Plasminogen Activator Inhibitor-1 Levels Research Articles

Changes in the Fibrinolytic System of Patients Infected with Severe Acute Respiratory Syndrome Coronavirus 2

Introduction: In this study, coagulation and fibrinolysis parameters and their association with disease severity were investigated in coronavirus disease (COVID-19) patients. Materials and Methods: COVID-19 patients (n=446) admitted to our institute between February 21, 2021 and March 17, 2022, were recruited. Clinical data and staging were collected from all patients. Blood samples were collected and analyzed for several parameters of fibrinolysis and coagulation, including alpha-2-antiplasmin(α2AP) and plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), D dimer, and fibrinogen levels. Results: The TAFI, fibrinogen, and tPA levels were significantly higher in participants who died compared to that of patients who recovered (P<0.001). However, PAI-1, tPA, and TAFI were significantly higher in patients admitted to the ICU than those of the healthy controls (P<0.001 for PAI-1 and tPA; P=0.0331 for TAFI). Our results showed that stage C and D COVID-19 patients had significantly higher levels of PAI-1 (P = 0.003). Furthermore, the stage D COVID-19 patients had significantly higher tPA and TAFI values (P=0.003). Conclusions: Hypofibrinolysis was the most prevalent condition among patients with severe COVID-19. In this study, several coagulation markers were elevated, making them suitable prognostic markers for hypofibrinolysis. Figure 1. Plasma levels of different coagulation factors in COVID-19 patients. Plasma isolated from patients that had died due to COVID-19 and those recovering from the disease (top panel).

Ziqi Dihuang decoction ameliorates thrombosis in septic rats by inhitbiting plasminogen activator inhibitor-1.

Sepsis is now a global medical burden with high morbility and mortality. The focus of this study was to evaluate the effects of Ziqi Dihuang (ZQDH) decoction on inflammatory and thrombosis-related parameters in septic rats. A rat model of sepsis was established by cecal ligation and puncture (CLP). Male Sprague-Dawley rats were randomly divided into Sham group, CLP group, ZQDH-1ow group (0.735g/kg) and ZQDH-high group (1.47g/kg). Rats in ZQDH groups were given ZQDH decoction by gavage for 7 days before CLP. White blood cells (WBC), inflammatory cell infiltration of liver, kidney and lung, as well as serum levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and reactive oxygen species (ROS) were used to assess systemic inflammatory response. Coagulation and fibrinolytic indexes included platelet count, coagulation function, fibrin deposition, and levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in serum, liver, kidney and lung. LPS rats showed significant changes in inflammatory and thrombosis-related parameters such as increased WBC and inflammatory factors, decreased platelet counts, and increased tPA and PAI-1 concentrations in serum and organs. ZQDH decoction pretreatment can significantly inhibit the infiltration of inflammatory cells in the lung, and inhibit the production of TNF-α, IL-6 and ROS in a dose-dependent manner. ZQDH decoction also ameliorated thrombocytopenia, renal fibrin deposition, and tPA and PAI-1 levels in serum and organs. These results suggest that ZQDH decoction can dose-dependently relieve systemic inflammatory injury and regulate fibrinolysis system in septic rats, which may be mediated by PAI-1.

Salivary expression of novel inflammatory marker Plasminogen Activator Inhibitor-1 in health and disease: an interventional study

Objective: To assess levels of the biomarkers Plasminogen Activator Inhibitor-1 (PAI-1) and alpha 2-macroglobulin (2MG) in saliva and serum in healthy individuals and patients with and without type 2 diabetes mellitus (T2DM) before and after periodontal therapy. Materials and Methods: The 90 recruited subjects were divided into the three following groups: Group 1, with 30 healthy subjects; Group 2, with 30 systemically healthy subjects with stage II and III periodontitis; and Group 3, with 30 patients with periodontitis and well-controlled T2DM (PDM). Salivary and serum PAI-1 and α2MG levels were estimated by enzyme-linked immunosorbent assay and correlated with clinical parameters before and three months after periodontal therapy, and the data obtained was statistically analyzed. Results: There was an improvement in clinical parameters in both groups that underwent initial periodontal therapy. Salivary and serum PAI-1 and α2MG levels were upregulated in PDM group, compared to periodontitis alone at baseline. A significant reduction in the levels of the biomarkers was observed three months after periodontal therapy, and an improvement in glycaemic control was also seen in the PDM group. Conclusion: PAI-1 was expressed in saliva and serum in healthy patients, and increased in periodontitis and diabetes patients, thus evidencing its possible role in periodontal inflammation and glucose regulation, and its levels decreased after periodontal therapy.

