Serum Ang-2 Research Articles

Myxomatous mitral valve disease and associated pulmonary hypertension might increase serum angiopoietin-2 in dogs.

To evaluate the relationships between the severity of myxomatous mitral valve disease (MMVD) and pulmonary hypertension (PH) and serum angiopoietin (Ang)-1 and Ang-2 concentrations in dogs with MMVD. 74 dogs (control, n = 12; MMVD, n = 62) were included. Serum Ang-1 and Ang-2 concentrations were estimated using the canine-specific ELISA kit. The concentrations were compared between dogs with MMVD and healthy dogs, and they were analyzed according to the severity of MMVD and PH. The median serum Ang-1 concentration did not differ among the study groups. The median serum Ang-2 concentration was higher in dogs with stage B2 MMVD (P = .041) and acute congestive heart failure (P = .002) than in control dogs. In addition, the median serum Ang-2 concentration was higher in MMVD dogs with PH than in those without PH (P = .031). Serum Ang-2 concentration was correlated with vertebral heart score (rs = 0.36, P = .004) and vertebral left atrial score (r = 0.50, P < .001) in dogs with MMVD, and correlated with vertebral heart score (r = 0.63, P = .01), maximum E wave amplitude of the diastolic transmitral flow (rs = 0.61, P = .018), ejection fraction (rs = -0.77, P < .001) and fractional shortening (rs = -0.56, P = .032) in dogs with acute congestive heart failure. Circulating Ang-2 levels increase in dogs with the severity of MMVD and the presence of PH.

Serum Angiopoietin-2 Levels Predict the Development of Hepatocellular Carcinoma following Hepatitis C Virus Eradication Using Direct-Acting Antiviral Agents

Plain Language SummaryOur previous studies showed that serum angiopoietin-2 (Ang-2) and C-X-C motif chemokine ligand 10 (CXCL10) levels predicted improvement in liver fibrosis following sustained virological response (SVR) of hepatitis C virus (HCV) obtained with administration of with direct-acting antiviral agents (DAAs). These levels were evaluated retrospectively as predictive indicators of hepatocellular carcinoma (HCC) development following SVR. We enrolled individuals from a historical cohort of 89 chronic HCV patients without history of HCC at baseline with SVR following DAA therapy and had baseline serum levels of Mac-2 binding protein glycosylation isomer ≥2.0 C.O.I. Multivariate analyses of patients revealed that only the Ang-2 level at 24 weeks following the end of treatment (EOT24W) was significantly related to HCC development (hazard ratio 2.27; p = 0.003). This result was reproduced in individuals with advanced liver fibrosis (M2BPGi level ≥3.3 C.O.I. at baseline). Time-dependent receiver operating characteristic curve analyses for the future risk of developing HCC within 5 years of follow-up (5y-HCC) showed the best cut-off Ang-2 level at EOT24W was 2,780 pg/mL, and significantly stratified the cumulative incidence of HCC (≥2,780 vs. < 2,780 pg/mL, 5y-HCC: 45.5 vs. 8.2%, p < 0.001). The serum Ang-2 level at EOT24W is a feasible predictor of HCC development after achieving SVR to DAAs therapy.

Serum Angiopoietin-2 level increase differs between polytraumatized patients with and without central nervous system injuries

Since endothelial cells rapidly release Angiopoietin-2 (Ang-2) in response to vascular injury and inflammatory stimuli, we aimed to investigate if its serum levels increase in polytraumatized patients. Our cohort study evaluated 28 blunt polytrauma survivors (mean age, 38.4 years; median ISS, 34) who were directly admitted to our level I trauma center in 2018. We assessed the serum Ang-2 level at admission and on days 1, 3, 5, 7, and 10 during hospitalization. Ang-2 was released into the circulation immediately after polytrauma. At admission (day 0), it amounted to 8286 ± 5068 pg/mL, three-and-a-half times the reference value of 2337 ± 650 pg/mL assessed in a healthy control group. Subgroup analysis provided a higher mean Ang-2 level in the CNSI group combining all patients suffering a brain or spinal cord injury compared to the non-CNSI group solely on day 0 [11083 ± 5408 pg/mL versus 3963 ± 2062 pg/mL; p < 0.001]. Whereas the mean Ang-2 level increased only in the non-CNSI group from day 0 to day 3 (p = 0.009), the respective curves showed similar continuous decreases starting with day 3. Multivariate logistic regression analysis revealed an association between the Ang-2 day 0 level and the presence of a CNSI (OR = 1.885; p = 0.048). ROC analysis provided a cutoff level of 5352 pg/mL. In our study group, serum Ang-2 levels assessed at admission differed between polytraumatized patients with and without brain or spinal cord injuries. Based on our findings, we consider serum Ang-2 levels an effective biomarker candidate for indicating CNSI in these patients at admission, worthy of further evaluation in large multicenter studies.

