Transglutaminase 2 as a Marker for Inflammation and Therapeutic Target in Sepsis

Sepsis results in lethal organ malfunction due to dysregulated host response to infection, which is a condition with increasing prevalence worldwide. Transglutaminase 2 (TG2) is a crosslinking enzyme that forms a covalent bond between lysine and glutamine. TG2 plays important roles in diverse cellular processes, including extracellular matrix stabilization, cytoskeletal function, cell motility, adhesion, signal transduction, apoptosis, and cell survival. We have shown that the co-culture of Candida albicans and hepatocytes activates and induces the translocation of TG2 into the nucleus. In addition, the expression and activation of TG2 in liver macrophages was dramatically induced in the lipopolysaccharide-injected and cecal ligation puncture-operated mouse models of sepsis. Based on these findings and recently published research, we have reviewed the current understanding of the relationship between TG2 and sepsis. Following the genetic and pharmacological inhibition of TG2, we also assessed the evidence regarding the use of TG2 as a potential marker and therapeutic target in inflammation and sepsis.

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CASC15：A tumor-associated long non-coding RNA

Current Pharmaceutical Design ◽

10.2174/1381612826666200922153701 ◽

2020 ◽

Vol 26 ◽

Author(s):

Bei Wang ◽

Wen Xu ◽

Yuxuan Cai ◽

Chong Guo ◽

Gang Zhou ◽

...

Keyword(s):

Breast Cancer ◽

Therapeutic Target ◽

Cancer Colorectal ◽

Tumor Development ◽

Pathophysiological Mechanism ◽

Biological Processes ◽

Non Coding Rna ◽

Cancer Côlon ◽

The Relationship ◽

Long Non Coding Rna

Background: CASC15, one of long non-coding RNA, is involved in the regulation of many tumor biological processes, and is expected to become a new biological therapeutic target. This paper aims to elucidate the pathophysiological function of CASC15 in various tumors. Methods: The relationship between CASC15 and tumors was analyzed by searching references, and summarizes the specific pathophysiological mechanism of CASC15. Results: LncRNA CASC15 is closely related to tumor development, and has been shown to be abnormally high expressed in all kinds of tumors, including breast cancer, cervical cancer, lung cancer, hepatocellular carcinoma, gastric cancer, bladder cancer, colon cancer, colorectal cancer, cardiac hypertrophy, intrahepatic cholangiocarcinoma, leukemia, melanoma, tongue squamous cell carcinoma, nasopharyngeal carcinoma. However, CASC15 has been found to be downexpressed abnormally in ovarian cancer, glioma and neuroblastoma. Besides, it is identified that CASC15 can affect the proliferation, invasion and apoptosis of tumors. Conclusion: LncRNA CASC15 has the potential to become a new therapeutic target or marker for a variety of tumors.

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XIST: A Meaningful Long Noncoding RNA in NSCLC Process

Current Pharmaceutical Design ◽

10.2174/1381612826999201202102413 ◽

2020 ◽

Vol 26 ◽

Author(s):

Yujie Shen ◽

Yexiang Lin ◽

Kai Liu ◽

Jinlan Chen ◽

Juanjuan Zhong ◽

...

Keyword(s):

Therapeutic Target ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Critical Role ◽

Biological Functions ◽

Potential Therapeutic Target ◽

Considerable Evidence ◽

Lncrna Xist ◽

Nsclc Patients ◽

The Relationship

Background: A number of studies have proposed that lncRNA XIST plays a role in the development and chemosensitivity of NSCLC. Besides, XIST may become a potential therapeutic target for NSCLC patients. The aim of this review is to reveal the biological functions and exact mechanisms of XIST in NSCLC. Methods: In this review, relevant researches involving in the relationship between XIST and NSCLC are collected through systematic retrieval of PubMed Results: XIST is an oncogene in NSCLC and is abnormally upregulated in NSCLC tissues. Considerable evidence has shown that XIST exerts a critical role in the proliferation, invasion, migration, apoptosis and chemosensitivity of NSCLC cells. XIST mainly functions as a ceRNA in NSCLC process, while XIST also functions at transcriptional levels. Conclusion: LncRNA XIST has potential to become a novel biomolecular marker of NSCLC and a therapeutic target for NSCLC.

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Otitis Media and Obesity—An Unusual Relationship in Children

Healthcare ◽

10.3390/healthcare9040458 ◽

2021 ◽

Vol 9 (4) ◽

pp. 458

Author(s):

Cristina Gavrilovici ◽

Elena-Lia Spoială ◽

Anca-Viorica Ivanov ◽

Adriana Mocanu ◽

Violeta Ștreangă ◽

...

