Mitochondria regulate hepatic lipid metabolism and oxidative stress. Ultrastructural mitochondrial lesions, altered mitochondrial dynamics, decreased activity of respiratory chain complexes, and ...impaired ability to synthesize adenosine triphosphate are observed in liver tissues from patients with alcohol-associated and non-associated liver diseases. Increased lipogenesis with decreased fatty acid β-oxidation leads to the accumulation of triglycerides in hepatocytes, which, combined with increased levels of reactive oxygen species, contributes to insulin resistance in patients with steatohepatitis. Moreover, mitochondrial reactive oxygen species mediate metabolic pathway signaling; alterations in these pathways affect development and progression of chronic liver diseases. Mitochondrial stress and lesions promote cell death, liver fibrogenesis, inflammation, and the innate immune responses to viral infections. We review the involvement of mitochondrial processes in development of chronic liver diseases, such as nonalcoholic fatty, alcohol-associated, and drug-associated liver diseases, as well as hepatitis B and C, and discuss how they might be targeted therapeutically.
Women represent 80% of people affected by autoimmune diseases. Although, many studies have demonstrated a role for sex hormone receptor signaling, particularly estrogens, in the direct regulation of ...innate and adaptive components of the immune system, recent data suggest that female sex hormones are not the only cause of the female predisposition to autoimmunity. Besides sex steroid hormones, growing evidence points towards the role of X-linked genetic factors. In female mammals, one of the two X chromosomes is randomly inactivated during embryonic development, resulting in a cellular mosaicism, where about one-half of the cells in a given tissue express either the maternal X chromosome or the paternal one. X chromosome inactivation (XCI) is however not complete and 15 to 23% of genes from the inactive X chromosome (Xi) escape XCI, thereby contributing to the emergence of a female-specific heterogeneous population of cells with bi-allelic expression of some X-linked genes. Although the direct contribution of this genetic mechanism in the female susceptibility to autoimmunity still remains to be established, the cellular mosaicism resulting from XCI escape is likely to create a unique functional plasticity within female immune cells. Here, we review recent findings identifying key immune related genes that escape XCI and the relationship between gene dosage imbalance and functional responsiveness in female cells.
Advances in Paper-Based Analytical Devices Ozer, Tugba; McMahon, Catherine; Henry, Charles S
Annual review of analytical chemistry,
06/2020, Letnik:
13, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Microfluidic paper-based analytical devices (μPADs) are the newest generation of lab-on-a-chip devices and have made significant strides in both our understanding of fundamental behavior and ...performance characteristics and expansion of their applications. μPADs have become useful analytical techniques for environmental analysis in addition to their more common application as medical point-of-care devices. Although the most common method for device fabrication is wax printing, numerous other techniques exist and have helped address factors ranging from solvent compatibility to improved device function. This review highlights recent reports of fabrication and design, modes of detection, and broad applications of μPADs. Such advances have enabled μPADs to be used in field and laboratory studies to address critical needs in fast, cheaper measurement technologies.
The importance of user-friendly, inexpensive, sensitive, and selective detection of viruses has been highlighted again due to the recent Coronavirus disease 2019 (COVID-19) pandemic. Among the ...analytical tools, paper-based devices (PADs) have become a leading alternative for point-of-care (POC) testing. In this review, we discuss the recent development strategies and applications in nucleic acid-based, antibody/antigen-based and other affinity-based PADs using optical and electrochemical detection methods for sensing viruses. In addition, advantages and drawbacks of presented PADs are identified. Current state and insights towards future perspectives are presented regarding developing POC diagnosis platform for COVID-19. This review considers state-of-the-art technologies for further development and improvement in PADs performance for virus detection.
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•Reviewed developments in PADs for optical and electrochemical detection of viruses.•Highlighted recent applications in antibody/antigen-, nucleic acid-, aptamer- and CRISPR-based PADs for viral detection.•Emphasized low-cost POC diagnostic tools to control the global COVID-19 pandemic.