The possible dual role of Ang-2 in the prognosis of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) features a dense desmoplastic stroma, which raises the intratumoral interstitial pressure leading to vascular collapse and hypoxia, inducing angiogenesis. Vascular growth factors, such as vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), increase in PDAC. A high VEGF and a high circulating Ang-2 associate with shorter survival in PDAC. In addition to the circulatory Ang-2, PDAC endothelial and epithelial cells express Ang-2. No correlation between tumor epithelial nor endothelial cell Ang-2 expression and survival has been published. We aimed to examine Ang-2 expression and survival. This study comprised PDAC surgical patients at Helsinki University Hospital in 2000–2013. Ang-2 immunohistochemistry staining was completed on 168 PDAC patient samples. Circulating Ang-2 levels were measured using ELISA in the sera of 196 patients. Ang-2 levels were assessed against clinical data and patient outcomes. A low tumor epithelial Ang-2 expression predicted shorter disease-specific survival (DSS) compared with a high expression (p = 0.003). A high serum Ang-2 associated with shorter DSS compared with a low circulating Ang-2 (p = 0.016). Ang-2 seemingly plays a dual role in PDAC survival. Further studies are needed to determine the mechanisms causing tumor cell Ang-2 expression and its positive association with survival.

Angiopoietin-2 as a Predictor of Fibrosis Regression in Hepatitis C Virus-Patients after Direct Acting Antiviral Drugs

Abstract Background Hepatitis C virus (HCV) infection is the major cause of liver cirrhosis and hepatocellular carcinoma (HCC); thus, effective and safe treatment is crucial. Aim of the Work to evaluate the serum angiopoietin-2 as non-invasive marker of fibrosis regression in patients with Hepatitis C Virus receiving DAA drugs. Patients and Methods This study was conducted on 40 chronic HCV-patients who received DAA therapy in the Hepatic Virology Unit and the gastroenterology department of Ain Shams University hospitals. All patients were subjected to the following: Full history taking with stress concerning the hepatology system, clinical evaluation, laboratory investigations, Routine investigations: Abdominal and Pelvic ultrasonography and Transient elastography (Fibroscan) to measure liver stiffness measurement (LSM) for detection the degree of liver fibrosis in the chronic HCV-patients. Results Hematological findings, biochemical liver profile and liver fibrosis indices except hemoglobin level and platelets counts were significantly improved after DAA therapy. There was a significant improvement concerning the fibrosis stage after the treatment fibrosis staging at SVR12. The liver size, the spleen size and portal vein diameter were also significant after DAA therapy. There was improvement in the Child-Pugh score after successful HCV eradication by DAAs but the difference was no statistically significant. There was a statistically significant higher mean of Ang-2 levels in higher stages of liver fibrosis stages. Overall, serum Ang-2 levels significantly decrease after DAA therapy. In F0, F1, F2 &amp; F3 fibrosis stage; the mean Ang2 levels decrease after DAA therapy but in F4 fibrosis stage; the mean Ang2 levels did not change almost. Baseline Ang-2 and WBCs, AST, ALT, total bilirubin, INR, serum albumin, alpha-fetoprotein, serum creatinine, LSM, FIB-4 index, APRI score, liver size and portal vein diameter were significantly correlated. There were also a significant correlation between Ang-2 and all the fibrosis stages (from F0 to F4) before DAA treatment. Ang-2 levels were significantly associated with LSM based liver fibrosis stage regression after successful DAA therapy. Ang-2 levels did not correlate with hemoglobin, platelets and spleen size at baseline. Ang-2 levels did not correlate with hemoglobin, platelets, WBCs, INR, spleen size and portal vein diameter after DAA therapy. Ang-2 levels did not show significant correlation with the Child-Pugh score after DAA therapy. Conclusion Liver fibrosis stage after successful HCV eradication by DAAs. But in stage F4 (cirrhosis), mean Ang-2 remained almost unchanged after DAA therapy. Significant decrease of Serum Ang-2 could suggest its use as a predictor of liver fibrosis regression in Hepatitis C Virus-patients after Direct Acting Antiviral drugs after DAA therapy.