Keyword(s):

Risk Factors ◽

Otitis Media ◽

Tobacco Exposure ◽

Taste Changes ◽

Electronic Search ◽

Obesity And Overweight ◽

High Incidence ◽

Ear Infections ◽

The Relationship ◽

Published Research

Otitis media (OM) represents a public health matter, being the main cause of preventable hearing loss in pediatric patients. Besides well-established risk factors for developing OM, such as craniofacial abnormalities, prematurity, low birth weight, or tobacco exposure, there is evidence that obesity could be associated with a high incidence of OM. Our aim is to perform a literature review on the state of current published research on the relationship between OM and obesity and to discuss the interconnectivity between these two entities. We conducted an electronic search in PubMed and EMBASE databases. Out of 176 references, 15 articles were included in our study. Our findings suggest that obesity and overweight might be risk factors for developing OM, and vice versa. The main mechanisms for developing OM in obese patients include alteration in cytokine profile, increased gastroesophageal reflux, and/or fat accumulation. Conversely, ear infections exposure might increase the risk of obesity, mostly by taste changes through middle ear cavity inflammation.

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Age-Dependency of Total Tau in the Cerebrospinal Fluid Is Corrected by Amyloid-β 1–40: A Correlational Study in Healthy Adults

Journal of Alzheimer s Disease ◽

10.3233/jad-210286 ◽

2021 ◽

pp. 1-8

Author(s):

Paul Theo Zebhauser ◽

Achim Berthele ◽

Marie-Sophie Franz ◽

Oliver Goldhardt ◽

Janine Diehl-Schmid ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Amyloid Β ◽

Healthy Adults ◽

Tau Proteins ◽

Clinical Settings ◽

Inclusion Criteria ◽

Total Tau ◽

Potential Marker ◽

Wide Range ◽

The Relationship

Background: Tau proteins are established biomarkers of neuroaxonal damage in a wide range of neurodegenerative conditions. Although measurement of total-Tau in the cerebrospinal fluid is widely used in research and clinical settings, the relationship between age and total-Tau in the cerebrospinal fluid is yet to be fully understood. While past studies reported a correlation between age and total-Tau in the cerebrospinal fluid of healthy adults, in clinical practice the same cut-off value is used independently of patient’s age. Objective: To further explore the relationship between age and total-Tau and to disentangle neurodegenerative from drainage-dependent effects. Methods: We analyzed cerebrospinal fluid samples of 76 carefully selected cognitively healthy adults and included amyloid-β 1–40 as a potential marker of drainage from the brain’s interstitial system. Results: We found a significant correlation of total-Tau and age, which was no longer present when correcting total-Tau for amyloid-β 1–40 concentrations. These findings were replicated under varied inclusion criteria. Conclusion: Results call into question the association of age and total-Tau in the cerebrospinal fluid. Furthermore, they suggest diagnostic utility of amyloid-β 1–40 as a possible proxy for drainage-mechanisms into the cerebrospinal fluid when interpreting biomarker concentrations for neurodegenerative diseases.

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Potential of transglutaminase 2 as a therapeutic target

Expert Opinion on Therapeutic Targets ◽

10.1517/14728222.2010.510134 ◽

2010 ◽

Vol 14 (9) ◽

pp. 989-1003 ◽

Cited By ~ 27

Author(s):

Daniela Caccamo ◽

Monica Currò ◽

Riccardo Ientile

Keyword(s):

Therapeutic Target ◽

Transglutaminase 2

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Resting Heart Rate as a Predictor of Cancer Mortality: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10071354 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1354

Author(s):

Diana P. Pozuelo-Carrascosa ◽

Iván Cavero-Redondo ◽

I.M. Lee ◽

Celia Álvarez-Bueno ◽

Sara Reina-Gutierrez ◽

...

Keyword(s):

Heart Rate ◽

Cancer Mortality ◽

Meta Analysis ◽

Positive Association ◽

Cochrane Library ◽

Resting Heart Rate ◽

Potential Marker ◽

Meta Analyses ◽

Risk Of Cancer ◽

The Relationship

This work was aimed to synthetize the evidence available about the relationship between resting heart rate (RHR) and the risk of cancer mortality. A computerized search in the Medline, EMBASE, Web of Science, and Cochrane Library databases from their inception to 24 September 2020 was performed. We performed three meta-analyses: (1) cancer mortality comparing the “less than 60 bpm” and “more than 60 bpm” categories; (2) cancer mortality comparing “less than 60 bpm”, “60 to 80 bpm”, and “more than 80 bpm” categories; and (3) analysis for 10–12 and 20 bpm increase in RHR and risk of cancer mortality. Twenty-two studies were included in the qualitative review, and twelve of them met the inclusion criteria for the meta-analysis. Our results showed a positive association between RHR and the risk of cancer mortality. This association was shown in a meta-analysis comparing studies reporting mean RHR values below and above 60 bpm, when comparing three RHR categories using less than 60 bpm as the reference category and, finally, in dose response analyses estimating the effect of an increase of 10–12 bpm in RHR, both in men and in women. In conclusion, a low RHR is a potential marker of low risk of cancer mortality.