Supplementation with Ashitaba (Angelica keiskei) Yellow Stem Exudate Prevents Aging-Induced Thrombotic Tendencies and Systemic Inflammation Without Affecting Body Weight Gain in Mice.

Angelica keiskei Koidzumi (Ashitaba) is a traditional folk medicine and health supplement in Japan. Ashitaba yellow stem exudate (AYE) contains abundant chalcones and thus has the potential to treat and prevent many pathological states such as cancer, inflammation, obesity, diabetics, thrombosis, and hypertension. Levels of plasminogen activator inhibitor 1 (PAI-1), a key regulator of the fibrinolytic system, increase with age in mouse plasma. Therefore, we aimed to determine the effects of AYE on plasma thrombotic parameters in aging mice. Long-term (52 weeks) AYE supplementation significantly decreased age-induced increases of PAI-1 in mouse plasma. Supplementation with AYE decreased levels of the acute-phase and fibrinolytic protein plasma plasminogen, and significantly decreased those of tumor necrosis factor α. These results suggested that continuous intake of AYE throughout life decreases age-induced systemic inflammation and prevents thrombotic tendencies without affecting body weight gain in aged mice. Our findings showed that supplementing diets with AYE might help to prevent thrombotic diseases in elderly individuals.

Increased Levels of IFN-γ, PAI-1, and NT-proBNP are Associated with the Occurrence of Hypoxemia in COVID-19

BACKGROUND: Acute respiratory distress syndrome (ARDS) is one of the severe complications of Coronavirus disease 2019 (COVID-19) that can lead to the occurrence of hypoxemia. Hypoxemia occurs due to the role of pro-inflammatory cytokines and coagulation factors. Several studies have shown that interferon (IFN)-γ, plasminogen activator inhibitor 1 (PAI-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are biological markers that can be used to evaluate the severity and prognosis of the disease in severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection. This study was conducted to evaluate the association between IFN-γ, PAI-1, NT-proBNP and hypoxemia in COVID-19 patients.METHODS: This was a cross-sectional study of COVID-19 subjects with hypoxemia. Hypoxemia assessment was performed based on arterial blood gas analysis. IFN-γ and PAI-1 were measured with ELISA, while NT-proBNP levels were measured with Roche NT-proBNP.RESULTS: Fifty-five COVID-19 subjects with hypoxemia were observed. Thirty subjects experiencing moderate to severe hypoxemia and 25 with mild hypoxemia. Levels of IFN-γ, PAI-1, and NT-proBNP were higher in COVID-19 subjects with moderate to severe hypoxemia compared to those with mild hypoxemia (261.14 (121-348.60) pg/mL vs. 145.50 (59.90-348.60) pg/mL, p<0.001; 5.47 (3.50-8.50) pg/mL vs. 3.40 (2.20-9.30) pg/mL, p<0.001; 760 (112-34,066) pg/mL vs. 71 (48-364) pg/mL, p<0.001).CONCLUSION: Elevated levels of IFN-γ, PAI-1, and NT-proBNP are associated with hypoxemia in COVID-19 patients, suggesting that these markers may be useful in assessing hypoxemia in COVID-19 patients.KEYWORDS: IFN-γ, PAI-1, NT-proBNP, hypoxemia, COVID-19

Clinical value of echocardiography combined with serum Cav-1, NFATc1, and PAI-1 in the diagnosis of Kawasaki disease complicated with coronary artery lesions.

