scholarly journals RNA m6A Modification in Immunocytes and DNA Repair: The Biological Functions and Prospects in Clinical Application

2021 ◽  
Vol 9 ◽  
Author(s):  
Mingjie Zhou ◽  
Wei Liu ◽  
Jieyan Zhang ◽  
Nan Sun
Keyword(s):  
Dna Repair ◽  
Clinical Application ◽  
B Lymphocyte ◽  
Therapeutic Potential ◽  
Clinical Applications ◽  
Fine Tuning ◽  
Translation Efficiency ◽  
Biological Functions ◽  
Transcription Level ◽  
The Stability

As the most prevalent internal modification in mRNA, N6-methyladenosine (m6A) plays broad biological functions via fine-tuning gene expression at the post-transcription level. Such modifications are deposited by methyltransferases (i.e., m6A Writers), removed by demethylases (i.e., m6A Erasers), and recognized by m6A binding proteins (i.e., m6A Readers). The m6A decorations regulate the stability, splicing, translocation, and translation efficiency of mRNAs, and exert crucial effects on proliferation, differentiation, and immunologic functions of immunocytes, such as T lymphocyte, B lymphocyte, dendritic cell (DC), and macrophage. Recent studies have revealed the association of dysregulated m6A modification machinery with various types of diseases, including AIDS, cancer, autoimmune disease, and atherosclerosis. Given the crucial roles of m6A modification in activating immunocytes and promoting DNA repair in cells under physiological or pathological states, targeting dysregulated m6A machinery holds therapeutic potential in clinical application. Here, we summarize the biological functions of m6A machinery in immunocytes and the potential clinical applications via targeting m6A machinery.

scholarly journals Exosome-derived noncoding RNAs in gastric cancer: functions and clinical applications

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiao-Huan Tang ◽  
Ting Guo ◽  
Xiang-Yu Gao ◽  
Xiao-Long Wu ◽  
Xiao-Fang Xing ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Noncoding Rnas ◽  
Tumour Microenvironment ◽  
Clinical Applications ◽  
Biological Molecules ◽  
Biological Functions ◽  
Membrane Structures ◽  
Chemical Substances ◽  
Expression Levels ◽  
The Stability

AbstractExosomes are a subpopulation of the tumour microenvironment (TME) that transmit various biological molecules to promote intercellular communication. Exosomes are derived from nearly all types of cells and exist in all body fluids. Noncoding RNAs (ncRNAs) are among the most abundant contents in exosomes, and some ncRNAs with biological functions are specifically packaged into exosomes. Recent studies have revealed that exosome-derived ncRNAs play crucial roles in the tumorigenesis, progression and drug resistance of gastric cancer (GC). In addition, regulating the expression levels of exosomal ncRNAs can promote or suppress GC progression. Moreover, the membrane structures of exosomes protect ncRNAs from degradation by enzymes and other chemical substances, significantly increasing the stability of exosomal ncRNAs. Specific hallmarks within exosomes that can be used for exosome identification, and specific contents can be used to determine their origin. Therefore, exosomal ncRNAs are suitable for use as diagnostic and prognostic biomarkers or therapeutic targets. Regulating the biogenesis of exosomes and the expression levels of exosomal ncRNAs may represent a new way to block or eradicate GC. In this review, we summarized the origins and characteristics of exosomes and analysed the association between exosomal ncRNAs and GC development.

Radioimmunodetection of Malignant Melanoma with the 225.28S Monoclonal Antibody to HMW-MAA

1986 ◽  
Vol 25 (06) ◽  
pp. 220-224 ◽  
Author(s):  
G. L. Buraggi
Keyword(s):  
Monoclonal Antibody ◽  
Pilot Study ◽  
Malignant Melanoma ◽  
Prospective Study ◽  
Clinical Application ◽  
Multicenter Trial ◽  
Clinical Applications ◽  
Gamma Energy ◽  
A Prospective Study ◽  
Antigen Antibody

A review of the studies on the use of the antigen-antibody system HMW-MAA 225.28S in melanoma radioimmunodetection is reported. The results obtained in a pilot study (42 patients with 74 lesions), a multicenter trial (254 patients with 553 lesions) and a prospective study still outstanding (29 patients with 38 lesions) allow to consider this system as suitable for clinical application. F(ab′)2 labelled with 99mTc gave the best results in terms of positivity. Moreover this radioisotope allows the best dosimetric conditions. The gamma energy emitted by this radionuclide is particularly convenient for conventional scintillation cameras and ECT. Very good results in terms of sensitivity (70%-85%) and especially specificity (about 100%) were achieved. Possible clinical applications of the method are discussed.

