Editorial: Antimicrobial Photodynamic Therapy: A New Paradigm in the Fight Against Infections

According to a 2019 report from the Center for Disease Control and Prevention (CDC), more than 2.8 million antibiotic-resistant infections occur in the U.S. each year, and more than 35, 000 people die as a result. This special issue is focused on Antimicrobial Photodynamic Therapy (PDT), which is a new strategy to fight against infections. PDT is mostly used in the treatment of cancer, and non-melanoma skin cancer is the most widely recognized indication. A photosensitizer that is activated by visible light in the presence of oxygen can generate reactive oxygen species resulting in the death of the microorganisms, without damaging the surrounding tissue. This innovative way of destroying microbial pathogens has many advantages compared with the conventional antimicrobials and antibiotics used so far. It has a broad spectrum of action, being able to kill or inactivate bacteria, fungi, viruses and protozoa..

Non-coding RNAs and Exosomes: Their Role in the Pathogenesis of Sepsis

Non-coding RNAs and exosomes present an opportunity for early diagnosis as well as an ability to interact with key points of the biological mechanisms, suggesting that measurement of non-coding RNAs and exosomes are a promising approach for intensive care patients. © 2020 The Author(s) Sepsis is characterized as an uncontrolled host response to infection, and it represents a serious health challenge, causing excess mortality and morbidity worldwide. The discovery of sepsis-related epigenetic and molecular mechanisms could result in improved diagnostic and therapeutic approaches, leading to a reduced overall risk for affected patients. Accumulating data show that microRNAs, non-coding RNAs, and exosomes could all be considered as novel diagnostic markers for sepsis patients. These biomarkers have been demonstrated to be involved in regulation of sepsis pathophysiology. However, epigenetic modifications have not yet been widely reported in actual clinical settings, and further investigation is required to determine their importance in intensive care patients. Further studies should be carried out to explore tissue-specific or organ-specific epigenetic RNA-based biomarkers and their therapeutic potential in sepsis patients. © 2020 The Author(s

Autophagy in cancers including brain tumors: role of MicroRNAs

Autophagy has a crucial role in many cancers, including brain tumors. Several types of endogenous molecules (e.g. microRNAs, AKT, PTEN, p53, EGFR, and NF1) can modulate the process of autophagy. Recently miRNAs (small non-coding RNAs) have been found to play a vital role in the regulation of different cellular and molecular processes, such as autophagy. Deregulation of these molecules is associated with the development and progression of different pathological conditions, including brain tumors. It was found that miRNAs are epigenetic regulators, which influence the level of proteins coded by the targeted mRNAs with any modification of the genetic sequences. It has been revealed that various miRNAs (e.g., miR-7-1-3p, miR-340, miR-17, miR-30a, miR-224-3p, and miR-93), as epigenetic regulators, can modulate autophagy pathways within brain tumors. A deeper understanding of the underlying molecular targets of miRNAs, and their function in autophagy pathways could contribute to the development of new treatment methods for patients with brain tumors. In this review, we summarize the various miRNAs, which are involved in regulating autophagy in brain tumors. Moreover, we highlight the role of miRNAs in autophagy-related pathways in different cancers. Video abstract

Circular RNAs and gastrointestinal cancers: Epigenetic regulators with a prognostic and therapeutic role

Both environmental and genetic factors are involved in the initiation and development of gastrointestinal cancer. Covalent closed circular RNAs (circRNAs) are produced by a mechanism called �back-splicing� from mRNAs. They are highly stable and show cell and tissue specific expression patterns. Although some functions such as �microRNA sponge� and �RNA binding protein sponge� have been reported for a small number of circRNAs, the function of thousands of other circRNAs is still unknown. Dysregulation of circRNAs has been reported in many GI cancers and are involved in metastasis and invasion. CircRNAs have been reported to be useful as prognostic markers and targets for developing new treatments. We first describe the properties and biogenesis of circRNAs. We then summarize recent reports about circRNA functions, expression status, and their potential to be used as biomarkers in GI cancers including, gastric cancer, colorectal cancer, esophageal cancer, hepatocellular carcinoma, gallbladder cancer and pancreatic cancer. © 2019 Elsevier B.V

CFIm25 and alternative polyadenylation: Conflicting roles in cancer

Alternative polyadenylation (APA) is now widely recognized to regulate gene expression. APA is an RNA-processing mechanism that generates distinct 3� termini on mRNAs, producing mRNA isoforms. Different factors influence the initiation and development of this process. CFIm25 (among others) is a cleavage and polyadenylation factor that plays a key role in the regulation of APA. Shortening of the 3�UTRs on mRNAs leads to enhanced cellular proliferation and tumorigenicity. One reason may be the up-regulation of growth promoting factors, such as Cyclin D1. Different studies have reported a dual role of CFIm25 in cancer (both oncogenic and tumor suppressor). microRNAs (miRNAs) may be involved in CFIm25 function as well as competing endogenous RNAs (ceRNAs). The present review focuses on the role of CFIm25 in cancer, cancer treatment, and possible involvement in other human diseases. We highlight the involvement of miRNAs and ceRNAs in the function of CFIm25 to affect gene expression. The lack of understanding of the mechanisms and regulation of CFIm25 and APA has underscored the need for further research regarding their role in cancer and other diseases. © 201

Mesenchymal stem cell-derived exosomes: A new therapeutic approach to osteoarthritis?

