GTP modulates calcium binding and cation-induced conformational changes in erythrocyte transglutaminase

AbstractCalcium binding to erythrocyte transglutaminase was determined by equilibrium dialysis. Results indicate that 6 ions are bound to the enzyme both in the absence and in the presence of GTP and. that the nucleotide reduces the affinity of the enzyme for calcium. Furthermore, I− fluorescence quenching and proteolytic inactivation experiments proved that GTP also alters the conformation of the enzyme. It is thus suggested that multiple mechanisms are involved in the regulation of the enzyme activity by GTP

Changes in protein expression in two cholangiocarcinoma cell lines undergoing formation of multicellular tumor spheroids In vitro

Epithelial-to-Mesenchymal Transition (EMT) is relevant in malignant growth and frequently correlates with worsening disease progression due to its implications in metastases and re- sistance to therapeutic interventions. Although EMT is known to occur in several types of solid tumors, the information concerning tumors arising from the epithelia of the bile tract is still limited. In order to approach the problem of EMT in cholangiocarcinoma, we decided to investigate the changes in protein expression occurring in two cell lines under conditions leading to growth as adherent monolayers or to formation of multicellular tumor spheroids (MCTS), which are considered culture models that better mimic the growth characteristics of in-vivo solid tumors. In our system, changes in phenotypes occur with only a decrease in transmembrane E-cadherin and vimentin expression, minor changes in the transglutami- nase protein/activity but with significant differences in the proteome profiles, with declining and increasing expression in 6 and in 16 proteins identified by mass spectrometry. The aris- ing protein patterns were analyzed based on canonical pathways and network analysis. These results suggest that significant metabolic rearrangements occur during the conver- sion of cholangiocarcinomas cells to the MCTS phenotype, which most likely affect the car- bohydrate metabolism, protein folding, cytoskeletal activity, and tissue sensitivity to oxygen

Oxidative stress and menopause-related hot flashes may be independent events.

Abstract Objective At present, there is growing demand for alternative, or additional, treatments to hormone replacement therapy for menopause-related hot flashes (HF). Antioxidant supplements have been recently proposed as possible candidates for this purpose, regardless of the absence of clear evidence in support of a link between these vasomotor symptoms and oxidative stress (OxS). The aim of our study was to evaluate the association between HF and OxS serum markers in a large sample of middle-aged women. Materials and methods We conducted a cross-sectional study on 245 perimenopausal and early postmenopausal women (age 45–60 years). The variables examined were presence of self-reported HF and levels of 8-iso-prostaglandin F2α, 8-OH-deoxy-2′-guanosine, advanced oxidation protein products, total antioxidant power, uric acid, thiols, and paroxonase-1. Results Seventy-six women (31%) reported to suffer from HF (either medium or high intensity). None of the peripheral markers of OxS examined was found to be significantly associated with the presence of HF. Conclusion Taken together, our data suggest that systemic OxS might not be implicated with the onset of the climacteric vasomotor symptoms that most commonly affect women experiencing perimenopause and early postmenopause

Safety and efficacy of tranexamic acid for prevention of obstetric haemorrhage. An updated systematic review and meta-analysis

Background. A number of clinical systematic review and meta-analysis have been published on the use of tranexamic in the obstetric setting. The aim of this meta-analysis was to evaluate the safety and effectiveness of tranexamic acid in reducing blood loss when given prior to caesarean delivery. Materials and methods. We searched the Cochrane Wounds Specialized Register, Cochrane Central, MEDLINE (through PUBMED), Embase, and SCOPUS electronic databases. We also searched clinical trials registries for ongoing and unpublished studies, and checked reference lists to identify additional studies. We used no restrictions with respect to language and date of publication. Two review authors independently performed study selection, "Risk of bias" assessment, and data extraction. Initial disagreements were resolved by discussion, or by including a third review author when necessary. Results. We found 18 randomised controlled trials (RCTs) that met our inclusion criteria. Overall, 1,764 women receiving intravenous tranexamic acid for prevention of bleeding following caesarean sections and 1,793 controls receiving placebo were enrolled in the 18 RCTs evaluated. The use of tranexamic acid compared to controls (placebo or no intervention) reduces post-partum haemorrhage >400 mL (risk ratio [RR] 0.40, 95% confidence interval [CI] 0.24-0.65; 5 trials with a total of 786 participants), severe post-partum haemorrhage >1,000 mL (RR 0.32, 95% CI: 0.12-0.84; 5 trials with a total of 1,850 participants), and need for red blood cell transfusion (RR 0.30, 95% CI: 0.18-0.49; 10 trials with a total of 1,873 participants). No particular safety concerns on the use of this antifibrinolytic agent emerged from the analysis of the 18 RCTs included. Discussion. Overall, the results of this meta-analysis support the evidence of a beneficial effect of tranexamic acid in reducing blood loss and need for blood transfusion in pregnant women undergoing caesarean section

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Transglutaminase 2, a double face enzyme

During the years Amino Acids have dedicated much attention to the transglutaminase (Tgase) field and this special issue is therefore the fifth of a series. In a previous occasion, we celebrated the 50 years from transglutaminase discovery with the editorial “An overview of the first 50 years of transglutaminase research” (Beninati et al. 2009). Following ideally from that point, we have now chosen as general theme for this issue the multiple roles played by type 2 transglutaminase as a multi-face protein. Most people are accustomed to analyze events and facts by taking into account objects and their opposite to get the whole, as in the case of light and darkness, day and night, or black and white as within a chessboard. This is also the case for type 2 transglutaminase (Tgase2): to get the complete picture we must examine both sides of the problem, the protein with its opposite activities, the involvement in cells and tissues leading either to cell growth/differentiation or conversely to cell death/atrophy, and their implications in health protection and pathology. The aim in launching this special issue was to contribute to settle these topics and we introduce now these general concepts dividing ideally the path in the steps mentioned above

Spotlight on the transglutaminase 2 gene: A focus on genomic and transcriptional aspects

The type 2 isoenzyme is the most widely expressed transglutaminase in mammals displaying several intra- and extracellular activities depending on its location (protein modification, modulation of gene expression, membrane signalling and stabilization of cellular interactions with the extracellular matrix) in relation to cell death, survival and differentiation. In contrast with the appreciable knowledge about the regulation of the enzymatic activities, much less is known concerning its inducible expression, which is altered in inflammatory and neoplastic diseases. In this context, we first summarize the gene’s basic features including single-nucleotide polymorphism characterization, epigenetic DNA methylation and identification of regulatory regions and of transcription factor-binding sites at the gene promoter, which could concur to direct gene expression. Further aspects related to alternative splicing events and to ncRNAs (microRNAs and lncRNAs) are involved in the modulation of its expression. Notably, this important gene displays transcriptional variants relevant for the protein’s function with the occurrence of at least seven transcripts which support the synthesis of five isoforms with modified catalytic activities. The different expression of the TG2 (type 2 transglutaminase) variants might be useful for dictating the multiple biological features of the protein and their alterations in pathology, as well as from a therapeutic perspective