The development of simple fluorescent and colorimetric assays that enable point-of-care DNA and RNA detection has been a topic of significant research because of the utility of such assays in ...resource limited settings. The most common motifs utilize hybridization to a complementary detection strand coupled with a sensitive reporter molecule. Here, a paper-based colorimetric assay for DNA detection based on pyrrolidinyl peptide nucleic acid (acpcPNA)-induced nanoparticle aggregation is reported as an alternative to traditional colorimetric approaches. PNA probes are an attractive alternative to DNA and RNA probes because they are chemically and biologically stable, easily synthesized, and hybridize efficiently with the complementary DNA strands. The acpcPNA probe contains a single positive charge from the lysine at C-terminus and causes aggregation of citrate anion-stabilized silver nanoparticles (AgNPs) in the absence of complementary DNA. In the presence of target DNA, formation of the anionic DNA-acpcPNA duplex results in dispersion of the AgNPs as a result of electrostatic repulsion, giving rise to a detectable color change. Factors affecting the sensitivity and selectivity of this assay were investigated, including ionic strength, AgNP concentration, PNA concentration, and DNA strand mismatches. The method was used for screening of synthetic Middle East respiratory syndrome coronavirus (MERS-CoV), Mycobacterium tuberculosis (MTB), and human papillomavirus (HPV) DNA based on a colorimetric paper-based analytical device developed using the aforementioned principle. The oligonucleotide targets were detected by measuring the color change of AgNPs, giving detection limits of 1.53 (MERS-CoV), 1.27 (MTB), and 1.03 nM (HPV). The acpcPNA probe exhibited high selectivity for the complementary oligonucleotides over single-base-mismatch, two-base-mismatch, and noncomplementary DNA targets. The proposed paper-based colorimetric DNA sensor has potential to be an alternative approach for simple, rapid, sensitive, and selective DNA detection.
Toll‐like receptor 7 (TLR7) triggers antiviral immune responses through its capacity to recognize single‐stranded RNA. TLR7 loss‐of‐function mutants are associated with life‐threatening pneumonia in ...severe COVID‐19 patients. Whereas TLR7‐driven innate induction of type I IFN appears central to control SARS‐CoV2 virus spreading during the first days of infection, the impact of TLR7‐deficiency on adaptive B‐cell immunity is less clear. In the present study, we examined the role of TLR7 in the adaptive B cells response to various pathogen‐like antigens (PLAs). We used inactivated SARS‐CoV2 and a PLA‐based COVID‐19 vaccine candidate designed to mimic SARS‐CoV2 with encapsulated bacterial ssRNA as TLR7 ligands and conjugated with the RBD of the SARS‐CoV2 Spike protein. Upon repeated immunization with inactivated SARS‐CoV2 or PLA COVID‐19 vaccine, we show that Tlr7‐deficiency abolished the germinal center (GC)‐dependent production of RBD‐specific class‐switched IgG2b and IgG2c, and neutralizing antibodies to SARS‐CoV2. We also provide evidence for a non‐redundant role for B‐cell‐intrinsic TLR7 in the promotion of RBD‐specific IgG2b/IgG2c and memory B cells. Together, these data demonstrate that the GC reaction and class‐switch recombination to the Myd88‐dependent IgG2b/IgG2c in response to SARS‐CoV2 or PLAs is strictly dependent on cell‐intrinsic activation of TLR7 in B cells.
TLR7 is required for production of high titers of RBD‐specific IgG2b/2c neutralizing antibody and Germinal Center formation upon vaccination with inactivated SARS‐CoV2 or virus‐like particles AP205‐RBD. GC anatomical structures are absent in the spleen of TLR7‐deficient mice. This study supports a model where B‐cell intrinsic TLR7 is required for optimal GC reaction and antibody response to pathogen‐like antigens.
The use of paper microfluidics to perform chemical measurements for various analytical applications has gained interest over the last decade. One of the growing applications of these platforms is for ...the qualitative and quantitative determination of drugs. The low cost and self-pumping ability of paper microfluidics are attractive for developing analytical tools capable of on-site drug screening. This review aims to present the unique features of microfluidic paper-based analytical devices (μPADs) that offer advantages to pharmaceutical analysis and evaluate the state-of-the-art technologies and applications of the platform for drug analysis in research and real-world settings. The current challenges and potential future directions of the field are also highlighted.