To analyze the clinical value of echocardiography combined with serum lacuna protein-1 (Cav-1), activated T cell nuclear factor C1 (NFATc1), and plasminogen activator inhibitor-1 (PAI-1) in the diagnosis of Kawasaki disease (KD) complicated with coronary artery lesions (CAL). A total of 200 children with KD treated in our hospital from January 2019 to October 2021 were grouped as the KD alone group (n = 56) and the KD complicated with CAL group (n = 144) according to the results of coronary angiography. The levels of Cav-1, NFATc1, and PAI-1 were detected by enzyme-linked immunosorbent assay. Echocardiography was performed and the internal diameters of left and right coronary arteries were compared between the two groups. The area under the curve (AUC), sensitivity, and specificity of echocardiography combined with serum Cav-1, NFATc1, and PAI-1 in the diagnosis of KD complicated with CAL were analyzed with receiver operating characteristic (ROC) curve. Coronary angiography, as the gold standard, showed that the sensitivity of echocardiography in diagnosing KD with CAL was 88.19% (127/144), the specificity was 66.07% (37/56), and the accuracy was 82.00% (164/200). ROC curve analysis revealed that the AUC of KD complicated with CAL diagnosed by echocardiography, Cav-1, NFATc1, and PAI-1 was 0.819, 0.715, 0.688, and 0.663, respectively, and the AUC of combined diagnosis of the four was 0.896. The combination of echocardiography, Cav-1, NFATc1, and PAI-1 has high value in diagnosing KD complicated with CAL, which can be widely used in clinical practice.

Serum PAI-1/BDNF Ratio Is Increased in Alzheimer's Disease and Correlates with Disease Severity.

We previously demonstrated that serum levels of plasminogen activator inhibitor-1 (PAI-1), which inhibits both the tissue plasminogen activator (tPA) and plasmin activity, are increased in patients with Alzheimer's disease. tPA/plasmin not only prevents the accumulation of β-amyloid in the brain but also is involved in the synthesis of the brain-derived neurotrophic factor (BDNF), a neurotrophin whose levels are reduced in Alzheimer. In the present study, we compared BDNF serum levels in Alzheimer patients with dementia to those in Alzheimer patients with amnestic mild cognitive impairment and to cognitively healthy controls. Moreover, we examined whether the PAI-1/BDNF ratio correlates with disease severity, as measured by Mini-Mental State Examination. Our results showed that BDNF serum levels are lower (13.7% less) and PAI-1 levels are higher in Alzheimer patients with dementia than in Alzheimer patients with amnestic mild cognitive impairment patients (23% more) or controls (36% more). Furthermore, the PAI-1/BDNF ratio was significantly increased in Alzheimer patients as compared to amnestic mild cognitive impairment (36.4% more) and controls (40% more). Lastly, the PAI-1/BDNF ratio negatively correlated with the Mini-Mental score. Our results suggest that increased PAI-1 levels in Alzheimer, by impairing the production of the BDNF, are implicated in disease progression. They also indicate that the PAI-1/BDNF ratio could be used as a marker of Alzheimer. In support of this hypothesis, a strong negative correlation between the PAI-1/BDNF ratio and the Mini-Mental score was observed.

Protective efficacy of pirfenidone in rats with pulmonary fibrosis induced by bleomycin.

