Association of peripheral blood-derived mesenchymal stem cells exosomal circular RNAs with diagnosis and inflammatory response in acute mesenteric ischemia

Can Intestinal Fatty Acid Binding Protein (I-FABP) Be A Marker in the Diagnosis of Abdominal Pathology?

Plasma intestinal fatty acid binding protein (I-FABP) concentrations increase following intestinal ischemia in pigs

The pathophysiological sequelae of meningococcal sepsis are mainly caused by deregulated microvasculature function, leading to impaired tissue blood flow. Because mature enterocytes are known to be susceptible to altered perfusion, we aimed to investigate: (1) the development of enterocyte damage; and (2) the relation between enterocyte damage and severity of disease and outcome in children with meningococcal sepsis. Retrospective human study. Pediatric intensive care unit at a university hospital. Nineteen consecutive children with meningococcal sepsis were studied during their pediatric intensive care unit stay. None. MEASUREMENT AND MAIN RESULTS Circulating levels of intestinal fatty acid binding protein, a small cytosolic protein constitutively present in mature enterocytes and released on cell injury, were assessed. Severity of disease was represented by meningococcal-specific Rotterdam Score, generic Pediatric Risk of Mortality II score, and circulating interleukin-6. Clinical outcome was measured by length of pediatric intensive care unit stay and number of ventilator days. Highest plasma intestinal fatty acid binding protein values were measured on pediatric intensive care unit stay admission. At the time of admission, eight of 19 patients had higher intestinal fatty acid binding protein plasma levels than the upper reference limit of 30 healthy volunteers. In all survivors, intestinal fatty acid binding protein levels declined to normal values within 12 hrs after starting intensive treatment, whereas the three nonsurvivors maintained elevated intestinal fatty acid binding protein plasma levels. A significant correlation was found among intestinal fatty acid binding protein and Rotterdam Score, Pediatric Risk of Mortality II, interleukin-6 at admission (Spearman's r = 0.402, p = .006; r = 0.243, p = .045; r = 0.687, p < .001, respectively). Next, a significant correlation was found between intestinal fatty acid binding protein and clinical outcome. Elevated plasma intestinal fatty acid binding protein is found in eight of 19 children with severe pediatric intensive care unit stay at the time of clinical presentation, suggesting the presence of enterocyte damage. Furthermore, prolonged enterocyte damage is found in nonsurvivors. Further studies are needed to clarify the potential role for assessment of plasma intestinal fatty acid binding protein in monitoring treatment of pediatric intensive care unit stay.

acute mesenteric ischemia (AMI) is a life-threatening condition that is caused by inadequate blood flow through the mesenteric vessel and is related to high mortality rates due to systemic complications. This study aims to systematically review the available literature concerning the major findings of possible biomarkers for early detection of acute mesenteric ischemia in the human population. studies that measured the performance of biomarkers during acute mesenteric ischemia were identified with the search of PubMed, Embase, Medline, and Cochrane library. from a total of 654 articles, 46 articles examining 14 different biomarkers were filtered, falling within our inclusion criteria. Intestinal fatty acid-binding protein (I-FABP) was the most commonly researched biomarker regarding AMI, with sensitivity ranging from 61.5% to 100% and specificity ranging from 40% to 100%. The second most commonly researched biomarker was D-dimer, with a sensitivity of 60-100% and a specificity of 18-85.71%. L-lactate had a sensitivity of 36.6-90.91% and a specificity of 64.29-96%. Several parameters within the blood count were examined as potential markers for AMI, including NLR, PLR, MPV, RDW, DNI, and IG. Citrulline, interleukin 6 (IL-6), and procalcitonin (PCT) were the least-researched biomarkers. different biomarkers showed different accuracies in detecting AMI. I-FABP and D-dimer have been the most researched and shown to be valuable in the diagnosis of AMI, whereas L-lactate could be used as an additional tool. Ischemia-modified albumin (IMA), alpha glutathione S-transferase (αGST), interleukin 6 (IL-6), and citrulline showed potential use in their respective studies. However, further research needs to be done on larger sample sizes and with controls to reduce bias. Several studies showed that neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), mean platelet volume (MPV), red-cell distribution width (RDW), delta neutrophil index (DNI), and immature granulocytes (IGs) might be useful, as well at the same time be widely distributed and affordable in combination with other markers presenting higher specificity and sensitivity.

