Long non-coding RNAs (lncRNAs) are emerging as new players in the cancer paradigm demonstrating potential roles in both oncogenic and tumor suppressive pathways. These novel genes are frequently ...aberrantly expressed in a variety of human cancers, however the biological functions of the vast majority remain unknown. Recently, evidence has begun to accumulate describing the molecular mechanisms by which these RNA species function, providing insight into the functional roles they may play in tumorigenesis. In this review, we highlight the emerging functional role of lncRNAs in human cancer.
Polyphenols are naturally occurring compounds in plants and they are the most abundant antioxidants in the human diet. Due to their considerable structural diversity, this largely influences their ...bioavailability. Since a large proportion of polyphenols remains unabsorbed along the gastrointestinal tract, they may accumulate in the large intestine, where most of them are extensively metabolized by the intestinal microbiota. The formation of bioactive polyphenol-derived metabolites may also benefit the health status of the subjects, although the mechanisms have not been delineated. This review aims to highlight the impact of polyphenols on gut health and the modes of action could be through modulation of intestinal barrier function, innate and adaptive immune response, signaling pathways, as well as the ability to modify gut microbiota composition. The review will conclude by presenting future perspective and challenges of polyphenols application in food products to be used for preventing or treating diseases.
Probiotics are live microorganisms, which when administered in food confer numerous health benefits. In previous studies about beneficial effects of probiotic bacteria to health, particularly in the ...fields of intestinal mucosa defense responses, specific probiotics, in a strain-dependent manner, show certain degree of potential to reinforce the integrity of intestinal epithelium and/or regulate some immune components. The mechanism of probiotic action is an area of interest. Among all possible routes of modulation by probiotics of intestinal epithelial cell-mediated defense responses, modulations of intestinal barrier function, innate, and adaptive mucosal immune responses, as well as signaling pathways are considered to play important role in the intestinal defense responses against pathogenic bacteria. This review summarizes the beneficial effects of probiotic bacteria to intestinal health together with the mechanisms affected by probiotic bacteria: barrier function, innate, and adaptive defense responses such as secretion of mucins, defensins, trefoil factors, immunoglobulin A (IgA), Toll-like receptors (TLRs), cytokines, gut associated lymphoid tissues, and signaling pathways.
cGMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) sensing has emerged as a key regulator of innate immune responses to both exogenous and endogenous DNA. Recent studies reveal critical ...roles for this pathway in natural antitumor immunity across cancer types as well as in immune checkpoint blockade therapy. However, it is also clear that some tumors evade cGAS–STING-mediated immune responses, and immunomodulatory therapeutics are currently being explored to target this pathway. Finally, we also discuss recent observations that cGAS–STING-mediated inflammation may promote tumor initiation, growth, and metastasis in certain malignancies and how this may complicate the utility of this pathway in therapeutic development.
cGMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) recognizes cytosolic DNA and induces a type I interferon response in both tumor and phagocytic immune cells.
cGAS–STING-induced immunity has potent antitumor effects and magnifies the effects of a variety of anticancer therapeutics.
In certain tumor types, cGAS–STING promotes cancer growth and metastasis through modulation of the tumor microenvironment.
Large-scale, highly integrated and low-power-consuming hardware is becoming progressively more important for realizing optical neural networks (ONNs) capable of advanced optical computing. ...Traditional experimental implementations need N
units such as Mach-Zehnder interferometers (MZIs) for an input dimension N to realize typical computing operations (convolutions and matrix multiplication), resulting in limited scalability and consuming excessive power. Here, we propose the integrated diffractive optical network for implementing parallel Fourier transforms, convolution operations and application-specific optical computing using two ultracompact diffractive cells (Fourier transform operation) and only N MZIs. The footprint and energy consumption scales linearly with the input data dimension, instead of the quadratic scaling in the traditional ONN framework. A ~10-fold reduction in both footprint and energy consumption, as well as equal high accuracy with previous MZI-based ONNs was experimentally achieved for computations performed on the MNIST and Fashion-MNIST datasets. The integrated diffractive optical network (IDNN) chip demonstrates a promising avenue towards scalable and low-power-consumption optical computational chips for optical-artificial-intelligence.
Tumor progression, including metastasis, is significantly influenced by factors in the tumor microenvironment (TME) such as mechanical force, shear stress, chemotaxis, and hypoxia. At present, most ...cancer studies investigate tumor metastasis by conventional cell culture methods and animal models, which are limited in data interpretation. Although patient tissue analysis, such as human patient-derived xenografts (PDX), can provide important clinical relevant information, they may not be feasible for functional studies as they are costly and time-consuming. Thus, in vitro three-dimensional (3D) models are rapidly being developed that mimic TME and allow functional investigations of metastatic mechanisms and drug responses. One of those new 3D models is tumor-on-a-chip technology that provides a powerful in vitro platform for cancer research, with the ability to mimic the complex physiological architecture and precise spatiotemporal control. Tumor-on-a-chip technology can provide integrated features including 3D scaffolding, multicellular culture, and a vasculature system to simulate dynamic flow in vivo. Here, we review a select set of recent achievements in tumor-on-a-chip approaches and present potential directions for tumor-on-a-chip systems in the future for areas including mechanical and chemical mimetic systems. We also discuss challenges and perspectives in both biological factors and engineering methods for tumor-on-a-chip progress. These approaches will allow in the future for the tumor-on-a-chip systems to test therapeutic approaches for individuals through using their cancerous cells gathered through approaches like biopsies, which then will contribute toward personalized medicine treatments for improving their outcomes.
