TWEAK Levels Research Articles

Fu-Zheng-Li-Fei Recipe (FZLFR) in the treatment of cancer cachexia: Exploration of the efficacy and molecular mechanism based on chemical characterization, experimental research and network pharmacology

Ethnopharmacological relevanceFZLFR was derived from a classic traditional Chinese medicine recipe, the Shiquan-Dabu decoction. FZLFR is commonly used in clinical practice to address muscle loss and associated cancer cachexia. However, the mechanism of by which FZLFR acts in cancer cachexia remains unclear. AimThis study aimed to assess the effects and explore the potential mechanism of action of FZLFR in treating cancer cachexia. MethodsCancer cachexia was induced by inoculating Lewis lung carcinoma cells into the right flank of male C57BL/6 mice. The efficacy of FZLFR was evaluated by comparing changes in body weight, tumor mass, food intake, survival time, weight, and cross-sectional area of the gastrocnemius and anterior tibial muscles. Moreover, inflammatory cytokines, such as TNF-α and IL-6, were detected by ELISA. The chemical components of FZLFR were analyzed using ultra-performance liquid chromatography-coupled with time-of-flight mass spectrometry. Network pharmacology analysis was performed to screen the core targets and potential pathways involved in FZLFR treatment of cancer cachexia. Molecular docking was used to analyze the binding ability of the core targets and key compounds. The expression levels of core targets and targets correlated with skeletal muscle atrophy were also assessed using western blotting. ResultsFZLFR enhanced the food intake and survival rate of mice with cancer cachexia. It also alleviated tumor-induced body weight loss, tumor growth, and muscle fiber atrophy in these mice. Additionally, it improved the weight and cross-sectional area of the gastrocnemius and anterior tibial muscles. FZLFR down-regulated the serum levels of TNF-α and IL-6. UPLC-ESI-Q-TOF-MS analysis identified 184 compounds in FZLFR. Network pharmacology analysis predicted that TNF signaling pathway, ErbB signaling pathway and VEGF signaling pathway might be essential in FZLFR action. Molecular docking showed that kaempferol, upafolin, apigenin, and luteolin might play key roles in FZLFR treatment. Moreover, FZLFR decreased MAFBx1, MURF1, NF-κB, TWEAK, MAPK8, and EGFR expression levels. FZLFR enhanced the expression of VEGFA and ESR1, as demonstrated by western blotting. ConclusionsFZLFR increased food intake and alleviated muscle atrophy in mice with cancer cachexia. The potential pharmacological mechanisms underlying its anticachexia effects include reducing inflammation, enhancing muscle vascular growth, inhibiting tumor angiogenesis, and modulating estrogen receptors.

Serum BAFF, APRIL, TWEAK, TNFSF18, TNFR2, and TNFRS12A levels in preschool children with autism spectrum disorder

Objectives A gradually increasing number of studies have reported that dysregulation in the immune system may be a contributing factor in the etiopathogenesis of autism spectrum disorder (ASD). However, only limited data has existed about the role of tumor necrosis factor (TNF) superfamily members in ASD. This study aimed to investigate whether serum levels of BAFF, APRIL, TWEAK, TNFSF18 TNFR2, and TNFRS12A are associated with ASD in preschool children. Methods A total of 65 (52 boys/13 girls) preschool children with ASD and 40 (28 boys/12 girls) healthy controls were included in the study. The severity of the ASD symptoms was assessed by the Autism Behavior Checklist and the Childhood Autism Rating Scale. Serum levels of immunologic parameters were measured by enzyme-linked immunosorbent assay. Results Analysis indicated that serum BAFF, TNFSF18, TNFR2, and TNFRS12A levels were significantly lower and serum APRIL and TWEAK levels were significantly higher in the ASD group than in the control group. However, with logistic regression only low BAFF levels and high APRIL levels had relationships with the presence of ASD. Conclusions These findings suggest that TNF superfamily members, especially the BAFF/APRIL system may play a role in the pathophysiology of ASD.