Background Intestinal fatty acid-binding protein (I-FABP) has been shown to be of high diagnostic value in patients with acute mesenteric ischemia. Whether these results can be reproduced in critically ill patients on the ICU was to be investigated. Materials and Methods I-FABP was measured in serum and urine of 43 critically ill patients in ICU when mesenteric ischemia was suspected. Bowel ischemia was confirmed in 21 patients (group 1). 22 patients who survived at least seven days without confirmation of ischemia were assigned to group 2. I-FABP levels were compared between the groups, and interval from the event that has triggered ischemia to I-FABP measurement was recorded. Results For the identification of patients with mesenteric ischemia, sensitivity, specificity, and area under the curve (AUC) for serum and urine I-FABP were 33.3%, 95.5%, and 0.565 and 81.3%, 70.0%, and 0.694, respectively. I-FABP measurements performed within 12 to 48 h after the event that triggered ischemia showed a sensitivity, specificity, and AUC for serum and urine of 75%, 100%, and 0.853 and 100%, 73.3%, and 0.856, respectively. Conclusions In ICU patients, one single I-FABP measurement at the time of clinical suspicion failed to reliably detect or exclude mesenteric ischemia. A higher diagnostic value of I-FABP was only confirmed in the early stages of mesenteric ischemia. I-FABP may be used most appropriately in perioperative monitoring.

Background: Acute mesenteric ischemia accounts for around 0.1% of all hospital admission and less than 1% of emergency admissions. However, the presentation is varied, and diagnosis is obscure. The diagnosis of intestinal ischemia demands a high index of suspicion. The overall mortality associated with mesenteric ischemia is between 60% and 93% but rises acutely once bowel wall infarction has occurred. Early diagnosis of ischemia remains the key to reduce morbidity and mortality. I-FABP is a cytosolic protein present in epithelial cells of intestines and released upon ischemia or necrosis of bowel. Author estimated the levels of I-FABP in serum and established it as a marker for acute intestinal ischemia.Methods: 40 patients admitted to JSS Hospital with suspected acute intestinal ischemia were included in the study. Plasma concentrations were quantified using ELISA for fatty acid binding protein 2. Statistical methods were applied and sensitivity and specificity of serum I-FABP were determined. Confirmation of ischemia was by histopathological analysis of the resected bowel specimen.Results: 23 patients out of the 40 were diagnosed to have intestinal ischemia. Mean values of serum IFABP levels were significantly higher in patients diagnosed with intestinal ischemia (65.94pg/ml in the non-ischemic group vs 673.53pg/ml in the ischemic group P=0.0002). Cut off chosen in diagnosing intestinal ischemia in this study was 187.59pg/ml. Sensitivity was 95.7% and specificity 88%.Conclusions: Serum I-FABP can be used for the diagnosis for intestinal ischemia. It is specific and sensitive marker to detect early bowel ischemia.

Early diagnosis of acute mesenteric ischemia (AMI) remains a clinical challenge, and no biomarker has been consistently validated. We aimed to assess the accuracy of three promising circulating biomarkers for diagnosing AMI—citrulline, intestinal fatty acid-binding protein (I-FABP), and d-lactate. A cross-sectional diagnostic study enrolled AMI patients admitted to the intestinal stroke center and controls with acute abdominal pain of another origin. We included 129 patients—50 AMI and 79 controls. Plasma citrulline concentrations were significantly lower in AMI patients compared to the controls [15.3 μmol/L (12.0–26.0) vs. 23.3 μmol/L (18.3–29.8), p = 0.001]. However, the area under the receiver operating curves (AUROC) for the diagnosis of AMI by Citrulline was low: 0.68 (95% confidence interval = 0.58–0.78). No statistical difference was found in plasma I-FABP and plasma d-lactate concentrations between the AMI and control groups, with an AUROC of 0.44, and 0.40, respectively. In this large cross-sectional study, citrulline, I-FABP, and d-lactate failed to differentiate patients with AMI from patients with acute abdominal pain of another origin. Further research should focus on the discovery of new biomarkers.