Bleomycin causes increased production of reactive oxygen species, leads to pulmonary toxicity, fibroblast activation, and fibrosis. This study aimed to evaluate the protective effect of pirfenidone on bleomycin-induced lung toxicity in rats. Twenty-eight adult rats were randomly divided into 3 groups; Bleomycin (B group, n=10), Bleomycin and Pirfenidone (B-PND group, n=13), and the control group (n=5). The bleomycin regimen was administered for 9 weeks. Pirfenidone was administered at 100 mg/kg daily. Total antioxidant level (TAS), total oxidant level (TOS), tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1), matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor (PAI) levels were studied. Histopathologically, sections were stained with Hematoxylin-eosin and Masson-trichrome for grading-scoring according to the Ashcroft score. Stage 3 fibrosis was observed in 50% of the B group rats, stage 3 and higher fibrosis was never detected in the B-PND group and the difference was statistically significant (p=0.003). When evaluating tissue inflammation, the inflammation was higher in the B-PND group than in the other groups (p<0.001). Pleuritis was detected in all rats in group B, while was not observed in B-PND and control group (p<0.001). The TAS level was found to be significantly higher in group B than in group B-PND (p=0.034), while no difference was found between TOS, TNF-α, MMP-2, PAI, TGF-β1. Pirfenidone had a statistically significant protective effect in bleomycin-induced lung fibrosis and pleuritis in rats. Despite the presence of inflammation in the tissue, no significant changes were observed in inflammation markers in the peripheral blood. Novel serum biomarkers are needed to indicate the presence of inflammation and fibrosis in the lung.

Pharmacological inhibition of plasminogen activator inhibitor-1 prevents memory deficits and reduces neuropathology in APP/PS1 mice.

Extracellular proteolytic activity plays an important role in memory formation and the preservation of cognitive function. Previous studies have shown increased levels of plasminogen activator inhibitor-1 (PAI-1) in the brain of mouse models of Alzheimer's disease (AD) and plasma of AD patients, associated with memory and cognitive decline; however, the exact function of PAI-1 in AD onset and progression is largely unclear. In this study, we evaluated a novel PAI-1 inhibitor, TM5A15, on its ability to prevent or reverse memory deficits and decrease Aβ levels and plaque deposition in APP/PS1 mice. We administered TM5A15 mixed in a chow diet to 3-month and 9-month-old APP/PS1 mice before and after neuropathological changes were distinguishable. We then evaluated the effects of TM5A15 on memory function and neuropathology at 9 months and 18 months of age. In the younger mice, 6 months of TM5A15 treatment protected against recognition and short-term working memory impairment. TM5A15 also decreased oligomer levels and amyloid plaques, and increased mBDNF expression in APP/PS1 mice at 9 months of age. In aged mice, 9 months of TM5A15 treatment did not significantly improve memory function nor decrease amyloid plaques. However, TM5A15 treatment showed a trend in decreasing oligomer levels in APP/PS1 mice at 18 months of age. Our results suggest that PAI-1 inhibition could improve memory function and reduce the accumulation of amyloid levels in APP/PS1 mice. Such effects are more prominent when TM5A15 is administered before advanced AD pathology and memory deficits occur.

Damage-associated molecular patterns and fibrinolysis perturbation are associated with lethal outcomes in traumatic injury

BackgroundUpon cellular injury, damage-associated molecular patterns (DAMPs) are released into the extracellular space and evoke proinflammatory and prothrombotic responses in animal models of sterile inflammation. However, in clinical settings, the dynamics of DAMP levels after trauma and links between DAMPs and trauma-associated coagulopathy remain largely undetermined.MethodsThirty-one patients with severe trauma, who were transferred to Kagoshima City Hospital between June 2018 and December 2019, were consecutively enrolled in this study. Blood samples were taken at the time of delivery, and 6 and 12 h after the injury, and once daily thereafter. The time-dependent changes of coagulation/fibrinolysis markers, including thrombin-antithrombin complex, α2-plasmin inhibitor (α2-PI), plasmin-α2-PI complex, and plasminogen activator inhibitor-1 (PAI-1), and DAMPs, including high mobility group box 1 and histone H3, were analyzed. The relationship between coagulation/fibrinolysis markers, DAMPs, Injury Severity Score, in-hospital death, and amount of blood transfusion were analyzed.ResultsThe activation of coagulation/fibrinolysis pathways was evident at the time of delivery. In contrast, PAI-1 levels remained low at the time of delivery, and then were elevated at 6–12 h after traumatic injury. Histone H3 and high mobility group box 1 levels were elevated at admission, and gradually subsided over time. PAI-1 levels at 6 h were associated with serum histone H3 levels at admission. Increased histone H3 levels and plasmin-α2-PI complex levels were associated with in-hospital mortality. α2-PI levels at admission showed the strongest negative correlation with the amount of blood transfusion.ConclusionThe elevation of histone H3 levels and fibrinolysis perturbation are associated with fatal outcomes in patients with traumatic injury. Patients with low α2-PI levels at admission tend to require blood transfusion.