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Effect of Flotation Time and Collector Dosage on Estonian Phosphorite Beneficiation

Minerals ◽

10.3390/min11020114 ◽

2021 ◽

Vol 11 (2) ◽

pp. 114

Author(s):

Kadriann Tamm ◽

Zeinab Arab Zadeh ◽

Rein Kuusik ◽

Juha Kallas ◽

Jason Yang ◽

...

Keyword(s):

Phosphate Rock ◽

Froth Flotation ◽

Fine Fraction ◽

The European Union ◽

High Recovery ◽

Know How ◽

Cellular Processes ◽

Reliable Source ◽

Living Organisms ◽

The Relationship

Phosphorus is an essential and non-substitutable element for the cellular processes of all living organisms. The main source of phosphorus in the biosphere is phosphate rock. With more than 700 Mt phosphate rock, Estonia holds the largest sedimentary phosphate rock deposits in the European Union. Estonian phosphate rock is particularly outstanding due to its remarkably low content of hazardous heavy metals such as Cadmium (<5 ppm) and trace elements of Uranium (<50 ppm). It is also a reliable source of valuable elements such as rear earth elements (REEs). The aim of this study was to investigate the distribution of the main minerals (apatite and quartz) between slimes, tailings, and concentrates that formed at the froth flotation of Estonian phosphate rock with the up-to-date level of know-how and techniques. Subsequently, the relationship between the obtained grades and recovery levels in concentrates was determined based on the collector dosage and flotation duration. It was observed that the fine fraction of the tailings contains 17.9–33.49 wt% P2O5 that can be added to the final product. Moreover, it was found that, with the lower dosage of the collector, the extended flotation time does not influence the phosphate grade and a high amount of quartz remains in the concentrates. It was also shown that, by raising the collector dosage and setting the flotation time, an adequate grade (>32 wt% P2O5) and recovery (up to 98%) can be gained. The results showed that Estonian phosphate rock can be beneficiated to produce a high-quality concentrate at high recovery levels by modifying the main flotation parameters depending on the properties of the ore.

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Screening ,development of Transglutaminase-2 Inhibitors and its derivative as anti-lung cancer agent by insilico and invitro approach

Current Computer - Aided Drug Design ◽

10.2174/1573409917666210322120350 ◽

2021 ◽

Vol 17 ◽

Author(s):

Prachi P. Parvatikar ◽

Sumangala Patil ◽

Joy Hoskeri ◽

Sandeep Swargam ◽

Raghvendra Kulkarni ◽

...

Keyword(s):

Lung Cancer ◽

Transglutaminase 2 ◽

Docking Studies ◽

Target Protein ◽

Cellular Processes ◽

Cytotoxicity Studies ◽

Pharmacokinetic Properties ◽

Cancer Agent ◽

Inhibition Property ◽

Cancer Inhibition

Aim: Screening and development of TG2 inhibitors as anti lung cancer agent. Background: Transglutaminase 2 (TG2) is multifunctional and ubiquitously expressed protein from transglutaminase family. It takes part in various cellular processes and plays an important role in the pathogenesis of autoimmune, neurodegerative and also cancer. Background: Transglutaminase 2 (TG2) is multifunctional and ubiquitously expressed protein from transglutaminase family. It takes part in various cellular processes and plays an important role in the pathogenesis of autoimmune, neurodegerative and also cancer. Objective : The of proposed study is to focused on screening of potent inhibitors of TG2 by in-silico method and synthesis its derivative as well as analysis of its activity by invitro approach. Material and Methods: Molecular docking studies have been carried on the different classes of TG2 inhibitors against the target protein. Nearly thirty TG2 inhibitors were selected from literature and docking was performed against transglutaminase 2. The computational ADME property screening was also carried out to check their pharmacokinetic properties. The compounds which exhibited positive ADME properties with good interaction with possessing least binding energy were further validated for their anti-lung cancer inhibition property against A549 cell lines by cytotoxicity studies. Results: The results of present study indicate that the docked complex formed by cystamine showed better binding affinity towards target protein so, this derivative of cystamine is formed using 2,5 dihydrobenzoic acid. Invitro results revealed that both molecule proved good cytotoxic agent against A549 lung cancer (875.10, 553.22 µg/ml) respectively. Further its activity should be validated on TG2 expressing lung cancer. Conclusion : Cystamine and its derivative can be act as potential therapeutic target for lung cancer but further its activity should be validated on TG2 expressing lung cancer.