From Ocean to Bedside: the Therapeutic Potential of Molluscan Hemocyanins

2018 ◽  
Vol 25 (20) ◽  
pp. 2292-2303 ◽  
Author(s):  
Negar Talaei Zanjani ◽  
Monica Miranda Saksena ◽  
Fariba Dehghani ◽  
Anthony L. Cunningham
Keyword(s):  
Antiviral Activity ◽  
Clinical Efficacy ◽  
Mechanism Of Action ◽  
Therapeutic Agent ◽  
Marine Invertebrates ◽  
Therapeutic Potential ◽  
Biological Functions ◽  
Anticancer Properties ◽  
Mechanistic Understanding

Hemocyanins are large and versatile glycoproteins performing various immunological and biological functions in many marine invertebrates including arthropods and molluscs. This review discusses the various pharmacological applications of mollusc hemocyanin such as antiviral activity, immunostimulatory and anticancer properties that have been reported in the literature between the years 2000 and 2016. Emphasis is placed on a better mechanistic understanding of hemocyanin as a therapeutic agent. Elucidation of the mechanism of action is essential to improve the clinical efficacy and for a better understanding of some endogenous immunological functions of this complex glycoprotein.

scholarly journals AI MSK clinical applications: spine imaging

2021 ◽  
Author(s):  
Florian A. Huber ◽  
Roman Guggenberger
Keyword(s):  
Artificial Intelligence ◽  
Clinical Application ◽  
Value Chain ◽  
Clinical Applications ◽  
Status Quo ◽  
Use Cases ◽  
Musculoskeletal Imaging ◽  
Future Perspective ◽  
Spine Imaging ◽  
The Status

AbstractRecent investigations have focused on the clinical application of artificial intelligence (AI) for tasks specifically addressing the musculoskeletal imaging routine. Several AI applications have been dedicated to optimizing the radiology value chain in spine imaging, independent from modality or specific application. This review aims to summarize the status quo and future perspective regarding utilization of AI for spine imaging. First, the basics of AI concepts are clarified. Second, the different tasks and use cases for AI applications in spine imaging are discussed and illustrated by examples. Finally, the authors of this review present their personal perception of AI in daily imaging and discuss future chances and challenges that come along with AI-based solutions.

scholarly journals Characteristics and Clinical Application of Extracellular Vesicle-Derived DNA

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3827
Author(s):  
Jae Young Hur ◽  
Kye Young Lee
Keyword(s):  
Therapeutic Potential ◽  
Extracellular Vesicle ◽  
Clinical Settings ◽  
Biomarker Detection ◽  
Diagnosis And Prognosis ◽  
Double Stranded Dna ◽  
Fundamental Research ◽  
The Stability ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Extracellular vesicles (EVs) carry RNA, proteins, lipids, and diverse biomolecules for intercellular communication. Recent studies have reported that EVs contain double-stranded DNA (dsDNA) and oncogenic mutant DNA. The advantage of EV-derived DNA (EV DNA) over cell-free DNA (cfDNA) is the stability achieved through the encapsulation in the lipid bilayer of EVs, which protects EV DNA from degradation by external factors. The existence of DNA and its stability make EVs a useful source of biomarkers. However, fundamental research on EV DNA remains limited, and many aspects of EV DNA are poorly understood. This review examines the known characteristics of EV DNA, biogenesis of DNA-containing EVs, methylation, and next-generation sequencing (NGS) analysis using EV DNA for biomarker detection. On the basis of this knowledge, this review explores how EV DNA can be incorporated into diagnosis and prognosis in clinical settings, as well as gene transfer of EV DNA and its therapeutic potential.

scholarly journals Hot-Wire Laser-Directed Energy Deposition: Process Characteristics and Benefits of Resistive Pre-Heating of the Feedstock Wire

