Factor-like Weak Inducer Of Apoptosis Research Articles

Urinary Tumor Necrosis Factor-Like Weak Inducer of Apoptosis as a Biomarker for Diagnosis and Evaluating Activity in Lupus Nephritis: A Meta-analysis.

Urinary tumor necrosis factor-like weak inducer of apoptosis (uTWEAK) has been identified as a candidate biomarker for lupus nephritis (LN). However, its diagnostic value remains unclear. This meta-analysis was conducted to comprehensively evaluate the value of uTWEAK for diagnosis and evaluating activity in LN. Medline, Web of Science, Chinese Biomedical Medical, and Chinese National Knowledge Infrastructure databases were searched to acquire eligible studies published before September 30, 2019. The quality of the studies was evaluated by Quality Assessment of Diagnostic Accuracy Studies-2. Summary receiver operating characteristic curve and area under the curve were applied to summarize the overall diagnostic performances. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated with the fixed-effects model. RevMan 5.3, Stata 12.0, and Meta-disc 1.4 software were used. A total of 7 studies were included. Of these, 4 studies were available for comparison between SLE with and without LN, and 3 studies were for active and inactive LN. The total area under the curve was 0.8640, and DOR was 14.89 (95% confidence interval [CI], 7.95-27.86). For LN diagnosis, the pooled sensitivity, specificity, and DOR were 0.55 (95% CI, 0.47-0.63), 0.92 (95% CI, 0.86-0.96), and 16.54 (95% CI, 7.57-36.15), respectively. For assessing LN activity, the pooled sensitivity, specificity, and DOR were 0.91 (95% CI, 0.82-0.96), 0.70 (95% CI, 0.58-0.81), and 18.45 (95% CI, 7.45-45.87), respectively. This meta-analysis indicated that uTWEAK has relatively moderate sensitivity and specificity for diagnosis and evaluating activity in LN, suggesting that uTWEAK can serve as a helpful biomarker for LN.

Clinical significance of urinary tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in immunoglobulin A nephropathy .

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has been implicated as a mediator of chronic inflammatory processes. Recently, it was reported that TWEAK may play an important role in the pathogenesis of kidney damage. In the present study, we investigated the role of TWEAK in immunoglobulin A nephropathy (IgAN). The levels of serum TWEAK (sTWEAK) and urinary TWEAK (uTWEAK) in 45 patients with IgAN and 15 healthy subjects were measured. We analyzed the correlations of uTWEAK level with clinical and pathological parameters in patients with IgAN. We then divided the patients into two groups according to uTWEAK level and investigated 5-year chronic kidney disease (CKD) progression. The level of uTWEAK was significantly higher in patients with IgAN than in healthy controls (p<0.001). sTWEAK level showed no significant difference between the two groups (p=0.225). The level of uTWEAK correlated significantly with serum albumin (p<0.001), urine protein excretion (p<0.001), and histological classification (p<0.016) in patients with IgAN. uTWEAK was significantly increased even in patients with IgAN who had lower proteinuria. There was a significant association between uTWEAK level and CKD progression (p=0.049). Although uTWEAK is not a superior biomarker compared to proteinuria, it has a significant correlation with IgAN patients and seems to be useful in determining disease progression.

MicroRNA-1 Negatively Regulates Peripheral NK Cell Function via Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) Signaling Pathways During PPRV Infection.