Endothelial Injury Syndromes after Allogeneic Hematopoietic Stem Cell Transplantation: Angiopetin-2 as a Novel Predictor of the Outcome and the Role of Functional Autoantibodies against Angiotensin II Type 1 and Endothelin A Receptor.

Transplant-associated thrombotic microangiopathy (TMA) occurs in a significant percentage of patients after allogeneic stem cell transplantation (allo-SCT) and is associated with significant morbidity and mortality. The aim of the present study was to examine the association of serum angiopoetin-2 (Ang2) levels and the presence of antibodies against angiotensin II type 1 (AT1R) and ndothelin A Recreptor (ETAR) with the outcome of patients with TMA and/or graft-versus-host disease (GVHD) after allo-SCT. Analysis of our data showed that elevated serum Ang2 levels at the time of TMA diagnosis are significantly associated with increased non-relapse mortality and decreased overall survival. To our knowledge, this is the first study demonstrating an association between raised Ang2 levels and poor outcomes in patients with TMA. Antibodies against AT1R (AT1R-Abs) and ETAR (ETAR-Abs) were detected in 27% and 23% of the patients, respectively, but there was no association between the presence of autoantibodies and the outcome of patients with TMA. However, a significant finding was the strong positive correlation between the presence of AT1R-Abs with the occurrence of chronic fibrotic GVHD, such as scleroderma and cryptogenic organizing pneumonia, raising the possibility of the contribution of autoantibodies in the pathogenesis of fibrotic GVHD manifestations.

Angiopoietin-1 as a marker of endothelial dysfunction and a risk factor for acute kidney injury in patients with COVID-19: retrospective cohort study

Recently, data have been published on the leading role of endothelial dysfunction in the development of severe COVID-19, including acute renal failure (AKI) and poor prognosis in this group of patients.Aim. To define the role of angiopoetin-1(Ang-1) as a marker of endothelial dysfunction in development of AKI in patients, hospitalized with COVID-19.Materials and methods. 76 patients with confirmed coronavirus infection were included in the study. AKI was diagnosed according to KDIGO 2012 criteria in 44 patients (group 1), 32 patients without sings of kidney disfunction were in group 2. Beside standard clinical and laboratory markers on admission we evaluated serum Ang-1 level with ELISA. We used regression analysis for AKI risk factors evaluation, we calculated odds ratio (OR) and 95% confidence intervals (CI). We used Cox regression for evaluation of risk of death.Results. The serum level of angiopoietin-1 was significantly higher in patients with COVID-19 with AKI: 1.8 (1.5; 2.1) ng/ml vs 1.58 (1.29; 1.7) ng/ml in group 2, р &lt; 0.01. In deceased patients, the level of Ang-1 at admission was significantly higher than in patients who was discharged: 1.91 (1.71; 2.32) ng/ml vs 1.58 (1.34; 1.67) ng/ml, respectively, p = 0.0001. In unifactorial regression analysis we confirmed, that increase of serum Ang-1 level &gt;1.66 ng/ml on admission is the risk factor for AKI development in patients with COVID-19 (OR 5.7, 95% CI 1.7–19.1, р &lt; 0.01). In Cox regression development of AKI increased the absolute risk of death: Hazard ratio = 5.159 (95% CI 1.839–14.469), p = 0.002.Conclusion. The high serum level of Ang-1 in patients with COVID-19 at hospital admission is the marker of systemic endothelial dysfunction and the risk factor for AKI and poor prognosis.