Plasminogen Activator Inhibitor-1 and Vitamin D Association in the Overweight and Obese Pediatric Population.

Childhood overweight and obesity have been described by the World Health Organization as noncommunicable diseases and among the greatest public health threats since they have reached epidemic proportions. A child with obesity risks becoming an adult with obesity and developing metabolic and hemostatic disorders which are the basis for the development of coronary heart diseases. Recently, a number of clinical reports have demonstrated that both an increase in plasminogen activator inhibitor-1 (PAI-1) and a deficiency in 25OH-vitamin D3 (VD) are associated with an increase in thrombotic episodes. PAI-1 and VD levels were measured in 259 clinically overweight and obese children aged between 2 and 18 years enrolled in the Nutritional Education Program of the Bambino Gesù Children's Hospital and Research Institute of Rome (Italy) and 80 normal-weight subjects. We observed increased HOMA-IR, PAI-1, and other inflammation indices associated with decreased VD levels when compared to normal-weight children. Our results demonstrated that overweight and obesity are correlated with higher levels of the inflammation index. Moreover, our patients show high PAI-1 and low VD levels, confirming the high thrombotic risk in our pediatric population.

Changes in the Fibrinolytic System of Patients Infected with Severe Acute Respiratory Syndrome Coronavirus 2.

In this study, coagulation and fibrinolysis parameters and their association with disease severity were investigated in coronavirus disease (COVID-19) patients. COVID-19 patients (n = 446) admitted to our institute between 21 February 2021 and 17 March 2022, were recruited. Clinical data and staging were collected from all patients. Blood samples were collected and analyzed for several parameters of fibrinolysis and coagulation, including alpha-2-antiplasmin(α2AP) and plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, and fibrinogen levels. The TAFI, fibrinogen, and tPA levels were significantly higher in participants who died compared to that of patients who recovered (p < 0.001). However, PAI-1, tPA, and TAFI were significantly higher in patients admitted to the ICU than those of the healthy controls (p < 0.001 for PAI-1 and tPA; p = 0.0331 for TAFI). Our results showed that stage C and D COVID-19 patients had significantly higher levels of PAI-1 (p = 0.003). Furthermore, stage D COVID-19 patients had significantly higher tPA and TAFI values (p = 0.003). Hypofibrinolysis was the most prevalent condition among patients with severe COVID-19. In this study, several coagulation markers were elevated, making them suitable prognostic markers for hypofibrinolysis.

Women with severe postpartum hemorrhage have a decreased endogenous thrombin potential before delivery

BackgroundSevere postpartum hemorrhage (PPH), defined as a blood loss ≥1000 mL, is associated with maternal morbidity and mortality. ObjectivesWe aimed at characterizing coagulation properties of predelivery plasmas from pregnant women with thrombin generation assay and hemostatic biomarkers (plasminogen activator inhibitor-1, tissue factor [TF], and thrombomodulin). MethodsA nested case-control study was conducted within the “Study of Biological Determinants of Bleeding Postpartum,” a French prospective cohort study, in order to compare women with severe PPH (cases) and controls matched for age, body mass index, term, and mode of delivery. Plasma was collected at entry in the delivery room, and blood loss was measured objectively. The predelivery endogenous thrombin generation potential (ETP) was measured in plasma using calibrated automated thrombinography and low TF concentration. Hemostatic biomarkers were measured using ELISA kits. ResultsA total of 142 women (71 cases and 71 controls) were investigated. There was no difference in the median lag phase, thrombin peak, and time to peak between cases and controls. However, median predelivery ETP was lower in cases than in controls (2170 vs 2408 nM.min, P < .0001), independently of mode of delivery and PPH etiology. Median plasminogen activator inhibitor-1 and TF levels were higher in cases compared with controls (107.4 vs 68.1 ng/mL, P = .0003; 34.4 vs 27.4 pg/mL, P = .007), whereas thrombomodulin levels did not differ between the 2 groups. ConclusionAmong thrombin generation assay parameters, predelivery ETP levels may have a predictive value for severe PPH.