Comprehensive analysis showed that the popularity of research peripheral blood-derived mesenchymal stem cells for knee cartilage repair is still lacking, as they peripherally exist at a very low level. Despite its small cell number, peripheral blood is yet one of the most convenient sources of mesenchymal stem cells due to its less invasive method to harvest. This study aimed to systematically review the current evidence of peripheral blood-derived mesenchymal stem cells towards the repair of articular cartilage defect. A comprehensive literature search was performed to identify all in vivo studies reporting the structural outcome of articular cartilage repair in the knee following electronic databases: PubMed, WOS and SCOPUS. The in vitro characterizations of peripheral blood-derived mesenchymal stem cells were evaluated to enable quality assessment. Literature from 1934 to 2019 showed 4822 of total articles with only three findings related to pre-clinical studies were included in the analysis. The selection of animal model, type of transplantation, mobilization of the peripheral blood, in vitro culture condition, type of scaffold, assessments on the cartilage defect, and the outcome measures were heterogeneous. Evidence showed that mobilized peripheral blood-derived mesenchymal stem cells were more superior in repairing articular cartilage compared to those that were non-mobilized. These cells also showed a comparable capability in repairing articular cartilage than the commonly used bone marrow mesenchymal stem cells. Overall, more progress is needed to expand the usage of peripheral blood-derived mesenchymal stem cells from basic biological science to the translational studies in clinical practice.

BackgroundMesenchymal stem cell treatments in dogs have been investigated as a potential innovative alternative to current conventional therapies for a variety of conditions. So far, the precise mode of action of the MSCs has yet to be determined. The aim of this study was to gain more insights into the pharmacokinetics of MSCs by evaluating their biodistribution in healthy dogs after different injection routes.MethodsThree different studies were performed in healthy dogs to evaluate the biodistribution pattern of radiolabelled equine peripheral blood-derived mesenchymal stem cells following intravenous, intramuscular and subcutaneous administration in comparison with free 99mTechnetium. The labelling of the equine peripheral blood-derived mesenchymal stem cells was performed using stannous chloride as a reducing agent. Whole-body scans were obtained using a gamma camera during a 24-h follow-up.ResultsThe labelling efficiency ranged between 59.58 and 83.82%. Free 99mTechnetium accumulation was predominantly observed in the stomach, thyroid, bladder and salivary glands, while following intravenous injection, the 99mTechnetium-labelled equine peripheral blood-derived mesenchymal stem cells majorly accumulated in the liver throughout the follow-up period. After intramuscular and subcutaneous injection, the injected dose percentage remained very high at the injection site.ConclusionsA distinct difference was noted in the biodistribution pattern of the radiolabelled equine peripheral blood-derived mesenchymal stem cells compared to free 99mTechnetium indicating equine peripheral blood-derived mesenchymal stem cells have a specific pharmacokinetic pattern after systemic administration in healthy dogs. Furthermore, the biodistribution pattern of the used xenogeneic equine peripheral blood-derived mesenchymal stem cells appeared to be different from previously reported experiments using different sources of mesenchymal stem cells.

Introduction Intestinal toxicity can occur following ingestion of various drugs, chemicals, and toxins. Intestinal fatty acid binding protein is a cytosolic protein specific to intestinal epithelial cells released into the systemic circulation following intestinal injury. Understanding intestinal toxicity in poisoning has the potential to explain mechanisms of toxicity and gastrointestinal symptoms. Methods Plasma samples were retrospectively analysed for intestinal fatty acid binding protein in 25 healthy controls and in those poisoned with Gloriosa superba (n = 18), Thevetia peruviana (n = 26), organophosphates (in various solvents) (n = 17), paracetamol (n = 14), glyphosate (n = 20), 2-methyl-4-chlorophenoxyacetic acid (n = 18) and propanil (n = 19). Results Median peak plasma intestinal fatty acid binding protein concentrations were significantly higher in patients poisoned with Gloriosa superba (2,994.1 µg/L; interquartile range 600.0–5,158.2, P < 0.001), Thevetia peruviana (1,292.5 µg/L; interquartile range 760.3 − 2,076.2; P < 0.001), glyphosate (1,803.6 µg/L; interquartile range 225.7–8,927.7; P < 0.001), 2-methyl-4-chlorophenoxyacetic acid (1,236.2 µg/L; interquartile range 192.6 − 1,709.7; P = 0.010), paracetamol (1,066.5 µg/L; interquartile range 512.9 − 1,336.9; P = 0.035), and organophosphate poisoning (729.8 µg/L; interquartile range 431.5 − 1,588.2; P = 0.046) than in healthy controls (221.6 µg/L; interquartile range 134.8 − 460.1). Median intestinal fatty acid binding protein was not statistically significantly increased compared to controls after propanil poisoning (630.0 µg/L; interquartile range 23.5 − 1,390.3; P = 0.423). Conclusions Our pilot study describes intestinal injury assessed by elevated plasma intestinal fatty acid binding protein concentrations following the ingestion of several poisons. This serves as a foundation for further exploration into enterocyte damage in toxicology.