Metals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 634
Author(s):  
Agnieszka Kisielewicz ◽  
Karthikeyan Thalavai Pandian ◽  
Daniel Sthen ◽  
Petter Hagqvist ◽  
Maria Asuncion Valiente Bermejo ◽  
...  
Keyword(s):  
Heat Input ◽  
Energy Deposition ◽  
Fine Tuning ◽  
Hot Wire ◽  
Process Stability ◽  
Electrical Signals ◽  
Melt Pool ◽  
Directed Energy Deposition ◽  
Directed Energy ◽  
The Stability

This study investigates the influence of resistive pre-heating of the feedstock wire (here called hot-wire) on the stability of laser-directed energy deposition of Duplex stainless steel. Data acquired online during depositions as well as metallographic investigations revealed the process characteristic and its stability window. The online data, such as electrical signals in the pre-heating circuit and images captured from side-view of the process interaction zone gave insight on the metal transfer between the molten wire and the melt pool. The results show that the characteristics of the process, like laser-wire and wire-melt pool interaction, vary depending on the level of the wire pre-heating. In addition, application of two independent energy sources, laser beam and electrical power, allows fine-tuning of the heat input and increases penetration depth, with little influence on the height and width of the beads. This allows for better process stability as well as elimination of lack of fusion defects. Electrical signals measured in the hot-wire circuit indicate the process stability such that the resistive pre-heating can be used for in-process monitoring. The conclusion is that the resistive pre-heating gives additional means for controlling the stability and the heat input of the laser-directed energy deposition.

Designed Synthesis of Diversely Substituted Hydantoins and Hydantoin-Based Hybrid Molecules: A Personal Account

Synlett ◽  
2021 ◽  
Author(s):  
Vinod Kumar
Keyword(s):  
Clinical Applications ◽  
Point Of View ◽  
Biological Functions ◽  
Personal Account ◽  
Pharmacological Activities ◽  
Structural Modifications ◽  
Hybrid Molecules ◽  
Biological Target ◽  
Designed Synthesis ◽  
Mixed Mechanism

Hydantoin and its analogs such as thiohydantoin and iminohydantoin have received substantial attention both from a chemical and biological point of view. Several compounds of this class have shown useful pharmacological activities such as anticonvulsant, antitumor, antiarrhythmic, herbicidal, and others that lead in some cases to clinical applications. Because of broad-spectrum activities, intensive research efforts have been dedicated in industry and academia to the synthesis and structural modifications of hydantoin and its derivatives. Realizing the importance of hydantoin in organic and medicinal chemistry, we also initiated a research program to successfully design and develop the new routes/methods resulting in the formation of hydantoin, thiohydantoin, and iminohydantoin substituted at different positions particularly at the N-1 position without following protection-deprotection strategy. Given the fact that the combination of two or more pharmacophoric groups may lead to hybrid molecules which result in a mixed mechanism of action on the biological target. We, therefore, further extended the developed strategy for the synthesis of new types of hydantoin-based hybrid molecules by combining hydantoin with a triazole, isoxazoline, and phosphate scaffolds as another pharmacophoric group to exploit diverse biological functions.

Study on the characteristics of secondary arc current of UHV high compensation degree TCSC line under the fine-tuning mode

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Baina He ◽  
Yadi Xie ◽  
Jingru Zhang ◽  
Nirmal-Kumar C. Nair ◽  
Xingmin He ◽  
...  
Keyword(s):  
Transmission Line ◽  
Transmission Lines ◽  
Stability Margin ◽  
Transmission Capacity ◽  
Fine Tuning ◽  
Series Compensation ◽  
Arc Current ◽  
Compensation Device ◽  
The Stability ◽  
Recovery Voltage

Abstract In the transmission line, the series compensation device is often used to improve the transmission capacity. However, when the fixed series capacitor (FSC) is used in high compensation series compensation device, the stability margin cannot meet the requirements. Therefore, thyristor controlled series compensator (TCSC) is often installed in transmission lines to improve the transmission capacity of the line and the stability of the system. For cost considerations, the hybrid compensation mode of FSC and TCSC is often adopted. However, when a single-phase grounding fault occurs in a transmission line with increased series compensation degree, the unreasonable distribution of FSC and TCSC will lead to the excessive amplitude of secondary arc current, which is not conducive to rapid arc extinguishing. To solve this problem, this paper is based on 1000 kV Changzhi-Nanyang-Jingmen UHV series compensation transmission system, using PSCAD simulation program to established UHV series compensation simulation model, The variation law of secondary arc current and recovery voltage during operation in fine tuning mode after adding TCSC to UHV transmission line is analyzed, and the effect of increasing series compensation degree on secondary arc current and recovery voltage characteristics is studied. And analyze the secondary arc current and recovery voltage when using different FSC and TCSC series compensation degree schemes, and get the most reasonable series compensation configuration scheme. The results show that TCSC compensation is more beneficial to arc extinguishing under the same series compensation. Compared with several series compensation schemes, it is found that with the increase of the proportion of TCSC, the amplitude of secondary arc current and recovery voltage vary greatly. Considering various factors, the scheme that is more conducive to accelerating arc extinguishing is chosen.