Degenerative disorders of joints, especially osteoarthritis (OA), result in persistent pain and disability and high costs to society. Nevertheless, the molecular mechanisms of OA have not yet been fully explained. OA is characterized by destruction of cartilage and loss of extracellular matrix (ECM). It is generally agreed that there is an association between pro-inflammatory cytokines and the development of OA. There is increased expression of matrix metalloproteinase (MMP) and "a disintegrin and metalloproteinase with thrombospondin motifs" (ADAMTS). Mesenchymal stem cells (MSCs) have been explored as a new treatment for OA during the last decade. It has been suggested that paracrine secretion of trophic factors, in which exosomes have a crucial role, contributes to the mechanism of MSC-based treatment of OA. The paracrine secretion of exosomes may play a role in the repair of joint tissue as well as MSC-based treatments for other disorders. Exosomes isolated from various stem cells may contribute to tissue regeneration in the heart, limbs, skin, and other tissues. Recent studies have indicated that exosomes (or similar particles) derived from MSCs may suppress OA development. Herein, for first time, we summarize the recent findings of studies on various exosomes derived from MSCs and their effectiveness in the treatment of OA. Moreover, we highlight the likely mechanisms of actions of exosomes in OA. © 2019 The Author(s)

Neurofilament Light Chain as a Biomarker, and Correlation with Magnetic Resonance Imaging in Diagnosis of CNS-Related Disorders

The search for diagnostic and prognostic biomarkers for neurodegenerative conditions is of high importance, since these disorders may present difficulties in differential diagnosis. Biomarkers with high sensitivity and specificity are required. Neurofilament light chain (NfL) is a unique biomarker related to axonal damage and neural cell death, which is elevated in a number of neurological disorders, and can be detected in cerebrospinal fluid (CSF), as well as blood, serum, or plasma samples. Although the NfL concentration in CSF is higher than that in blood, blood measurement may be easier in practice due to its lesser invasiveness, reproducibility, and convenience. Many studies have investigated NfL in both CSF and serum/plasma as a potential biomarker of neurodegenerative disorders. Neuroimaging biomarkers can also potentially improve detection of CNS-related disorders at an early stage. Magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) are sensitive techniques to visualize neuroaxonal loss. Therefore, investigating the combination of NfL levels with indices extracted from MRI and DTI scans could potentially improve diagnosis of CNS-related disorders. This review summarizes the evidence for NfL being a reliable biomarker in the early detection and disease management in several CNS-related disorders. Moreover, we highlight the correlation between MRI and NfL and ask whether they can be combined. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

Exosomal miRNAs: Novel players in viral infection

Exosomes are secreted nanovesicles that are able to transfer their cargo (such as miRNAs) between cells. To determine to what extent exosomes and exosomal miRNAs are involved in the pathogenesis, progression and diagnosis of viral infections. The scientific literature (PubMed and Google Scholar) was searched from 1970 to 2019. The complex biogenesis of exosomes and miRNAs was reviewed. Exosomes contain both viral and host miRNAs that can be used as diagnostic biomarkers for viral diseases. Viral proteins can alter miRNAs, and conversely miRNAs can alter the host response to viral infections in a positive or negative manner. It is expected that exosomal miRNAs will be increasingly used for diagnosis, monitoring and even treatment of viral infections. © 2020 Future Medicine Ltd

Organic dots (O-dots) for theranostic applications: preparation and surface engineering

Organic dots is a term used to represent materials including graphene quantum dots and carbon quantum dots because they rely on the presence of other atoms (O, H, and N) for their photoluminescence or fluorescence properties. They generally have a small size (as low as 2.5 nm), and show good photostability under prolonged irradiation. The excitation and emission wavelengths of O-dots can be tailored according to their synthetic procedure, where although their quantum yield is quite low compared with organic dyes, this is partly compensated by their large absorption coefficients. A wide range of strategies have been used to modify the surface of O-dots for passivation, improving their solubility and biocompatibility, and allowing the attachment of targeting moieties and therapeutic cargos. Hybrid nanostructures based on O-dots have been used for theranostic applications, particularly for cancer imaging and therapy. This review covers the synthesis, physics, chemistry, and characterization of O-dots. Their applications cover the prevention of protein fibril formation, and both controlled and targeted drug and gene delivery. Multifunctional therapeutic and imaging platforms have been reported, which combine four or more separate modalities, frequently including photothermal or photodynamic therapy and imaging and drug release. © 2021 The Royal Society of Chemistry

In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging

Traditional methods of localizing and quantifying the presence of pathogenic microorganisms in living experimental animal models of infections have mostly relied on sacrificing the animals, dissociating the tissue and counting the number of colony forming units. However, the discovery of several varieties of the light producing enzyme, luciferase, and the genetic engineering of bacteria, fungi, parasites and mice to make them emit light, either after administration of the luciferase substrate, or in the case of the bacterial lux operon without any exogenous substrate, has provided a new alternative. Dedicated bioluminescence imaging (BLI) cameras can record the light emitted from living animals in real time allowing non-invasive, longitudinal monitoring of the anatomical location and growth of infectious microorganisms as measured by strength of the BLI signal. BLI technology has been used to follow bacterial infections in traumatic skin wounds and burns, osteomyelitis, infections in intestines, Mycobacterial infections, otitis media, lung infections, biofilm and endodontic infections and meningitis. Fungi that have been engineered to be bioluminescent have been used to study infections caused by yeasts (Candida) and by filamentous fungi. Parasitic infections caused by malaria, Leishmania, trypanosomes and toxoplasma have all been monitored by BLI. Viruses such as vaccinia, herpes simplex, hepatitis B and C and influenza, have been studied using BLI. This rapidly growing technology is expected to continue to provide much useful information, while drastically reducing the numbers of animals needed in experimental studies. © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group