Role of E2F transcription factor in oral cancer: Recent insight and advancements.

The family of mammalian E2F transcription factors (E2Fs) comprise of 8 members (E2F1-E2F8) classified as activators (E2F1-E2F3) and repressors (E2F4-E2F8) primarily regulating the expression of several genes related to cell proliferation, apoptosis and differentiation, mainly in a cell cycle-dependent manner. E2F activity is frequently controlled via the retinoblastoma protein (pRb), cyclins, p53 and the ubiquitin-proteasome pathway. Additionally, genetic or epigenetic changes result in the deregulation of E2F family genes expression altering S phase entry and apoptosis, an important hallmark for the onset and development of cancer. Although studies reveal E2Fs to be involved in several human malignancies, the mechanisms underlying the role of E2Fs in oral cancer lies nascent and needs further investigations. This review focuses on the role of E2Fs in oral cancer and the etiological factors regulating E2Fs activity, which in turn transcriptionally control the expression of their target genes, thus contributing to cell proliferation, metastasis, and drug/therapy resistance. Further, we will discuss therapeutic strategies for E2Fs, which may prevent oral tumor growth, metastasis, and drug resistance.

The Role of Systemic Filtrating Organs in Aging and Their Potential in Rejuvenation Strategies.

Advances in aging studies brought about by heterochronic parabiosis suggest that agingmight be a reversable process that is affected by changes in the systemic milieu of organs andcells. Given the broadness of such a systemic approach, research to date has mainly questioned theinvolvement of "shared organs" versus "circulating factors". However, in the absence of a clearunderstanding of the chronological development of aging and a unified platform to evaluate thesuccesses claimed by specific rejuvenation methods, current literature on this topic remains scattered.Herein, aging is assessed from an engineering standpoint to isolate possible aging potentiators via ajuxtaposition between biological and mechanical systems. Such a simplification provides a generalframework for future research in the field and examines the involvement of various factors in aging.Based on this simplified overview, the kidney as a filtration organ is clearly implicated, for the firsttime, with the aging phenomenon, necessitating a re-evaluation of current rejuvenation studies tountangle the extent of its involvement and its possible role as a potentiator in aging. Based on thesefindings, the review concludes with potential translatable and long-term therapeutics for aging whileoffering a critical view of rejuvenation methods proposed to date.

Unveiling Fabrication and Environmental Remediation of MXene-Based Nanoarchitectures in Toxic Metals Removal from Wastewater: Strategy and Mechanism.

Efficient approaches for toxic metal removal from wastewater have had transformative impacts to mitigating freshwater scarcity. Adsorption is among the most promising purification techniques due to its simplicity, low cost, and high removal efficiency at ambient conditions. MXene-based nanoarchitectures emerged as promising adsorbents in a plethora of toxic metal removal applications. This was due to the unique hydrophilicity, high surface area, activated metallic hydroxide sites, electron-richness, and massive adsorption capacity of MXene. Given the continual progress in the rational design of MXene nanostructures for water treatment, timely updates on this field are required that deeply emphasize toxic metal removal, including fabrication routes and characterization strategies of the merits, advantages, and limitations of MXenes for the adsorption of toxic metals (i.e., Pb, Cu, Zn, and Cr). This is in addition to the fundamentals and the adsorption mechanism tailored by the shape and composition of MXene based on some representative paradigms. Finally, the limitations of MXenes and their potential future research perspectives for wastewater treatment are also discussed. This review may trigger scientists to develop novel MXene-based nanoarchitectures with well-defined shapes, compositions, and physiochemical merits for efficient, practical removal of toxic metals from wastewater.

Wireless recording systems: from noninvasive EEG-NIRS to invasive EEG devices.

In this paper, we present the design and implementation of a wireless wearable electronic system dedicated to remote data recording for brain monitoring. The reported wireless recording system is used for a) simultaneous near-infrared spectrometry (NIRS) and scalp electro-encephalography (EEG) for noninvasive monitoring and b) intracerebral EEG (icEEG) for invasive monitoring. Bluetooth and dual radio links were introduced for these recordings. The Bluetooth-based device was embedded in a noninvasive multichannel EEG-NIRS system for easy portability and long-term monitoring. On the other hand, the 32-channel implantable recording device offers 24-bit resolution, tunable features, and a sampling frequency up to 2 kHz per channel. The analog front-end preamplifier presents low input-referred noise of 5 µ VRMS and a signal-to-noise ratio of 112 dB. The communication link is implemented using a dual-band radio frequency transceiver offering a half-duplex 800 kb/s data rate, 16.5 mW power consumption and less than 10(-10) post-correction Bit-Error Rate (BER). The designed system can be accessed and controlled by a computer with a user-friendly graphical interface. The proposed wireless implantable recording device was tested in vitro using real icEEG signals from two patients with refractory epilepsy. The wirelessly recorded signals were compared to the original signals recorded using wired-connection, and measured normalized root-mean square deviation was under 2%.