Inhibition Effect of Physalis angulata Leaf Extract on Viability, Collagen Type I, and Tissue Inhibitor of Metalloproteinase 1 (TIMP-1) but Not Plasminogen Activator Inhibitor-1 (PAI-1) of Keloid Fibroblast Culture.

Keloids are excessive fibroproliferative diseases that are caused by abnormal wound healing. The anti-proliferative activity of Physalis angulata compounds has potential as a keloid therapeutic agent. This study aimed to observe the effects of P. angulata on fibroblast viability and collagen type I, tissue inhibitor of metalloproteinase 1 (TIMP-1), and plasminogen activator inhibitor 1 (PAI-1) levels in human keloid fibroblasts. We conducted an experimental study of P. angulata ethanol extract on three primary human keloid fibroblast 3 passage cultures with four replications. Fibroblast viability was measured using the MTT assay after incubation with 3, 5, and 10 µg/mL P. angulata. Concentrations of P. angulata used to observe effects on TIMP-1, PAI-1, and collagen type I levels were 10%, 20%, 30%, and 40% of inhibitory concentration 50 (IC50). The levels of collagen type I, TIMP-1, and PAI-1 were measured by ELISA. Mean comparisons between multiple treatment groups were analyzed using one-way ANOVA followed by post-hoc analysis. The 10 µg/mL P. angulata group had significantly lower fibroblast viability than the control group (p<0.05) with an IC50 6.3 µg/mL. The collagen type I level of 10% IC50 (0.63 µg/mL) P. angulata group was lower than control (12.910 vs 47.866 ng/mL) (p=0.042). Level of TIMP-1 in 40% IC50 (2.51 µg/mL) P. angulata group was lower than control (5.350 vs 9.972 ng/mL) (p=0.043). There was no significant difference in the PAI-1 levels. This study showed the inhibitory effect of 10 µg/mL P. angulata extract on keloid fibroblast viability, with an IC50 of 6.3 µg/mL. This study also showed collagen type-1 and TIMP-1 inhibition, but not PAI-1 inhibition, after P. angulate treatment.

Hemostatic system in Takotsubo patients at long-term follow-up: A hidden activation?

BackgroundTakotsubo cardiomyopathy (TTS) has long been considered a benign condition, despite recurrent events and long-term adverse outcomes are often reported. Endothelial damage, blood hyperviscosity, and platelet activation described in acute phase persist in long-term follow-up; however, TTS pathophysiology is still not fully understood. Here, we explored the hemostatic system at a median of 3.1 years after TTS to uncover additional long-lasting changes in these patients. MethodsWe assessed hemostatic parameters in women with TTS (n = 23) or coronary artery disease (CAD; n = 31) and in control women (n = 26) age-matched, by thromboelastographic analysis, prothrombin time (PT) and partial thromboplastin time (aPTT) coagulation assays and microparticle exposing Tissue Factor (MP-TF). Functional fibrinogen and fibrin polymerization were analyzed by Clauss method and spectrophotometry, respectively. Platelet reactivity was evaluated by light transmission aggregometry, whereas plasminogen activator inhibitor-1 (PAI-1) and brain-derived neurotrophic factor (BDNF) were measured by ELISA kit. ResultsCompared with control subjects, TTS patients exhibit an accelerated clot formation, higher percentage of fibrin polymerization and higher PAI-1 levels. Compared with CAD, TTS patients showed sustained residual platelet activation but decreased functional fibrinogen, fibrin polymerization and MP-TF levels, prolonged aPTT and a marked BDNF increase. ConclusionsThe long-term activation of hemostatic system observed in TTS patients compared to control subjects suggests a persistent humoral abnormality that may be related to the propensity for TTS recurrence. The higher residual platelet activity observed in TTS than in CAD patients invites investigation on TTS-tailored antiplatelet therapy potentially needed to prevent TTS adverse outcomes.

