oscillator circuits using the current-feedback operational amplifier (CFOA) are presented. Each circuit uses one CFOA and five passive elements. Some of the circuits enjoy independent control of the frequency and the condition of oscillation. Experimental results are include

Epigenetic Mechanisms of Metal Carcinogenicity

Many metals exhibit genotoxic and/or carcinogenic effects. These toxic metals can be found ubiquitously – in drinking water, food, air, general use products, in everyday and occupational settings. Exposure to such carcinogenic metals can result in serious health disorders, including cancer. Arsenic, cadmium, chromium, nickel, and their compounds have already been recognized as carcinogens by the International Agency for Research on Cancer. This review summarizes a wide range of epigenetic mechanisms contributing to carcinogenesis induced by these metals, primarily including, but not limited to, DNA methylation, miRNA regulation, and histone posttranslational modifications. The mechanisms are described and discussed both from a metal-centric and a mechanism-centric standpoint. The review takes a broad perspective, putting the mechanisms in the context of real-life exposure, and aims to assist in guiding future research, particularly with respect to the assessment and control of exposure to carcinogenic metals and novel therapy development

Dealing naturally with stumbling blocks on highways and byways of TRAIL induced signaling.

In-depth analysis of how TRAIL signals through death receptors to induce apoptosis in cancer cells using high throughput technologies has added new layers of knowledge. However, the wealth of information has also highlighted the fact that TRAIL induced apoptosis may be impaired as evidenced by experimental findings obtained from TRAIL resistant cancer cell lines. Overwhelmingly, increasing understanding of TRAIL mediated apoptosis has helped in identifying synthetic and natural compounds which can restore TRAIL induced apoptosis via functionalization of either extrinsic or intrinsic pathways. Increasingly it is being realized that biologically active phytochemicals modulate TRAIL induced apoptosis, as evidenced by cell-based studies. In this review we have attempted to provide an overview of how different phytonutrients have shown efficacy in restoring apoptosis in TRAIL resistant cancer cells. We partition this review into how the TRAIL mediated signaling landscape has broadened over the years and how TRAIL induced signaling machinery crosstalks with autophagic protein networks. Subsequently, we provide a generalized view of considerable biological activity of coumarins against a wide range of cancer cell lines and how coumarins (psoralidin and esculetin) isolated from natural sources have improved TRAIL induced apoptosis in resistant cancer cells. We summarize recent updates on piperlongumine, phenethyl isothiocyanate and luteolin induced activation of TRAIL mediated apoptosis. The data obtained from pre-clinical studies will be helpful in translation of information from benchtop to the bedside

EGCG mediated targeting of deregulated signaling pathways and non-coding rnas in different cancers: Focus on JAK/STAT, Wnt/\u3b2-catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL mediated signaling pathways

Decades of research have enabled us to develop a better and sharper understanding of multifaceted nature of cancer. Next-generation sequencing technologies have leveraged our existing knowledge related to intra-and inter-tumor heterogeneity to the next level. Functional genomics have opened new horizons to explore deregulated signaling pathways in different cancers. Therapeutic targeting of deregulated oncogenic signaling cascades by products obtained from natural sources has shown promising results. Epigallocatechin-3-gallate (EGCG) has emerged as a distinguished chemopreventive product because of its ability to regulate a myriad of oncogenic signaling pathways. Based on its scientifically approved anticancer activity and encouraging results obtained from preclinical trials, it is also being tested in various phases of clinical trials. A series of clinical trials associated with green tea extracts and EGCG are providing clues about significant potential of EGCG to mechanistically modulate wide ranging signal transduction cascades. In this review, we comprehensively analyzed regulation of JAK/STAT, Wnt/\u3b2-catenin, TGF/SMAD, SHH/GLI, NOTCH pathways by EGCG. We also discussed most recent evidence related to the ability of EGCG to modulate non-coding RNAs in different cancers. Methylation of the genome is also a widely studied mechanism and EGCG has been shown to modulate DNA methyltransferases (DNMTs) and protein enhancer of zeste-2 (EZH2) in multiple cancers. Moreover, the use of nanoformulations to increase the bioavailability and thus efficacy of EGCG will be also addressed. Better understanding of the pleiotropic abilities of EGCG to modulate intracellular pathways along with the development of effective EGCG delivery vehicles will be helpful in getting a step closer to individualized medicines