Peste des petits ruminants virus (PPRV) has emerged as a significant threat to the productivity of small ruminants worldwide. PPRV is lymphotropic in nature and induces in the hosts a transient but severe immunosuppression, especially innate immunity. However, it remains largely unknown how NK cells respond and are regulated at the earliest time points after an acute viral PPRV infection in goats. In this study, we revealed that multiple immune responses of goat peripheral NK cells were compromised during PPRV infection, including the cytolytic effector molecule expression and cytokine production. Importantly, we demonstrated that PPRV infection stimulated the expression of TWEAK, a negative regulator of cytotoxic function of NK cells, which may be involved in the suppression of cytotoxicity as well as cytokine production in infected goat NK cells. Furthermore, we found that PPRV infection induced TWEAK expression in goat NK cells involving post-transcription by suppressing miR-1, a novel negative miRNA directly targeting the TWEAK gene. Moreover, replication of virus is required for inhibition of miR-1 expression during PPRV infection, and the non-structural V protein of PPRV plays an important role in miR-1 mediated TWEAK upregulation. Additionally, we revealed that the regulation of NK cell immune responses by TWEAK is mediated by MyD88, SOCS1, and STAT3. Taken together, our results demonstrated that TWEAK may play a key role in regulating goat peripheral NK cell cytotoxicity and cytokine expression levels during PPRV infection.

Changes in Soluble TWEAK Concentrations, but Not Those in Amyloid-β(1–40), Are Associated with a Decrease in Carotid Intima-Media Thickness after Bariatric Surgery in Obese Women

Background/Aim: Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and amyloid-β(1–40) (Aβ₄₀) emerged as markers of cardiovascular risk because of their actions in the endothelium and their role in atherosclerotic progression. The aim of this study was to analyze the association of these two factors with the decrease in carotid intima-media thickness (cIMT) after bariatric surgery in obese women. Methods: We studied 60 severely obese women, of whom 20 were submitted to laparoscopic Roux-en-Y gastric bypass (RYGB), 20 to sleeve gastrectomy (SG), and 20 to lifestyle modification therapy. Circulating sTWEAK, Aβ₄₀, high-sensitivity C-reactive protein, plasminogen activator inhibitor type 1, insulin resistance (HOMA-IR), and cIMT were measured at baseline and after 1 year of follow-up. Results: sTWEAK increased similarly after both surgical procedures, whereas the increase observed after lifestyle intervention did not reach statistical significance. Aβ₄₀ showed no differences between groups of women, nor did it change during follow-up. The decrease in cIMT at 12 months correlated with the decrease in body mass index (BMI) (r = 0.45; p < 0.001) and fasting insulin (r = 0.30; p = 0.038), and also with the increase in sTWEAK (r = –0.43; p = 0.002). Multivariate linear regression showed that only the changes in BMI (β = 0.389; p = 0.005) and sTWEAK (β = –0.358; p = 0.009) were associated with the decrease in cIMT (R² = 0.313; F = 9.348; p < 0.001). Conclusions: One year after bariatric surgery, RYGB and SG induced a similar increase in circulating sTWEAK that occurred in parallel to the decrease observed in cIMT.

Effect of remote ischemic preconditioning on hepatic ischemia-reperfusion injury in patients undergoing liver resection: a randomized controlled trial.

Studies in animal models have shown that remote ischemic preconditioning (RIPC) could protect the liver from hepatic ischemia-reperfusion injury (HIRI). The aim of this study was to examine whether RIPC could reduce HIRI in patients undergoing liver resection. A total of 120 patients were randomly assigned to three groups: a control group receiving no conditioning, an ischemic preconditioning (IPC) group, and an RIPC group. In the IPC group, the hepatoduodenal ligament was blocked for 10 min followed by 10 min of reperfusion prior to hepatic resection. Patients in the RIPC group received three cycles of 5-min ischemia followed by 5-min reperfusion to the right arm. Alanine transaminase (ALT), aspartate transaminase (AST), and tumor necrosis factor-like weak inducer of apoptosis (TWEAK) were examined before and after surgery. A total of 105 patients completed the trial: 39 in the control group, 32 in the IPC group, and 34 in the RIPC group. In comparison to the control, serum ALT and AST levels significantly decreased in the IPC (ALT: 507.0±401.3 vs. 1040.7±649.5 IU/L, P<0.001; AST: 495.8±369.4 vs. 935.9±640.7 IU/L, P=0.001) and RIPC (ALT: 680.8±291.5 vs. 1040.7±649.5 IU/L, P=0.002; AST: 661.7±290.6 vs. 935.9±640.7 IU/L, P=0.014) groups on the first postoperative day. In comparison to the control, TWEAK significantly decreased in the IPC group (IPC 57.99±17.8 vs. control 76.13±12.4 ng/L, P=0.025) after surgery. TWEAK did not differ between the RIPC and IPC groups (RIPC 64.84±14.2 vs. IPC 57.99±17.8 ng/L, P=0.385). RIPC could reduce hepatic ischemia-reperfusion injury after liver resection.

