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Biomaterials Research 2024Liver fibrosis is a wound-healing response to chronic liver injury, which may lead to cirrhosis and cancer. Early-stage fibrosis is reversible, and it is difficult to... (Review)
Review
Liver fibrosis is a wound-healing response to chronic liver injury, which may lead to cirrhosis and cancer. Early-stage fibrosis is reversible, and it is difficult to precisely diagnose with conventional imaging modalities such as magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, and ultrasound imaging. In contrast, probe-assisted molecular imaging offers a promising noninvasive approach to visualize early fibrosis changes in vivo, thus facilitating early diagnosis and staging liver fibrosis, and even monitoring of the treatment response. Here, the most recent progress in molecular imaging technologies for liver fibrosis is updated. We start by illustrating pathogenesis for liver fibrosis, which includes capillarization of liver sinusoidal endothelial cells, cellular and molecular processes involved in inflammation and fibrogenesis, as well as processes of collagen synthesis, oxidation, and cross-linking. Furthermore, the biological targets used in molecular imaging of liver fibrosis are summarized, which are composed of receptors on hepatic stellate cells, macrophages, and even liver collagen. Notably, the focus is on insights into the advances in imaging modalities developed for liver fibrosis diagnosis and the update in the corresponding contrast agents. In addition, challenges and opportunities for future research and clinical translation of the molecular imaging modalities and the contrast agents are pointed out. We hope that this review would serve as a guide for scientists and students who are interested in liver fibrosis imaging and treatment, and as well expedite the translation of molecular imaging technologies from bench to bedside.
PubMed: 38952717
DOI: 10.34133/bmr.0042 -
Molecular Imaging 2024This meeting report summarizes a consultants meeting that was held at International Atomic Energy Agency Headquarters, Vienna, in July 2022 to provide an update on the...
This meeting report summarizes a consultants meeting that was held at International Atomic Energy Agency Headquarters, Vienna, in July 2022 to provide an update on the development of multimodality imaging by combining nuclear medicine imaging agents with other nonradioactive molecular probes and/or biomedical imaging techniques.
Topics: Nuclear Medicine; Multimodal Imaging; Humans
PubMed: 38952398
DOI: 10.1177/15353508241245265 -
British Journal of Pharmacology Jul 2024Pulmonary hypertension (PH) results from pulmonary vasculopathy, initially leading to a compensatory right ventricular (RV) hypertrophy, and eventually to RV failure....
BACKGROUND AND PURPOSE
Pulmonary hypertension (PH) results from pulmonary vasculopathy, initially leading to a compensatory right ventricular (RV) hypertrophy, and eventually to RV failure. Hypoxia can trigger both pulmonary vasculopathy and RV failure. Therefore, we tested if myo-inositol trispyrophosphate (ITPP), which facilitates oxygen dissociation from haemoglobin, can relieve pulmonary vasculopathy and RV hypoxia, and eventually prevent RV failure and mortality in the rat model of monocrotaline-induced PH.
EXPERIMENTAL APPROACH
Rats were injected with monocrotaline (PH) or saline (control) and received ITPP or placebo for 5 weeks. Serial echocardiograms were obtained to monitor the disease, pressure-volume loops were recorded and evaluated, myocardial pO was measured using a fluorescent probe, and histological and molecular analyses were conducted at the conclusion of the experiment.
KEY RESULTS AND CONCLUSIONS
ITPP reduced PH-related mortality. It had no effect on progressive increase in pulmonary vascular resistance, yet significantly relieved intramyocardial RV hypoxia, which was associated with improvement of RV function and reduction of RV wall stress. ITPP also tended to prevent increased hypoxia inducible factor-1α expression in RV cardiac myocytes but did not affect RV capillary density.
IMPLICATIONS
Our study suggests that strategies aimed at increasing oxygen delivery to hypoxic RV in PH could potentially be used as adjuncts to other therapies that target pulmonary vessels, thus increasing the ability of the RV to withstand increased afterload and reducing mortality. ITPP may be one such potential therapy.
PubMed: 38952183
DOI: 10.1111/bph.16482 -
Journal of Biosciences 2024Owing to the lack of effective vaccines, current control measures and eradication strategies for the African swine fever virus (ASFV) rely on early detection and... (Comparative Study)
Comparative Study
Owing to the lack of effective vaccines, current control measures and eradication strategies for the African swine fever virus (ASFV) rely on early detection and stringent stamping-out procedures. In the present study, we developed two independent isothermal amplification assays, namely, loop-mediated isothermal amplification (LAMP) and polymerase spiral reaction (PSR), for quick visualization of the ASFV genome in clinical samples. Additionally, a quantitative real-time PCR (qRT-PCR)-based hydrolysis probe assay was developed for comparative assessment of sensitivity with the developed isothermal assays. The analytical sensitivity of the LAMP, PSR, and qRT-PCR was found to be 2.64 ×10 copies/µL, 2.64 ×10 copies/µL, and 2.64 ×10 copies/µL, respectively. A total of 165 clinical samples was tested using the developed visual assays. The relative accuracy, relative specificity, and relative diagnostic sensitivity for LAMP vs PSR were found to be 95.37% vs 102.48%, 97.46% vs 101.36%, and 73.33% vs 113.33%, respectively.