Malat1 as a versatile regulator of cancer: Overview of the updates from predatory role as competitive endogenous rna to mechanistic insights

The central dogma of molecular biology, has remained a cornerstone of classical molecular biology. However, serendipitously discovered microRNAs (miRNAs) in nematodes paradigmat-ically shifted our current knowledge of the intricate mechanisms during transitions from transcrip-tion to translation. Thediscovery of miRNA captured considerable attention and appreciation, and we had witnessed an explosion in the field of non-coding RNAs. Ground-breaking discoveries in the field of non-coding RNAs have helped in better characterization of microRNAs and long non-coding RNAs (LncRNAs). There is an ever-increasing list of miRNA targets that are regulated by MALAT1 to stimulate or repress the expression of target genes. However, in this review, our main focus is to summarize mechanistic insights on MALAT1-mediated regulation of oncogenic signaling pathways. We have discussed how MALAT1 modulated TGF/SMAD and Hippo pathways in various cancers. We have also comprehensively summarized how JAK/STAT and Wnt/β-catenin pathways stimulated MALAT1 expression and consequentially how MALAT1 potentiated these signaling cascades to promote cancer. MALAT1 research has undergone substantial broadening. However, there is still a need to identify additional mechanisms. MALAT1 is involved in the multi--layered regulation of multiple transduction cascades, and detailed analysis of different pathways will be advantageous in getting a step closer to individualized medicine. © 2021 Bentham Science Publishers

Role of Autophagy in Breast Cancer Development and Progression: Opposite Sides of the Same Coin

PubMed ID: 31456180The term “autophagy”, which means “self (auto) - eating (phagy)”, describes a catabolic process that is evolutionarially conserved among all eukaryotes. Although autophagy is mainly accepted as a cell survival mechanism, it also modulates the process known as “type II cell death”. AKT/mTOR pathway is an upstream activator of autophagy and it is tightly regulated by the ATG (autophagy-related genes) signaling cascade. In addition, wide ranging cell signaling pathways and non-coding RNAs played essential roles in the control of autophagy. Autophagy is closely related to pathological processes such as neurodegenerative diseases and cancer as well as physiological conditions. After the Nobel Prize in Physiology or Medicine 2016 was awarded to Yoshinori Ohsumi “for his discoveries of mechanisms for autophagy”, there was an explosion in the field of autophagy and molecular biologists started to pay considerable attention to the mechanistic insights related to autophagy in different diseases. Since autophagy behaved dualistically, both as a cell death and a cell survival mechanism, it opened new horizons for a deeper analysis of cell type and context dependent behavior of autophagy in different types of cancers. There are numerous studies showing that the induction of autophagy mechanism will promote survival of cancer cells. Since autophagy is mainly a mechanism to keep the cells alive, it may protect breast cancer cells against stress conditions such as starvation and hypoxia. For these reasons, autophagy was noted to be instrumental in metastasis and drug resistance. In this chapter we have emphasized on role of role of autophagy in breast cancer. Additionally we have partitioned this chapter into exciting role of microRNAs in modulation of autophagy in breast cancer. We have also comprehensively summarized how TRAIL-mediated signaling and autophagy operated in breast cancer cells. © 2019, Springer Nature Switzerland AG

Regulation of ROCK1/2 by long non-coding RNAs and circular RNAs in different cancer types (Review)