Elevated serum tumour necrosis factor-like weak inducer of apoptosis in alopecia areata: a possible marker of disease severity.

Alopecia areata (AA) is, an organ-specific autoimmune disease, characterized by an aberrant expression of cytokines of the T helper 1 type. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifactorial cytokine that exerts a role in the pathogenesis ofinflammatory and autoimmune diseases, especially in cutaneous diseases. To estimate the serum level of TWEAK in AA and to correlate it with different parameters. This case-control study enrolled 40 patients with AA and 50 clinically healthy volunteers matched for age and sex. A blood sample (5mL) was extracted from each participant for analysis of serum TWEAK levels by ELISA. Levels of TWEAK were significantly higher in patients with AA (mean±SD 213.7±59.2pg/mL, range 109.1-341.6pg/mL) than in controls (95.97±13.28pg/mL, range 80.1-152.3pg/mL) (P<0.001). A significant positive correlation was found between serum TWEAK level and the Severity of Alopecia Tool (SALT) score (r=0.56, P<0.001). To our knowledge, thisstudy highlights for the first time a possible link between higher serum TWEAK level and AA. Serum TWEAK level appears to reflect AA disease severity.

Cryptotanshinone Attenuates Airway Remodeling by Inhibiting Crosstalk Between Tumor Necrosis Factor-Like Weak Inducer of Apoptosis and Transforming Growth Factor Beta 1 Signaling Pathways in Asthma.

The study is to investigate the effect of cryptotanshinone (CTS) on airway remodeling and the possible mechanism. Male BALB/c mice were pretreated with CTS or dexamethasone 30 min before nebulized inhalation of ovalbumin (OVA). CTS significantly inhibited OVA-induced increases of eosinophils and neutrophils infiltration of bronchoalveolar lavage fluids (BALFs), reduced airway resistance in asthmatic mice, decreased the accumulation of inflammatory cells, the hyperplasia of goblet cells and the deposition of collagen in asthmatic mice lung tissue, as well as markedly attenuated the leakage of inflammatory cells and the level of OVA-specific immunoglobulin E in BALFs. CTS also inhibited the expressions of alpha-smooth muscle actin, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), Fn14, transforming growth factor (TGF)-β1, Smad4, and phosphorylation of Smad2/3 and STAT3 (Tyr705). In comparison to TWEAK inhibitor or TWEAK small interfering RNA (siRNA), which were used to inhibit TWEAK/STAT3 signaling pathways, CTS caused a similar effect as them on airway remodeling. Additionally, CTS also played a similar role as the TGF-β1 inhibitor or TGF-β1 siRNA in TGF-β1/STAT3 signaling pathways in airway remodeling. The anti-inflammatory effects of CTS against OVA-induced airway remodeling may be through inhibiting STAT3, which further suppresses TWEAK and TGF-β1 signaling cross talk in asthma. CTS may be a promising therapeutic reagent for asthma treatment.