Combination of Radix Astragali and Safflower Promotes Angiogenesis in Rats with Ischemic Stroke via Silencing PTGS2.

Promotion of angiogenesis and restoration of the blood flow in the ischemic penumbra is an effective treatment for patients with ischemic stroke (IS). Radix astragali-safflower (AS), a classic herbal pair for accelerating blood circulation and dispersing blood stasis, has been used for thousands of years to treat patients with IS in China. Even so, the mechanism of the treatment of IS by AS is still undecipherable. In the current study, network pharmacology was firstly employed to unveil the mechanism of AS in treating IS, which showed that AS might promote angiogenesis associated with PTGS2 silence. Middle cerebral artery occlusion/reperfusion (MCAO/R) model rats were then used as the experimental animals to verify the prediction result. The experimental results revealed that treatment with AS improved the cerebral infarct volume, neurological damage, and cerebral histopathological damage; inhibited cell apoptosis; increased the contents of PDGF-BB, EPO, and TGF-β1; and reduced the levels of PF4, Ang-2, and TIMP-1 in serum. Immunohistochemical staining demonstrated that the expression of PTGS2 was dramatically increased in the hippocampus and cerebral cortex of rats with MCAO/R, and this trend was reversed by the treatment of AS. Immunofluorescent staining expressed that AS reversed the down-regulation of VEGF and further promoted the expression of CD31, which indicated that AS promoted angiogenesis in MCAO/R rats. The abnormal protein or mRNA expression of PTGS2, PGI2, bFGF, TSP-1, and VEGF in the penumbra were transposed by AS or Celecoxib (an inhibitor of PTGS2). In conclusion, the protective mechanism of AS for IS promoted angiogenesis and was involved with PTGS2 silence.

Changes in Serum Growth Factors during Resistance to Atezolizumab Plus Bevacizumab Treatment in Patients with Unresectable Hepatocellular Carcinoma.

The possible mechanisms of resistance to atezolizumab/bevacizumab for unresectable HCC, and the subsequent response to these therapies, remain underexplored. The sequential changes in serum growth factors, including VEGF-A, VEGF-C, VEGF-D, ANG-2, FGF-19, HGF, and EGF during atezolizumab/bevacizumab for unresectable HCC were evaluated in 46 patients. Patients who experienced PD after CR, PR, or SD to atezolizumab/bevacizumab were evaluated. A total of 4, 9, 19, and 14 patients showed CR, PR, SD, and PD, respectively. Of 32 patients with disease control, 28 experienced PD after CR, PR, or SD with atezolizumab/bevacizumab. Baseline growth factor levels were similar between patients with or without disease control and those with or without an objective response. Growth factor changes between the baseline and the best overall response points (BOR) for patients with disease control showed that FGF-19 significantly increased and ANG2 significantly decreased at the BOR. Growth factor changes between the BOR and the PD point in 28 patients who experienced PD after disease control showed that VEGF-D and ANG2 significantly increased at the PD point compared with that at the BOR. Summarily, increased serum VEGF-D and ANG-2 levels might contribute to developing resistance to atezolizumab/bevacizumab for unresectable HCC and might be target molecules in subsequent salvage therapies.

Serum Angiopoietin-2 Predicts the Occurrence and Recurrence of Hepatocellular Carcinoma after Direct-Acting Antiviral Therapy for Hepatitis C.

Progressive liver fibrosis after anti-HCV treatment is a risk factor for HCC. Angiopoietin-2 (Ang2) is associated with non-regression of liver fibrosis after direct-acting antiviral (DAA). This study evaluated the predictive value of serum Ang2 levels for HCC occurrence or recurrence after DAA administration. In this retrospective study, 310 HCV-infected patients treated with DAAs in 2014-2020 were screened and evaluated for HCC occurrence or recurrence every three-six months. Multivariate Cox regression analysis revealed that age ≥ 75 years (HR: 2.92, 95% CI: 1.34-6.33; p = 0.007) and baseline Ang2 level ≥ 464 pg/mL (HR: 2.75, 95% CI: 1.18-6.37; p = 0.019) were significantly associated with HCC occurrence after DAA therapy. A high or low risk of HCC after DAA therapy could be distinguished by the combination of age and baseline Ang2 level. The cumulative incidences of de-novo HCC at two and four years were 0.8% and 3.8% in the low-risk group and 22.6% and 27.1% in the high-risk group, respectively. Baseline Ang2 level ≥ 402 pg/mL was significantly associated with HCC recurrence in patients who achieved sustained virological response with DAAs (HR: 3.68). In conclusion, serum Ang2 levels can predict HCC occurrence and recurrence after successful HCV eradication by DAAs.