Topics: African Swine Fever Virus; Animals; Nucleic Acid Amplification Techniques; Swine; African Swine Fever; Sensitivity and Specificity; Real-Time Polymerase Chain Reaction; Molecular Diagnostic Techniques; Genome, Viral
PubMed: 38952078
DOI: No ID Found -
Scientific Reports Jul 2024This work introduces and discusses the impacts of the water bridge on gas adsorption and diffusion behaviors in a shale gas-bearing formation. The density distribution...
This work introduces and discusses the impacts of the water bridge on gas adsorption and diffusion behaviors in a shale gas-bearing formation. The density distribution of the water bridge has been analyzed in micropores and meso-slit by molecular dynamics. Na and Cl have been introduced into the system to mimic a practical encroachment environment and compared with pure water to probe the deviation in water bridge distribution. Additionally, practical subsurface scenarios, including pressure and temperature, are examined to reveal the effects on gas adsorption and diffusion properties, determining the shale gas transportation in realistic shale formation. The outcomes suggest carbon dioxide (CO) usually has higher adsorption than methane (CH) with a water bridge. Increasing temperature hinders gas adsorption, density distribution decreases in all directions. Increasing pressure facilitates gas adsorption, particularly as a bulk phase in the meso-slit, whereas it restricts gas diffusion by enhancing the interaction strength between gas and shale. Furthermore, ions make the water bridge distributes more unity and shifts to the slit center, impeding gas adsorption onto shale while encouraging gas diffusion. This study provides updated guidelines for gas adsorption and transportation characteristics and supports the fundamental understanding of industrial shale gas exploration and transportation.
PubMed: 38951644
DOI: 10.1038/s41598-024-66055-4 -
Journal of the American Chemical Society Jul 2024Kinetic proofreading is used throughout natural systems to enhance the specificity of molecular recognition. At its most basic level, kinetic proofreading uses a supply...
Kinetic proofreading is used throughout natural systems to enhance the specificity of molecular recognition. At its most basic level, kinetic proofreading uses a supply of chemical fuel to drive a recognition interaction out of equilibrium, allowing a single free-energy difference between correct and incorrect targets to be exploited two or more times. Despite its importance in biology, there has been little effort to incorporate kinetic proofreading into synthetic systems in which molecular recognition is important, such as nucleic acid nanotechnology. In this article, we introduce a DNA strand displacement-based kinetic proofreading motif, showing that the consumption of a DNA-based fuel can be used to enhance molecular recognition during a templated dimerization reaction. We then show that kinetic proofreading can enhance the specificity with which a probe discriminates single nucleotide mutations, both in terms of the initial rate with which the probe reacts and the long-time behavior.
PubMed: 38951503
DOI: 10.1021/jacs.3c14673 -
Mikrochimica Acta Jul 2024A stable DNA signal amplification sensor was developed on account of rolling circle amplification (RCA). This sensor includes target DNA-controlled rolling circle...
A stable DNA signal amplification sensor was developed on account of rolling circle amplification (RCA). This sensor includes target DNA-controlled rolling circle amplification technology and locking probe DNA replacement technology, which can be used to detect DNA fragments with genetic information, thus constructing a biosensor for universal detection of DNA. This study takes the homologous DNA of human immunodeficiency virus (HIV) and let-7a as examples to describe this biosensor. The padlock probe is first cyclized by T4 DNA ligase in response to the target's reaction with it. Then, rolling cycle amplification is initiated by Phi29 DNA polymerase, resulting in the formation of a lengthy chain with several triggers. These triggers can open the locked probe LP1 with the fluorescence signal turned off, so that it can continue to react with H2 to form a stable H1-H2 double strand. This regulates the distance between B-DNA modified by the quenching group and H1 modified by fluorescent group, and the fluorescence signal is recovered.
Topics: Biosensing Techniques; Nucleic Acid Amplification Techniques; Humans; DNA Probes; Fluorescent Dyes; DNA, Viral; DNA; Spectrometry, Fluorescence; Fluorescence; DNA-Directed DNA Polymerase; Limit of Detection; HIV
PubMed: 38951284
DOI: 10.1007/s00604-024-06501-2 -
Mikrochimica Acta Jun 2024A cancer-targeted glutathione (GSH)-gated theranostic probe (CGT probe) for intracellular miRNA imaging and combined treatment of self-sufficient starvation therapy...