Identification of deregulated genes by single wall carbon-nanotubes in human normal bronchial epithelial cells.

To identify genes affected by single-walled carbon nanotubes (SWCNTs) in human normal lung cells, we compared the gene expression profiles of untreated human normal bronchial epithelial (HNBE) cells to profiles of HNBE cells treated with SWCNTs. A complementary DNA microarray analysis consisting of 54,675 human genes revealed marked changes in the expression of 14,294 genes, with 7,029 genes being upregulated and 7,265 being downregulated. This comprehensive list of genes included those associated with cell cycle, apoptosis, cell survival, cell adhesion and motility, signal transduction, and transcription regulation. Additional analysis of 19 genes using reverse transcription-polymerase chain reaction confirmed the microarray analysis. More specifically, our study demonstrates to our knowledge for the first time, evidence that 9 of the 19 genes (most of which encode cell apoptotic, signal transduction, and transcription regulator products) are upregulated in the SWCNTs-treated HNBE cells as compared with untreated cells, whereas the remaining 10 of the 19 (involved in cell adhesion and motility, cell proliferation, and cell survival) are downregulated in SWCNTs-treated HNBE cells in comparison with untreated controls. These findings provide a large body of information regarding gene expression profiles associated with SWCNTs exposure in human lung bronchial epithelial cells, and also represent a source to investigate the mechanism of the effect of SWCNTs in human normal lung cells. From the clinical editor: In this study, the gene expression profile of human normal bronchial epithelial cells was compared with single-wall carbon nanotubes-treated cells. A cDNA microarray analysis consisting of 54,675 human genes revealed significant changes in the expression of 14,294 genes, with 7,029 genes being up-regulated and 7,265 being down-regulated. This serves as a first step in clarification of mechanisms of action and to investigate toxicity in this model.

High-risk HPV/ErbB-2 interaction on E-cadherin/catenin regulation in human carcinogenesis.

Human papillomaviruses (HPVs) are a group of host-specific DNA viruses, with more than 120 different types identified to date. HPVs are classified as high- or low-risk (HR or LR) depending on their potential to induce cancer. Persistent infections with HR types of HPVs present a major risk factor for the development of a variety of human cancers including cervical, colorectal, head and neck as well as breast cancers. On the other hand, the deregulation of ErbB family tyrosine kinase receptors has also been associated with several types of human cancers. For instance, ErbB2 has been shown to have an important role in human carcinomas, specifically breast cancer. Moreover, the E-cadherin/catenin complex plays a pivotal role in the maintenance of normal adhesion in epithelial cells, and has been demonstrated to suppress tumor invasion and participate in cell signaling in human carcinomas. This review focuses on the interaction between HR-HPV/ErbB2 tyrosine receptors and the E-cadherin/catenin complex in human carcinomas including cervical, colorectal, head and neck and breast cancers.

ErbB-2 receptor cooperates with E6/E7 oncoproteins of HPV type 16 in breast tumorigenesis.

The ErbB-2 receptor is overexpressed in roughly 30% of human breast cancers. Moreover, approximately 50% of breast cancers are positive for high-risk human papillomaviruses (HPVs), specifically types 16 and 18. Recently, we reported that ErbB-2 cooperates with E6/E7 oncoproteins of HPV type 16 to induce neoplastic transformation of human normal oral epithelial cells. We also demonstrated that E6/E7 of HPV type 16 converts non-invasive breast cancer cells to an invasive form. In order to investigate the effect of ErbB-2/E6/E7 cooperation in breast carcinogenesis, we generated double transgenic mice carrying ErbB-2 and E6/E7 of HPV type 16 under mouse mammary tumor virus (MMTV) and human keratin 14 promoters, respectively. Within six months, these double transgenic mice developed large and extensive invasive breast cancer in comparison to ErbB-2 or E6/E7 singly transgenic mice. Histological analysis of ErbB-2/E6/E7 transgenic mice tumors showed the presence of invasive breast carcinomas. However, the breast tissues from ErbB-2 and E6/E7 transgenic mice showed only in-situ cancer and normal mammary phenotype, respectively. In parallel, we examined the cooperation effect of ErbB-2 and E6/E7 in the human breast cancer cell line, BT20; in comparison to ErbB-2 and E6/E7 alone as well as wild type cells, we found that ErbB 2/E6/E7 together stimulate colony formation and cell migration in the BT20 cell line. Furthermore, we found that beta-catenin is constitutively phosphorylated by c-Src and consequently trans-located to the nucleus in ErbB-2/E6/E7-breast cancer cells. These findings provide evidence that the ErbB-2 receptor cooperates with high-risk HPVs in breast tumorigenesis via beta-catenin activation.