Value of Serum miR-34a and Ang-1 in Severity Evaluation and Prognosis of Neonatal Respiratory Distress Syndrome.

Methods A total of 96 neonates with RDS admitted to the hospital from February 2020 to April 2021 were selected as the research subjects. According to the neonatal critical illness score, the subjects were divided into non-critical group (n = 50), critical group (n = 27), and extremely critical group (n = 19). According to survival status, the subjects were divided into survival group (n = 76) and death group (n = 20). Serum miR-34a and Ang-1 levels and NCIS were compared between RDS neonates with different severity and prognosis. The predictive value of serum miR-34a, Ang-1, and NCIS for death was analyzed using the receiver operating characteristic (ROC) curve. Results Serum miR-34a and Ang-1 levels and NCIS were significantly different in the 3 groups (P < 0.05). Serum miR-34a level decreased in order, while serum Ang-1 level and NCIS increased in order from the extremely critical group, the critical group to the non-critical group (P < 0.05). The survival group had lower serum miR-34a level and higher Ang-1 level and NCIS than the death group (P < 0.05). ROC curve analysis showed that the area under the curve (AUC) values of serum miR-34a, Ang-1, and NCIS to predict death of RDS neonates were 0.745, 0.7667, and 0.736. The cutoff values were 1.175, 6.815 ng/mL, and 85 points. The AUC of joint prediction with the three was 0.924, significantly larger than that of each index. The sensitivity and specificity were 94.70% and 90.00%. Conclusion Serum miR-34a, Ang-1, and NCIS are closely related to the severity and prognosis of neonatal RDS. Combined detection of the three is helpful for prognosis of neonatal RDS.

Serum angiopoietin-2 levels predict regression of Mac-2 binding protein glycosylation isomer-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents.

It is desirable to identify predictors of regression of liver fibrosis after achieving a sustained virologic response (SVR) by direct-acting antiviral agents (DAAs) to antihepatitis C virus (HCV) therapy. Here, we retrospectively investigated the serum angiopoietin-2 (Ang-2) level as a predictive indicator of regression of liver fibrosis after successful HCV eradication by DAA therapy. The study subjects were recruited from a historical cohort of 109 chronically HCV-infected patients who had achieved SVR by DAA therapy and whose serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels at baseline (before DAA therapy) were ≥2.0 the cut-off index (COI). We defined patients with M2BPGi levels <1.76 and≥1.76 COI at 2years after the end of treatment (EOT) as the regression (R, n=69) and nonregression (NR, n=40) groups, respectively. Multivariate analyses revealed that the Ang-2 level at baseline and the Ang-2 level, albumin-bilirubin score, and FIB-4 index at 24weeks after the EOT were significantly associated with regression of M2BPGi-based liver fibrosis. Receiver operating characteristic curve analyses showed that the Ang-2 level at 24weeks after the EOT had the largest area under the curve values (0.859). The same results were obtained even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis: M2BPGi levels ≥3.3 COI at baseline. The serum Ang-2 level at 24weeks after the EOT is a feasible predictor of regression of M2BPGi-based liver fibrosis after achieving SVR by DAA therapy.