More than 200 million people in 70 countries are exposed to arsenic through drinking water. Chronic exposure to this metalloid has been associated with the onset of many diseases, including cancer. ...Epidemiological evidence supports its carcinogenic potential, however, detailed molecular mechanisms remain to be elucidated. Despite the global magnitude of this problem, not all individuals face the same risk. Susceptibility to the toxic effects of arsenic is influenced by alterations in genes involved in arsenic metabolism, as well as biological factors, such as age, gender and nutrition. Moreover, chronic arsenic exposure results in several genotoxic and epigenetic alterations tightly associated with the arsenic biotransformation process, resulting in an increased cancer risk. In this review, we: 1) review the roles of inter-individual DNA-level variations influencing the susceptibility to arsenic-induced carcinogenesis; 2) discuss the contribution of arsenic biotransformation to cancer initiation; 3) provide insights into emerging research areas and the challenges in the field; and 4) compile a resource of publicly available arsenic-related DNA-level variations, transcriptome and methylation data. Understanding the molecular mechanisms of arsenic exposure and its subsequent health effects will support efforts to reduce the worldwide health burden and encourage the development of strategies for managing arsenic-related diseases in the era of personalized medicine.
•The global magnitude of health effects resulting from arsenic exposure is understated.•Lifestyle and genetic variations can influence susceptibility to arsenic-related health effects.•Sequence-level data will aid in refining the role of arsenic in pathogenesis.
Magnetic reconnection is a fundamental physical process in various astrophysical, space, and laboratory environments. Many pieces of evidence for magnetic reconnection have been uncovered. However, ...its specific processes that could be fragmented and turbulent have been short of direct observational evidence. Here, we present observations of a super-hot current sheet during the SOL2017-09-10T X8.2-class solar flare that display the fragmented and turbulent nature of magnetic reconnection. As bilateral plasmas converge toward the current sheet, significant plasma heating and nonthermal motions are detected therein. Two oppositely directed outflow jets are intermittently expelled out of the fragmenting current sheet, whose intensity shows a power-law distribution in the spatial frequency domain. The intensity and velocity of the sunward outflow jets also display a power-law distribution in the temporal frequency domain. The length-to-width ratio of current sheet is estimated to be larger than the theoretical threshold and thus ensures its occurrence. The observations therefore suggest that fragmented and turbulent magnetic reconnection occurs in the long stretching current sheet.
Enrichment of nutrients and metals in seawater associated with anthropogenic activities can threaten aquatic ecosystems. Consequently, nutrient and metal concentrations are parameters used to define ...water quality. The European Union's Water Framework Directive (WFD) goes further than a contaminant-based approach and utilises indices to assess the Ecological Status (ES) of transitional water bodies (e.g. estuaries and lagoons). One assessment is based upon the abundance of opportunistic Ulva species, as an indication of eutrophication. The objective of this study was to characterise Ireland's Ulva blooms through the use of WFD assessment, metal concentrations and taxonomic identity. Furthermore, the study assessed whether the ecological assessment is related to the metal composition in the Ulva. WFD algal bloom assessment revealed that the largest surveyed blooms had an estimated biomass of 2164 metric tonnes (w/w). DNA sequences identified biomass from all locations as Ulva rigida, with the exception of New Quay, which was Ulva rotundata. Some blooms contained significant amounts of As, Cu, Cr, Pb and Sn. The results showed that all metal concentrations had a negative relationship (except Se) with the Ecological Quality Ratio (EQR). However, only in the case of Mn were these differences significant (p = 0.038). Overall, the metal composition and concentrations found in Ulva were site dependent, and not clearly related to the ES. Nevertheless, sites with a moderate or poor ES had a higher variability in the metals levels than in estuaries with a high ES.
Abstract Lung cancer is the leading cause of cancer death worldwide, accounting for more deaths than breast, prostate and colon cancer combined. While treatment decisions are determined primarily by ...stage, therapeutically non small cell lung cancer (NSCLC) has traditionally been treated as a single disease. However, recent findings have led to the recognition of histology and molecular subtypes as important determinants in treatment selection. Identifying the genetic differences that define these molecular and histological subtypes has the potential to impact treatment and as such is currently the focus of much research. Microarray and genomic sequencing efforts have provided unparalleled insight into the genomes of lung cancer subtypes, specifically adenocarcinoma (AC) and squamous cell carcinoma (SqCC), revealing subtype specific genomic alterations and molecular subtypes as well as differences in cell signaling pathways. In this review, we discuss the recurrent genomic alterations characteristic of AC and SqCC (including molecular subtypes), their therapeutic implications and emerging clinical practices aimed at tailoring treatments based on a tumor's molecular alterations with the hope of improving patient response and survival.
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