Recent breakthroughs in high-throughput technolo- gies have enabled the development of a better understanding of the functionalities of rho-associated protein kinases (ROCKs) under various physiological and pathological condi- tions. Since their discovery in the late 1990s, ROCKs have attracted the attention of interdisciplinary researchers due to their ability to pleiotropically modulate a myriad of cellular mechanisms. A rapidly growing number of published studies have started to shed light on the mechanisms underlying the regulation of ROCK1 and ROCK2 via long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in different types of cancer. Detailed analyses have suggested that lncRNAs may be characteristically divided into oncogenic and tumor suppressor lncRNAs. Several exciting recent discoveries have also indicated how different lncRNAs and circRNAs modulate ROCK1/2 and mediate multistep cancer onset and progression. The present review chronicles the major advances that have been made in our understanding of the regulatory role of ROCK1/2 in different types of cancer, and how wide-ranging lncRNAs and circRNAs potentiate ROCK-driven signaling by blocking the targeting activities of tumor suppressor microRNAs. © 2022 Spandidos Publications. All rights reserved

Granulin a synergizes with cisplatin to inhibit the growth of human hepatocellular carcinoma

Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. However, due to resistance and toxicity, the application of cisplatin for the treatment of hepatocellular carcinoma (HCC) is limited. Our previous study has shown that granulin A (GRN A), an anticancer peptide, is able to interact with enolase1 (ENO1) and inhibit the growth of HCC in vitro. In the present study, we studied the synergistic effect of the combination of cisplatin and GRN A for the inhibitory effect on HCC. An 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and Chou-Talalay approaches revealed that the combination of GRN A and cisplatin displayed potent synergistic effect. The colony formation and cell viability of HCC cells were inhibited significantly in cells treated with the combination of cisplatin and GRN A, compared with cells treated with cisplatin or GRN A alone. Overexpression of ENO1 diminished the synergistic effect of GRN A and cisplatin in HCC cells. The combination of the two drugs exhibited a more obvious inhibitory effect on cancer cell apoptosis, as analyzed by the cytometry flow, mitochondrial membrane potential (MMP) and western blot analysis. An in vivo study confirmed that the combined use of the two drugs displayed more potent antitumor activity compared to mice treated with cisplatin and GRN A alone; the inhibitory rate of tumor growth was 65.46% and 68.94%, respectively, in mice treated with GRN A and cisplatin. However, the inhibitory rate increased to 86.63% in mice treated with the combination of the two drugs. This study provides evidence that the combination of GRN A and cisplatin is able to sensitize the liver cancer to cisplatin, and that targeting ENO1 is a promising approach for enhancing the antitumor activity of cisplatin. © 2018 by the authors. Licensee MDPI, Basel, Switzerland

Ag/Au Bimetallic Nanoparticles Trigger Different Cell Death Pathways and Affect Damage Associated Molecular Pattern Release in Human Cell Lines

Apoptosis induction is a common therapeutic approach. However, many cancer cells are resistant to apoptotic death and alternative cell death pathways including pyroptosis and necroptosis need to be triggered. At the same time, danger signals that include HMGB1 and HSP70 can be secreted/released by damaged cancer cells that boost antitumor immunity. We studied the cytotoxic effects of AgAu NPs, Ag NPs and Au NPs with regard to the programmed cell death (apoptosis, necroptosis, pyroptosis) and the secretion/release of HSP70 and HMGB1. Cancer cell lines were incubated with 30, 40 and 50 µg/mL of AgAu NPs, Ag NPs and Au NPs. Cytotoxicity was estimated using the MTS assay, and mRNA fold change of CASP1, CASP3, BCL-2, ZPB1, HMGB1, HSP70, CXCL8, CSF1, CCL20, NLRP3, IL-1β and IL-18 was used to investigate the associated programmed cell death. Extracellular levels of HMGB1 and IL-1β were investigated using the ELISA technique. The nanoparticles showed a dose dependent toxicity. Pyroptosis was triggered for LNCaP and MDA-MB-231 cells, and necroptosis for MDA-MB-231 cells. HCT116 cells experience apoptotic death and show increased levels of extracellular HMGB1. Our results suggest that in a manner dependent of the cellular microenvironment, AgAu NPs trigger mixed programmed cell death in P53 deficient MDA-MB-231 cells, while they also trigger IL-1β release in MDA-MB-231 and LNCaP cells and release of HMGB1 in HCT116 cells. © 2022 by the authors. Licensee MDPI, Basel, Switzerland