Periodontitis and vascular inflammatory biomarkers: an experimental in vivo study in rats

The objective of this preclinical in vivo study was to determine changes in vascular inflammatory biomarkers in systemic circulation after injection of lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg) in rats. Experimental periodontitis was induced by injections of Pg-LPS. Gingival soft and hard tissues changes were analysed by means of magnetic resonance imaging and micro computed tomography. Serum levels of interleukin (IL)-6, IL-10, pentraxin (PTX) 3, and soluble fragment of tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) were determined at baseline and 24 h, 7, 14, and 21 days after periodontal induction. Significant periodontal inflammation and alveolar bone loss were evident at the end of periodontal induction. Experimental periodontitis posed an acute systemic inflammatory response with increased serum levels of IL-6 and PTX3 at 24 h post-induction, followed by a significant overexpression of sTWEAK at 7 days. This inflammatory state was maintained until the end of the experiment (21 days). As expected, IL-10 serum levels were significantly lower during the follow-up compared to baseline concentrations. In the present animal model, experimental periodontitis is associated with increased systemic inflammation. Further studies are needed to confirm whether PTX3 and sTWEAK could be useful biomarkers to investigate potential mechanisms underlying the relationship between periodontitis and atherosclerotic vascular diseases.

TWEAK promotes hepatic stellate cell migration through activating EGFR/Src and PI3K/AKT pathways.

Activated human hepatic stellate cells (HSCs) showed enhanced ability of migration compared with quiescent HSCs, which is pivotal in liver fibrogenesis. The aim of the present study was to investigate the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) on the migration of activated HSCs and to explore the relevant potential mechanisms. Human HSCs LX-2 cells were cultured with TWEAK. TNFRSF12A-downexpressing lentiviruses were used to infect LX-2 cells. The specific matrix metalloproteinases inhibitor BB94, the Src family kinase inhibitor, Dasatinib, and the specific inhibitor of phosphoinositide 3-kinase (PI3K), LY294002 were used to treat LX-2 cells combined with TWEAK. Cell migration and invasion was tested by the transwell assay. The expression of EGFR/Src, PI3K/AKT, and matrix metallopeptidase 9 (MMP9) was identified by real-time polymerase chain reaction or western blotting. The result showed TWEAK promoted HSC migration and collagen production. BB94 significantly attenuated the migration of LX-2 induced by TWEAK. Dasatinib inhibited the ability of cell migration stimulated by TWEAK. TWEAK upregulated the phosphorylation of epidermal growth factor receptor (EGFR) and Src. The phosphorylation of PI3K and AKT was significantly activated by TWEAK stimulation. Inhibition of PI3K/AKT reduced the expression of MMP9 induced by TWEAK. The present study, for the first time, demonstrated that TWEAK promoted HSC migration through the activation of EGFR/Src and PI3K/AKT pathways, and showed a novel potential mechanism of HSC migration regulated by TWEAK.

Immunohistochemical expression of tumor necrosis factor‐like weak inducer of apoptosis and fibroblast growth factor‐inducible immediate early response protein 14 in oral squamous cell carcinoma and its implications

To study the expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible immediate early response protein 14 (Fn14) in oral squamous cell carcinoma (OSCC), to elucidate the possible role of TWEAK-Fn14 in OSCC development. Immunohistochemistry for TWEAK-Fn14 was performed on 61 oral mucosal samples: healthy oral mucosa (HOM; N=15); oral dysplastic lesions (ODL; N=15); and OSCC (N=31). Extent of staining (ES) and immunoreactive score (IRS) were assessed. The data was statistically analyzed. All OSCC expressed TWEAK, and the Fn14 expression was noted in 90% of OSCC. A significant difference in the TWEAK and Fn14 expression was noted among the groups. ES and IRS of TWEAK-Fn14 significantly increased in OSCC compared with ODL and HOM. ES of TWEAK was significantly higher than Fn14 in all 3 groups. ES of TWEAK-Fn14 was significantly higher at the invasive tumor front (ITF) than in the whole tumor. TWEAK-Fn14 showed a significant association with clinicopathological parameters of prognostic significance. Findings suggest that TWEAK and Fn14 may participate in the growth and progression of OSCC. Increased expression of TWEAK-Fn14 at the ITF may facilitate increased proliferation, altered differentiation and invasion.