scholarly journals Development of A Continuous Fluorescence-Based Assay for N-Terminal Acetyltransferase D

2021 ◽  
Vol 22 (2) ◽  
pp. 594
Author(s):  
Yi-Hsun Ho ◽  
Lan Chen ◽  
Rong Huang
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
High Throughput Screening ◽  
Coenzyme A ◽  
Therapeutic Potential ◽  
Biological Functions ◽  
Histone H4 ◽  
Fluorescent Signal ◽  
Pharmacologically Active ◽  
Pharmacologically Active Compounds

N-terminal acetylation catalyzed by N-terminal acetyltransferases (NATs) has various biological functions in protein regulation. N-terminal acetyltransferase D (NatD) is one of the most specific NAT with only histone H4 and H2A proteins as the known substrates. Dysregulation of NatD has been implicated in colorectal and lung cancer progression, implying its therapeutic potential in cancers. However, there is no reported inhibitor for NatD yet. To facilitate the discovery of small-molecule NatD inhibitors, we report the development of a fluorescence-based acetyltransferase assay in 384-well high-throughput screening (HTS) format through monitoring the formation of coenzyme A. The fluorescent signal is generated from the adduct in the reaction between coenzyme A and fluorescent probe ThioGlo4. The assay exhibited a Z′-factor of 0.77 and a coefficient of variation of 6%, indicating it is a robust assay for HTS. A pilot screen of 1280 pharmacologically active compounds and subsequent validation identified two hits, confirming the application of this fluorescence assay in HTS.

The possibility of a stable flat dark energy-dominated Swiss-cheese brane-world universe

2020 ◽  
Vol 17 (05) ◽  
pp. 2050075
Author(s):  
Nasr Ahmed ◽  
Kazuharu Bamba ◽  
F. Salama
Keyword(s):  
Dark Energy ◽  
Cosmological Constant ◽  
Cosmological Models ◽  
Brane World ◽  
Fine Tuning ◽  
Energy Conditions ◽  
Late Time ◽  
Swiss Cheese ◽  
Black Strings ◽  
The Stability

In this paper, we study the possibility of obtaining a stable flat dark energy-dominated universe in a good agreement with observations in the framework of Swiss-cheese brane-world cosmology. Two different brane-world cosmologies with black strings have been introduced for any cosmological constant [Formula: see text] using two empirical forms of the scale factor. In both models, we have performed a fine-tuning between the brane tension and the cosmological constant so that the Equation of state (EoS) parameter [Formula: see text] for the current epoch, where the redshift [Formula: see text]. We then used these fine–tuned values to calculate and plot all parameters and energy conditions. The deceleration–acceleration cosmic transition is allowed in both models, and the jerk parameter [Formula: see text] at late-times. Both solutions predict a future dark energy-dominated universe in which [Formula: see text] with no crossing to the phantom divide line. While the pressure in the first solution is always negative, the second solution predicts a better behavior of cosmic pressure where the pressure is negative only in the late-time accelerating era but positive in the early-time decelerating era. Such a positive-to-negative transition in the evolution of pressure helps to explain the cosmic deceleration–acceleration transition. Since black strings have been proved to be unstable by some authors, this instability can actually reflect doubts on the stability of cosmological models with black strings (Swiss-cheese type brane-worlds cosmological models). For this reason, we have carefully investigated the stability through energy conditions and sound speed. Because of the presence of quadratic energy terms in Swiss-cheese type brane-world cosmology, we have tested the new nonlinear energy conditions in addition to the classical energy conditions. We have also found that a negative tension brane is not allowed in both models of the current work as the energy density will no longer be well defined.

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