Sarcopenia is associated with hypomethylation of TWEAK and increased plasma levels of TWEAK and its downstream inflammatory factor TNF-α in older adults: A case-control study

BackgroundSarcopenia is a harmful condition common among older adults for which no treatment is available. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (FN14) are known to play important roles in the pathogenesis of sarcopenia. This study investigated alterations in methylation in TWEAK and Fn14 to identify potential targets for the managing sarcopenia. Materials and methodsThrough an epidemiological investigation, we detected methylation of CpG islands (CpGs) in TWEAK and Fn14 in community-dwelling older adult of Xinjiang by bisulfite sequencing. Significant CpGs associated with sarcopenia were selected for detection in 152 older individuals by pyrosequencing. Associations between CpG methylation, plasma inflammatory marker levels, and sarcopenia were analyzed. ResultsOf 38 CpGs in TWEAK and 30 CpGs in Fn14 detected in 60 individuals, 6 CpGs showed lower methylation in sarcopenia patients compared with control individuals. In 152 older adults, covariance analysis with adjustment for age, gender, triglyceride level, obesity, diabetes, and hypertension showed that the methylation levels of 6 CpGs (CpG8, CpG12, CpG13, CpG20 and CpG21of TWEAK, and CpG24 of Fn14) were significantly lower in sarcopenia patients than in control individuals. With adjustment for additional confounding factors, covariate variance analysis showed that plasma TWEAK, TNF-α and IL-10 levels in the sarcopenia group were significant higher than those in the control group (P = 0.007, P < 0.001, P = 0.003). Multivariate logistic regression analysis showed that CpG8, CpG13, CpG21, and total methylation of TWEAK (OR = 0.767, 95 % CI = 0.622–0.947; OR = 0.740, 95 % CI = 0.583–0.941; OR = 0.734, 95 % CI = 0.561–0.958; OR = 0.883, 95 % CI = 0.795–0.980) as well as CpG22 and total methylation of Fn14 were significantly associated with sarcopenia (OR = 826, 95 % CI = 0.704–0.968; OR = 0.918, 95 % CI = 0.852–0.989). From partial correlation analysis, plasma TWEAK was correlated with plasma TNF-α (r = 0.172, P = 0.042). ConclusionSarcopenia is associated with hypomethylation of TWEAK and increased plasma levels of TWEAK and its downstream inflammatory factor TNF-α in a community-dwelling population of older adults in Xinjiang.

TWEAK levels in psoriatic patients treated with narrowband ultraviolet B and methotrexate.

Psoriasis is an autoimmune disease which has an effect on the joints and skin. Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) is a multi-functional cytokine which regulates the cellular processes and has been related to a variation of conditions. To measure the level of serum TWEAK in psoriatic diseased persons and its relationship to the PASI score pre- and post-therapy with narrowband ultraviolet B phototherapy (NB-UVB) and methotrexate (MTX). This randomized controlled trial was conducted on 40 patients and 20 healthy persons as controls. Patient Group was randomly subdivided to two groups. The 1st group consisted of 20 patients who received NB-UVB treatment. The 2nd group included 20 MTX-treated candidates. Blood samples were drawn from patients in order to detect serum TWEAK levels using ELISA. The research was registered on Clinical Trials Registration: RCT approval numbers: NCT0481191. The mean PASI score percent improvement after 12 weeks of treatment was higher in the MTX group (90%) than NB-UVB group (60%). The serum TWEAK level at baseline was 60.47 ± 12.6 pg/mL in NB-UVB group and 54.69 ± 21.7 pg/mL in MTX group which reduced to 24.93 ± 17.6 pg/mL and 32.13 ± 23.6 pg/mL, respectively (p < 0.001), after 12 weeks of treatment. There was a positive correlation between the serum levels of TWEAK and severity of PASI score (r = 0.399, p = 0.014). TWEAK grades in psoriasis are substantially higher than in controls. TWEAK levels were dramatically reduced during NB-UVB and MTX treatment. TWEAK may have a potential sign for psoriasis diagnosis and prognosis.