O087 Potential diagnostic biomarkers for congenital vascular malformations

Abstract Introduction To identify potential diagnostic serum biomarkers, particularly those pertaining to the processes of inflammation and angiogenesis in patients with congenital vascular malformations (CVM). Methods Isolated sera from the peripheral bloods of consented healthy controls (n = 10) and patients diagnosed as having either low-flow (LF) (n = 10) or high-flow (HF) (n = 10) CVMs. Various mediators of inflammation and angiogenesis were analysed in the sera using the Inflammation 20-Plex and Angiogenesis 18-Plex Human ProcartaPlex™ Panels. Analysis was conducted via Kruskall-Wallis test and correlated with lesion volumes and visual analogue scores for pain using the Spearman rank correlation test. Results Compared to healthy controls, the inflammatory mediators E-selectin, IFNa, IFNg, IL1b, IL4, IL12, IL17, MIP1a, MIP1b and TNFa were elevated in the sera of LF CVM patients, whereas only MIP1a was raised in the sera of HF CVM patients. None of the angiogenic mediators were altered in the sera of patients with LF or HF CVMs. Serum IFNa, IFNg, IL4, IL12, TNFa, VEGFA, VEGFD and syndecan correlated positively with pain scores in patients with LF CVMs, whereas only IP10 did in patients with HF CVMs. Serum Ang1 and leptin correlated negatively with lesion volumes in patients with LF or HF CVMs, respectively. Conclusion Serum inflammatory mediators could be used to distinguish LF from HF CVMs and their expression seemed to be associated with pain severity in patients with LF CVMs. The angiogenic mediators Ang1 and leptin were associated with lesion volumes in patients with LF or HF CVMs, respectively. Take-home message Serum inflammatory mediators could be used to distinguish LF from HF CVMs and their expression seemed to be associated with pain severity in patients with LF CVMs. The angiogenic mediators Ang1 and leptin were associated with lesion volumes in patients with LF or HF CVMs, respectively.

Serum Ang-1/Ang-2 ratio may be a promising biomarker for evaluating severity of diabetic retinopathy.

To investigate the predictive role of serum angiopoietin-1 and angiopoietin-2 (Ang-1/Ang-2) in evaluating the severity of diabetic retinopathy (DR). A total of 101 outpatients with type 2 diabetes mellitus (T2DM) were recruited and were further divided into the following five groups: T2DM without DR (non-DR), mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR and proliferative DR (PDR) in accordance with the International Clinical Diabetic Retinopathy Guidelines. Furthermore, 101 serum samples were included in the further analysis using enzyme-linked immunosorbent assays. A receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of each index. The expression of Ang-1 in the PDR group was significantly lower than that in the non-DR group, while Ang-2 showed an opposite upward trend (p < 0.05). The Ang-1/Ang-2 ratio of the non-DR group was significantly lower than that of the moderate NPDR, severe NPDR and PDR (p < 0.05, p < 0.01 and p < 0.01, respectively). Differences in the Ang-1/Ang-2 ratio were observed earlier than those in the individual Ang-1 and Ang-2 measurements. The maximal Youden index was 0.512 with a calculated area under the curve (AUC) value of 0.734 (p < 0.01). The Ang-1/Ang-2 ratio was helpful in assessing the severity of DR and may provide potential clinical benefits as a biomarker and early warning signs for DR diagnosis.

Biomarkers of endothelial dysfunction and atherosclerosis in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with an increased prevalence of subclinical atherosclerosis and cardiovascular risk. Angiopoietin-2 (Ang-2), asymmetric dimethylarginine (ADMA), and osteoprotegerin (OPG) are molecules related to endothelial dysfunction (ED) and atherosclerosis, but also to disease severity in patients with chronic inflammatory disorders. In this case-control study, we aimed to investigate serum Ang-2, ADMA, and OPG levels in patients with HS, and to assess the potential relationship between these levels and disease severity. Seventy-five patients with HS and 60 controls were assessed. Serum Ang-2, ADMA, and OPG concentrations were determined in all participants. HS patients had significantly higher Ang-2 and ADMA levels than controls after adjusting for confounders. Besides, Ang-2 concentrations positively correlated with disease severity in the adjusted multivariable analysis. Nevertheless, serum OPG levels did not significantly differ between HS patients and controls. Our results indicate that serum Ang-2 and ADMA levels are significantly increased in patients with HS. Furthermore, Ang-2 might be a suitable marker of HS severity.

Are programmed cell death protein-1 and Angiopoietins-2 effective biomarkers for detection the severity of psoriatic patients?