A major role of TWEAK/Fn14 axis as a therapeutic target for post-angioplasty restenosis

BackgroundTumor necrosis factor-like weak inducer of apoptosis (Tnfsf12; TWEAK) and its receptor Fibroblast growth factor-inducible 14 (Tnfrsf12a; Fn14) participate in the inflammatory response associated with vascular remodeling. However, the functional effect of TWEAK on vascular smooth muscle cells (VSMCs) is not completely elucidated. MethodsNext generation sequencing-based methods were performed to identify genes and pathways regulated by TWEAK in VSMCs. Flow-citometry, wound-healing scratch experiments and transwell migration assays were used to analyze VSMCs proliferation and migration. Mouse wire injury model was done to evaluate the role of TWEAK/Fn14 during neointimal hyperplasia. FindingsTWEAK up-regulated 1611 and down-regulated 1091 genes in VSMCs. Using a gene-set enrichment method, we found a functional module involved in cell proliferation defined as the minimal network connecting top TWEAK up-regulated genes. In vitro experiments in wild-type or Tnfrsf12a deficient VSMCs demonstrated that TWEAK increased cell proliferation, VSMCs motility and migration. Mechanistically, TWEAK increased cyclins (cyclinD1), cyclin-dependent kinases (CDK4, CDK6) and decreased cyclin-dependent kinase inhibitors (p15lNK4B) mRNA and protein expression. Downregulation of p15INK4B induced by TWEAK was mediated by mitogen-activated protein kinase ERK and Akt activation.Tnfrsf12a or Tnfsf12 genetic depletion and pharmacological intervention with TWEAK blocking antibody reduced neointimal formation, decreasing cell proliferation, cyclin D1 and CDK4/6 expression, and increasing p15INK4B expression compared with wild type or IgG-treated mice in wire-injured femoral arteries. Finally, immunohistochemistry in human coronary arteries with stenosis or in-stent restenosis revealed high levels of Fn14, TWEAK and PCNA in VSMCs enriched areas of the neointima as compared with healthy coronary arteries. InterpretationOur data define a major role of TWEAK/Fn14 in the control of VSMCs proliferation and migration during neointimal hyperplasia after wire injury in mice, and identify TWEAK/Fn14 as a potential target for treating in-stent restenosis. FundISCiii-FEDER, CIBERCV and CIBERDEM.

Novel Drug Targets for Ischemic Stroke Identified Through Mendelian Randomization Analysis of the Blood Proteome.

Novel, effective, and safe drugs are warranted for treatment of ischemic stroke. Circulating protein biomarkers with causal genetic evidence represent promising drug targets, but no systematic screen of the proteome has been performed. First, using Mendelian randomization (MR) analyses, we assessed 653 circulating proteins as possible causal mediators for 3 different subtypes of ischemic stroke: large artery atherosclerosis, cardioembolic stroke, and small artery occlusion. Second, we used MR to assess whether identified biomarkers also affect risk for intracranial bleeding, specifically intracerebral and subarachnoid hemorrhages. Third, we expanded this analysis to 679 diseases to test a broad spectrum of side effects associated with hypothetical therapeutic agents for ischemic stroke that target the identified biomarkers. For all MR analyses, summary-level data from genome-wide association studies (GWAS) were used to ascertain genetic effects on circulating biomarker levels versus disease risk. Biomarker effects were derived by meta-analysis of 5 GWAS (N≤20 509). Disease effects were derived from large GWAS analyses, including MEGASTROKE (N≤322 150) and UK Biobank (N≤408 961) studies. Several biomarkers emerged as causal mediators for ischemic stroke. Causal mediators for cardioembolic stroke included histo-blood group ABO system transferase, coagulation factor XI, scavenger receptor class A5 (SCARA5), and tumor necrosis factor-like weak inducer of apoptosis (TNFSF12). Causal mediators for large artery atherosclerosis included ABO, cluster of differentiation 40, apolipoprotein(a), and matrix metalloproteinase-12. SCARA5 (odds ratio [OR]=0.78; 95% CI, 0.70-0.88; P=1.46×10-5) and TNFSF12 (OR=0.86; 95% CI, 0.81-0.91; P=7.69×10-7) represent novel protective mediators of cardioembolic stroke. TNFSF12 also increased the risk of subarachnoid (OR=1.53; 95% CI, 1.31-1.78; P=3.32×10-8) and intracerebral (OR=1.34; 95% CI, 1.14-1.58; P=4.05×10-4) hemorrhages, whereas SCARA5 decreased the risk of subarachnoid hemorrhage (OR=0.61; 95% CI, 0.47-0.81; P=5.20×10-4). Multiple side effects beyond stroke were identified for 6 of 7 biomarkers, most (75%) of which were beneficial. No adverse side effects were found for coagulation factor XI, apolipoprotein(a), and SCARA5. Through a systematic MR screen of the circulating proteome, causal roles for 5 established and 2 novel biomarkers for ischemic stroke were identified. Side-effect profiles were characterized to help inform drug target prioritization. In particular, SCARA5 represents a promising target for treatment of cardioembolic stroke, with no predicted adverse side effects.