Relationships between Cxcl12, Tweak, Notch1, and Yap mRNA Expression Levels in Molecular Mechanisms of Liver Fibrogenesis

Current data on the molecular mechanisms of liver fibrosis and cirrhosis fail to fully explain all stages of their development. Interactions between individual genes and signaling pathways are known to play an important role in their functions. However, data on their relationships are insufficient and often contradictory. For the first time, mRNA expression of Notch1, Notch2, Yap1, Tweak (Tnfsf12), Fn14 (Tnfrsf12a), Ang, Vegfa, Cxcl12 (Sdf), Nos2, and Mmp-9 was studied in detail at several stages of thioacetamide-induced liver fibrosis in Wistar rats. A factor analysis isolated three factors, which combined highly correlated target genes. The first factor included four genes: Cxcl12 (r = 0.829, p < 0.05), Tweak (r = 0.841, p < 0.05), Notch1 (r = 0.848, p < 0.05), and Yap1 (r = 0.921, p < 0.05). The second factor described the correlation between Mmp-9 (r = 0.791, p < 0.05) and Notch2 (r = 0.836, p < 0.05). The third factor included Ang (r = 0.748, p < 0.05) and Vegfa (r = 0.679, p < 0.05). The Nos2 and Fn14 genes were not included in any of the factors. The gene grouping by mRNA expression levels made it possible to assume a pathogenetic relationship between their products in the development of fibrotic changes due to liver toxicity.

Circulating TWEAK levels in patients with acne vulgaris: Effect of oral isotretinoin therapy

AbstractBackgroundUpdates on the aetiopathogenesis of acne vulgaris, particularly the inflammatory process, are becoming more and more clear. The TNF superfamily includes tumor necrosis factor (TNF) related weak inducer of apoptosis (TWEAK). It plays a significant part in a variety of inflammatory skin conditions, including psoriasis, alopecia areata and many others. However, its role in acne vulgaris remains questionable.ObjectivesWe aim in this research to evaluate the circulating levels of TWEAK in various severities of acne vulgaris patients and their blood levels before and after oral treatment with isotretinoin.MethodsThis study includes 100 acne vulgaris patients and 100 healthy controls in a case‐control design. All cases, ranging in severity, were treated for 3 months with oral isotretinoin. Enzyme‐linked immunosorbent assay technique was used to measure serum TWEAK before and after 3 months of isotretinoin treatment.ResultsThe serum TWEAK levels were significantly higher in patients than the healthy volunteers (p &lt; 0.001). There were significantly higher serum TWEAK levels with increasing acne vulgaris severity. Additionally, a significant decrease in serum TWEAK level after treatment by oral isotretinoin of AV patients (p &lt; 0.001).ConclusionsTWEAK may play an important role in aetiopathogenesis and the severity of acne vulgaris. Also, oral isotretinoin may target TWEAK in the treatment and alleviate the acne vulgaris.

Procena odnosa između nivoa TWEAK-a u serumu i stepena vaskularne uključenosti kod pacijenata sa stabilnom anginom pektoris

Introduction: This study investigates the relationship between serum TWEAK levels and the degree of vascular involvement in patients with stable angina pectoris, offering insights beyond conventional cardiovascular risk factors. Materials and Methods: This study involved 88 patients (33 women, 55 men) diagnosed with stable angina pectoris. Patients were classified based on angiographic findings. Comprehensive demographic and medical history data were collected, and morning blood samples were analyzed, focusing on TWEAK and IL-6 levels. To assess the severity of coronary artery lesions, a modified version of the Gensini scoring system was employed. Results: Analyses revealed no significant correlation between TWEAK levels and the severity of coronary artery disease. Although some variations in biochemical markers were observed based on gender and diabetic status, these differences did not exhibit a statistically significant relationship with the degree of vascular involvement. Conclusion: The findings indicate that serum TWEAK levels do not have a significant association with the severity of vascular involvement in patients with stable angina pectoris. These results highlight the limited efficacy of TWEAK as a sole biomarker in assessing the severity of coronary artery disease, emphasizing the complexity of its role.