Early detection of psoriasis is still an open discussion. Psoriatic lesions are characterized by red/scaly plaques affecting different body-sites. To evaluate the levels of programmed cell death protein-1(PD-1) and Angiopoietins-2(Ang-2) in serum, lesional, and perilesional of psoriatic patients and correlate them with controls and disease severity. Serum samples were obtained from 40 participants subdivided equally into psoriatic and healthy controls, 4 mm punch_biopsy equally from lesional and perilesional skin of individuals. PD-1/ANG-2 ELISA kits were used for determining the serum and tissue levels among groups. Serum and tissue levels of PD-1 and Ang-2 were overexpressed in psoriatic patients compared with controls. There was a statistical difference between patients and controls in level of PD-1(serum and tissue) with p-value 0.006 and 0.0001, respectively. There was a statistical difference between both groups for ANG-2(serum and tissue) with p-value 0.03 and 0.0001, respectively. There were positive correlations between PASI score and PD-1 in tissue (r = 0.467, p = 0.038). Also, positive correlation between the level of PD-1 in serum and tissue (r = 0.369, p = 0.019), the serum levels of PD-1 and ANG-2 (r = 0.78, p > 0.0001), PD-1 and Ang-2 in tissue (r = 0.583,p = 0.0001) were detected. PD-1 and ANG-2 can be highly recommended to determine the severity of psoriasis.

Serum levels of angiopoietin 2 mRNA in the mortality outcome prediction of septic shock.

It has been reported that angiopoietin 2 (Ang-2) plays an integral role in the pathophysiology of sepsis and many other inflammatory diseases. However, the specific role of Ang-2 in septic shock has not been defined. The aim of the present study was to assess the predictive value of serum Ang-2 in patients with septic shock. Clinical data of 85 patients with septic shock and 10 healthy controls admitted to the intensive care unit with a diagnosis of septic shock were collected between January 2020 and October 2020 at Tongji Hospital (Wuhan, China). The serum levels of Ang-2 mRNA were quantified using a quantitative real-time PCR assay. Ang-2, SOFA and APACHE II scores were retrospectively analyzed in relation to 28-day mortality. The area under the receiver operating characteristic (ROC) curve (AUC) was used to discriminate the accuracy of the prediction. Mean Ang-2 mRNA levels in the patients with septic shock were significantly higher than those in the healthy controls (P<0.05), and the Ang-2 levels showed a downwards trend over time following treatment. The three indicators (AUCs, SEMs, P-values) were Ang-2 (0.82, 0.03, P<0.01), SOFA score (0.76, 0.04, P<0.01), and APACHE II score (0.73, 0.04, P<0.01). The present study confirmed that Ang-2 mRNA levels were significantly elevated in septic shock. The Ang-2 mRNA level at ICU admission in a patient with septic shock could be a predictive biomarker for mortality.

Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS)

BackgroundFatigue, exertion intolerance and post-exertional malaise are among the most frequent symptoms of Post-COVID Syndrome (PCS), with a subset of patients fulfilling criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). As SARS-CoV-2 infects endothelial cells, causing endotheliitis and damaging the endothelium, we investigated endothelial dysfunction (ED) and endothelial biomarkers in patients with PCS.MethodsWe studied the endothelial function in 30 PCS patients with persistent fatigue and exertion intolerance as well as in 15 age- and sex matched seronegative healthy controls (HCs). 14 patients fulfilled the diagnostic criteria for ME/CFS. The other patients were considered to have PCS. Peripheral endothelial function was assessed by the reactive hyperaemia index (RHI) using peripheral arterial tonometry (PAT) in patients and HCs. In a larger cohort of patients and HCs, including post-COVID reconvalescents (PCHCs), Endothelin-1 (ET-1), Angiopoietin-2 (Ang-2), Endocan (ESM-1), IL-8, Angiotensin-Converting Enzyme (ACE) and ACE2 were analysed as endothelial biomarkers.ResultsFive of the 14 post-COVID ME/CFS patients and five of the 16 PCS patients showed ED defined by a diminished RHI (< 1.67), but none of HCs exhibited this finding. A paradoxical positive correlation of RHI with age, blood pressure and BMI was found in PCS but not ME/CFS patients. The ET-1 concentration was significantly elevated in both ME/CFS and PCS patients compared to HCs and PCHCs. The serum Ang-2 concentration was lower in both PCS patients and PCHCs compared to HCs.ConclusionA subset of PCS patients display evidence for ED shown by a diminished RHI and altered endothelial biomarkers. Different associations of the RHI with clinical parameters as well as varying biomarker profiles may suggest distinct pathomechanisms among patient subgroups.