Long noncoding RNA (taurine upregulated gene 1) and micro RNA-377: emerging players in the development of metabolic syndrome among psoriasis patients

BackgroundPsoriasis (PsO) is an immune-mediated dermatosis and systemic inflammatory condition that can affect the skin, joints, and other organs and tissues with a range of comorbidities. The activation of proinflammatory cytokines is the primary cause of the development of skin lesions in PsO. Patients with PsO have a higher risk of developing cardiovascular metabolic comorbidities; among these is the metabolic syndrome (MetS). Particularly, MetS is characterized by abdominal obesity, hypertension, hyperglycemia, and hyperlipidemia, has been linked to PsO. The connection between PsO and MetS is believed to be caused by PsO generating systemic inflammation, which then results in elevated inflammatory adipokines, endothelial dysfunction, and insulin resistance. Micro RNA-377 and long noncoding RNA taurine upregulated 1 (TUG1) are both involved in the control of a variety of inflammatory disorders in humans and can be employed as biomarkers for the diagnosis and prognosis of psoriasis. The aim of the present study is to establish a panel of biomarkers for the early diagnosis of MetS incidence in psoriasis and thereby, reducing its lethal consequences.ResultsIn this study, 120 patients: 40 psoriatic patients, 40 psoriatic patients with metabolic syndrome, and 40 healthy subjects were conducted. Expressions of Long noncoding RNA Taurine Upregulated Gene-1 (TUG1), miRNA-377 and Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) were assessed in tissue lesion by real-time PCR. ELISA technique was carried out for the detection of serum levels of plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor β (TGFβ). Moreover, miRNA-377 expression was significantly elevated with the simultaneous down-regulation of both TUG-1 and PPAR-γ in PsO-MetS group when compared to those of PsO and control groups. Furthermore, PAI-1 and TGFβ levels were higher in PsO-MetS than PsO.ConclusionsThe dysregulated levels of TUG-1, miRNA-377, PPAR-γ, PAI-1, and TGFβ, biomarkers may provide information about their potential role in the emergence of MetS in psoriasis patients.

PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity.

Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in septic patients. A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study, with 28-day mortality as the primary outcome. The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms (SNPs) were examined. Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1, serum level of PAI-1, and 28-day mortality. The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1 (4G/4G and 4G/5G) (Odds ratio [OR]: 2.49; 95% confidence interval [CI]: 1.09, 5.68). Furthermore, a high serum level of PAI-1 strongly influenced 28-day mortality (OR 3.36; 95% CI 1.51, 7.49). The expression and activation of neutrophils (OR 0.96; 95% CI 0.93, 0.99), as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils (OR: 1.00; 95% CI: 1.00, 1.00), were both regulated by the genotype of PAI-1. Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1, which might contribute to mortality by affecting neutrophil activity. Thus, patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.

The cardioprotective effects of secoisolariciresinol diglucoside (flaxseed lignan) against cafeteria diet-induced cardiac fibrosis and vascular injury in rats: an insight into apelin/AMPK/FOXO3a signaling pathways.