Image of test cards is adapted with permission from A.A. Weaver, H. Reiser, T. Barstis, M. Benvenuti, D. Ghosh, M. Hunckler, B. Joy, L. Koenig, K. Raddell, M. Lieberman, Paper analytical devices for fast field screening of beta lactam antibiotics and antituberculosis pharmaceuticals, Anal. Chem. 85 (2013) 6453–6460. (Copyright 2013 American Chemical Society). Display omitted
•A critical review of the emerging use of paper-based devices/μPADs for drug analysis.•Attractive features of μPADs relevant to drug analysis are discussed.•State-of-the-art fabrication methods and detection motifs applicable to drugs.•Applications in discovery, quality control, and tests of drugs in various matrices.•Highlight of challenges and future outlooks of μPADs for drug analysis.
Paper-based sensors offer an affordable yet powerful platform for field and point-of-care (POC) testing due to their self-pumping ability and utility for many different analytical measurements. When ...combined with electrochemical detection using small and portable electronics, sensitivity and selectivity of the paper devices can be improved over naked eye detection without sacrificing portability. Herein, we review how the field of electrochemical paper-based analytical devices (ePADs) has grown since it was introduced a decade ago. We start by reviewing fabrication methods relevant to ePADs with more focus given to the electrode fabrication, which is fundamental for electrochemical sensing. Multiple sensing approaches applicable to ePADs are then discussed and evaluated to present applicability, advantages and challenges associated with each approach. Recent applications of ePADs in the fields of clinical diagnostics, environmental testing, and food analysis are also presented. Finally, we discuss how the current ePAD technologies have progressed to meet the analytical and practical specifications required for field and/or POC applications, as well as challenges and outlook.
Paper-based sensors offer an affordable yet powerful platform for field and point-of-care (POC) testing due to their self-pumping ability and utility for many different analytical measurements.
This work presents an all-in-one origami paper-based electrochemical platform for simple and inexpensive l-cysteine (Cys) detection using Cys as a monomer for modifying electrode surfaces. The ...proposed method combines the steps of electropolymerization and detection into a single device to offer a highly convenient method for the end-user. In comparison, the sensitivity toward Cys detection is a significantly increased using this modified electrode. The developed device provided a linear concentration range of 10–800 μM with a limit of detection of 5.5 μM. For application, the device was successfully applied to detect Cys in different food products such as wheat flour, bread, and cake with satisfactory results, yielding excellent intra-day and inter-day relative standard deviations (1.5–4.9%) and recoveries (84.2–110.8%). This discovery is important from the viewpoint of the development of Cys detection in other applications in the future.
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•A novel self-modification of poly(cysteine) for l-cysteine detection was proposed.•New all-in-one origami paper-based analytical device coupled with a novel sensor was developed to offer a convenient procedure over previous methods.•Good selectivity, accuracy, and precision for l-cysteine detection in food samples were demonstrated.
We report the first demonstration of electrochemical detection for paper-based microfluidic devices. Photolithography was used to make microfluidic channels on filter paper, and screen-printing ...technology was used to fabricate electrodes on the paper-based microfluidic devices. Screen-printed electrodes on paper were characterized using cyclic voltammetry to demonstrate the basic electrochemical performance of the system. The utility of our devices was then demonstrated with the determination of glucose, lactate, and uric acid in biological samples using oxidase enzyme (glucose oxidase, lactate oxidase, and uricase, respectively) reactions. Oxidase enzyme reactions produce H2O2 while decomposing their respective substrates, and therefore a single electrode type is needed for detection of multiple species. Selectivity of the working electrode for H2O2 was improved using Prussian Blue as a redox mediator. The determination of glucose, lactate, and uric acid in control serum samples was performed using chronoamperometry at the optimal detection potential for H2O2 (0 V versus the on-chip Ag/AgCl reference electrode). Levels of glucose and lactate in control serum samples measured using the paper devices were 4.9 ± 0.6 and 1.2 ± 0.2 mM (level I control sample), and 16.3 ± 0.7 and 3.2 ± 0.3 mM (level II control sample), respectively, and were within error of the values measured using traditional tests. This study shows the successful integration of paper-based microfluidics and electrochemical detection as an easy-to-use, inexpensive, and portable alternative for point of care monitoring.
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