Comparison of PREDICTS atherosclerosis biomarker changes after initiation of new treatments in patients with SLE

ObjectivePatients with SLE have an increased risk of atherosclerosis (ATH) that is not adequately explained by traditional risk factors. We previously described the Predictors of Risk for Elevated Flares, Damage...

Severe periodontitis is linked with increased peripheral levels of sTWEAK and PTX3 in chronic migraineurs

Periodontitis (PD) and chronic migraine (CM) have been recently linked, and inflammatory processes and vascular endothelial changes are hypothesized as potential mediators of this relationship. The aim of this cross-sectional analysis was to investigate the potential association of PD with vascular systemic inflammation and complement activation in patients with CM. Ninety-four chronic migraineurs underwent a full-mouth periodontal evaluation and a measure of PD activity and severity, namely the periodontal inflamed surface area (PISA) was calculated for each patient. We divided CM patients according to their periodontal status: mild PD (N = 14), moderate PD (N = 22), severe PD (N = 19), and non-PD (N = 39). Serum levels of C-reactive protein (CRP), pentraxin 3 (PTX3), soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK), and complements C3 and C4 were measured outside of migraine attacks. We found that severe periodontal patients had significantly higher circulating levels of PTX3 and sTWEAK compared with those without PD (2475.3 ± 1646.8pg/mL vs. 516.6 ± 1193.8pg/mL, P < 0.0001 and 672.4 ± 118.2pg/mL vs. 485.7 ± 112.2pg/mL, P < 0.0001; respectively). For the remaining biomarkers, no significant differences were found between groups. Severe PD was independently associated with higher levels of PTX3 (β = 1997.6, P < 0.0001) and sTWEAK (β = 187.1, P < 0.0001) but not with CRP, C3, and C4. PISA positively correlated to PTX3 (r = 0.475, P < 0.0001) and sTWEAK (r = 0.386, P < 0.0001). Based on these preliminary results, severe PD was linked with vascular systemic inflammation in patients with CM. However, further longitudinal studies should be performed to confirm these findings. sTWEAK and PTX3 measured in serum could be used as biomarkers in the PD-CM link.

Soluble CD163 and TWEAK in early pregnancy gestational diabetes and later glucose intolerance.