Early Diagnosis of Intestinal Ischemia Using Urinary and Plasma Fatty Acid Binding Proteins

BackgroundThe prognostic value of biochemical tests in critically ill patients with multiple organ failure and suspected bowel ischemia is unknown.MethodsIn a prospective observational cohort study intensive care patients were included when the attending intensivist considered intestinal ischemia in the diagnostic workup at any time during intensive care stay. Patients were only included once. When enrolment was ended each patient was classified as ‘proven intestinal ischemia’, ‘ischemia likely’, ‘ischemia unlikely’ or ‘no intestinal ischemia’. Proven intestinal ischemia was defined as the gross disturbance of blood flow in the bowel, regardless of extent and grade. Classification was based on reports from the operating surgeon, pathology department, endoscopy reports and CT-scan. Lactate dehydrogenase (LDH), creatine kinase (CK), alanine aminotransferase (ALAT), L-lactate were available for the attending physician. D-lactate and intestinal fatty acid binding protein (I-FABP) were analysed later in a batch. I-FABP was only measured in patients with proven ischemia or no ischemia.ResultsFor 44 of the 120 included patients definite diagnostic studies were available. 23/44 patients (52%) had proven intestinal ischemia as confirmed by surgery, colonoscopy, autopsy and/or histopathological findings. LDH in these patients was 285 U/l (217–785) vs 287 U/l (189–836) in no-ischemia; p = 0.72. CK was 226 U/l in patients with proven ischemia (126–2145) vs 347 U/l (50–1427), p = 0.88. ALAT was 53 U/l (18–300) vs 34 U/l (14–34), p-0,56. D-lactate 0.41 mmol/l (0.11-0.75) vs 0.56 mmol/l (0.27-0.77), p = 0.46. L-lactate 3.5 mmol/l (2.2-8.4) vs 2.6 mmol/l (1.7-3.9), p = 0.09. I-FABP 2872 pg/ml (229–4340) vs 1020 pg/ml (239–5324), p = 0.98. Patient groups proven and likely ischemia together compared to unlikely and no-ischemia together showed significant higher L-lactate (p = 0.001) and higher D-lactate (p = 0.003).ConclusionsMeasurement of LDH, CK, and ALAT did not discriminate critically ill patients with proven intestinal ischemia from those with definite diagnosis no-ischemia. However, L-lactate and D-lactate levels were higher in patients with proven or likely ischemia and need further study just as I-FABP.

The aim of this study was to evaluate the use of intestinal fatty acid binding protein (I-FABP) and traditional biomarkers in the early diagnosis of acute intestinal ischaemia of different causes. I-FABP, white blood cell (WBC) count, C-reactive protein, base deficit, lactate, lactate dehydrogenase, aspartate aminotransferase, creatine kinase and D-dimer were measured prospectively in consecutive patients suspected of having acute intestinal ischaemia. Biomarker levels were compared in patients with vascular and non-vascular ischaemia. Two hundred and eight patients with a clinical suspicion of acute intestinal ischaemia were enrolled. Vascular intestinal ischaemia was diagnosed in 24 patients (11·5 per cent), non-vascular ischaemia in 62 (29·8 per cent) and non-ischaemic disease in 122 (58·7 per cent). The levels of most biomarkers (except WBC count and creatine kinase) were significantly higher in the vascular ischaemia group than in the other groups (P < 0·010). However, none of the biomarker levels differed between patients with non-vascular intestinal ischaemia and those with non-ischaemic disease. Receiver operating characteristic (ROC) curve analysis suggested that I-FABP was best at diagnosing vascular intestinal ischaemia (area under the curve 0·88). Serum biomarkers may be useful in the diagnosis of vascular, but not non-vascular, intestinal ischaemia. Among them, I-FABP shows promise for detecting vascular ischaemia.

The role of serum intestinal fatty acid binding protein levels and D-lactate levels in the diagnosis of acute intestinal ischemia

Intestinal Fatty Acid Binding Protein (I-FABP) for the Detection of Strangulated Mechanical Small Bowel Obstruction