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The Significance of Long Noncoding RNA H19 in Predicting Progression and Metastasis of Cancers: A Meta-Analysis

BioMed Research International ◽

10.1155/2016/5902678 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 16

Author(s):

Wei Jing ◽

Man Zhu ◽

Xian-wei Zhang ◽

Zhong-ya Pan ◽

Shan-shan Gao ◽

...

Keyword(s):

Tumor Invasion ◽

Noncoding Rna ◽

Histological Grade ◽

Meta Analysis ◽

Cochrane Library ◽

Invasion Depth ◽

Potential Marker ◽

The Cochrane Library ◽

The Relationship ◽

Tumor Invasion Depth

Recently, numerous studies indicate that H19 plays a key role in tumorigenesis, but the results have been disputed, especially in the aspects of tumor progression and metastasis. Therefore, we performed this meta-analysis to systematically summarize the relationship between H19 and cancers. We searched PubMed, the Cochrane Library, CNKI, and Chinese Wan Fang to identify eligible studies. Odds ratios and 95% confidence intervals were calculated to assess the effect size. A total of 13 studies were enrolled in this meta-analysis, which was performed by Revman5.3 and Stata11.0 software. Our meta-analysis showed that the expression of H19 was associated with distant metastasis in nongastrointestinal tumors (OR = 3.85, 95% CI = 1.31–11.36,P=0.01) and, in gastrointestinal tumors (OR = 0.34, 95% CI = 0.15–0.78,P=0.01), lymph node metastasis (OR = 2.04, 95% CI = 1.19–3.48,P=0.009). Moreover, in gastric cancer, H19 expression was significantly related to histological grade (OR = 0.50, 95% CI = 0.29–0.86,P=0.01), TNM stage (OR = 0.19, 95% CI = 0.11–0.33,P<0.01), and tumor invasion depth (OR = 0.11, 95% CI = 0.04–0.27,P<0.01). Therefore, H19 could serve as a potential marker for progression and metastasis evaluation of cancers.

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Phosphotransfer and Nucleotidyltransfer

Enzymatic Reaction Mechanisms ◽

10.1093/oso/9780195122589.003.0014 ◽

2007 ◽

Author(s):

Perry A. Frey ◽

Adrian D. Hegeman

Keyword(s):

Transition State ◽

Molecular Mechanisms ◽

Enzymatic Reaction ◽

Covalent Bond ◽

Phosphoryl Group ◽

Dissociative Mechanism ◽

Chemical Mechanisms ◽

Cellular Processes ◽

Nucleic Acid Biosynthesis ◽

Transfer Mechanisms

Phosphotransferases, phosphatases, and nucleotidyltransferases catalyze nucleophilic substitution at phosphorus. They constitute a dominant class of enzymes in intermediary metabolism, energy transduction, nucleic acid biosynthesis and processing, and regulation of many cellular processes, including replication, cellular development, and apoptosis. The mechanisms of the action of these enzymes have been studied intensively at several levels, ranging from the biosynthesis of metabolites and nucleic acids to unmasking signaling networks to elucidating the molecular mechanisms of catalysis. We focus on the chemical mechanisms of the reactions of biological phosphates. More than 40 years of research on this chemistry reveals that the mechanisms can be grouped into two classes: the phosphoryl group (PO3−) transfer mechanisms and the nucleotidyl or alkylphosphoryl group (ROPO2−) transfer mechanisms. Because the fundamental chemical mechanisms of these reactions are not treated in textbooks, we begin by considering this chemistry and then move on to the enzymatic reaction mechanisms. Phosphomonoesters, phosphoanhydrides, and phosphoramidates undergo substitution at phosphorus by transfer of the phosphoryl (PO3–) group, that is, by P—O and P—N cleavage. The current description of a typical phosphoryl group transfer mechanism is one in which the phosphoryl donor and acceptor interact weakly with the phosphoryl group in flight in a transition state in which the total bonding to phosphorus is decreased relative to the ground state. The bonding is weak between phosphorus and the leaving group R–X and between phosphorus and the accepting group Y in the transition state of. Because of decreased bonding to phosphorus, this is a loose transition state that has been described as dissociative. The latter should not be confused with the dissociative mechanism, which is considered later. To avoid confusion, we use the term loose transition state. Detailed studies indicate that the bonding denoted by the dashed lines in represents partial covalency on the order of 10% to 20% of the strength of a full covalent bond, or a bond order of 0.1 to 0.2.

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