Gestational diabetes mellitus (GDM) is today universally diagnosed during late pregnancy. Treating hyperglycaemia during pregnancy reduces the risk of complications, the effect of interventions is however limited due to the late diagnosis. It is thus important to identify biomarkers reaching a high precision for GDM development in early pregnancy. Here we aim to investigate soluble CD163 (sCD163) and soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) in early pregnancy GDM and their association to the development of later glucose intolerance. In this case-control study, women diagnosed with GDM in early pregnancy (n = 70) at Lund University Hospital, Lund, Sweden in 2011–2015 were age- and BMI matched to pregnant volunteers without diabetes (n = 70) recruited in early pregnancy from maternal health care centres in 2014–2015. Plasma levels of sCD163 and sTWEAK were analysed using commercial ELISA. Plasma levels of sCD163 did not differ between patients with and without GDM in early pregnancy (p = 0.86), plasma levels of sTWEAK however was decreased in women with GDM (0.71 [0.4–1.75] ng/ml) compared to controls (1.38 [0.63–4.86] ng/ml; p = 0.003). Women with sTWEAK levels in the lowest tertile had an increased risk of GDM in early pregnancy (p = 0.014). Neither sCD163 nor sTWEAK were associated with later glucose intolerance in women with GDM. This study reports decreased levels of sTWEAK in women with early pregnancy GDM, independent of age and BMI. Neither sCD163 nor sTWEAK were found to be associated to later glucose intolerance.

How much apoptosis does carbon monoxide poisoning cause? Primary clinical soluble TWEAK protein level study.

Carbon monoxide (CO) is an important cause of deaths via poisoning. CO poisoning causes inhibition of O2 transport and development of tissue hypoxia, which then causes cell apoptosis. A significant indicator of cell apoptosis, soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) protein, is important for the stimulation of apoptosis. The primary purpose of this study is to determine whether apoptosis occurs during acute CO poisoning and to show that sTWEAK protein is an indicator of apoptosis that can be analyzed as a marker in the peripheral blood sample. The secondary aim is to determine the diagnostic and prognostic values of sTWEAK protein. The study was performed prospectively on 43 patients with CO poisoning and 30 healthy volunteer control individuals. The anamneses were taken from all patients, who also underwent physical examination. Complete blood count, biochemical markers, cardiac enzymes, and arterial blood gas measurements were analyzed. All the patients' sTWEAK protein levels were also analyzed. The sTWEAK protein level of patients with CO poisoning was 2278 pg/mL (1197-7234), while the level of the control group was 1609 pg/mL (310-3721). The patients' sTWEAK levels were significantly higher than the controls (area under the curve: 0.77 (0.66-0.89); p < 0.001), and the cutoff value was determined as 1895.50 pg/mL. The cutoff level had a sensitivity of 74.4%, a specificity of 76.7%, a positive predictive value of 82.0%, and a negative predictive value of 67.6%. sTWEAK is a significant indicator of apoptosis in CO poisoning that can be analyzed in the peripheral blood. However, further clinical trials are needed in terms of prognostic criteria.

Serum soluble TWEAK levels in severe traumatic brain injury and its prognostic significance

BackgroundSevere traumatic brain injury (sTBI) is characterized by a high mortality. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) participates in inflammation. We determined serum soluble TWEAK (sTWEAK) levels with respect to its prognostic ability. MethodsThis was a single-center prospective, observational study that was performed from December 2014 to December 2017. A total of 114 sTBI patients who met the inclusion criteria and 114 randomly selected healthy controls were included in the study. Serum sTWEAK levels were gauged. Patients were followed-up until death or completion of 6 months. Poor outcome was referred to as Glasgow outcome scale score of 1–3. ResultsIn comparison with controls, patients displayed predominantly higher serum sTWEAK levels. Serum sTWEAK levels were strongly correlated with Glasgow coma scale scores and serum C-reactive protein levels. 32 patients (28.1%) died and 60 patients (52.6%) suffered from a poor outcome. Receiver operating characteristic curve analysis clearly showed that serum sTWEAK levels had substantially high predictive performance for 6-month mortality and poor outcome. Serum sTWEAK emerged as an independent predictor for 6-month mortality, overall survival and poor outcome. ConclusionsRaised serum sTWEAK levels are closely related to increasing inflammatory response, elevated trauma severity and worse clinical outcome after sTBI.