Correlation of expression of silencing information regulator 2 related enzyme 1 and tumor necrosis factor-like weak inducer of apoptosis in articular effusion and knee osteoarthritis

To analyze the correlation between the expression of silencing information regulator 2 related enzyme 1 (SIRT1), tumor necrosis factor like weak inducer of apoptosis (TWEAK) and knee osteoarthritis. Total of 103 patients with knee joint (knee osteoarthritis group) from February 2019 to August 2021 were selected including 40 males and 63 females with an average age of (62.02±6.09) years;according to the modified Mankin score, 103 patients were divided into mild group (Mankin score 1-4 points, 31 cases) and moderate group (Mankin score 5-8 points, 40 cases) and severe group (Mankin score ≥9, 32 cases). Another 105 physical examination volunteers were selected as the control group including 46 males and 59 females with an average age of (62.11±6.34) years old. The levels of SIRT1 and TWEAK in articular effusion and serum were detected in the knee osteoarthritis group, while serum SIRT1 and TWEAK were detected in the control group only. The relationship between SIRT1, TWEAK and the occurrence and disease of knee osteoarthritis were analyzed. Articular cavity fluid TWEAK, serum TWEAK, CRP, IL-6, IL-1β, white blood cell count and ESR were higher than those in the control group(P<0.05), articular cavity fluid SIRT1 and serum SIRT1 were lower than those in the control group(P<0.05). TWEAK level in the severe group was higher than that in the moderate and mild groups(P<0.05), SIRT1 was lower than that in the moderate and mild groups (P<0.05). The level of SIRT1 in articular cavity effusion was positively correlated with the serum level of SIRT1 (P<0.05), and negatively correlated with CRP, IL-6, IL-1β, white blood cell count, modified Mankin score and ESR (P<0.05). TWEAK level in articular cavity fluid was positively correlated with serum TWEAK level (P<0.05), C-reactive protein(CRP), interleukin(IL)-6, IL-1β, white blood cell count, modified Mankin score and erythrocyte sedimentation rate(ESR) (P<0.05). Body mass index, undertaking heavy physical work, and articular cavity fluid TWEAK were risk factors for the occurrence of knee osteoarthritis(P<0.05), and articular cavity fluid SIRT1 was a protective factor for the occurrence of knee arthritis (P<0.05). The area under curve(AUC) of SIRT1 and TWEAK for knee osteoarthritis was 0.641 and 0.653, and the AUC of SIRT1 and TWEAK for knee osteoarthritis was 0.879, which was higher than SIRT1 and TWEAK alone (z=6.105 and 6.225, P<0.05). The level of SIRT1 in articular fluid in patients with knee arthritis is decreased and the level of TWEAK is increased. Low SIRT1 and high TWEAK are associated with the onset and exacerbation of knee osteoarthritis.

Immune mediators as predictive biomarkers for anti-PD-1 antibody therapy in urothelial carcinoma.

Introduction: This study aimed to identify immune mediators, including cytokines, chemokines, and growth factors, in the plasma for predicting treatment efficacy and immune-related adverse events (irAEs) in advanced urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICIs). Methods: We enrolled 57 patients with aUC who were treated with the anti-programmed cell death protein 1 (PD-1) antibody pembrolizumab after the failure of platinum-based chemotherapy between February 2018 and December 2020. Plasma levels of 73 soluble immune mediators were measured before and 6weeks after initiating pembrolizumab therapy. The association of estimated soluble immune mediators with clinical outcomes, including overall survival (OS), progression-free survival (PFS), anti-tumor responses, and irAEs, were statistically evaluated. Results: In the multivariate analysis, levels of 18 factors at baseline and 12 factors during treatment were significantly associated with OS. Regarding PFS, baseline levels of 17 factors were significantly associated with PFS. Higher levels of interleukin (IL)-6, IL-8, soluble tumor necrosis factor receptor 1 (sTNF-R1), and IL-12 (p40), both at baseline and post-treatment, were significantly associated with worse OS. Conversely, low IL-6 and high TWEAK levels at baseline were associated with irAEs. Among identified factors, interferon (IFN) γ and IL-12 (p40) were repeatedly identified; high baseline levels of these factors were risk factors for worse OS and PFS, as well as progressive disease. Notably, using correlation and principal component analysis, factors significantly associated with clinical outcomes were broadly classified into three groups exhibiting similar expression patterns. Discussion: Measuring plasma levels of soluble immune mediators, such as IL-6, IL-8, sTNF-R1, IFNγ, and IL-12 (p40), could be recommended for predicting prognosis and irAEs in ICI-treated patients with aUC.