A cancer-targeted glutathione (GSH)-gated theranostic probe (CGT probe) for intracellular miRNA imaging and combined treatment of self-sufficient starvation therapy (ST) and chemodynamic therapy (CDT) was developed. The CGT probe is constructed using MnO nanosheet (MS) as carrier material to adsorb the elaborately designed functional DNAs. It can be internalized by cancer cells via specific recognition between the AS1411 aptamer and nucleolin. After CGT probe entering the cancer cells, the overexpressed GSH, as gate-control, can degrade MS to Mn which can be used for CDT by Fenton-like reaction. Simultaneously, Mn-mediated CDT can further cascade with the enzyme-like activities (catalase-like activity and glucose oxidase-like activity) of CGT probe, achieving self-sufficient ST/CDT synergistic therapy. Meanwhile, the anchored DNAs are released, achieving in situ signal amplification via disubstituted-catalytic hairpin assembly (DCHA) and FRET (fluorescence resonance energy transfer) imaging of miR-21. The in vitro and in vivo experiments demonstrated that accurate and sensitive miRNA detection can be achieved using the CGT probe. Overall, the ingenious CGT probe opens a new avenue for the development of early clinical diagnosis and cancer therapy.
Topics: MicroRNAs; Humans; Glutathione; Fluorescence Resonance Energy Transfer; Animals; Manganese Compounds; Oxides; Aptamers, Nucleotide; Mice; Mice, Nude; Theranostic Nanomedicine; Nucleolin; Neoplasms; Nanostructures; Oligodeoxyribonucleotides; Mice, Inbred BALB C; Fluorescent Dyes
PubMed: 38951214
DOI: 10.1007/s00604-024-06503-0 -
Spectrochimica Acta. Part A, Molecular... Jun 2024Devising carbon dots with long wavelength emission (red light or near infrared), high selectivity and good bio-compatibility is critical in fluorescence detection and...
Devising carbon dots with long wavelength emission (red light or near infrared), high selectivity and good bio-compatibility is critical in fluorescence detection and imaging, but achieving this goal remains a great challenge. Herein, near-infrared emissive carbon dots (NIR-CDs) with obvious emission characteristic of 653 nm were synthesized through hydrothermally treatment of toluidine bule and gallic acid. Noticeably, the NIR-CDs exhibited excellent selectivity and sensitivity to hypochlorite (ClO), and the limit of detection is as low as 42.7 nM. The selective recognition reaction between ClO and the surface functional groups of NIR-CDs inhibits the fluorescence from NIR-CDs. The quenching mechanism was confirmed by fluorescence lifetime decays, FT-IR spectroscopy and UV-vis absorption spectra. More remarkably, the NIR-CDs have rich hydrophilic groups showed lower cytotoxicity, excellent bio-compatibility and specific cell membrane localization ability. The established spectrofluorometric method based on NIR-CDs has been used to determination of ClO level in tap water sample, the recoveries were 97.7 %-103.3 %. In addition, the NIR-CDs also has been successfully applied for the imaging of cell membrane. The study provides a novel idea for developing NIR ClO probe as well as cell membrane localization probe based on CDs, which present bright prospects in real water samples monitoring and cell membrane imaging.
PubMed: 38950478
DOI: 10.1016/j.saa.2024.124743 -
Proceedings of the National Academy of... Jul 2024While the intracellular-extracellular distribution of lactate has been suggested to play a critical role in the healthy and diseased brain, tools are lacking to...
While the intracellular-extracellular distribution of lactate has been suggested to play a critical role in the healthy and diseased brain, tools are lacking to noninvasively probe lactate in intracellular and extracellular spaces. Here, we show that, by measuring the diffusion of lactate with diffusion-weighted magnetic resonance (MR) spectroscopy in vivo and comparing it to the diffusion of purely intracellular metabolites, noninvasive quantification of extracellular and intracellular lactate fractions becomes possible. More specifically, we detect alterations of lactate diffusion in the APP/PS1 mouse model of Alzheimer's disease. Data modeling allows quantifying decreased extracellular lactate fraction in APP/PS1 mice as compared to controls, which is quantitatively confirmed with implanted enzyme-microelectrodes. The capability of diffusion-weighted MR spectroscopy to quantify extracellular-intracellular lactate fractions opens a window into brain metabolism, including in Alzheimer's disease.
Topics: Animals; Lactic Acid; Alzheimer Disease; Brain; Mice; Mice, Transgenic; Diffusion Magnetic Resonance Imaging; Extracellular Space; Disease Models, Animal; Magnetic Resonance Spectroscopy; Male; Amyloid beta-Protein Precursor
PubMed: 38950371
DOI: 10.1073/pnas.2403635121