Serum tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and IL-17 levels are associated with disease activity in systemic lupus erythematosus patients with and without nephritis

Introduction: Lupus nephritis (LN) is one of the most severe signs of systemic lupus erythematosus (SLE) and rapid diagnosis of kidney damage remains an important concern for LN. Objectives: The aim of this study was to investigate the association of the serum levels of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and interleukin 17 (IL-17) with SLE severity, renal involvement, and other clinical manifestations in lupus patients. Patients and Methods: In order to determine a better biomarker for the detection of renal damage, this study evaluated the ability of serum TWEAK (sTWEAK) and IL-17 in lupus patients with (n=25) and without (n=25) nephritis and healthy controls (n=39). Moreover, it compared the levels of these cytokines with disease activity and chronicity as well as traditional serum markers including complement C3 and C4, creatinine, and proteinuria in lupus patients. Results: Increased levels of sTWEAK and IL-17 were observed in SLE and LN groups compared to healthy controls and non-LN groups, respectively. Significant positive associations were observed between serum TWEAK and IL-17 levels and systemic lupus erythematosus disease activity index (SLEDAI), proteinuria, nephritis activity index, and some clinical manifestations (P&lt;0.05). Discriminating the ability of the studied cytokines were not better than the utility of any markers individually. Conclusion: The serum levels of TWEAK and IL-17 in the SLE and LN groups were significantly higher than the control group and both markers were indicative of the renal disease severity; therefore, they could possibly indicate renal involvement in the lupus patients.

The Evaluation of Serum Tumor Necrosis Factor-Like Weak Inducer of Apoptosis, Interleukin-6, Fetuin-A, Homeostatic Model Assessment-Insulin Resistance, and Insulin Levels in Rheumatoid Arthritis Patients in Clinical Remission

The Evaluation of Serum Tumor Necrosis Factor-Like Weak Inducer of Apoptosis, Interleukin-6, Fetuin-A, Homeostatic Model Assessment-Insulin Resistance, and Insulin Levels in Rheumatoid Arthritis Patients in Clinical Remission

Decrease in inflammatory biomarker concentration by intervention with selenium and coenzyme Q10: a subanalysis of osteopontin, osteoprotergerin, TNFr1, TNFr2 and TWEAK

BackgroundInflammation is central to the pathogenesis of many diseases. Supplementation with selenium and coenzyme Q10 has been shown to reduce cardiovascular mortality, and increase cardiac function in elderly persons with a low intake of selenium. There are indications that one of the mechanisms of this positive effect is a decrease in inflammation.MethodsOsteopontin, osteoprotegerin, sTNF receptor 1, sTNF receptor 2 and the tumor necrosis factor-like weak inducer of apoptosis called TWEAK, were determined in plasma after 6 months and 42 months in 219 community-living elderly persons, of whom 119 received supplements of selenium (200 μg/day) and coenzyme Q10 (200 mg/day), and 101 received a placebo. Repeated measures of variance were used to evaluate the levels, and the results were validated through ANCOVA analyses with adjustments for important covariates.ResultsSignificantly lower concentrations of four of the five biomarkers for inflammation were observed as a result of the intervention with the supplements. Only TWEAK did not show significant differences.ConclusionIn this sub-analysis of the intervention with selenium and coenzyme Q10 or placebo in an elderly community-living population, biomarkers for inflammation were evaluated. A significantly lower concentration in four of the five biomarkers tested could be demonstrated as a result of the supplementation, indicating a robust effect on the inflammatory system. The decrease in inflammation could be one of the mechanisms behind the positive clinical results on reduced cardiovascular morbidity and mortality reported earlier as a result of the intervention. The study is small and should be regarded as hypothesis-generating, but nonetheless adds important data about mechanisms presently known to increase the risk of clinical effects such as reduced cardiovascular mortality, increased cardiac function and better health-related quality of life scoring, as previously demonstrated in the active treatment group .Trial registrationThe intervention study was registered at Clinicaltrials.gov, and has the identifier NCT01443780 and registered on 09/30/2011.