Introduction: Fast food is a major risk factor for atherosclerosis, a leading cause of morbidity and mortality in the Western world. Apelin, the endogenous adipokine, can protect against cardiovascular disease via activating its receptor, APJ. Concurrently, secoisolariciresinol diglucoside (SDG), a flaxseed lignan extract (FLE), showed a therapeutic impact on atherosclerosis. The current study aimed to examine the effect of SDG on cafeteria diet (CAFD)-induced vascular injury and cardiac fibrosis via tracking the involvement of the apelin/APJ pathway. Methods: Thirty male rats were allocated into control, FLE-, CAFD-, CAFD/FLE-, and CAFD/FLE/F13A-treated rats, where F13A is an APJ blocker. All treatments lasted for 12weeks. Results and discussion: The CAFD-induced cardiovascular injury was evidenced by histological distortions, dyslipidemia, elevated atherogenic indices, cardiac troponin I, collagen percentage, glycogen content, and apoptotic markers. CAFD increased both the gene and protein expression levels of cardiac APJ, apelin, and FOXO3a, in addition to increasing endothelin-1, VCAM1, and plasminogen activator inhibitor-1 serum levels and upregulating cardiac MMP-9 gene expression. Moreover, CAFD reduced serum paraoxonase 1 and nitric oxide levels, cardiac AMPK, and nuclear Nrf2 expression. FLE attenuated CAFD-induced cardiovascular injury. Such effect was reduced in rats receiving the APJ blocker, implicating the involvement of apelin/APJ in FLE protective mechanisms. Conclusion: FLE supplementation abrogated CAFD-induced cardiac injury and endothelial dysfunction in an apelin/APJ-dependent manner.

Effect of serum adropin levels on circulating endothelial dysfunction biomarkers in COVID-19 patients

Purpose: Several studies show that the symptoms of severe COVID-19 infection reflect the clinical phenotype of endothelial dysfunction and share common pathophysiological mechanisms with endothelial dysfunction. Therefore, the aim of the study was to investigate the effect of serum adropin levels on endothelial dysfunction biomarkers and determine whether adropin could be a new biomarker for COVID-19.&#x0D; Materials and Methods: The study included 40 patients with mild/moderate COVID-19, 48 patients with severe/critical COVID-19, and 37 controls. Serum adropin and circulating biomarkers of endothelial dysfunction including asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), soluble intercellular adhesion molecule-1 (sICAM-1) and plasminogen activator inhibitor-1 (PAI-1) levels were determined by micro-ELISA.&#x0D; Results: Serum adropin levels were found to be significantly higher in COVID-19 patients (165.2±11.49 pg/ml) than in controls (85.46±12.08 pg/ml). Serum adropin levels of patients with severe/critical symptoms (194±16.23 pg/ml) were significantly higher than the patients with mild/moderate symptoms (130.6 ±14.53). In addition, serum ADMA, eNOS, and, ET-1 levels were significantly higher in the COVID-19 subjects (150.5±8.67 ng/ml, 172.4±14.01 pg/ml, 159.3±10.19 pg/ml, respectively) than that those in the controls (104.5±9.182 ng/ml, 141.4±17.74 pg/ml, 100.1±11.37 pg/ml, respectively). Significant positive correlations were found between adropin and ADMA, eNOS, ET-1, sICAM-1, and PAI-1 levels in the patients.&#x0D; Conclusion: We suggest that adropin may be a new potential biomarker for COVID-19 and an important molecule in restoring endothelial cell damage. Positive correlations between serum adropin levels and ADMA, eNOS, ET-1, sICAM-1 and PAI-1 levels in patients suggest that adropin may compensate for damage to endothelial cells.

Plasma plasminogen activator inhibitor-1 as a predictive marker of type 2 diabetic nephropathy in Egyptian patients

Background The study investigates the relationship between Plasminogen activator inhibitor-1 (PAI-1) levels and the progression of diabetic nephropathy (DN). The fibrinolytic system is impaired in type 2 diabetes mellitus (DM), leading to elevated PAI-1 levels, increasing the potential for renal fibrosis and worsening nephropathy. Patients and methods The research involved 196 type 2 DM patients and 50 healthy control individuals divided into four groups based on Urinary albumin excretion (UAE). Results The diabetic group had significantly higher PAI-1 levels than the control group. The study also found that diabetic patients with macroalbuminuria had higher PAI-1 levels than the control group. Patients with higher UAE and PAI-1 levels had significantly higher serum creatinine concentrations. The study found a significant negative link with creatinine clearance and a significant positive correlation between PAI-1 and serum creatinine and 24-h urine albumin in terms of PAI-1. Conclusions There was a notable positive association with the 24-h UAE, suggesting that increases in PAI-1 were linked to a decline in renal function.