Adoption of Magnetic Resonance Image Features under Segmentation Algorithm in Effect Evaluation of Ginkgo Diterpenoid Lactone Glucamine Injection in Treatment of Cerebral Infarction.

Magnetic resonance imaging (MRI) image segmentation based on a segmentation algorithm was performed to assess neurological function in patients with acute cerebral infarction, to investigate the efficacy evaluation of Ginkgo diterpene lactones meglumine injection (GDLI) in the treatment of cerebral infarction and the efficiency of MRI image segmentation algorithm. First, the results of the fast semisupervised segmentation algorithm (algorithm group) and traditional processing (control group) were compared and analyzed. The recall rate, accuracy, recognition accuracy, and segmentation time of the two groups were compared. The control group was given conventional treatment, while the algorithm group was given GDLI based on conventional treatment. Finally, the difference in serum vascular endothelial growth factor (VEGF), hypoxia-inducible factor-la (HIF-la), angiotensin (Ang)-1, Ang-2, and interleukin (IL)-6 protein concentration was analyzed after treatment. The algorithm evaluation results showed that the accuracy and recall rate of MRI images recognized by the algorithm group fluctuate at 90%. In the control group, the accuracy and recall rate of MRI image results fluctuated at 80%, and the data were statistically different (p < 0.05). The clinical index test results showed that the serum VEGF content of the test group was higher than that of the control group, and the data was statistically different (p < 0.05). In addition, the cerebral blood flow (CBF) and cerebral blood volume (CBV) of the lesion side of the algorithm group were greatly higher than those of the control group on the 30th day, and the differences were significant (p < 0.05). There was little difference between the method presented in this study and the manual delineation by a physician. Compared with traditional manual segmentation, this method greatly reduced the time required for the segmentation of lesions. The diagnostic specificity, sensitivity, and accuracy of the images segmented by the fast semisupervised algorithm were higher than those of the conventional method, and the diagnostic accuracy of acute cerebral infarction was high. In addition, it was sensitive and accurate to detect acute cerebral infarction, which provided a reliable reference for early diagnosis and condition judgment of patients.

DYNAMICS OF FIBROTIC CHANGES IN THE LIVER AFTER THE SUCCESSFUL ERADICATION OF HEPATITIS C VIRUS IN PATIENTS WITH NAFLD.

The aim: To assess the dynamics of serum levels of angiopoietin-2 and transforming growth factor-β1 in patients with chronic hepatitis C (CHC) with concomitant nonalcoholic fatty liver disease (NAFLD) after successful DAAs. Materials and methods: 82 patients with CHC were examined, of which 56 were diagnosed with NAFLD and increased body weight. Ang-2, TGF-β1, leptin, adiponectin, and the degree of liver fibrosis were determined for all participants. The patients were divided into groups: 1 gr. (n=23) - CHС + increased body weight + hepatic steatosis, 2 gr. (n=33) - СНС + increased body weight + nonalcoholic steatohepatitis, 3rd gr. (n=26) - CHC. All patients received DAAs for 12 weeks. Results: From 82 patients F3-4 had 31 people, F1-2 - 25, F0-1 - 11, F0 -15 patients. F3-4 and steatosis S2-3 (p<0.05) was more common in patients of 2 gr.. Serum Ang-2 levels were higher (p<0.05) in patients of 2 gr. with F3-4, than in patients with F0-2. Fibrosis regression occurred more often in patients with 1 and 3 gr. with F1-2 than in patients 2 gr. and F3-4 and was accompanied by a decrease in Ang-2 and TGF-β1 levels. Conclusions: High levels of Ang-2 and TGF-β1 are registered in patients with CHC+NAFLD, which correlate with the degree of liver fibrosis and significantly decrease after successful DAAs in patients with low initial stages of liver fibrosis and normal body weight.