The usefulness of tumor necrosis factor-like weak inducer of apoptosis in patients with acute ST-elevation myocardial infarction.

We aimed to determine the utility of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) for the early diagnosis and prognosis of acute ST-elevation myocardial infarction (STEMI). Patients presented with STEMI arrived at the hospital within 45 minutes after the onset of chest pain were included in this study. Blood samples for TWEAK, high-sensitivity C-reactive protein (hs-CRP), creatine kinase MB isoenzyme (CK-MB), and high-sensitivity cardiac troponin T (hs-TnT) levels were obtained at the time of arrival at the hospital. Subsequent samples were drawn at 4 h after primary percutaneous coronary intervention. The study cohort comprised patients with confirmed STEMI between January 2022 and September 2022, for a total of 45 enrolled STEMI patients. Plasma TWEAK levels were markedly elevated at hospital arrival, followed by a decrease at 4 hours after successful primary percutaneous coronary revascularization (PPCI). High-sensitive troponin T (Hs-TropT), CK-MB, and CRP were found within normal limits at the hospital arrival. Conversely, increased levels of CRP, CKMB, and hs-TropT were observed at 4 hours after PPCI. Plasma TWEAK levels were elevated earlier in the acute phase and decreased earlier after PPCI than other classic myocardial biomarkers.

Role of serum levels of tumour necrosis factor-like weak inducer of apoptosis (TWEAK) in predicting severity of acute appendicitis.

One of the most prevalent abdominal crises is acute appendicitis (AA). Clinical diagnosis, even for skilled surgeons, is frequently challenging, as indicated by the high proportion of negative investigations. The purpose of this study was to see if serum TWEAK levels might be used to diagnose acute appendicitis. Between June 2017 and May 2019, all patients who had surgery with the original diagnosis of AA were included in the study. TWEAK, WBC, CRP, and bilirubin levels were compared. The levels of WBC, CRP, and bilirubin were compared to pathology. All three blood indicators increased significantly in AA patients. However, no statistically significant difference in the levels of all three blood indicators was seen between individuals with simple AA and those with severe AA. TWEAK plasma concentrations were considerably greater in patients with severe AA than in the healthy control and NAA groups. TWEAK levels were significantly greater in individuals with severe AA compared to patients with simple AA. Serum TWEAK levels that are elevated may be used to diagnose acute appendicitis as well as prognostic indicators for the severity of appendicitis.

Salivary levels of BAFF, TWEAK, and soluble CD163 and salivary arginase activity before and after periodontal treatment.

To monitor salivary B-cell activating factor (BAFF), tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and soluble (s)CD163 levels and arginase activity in periodontitis patients following nonsurgical periodontal treatment. BAFF, TWEAK, and sCD163 and arginase are associated with activities of B cells and macrophages, which are important regulators of periodontal immune-inflammatory response and healing following treatment. Increased salivary BAFF and sCD163 levels and arginase activity in periodontitis have been demonstrated, but their changes following treatment have not been evaluated before. Forty-four Stage III/IV periodontitis patients and 35 periodontally healthy controls were included in the study. Full-mouth periodontal measurements were recorded and unstimulated saliva was obtained from all participants at baseline. Sample collection and measurements were repeated in periodontitis patients at 2, 6, 12, and 24 weeks following full-mouth scaling and root debridement, whereas controls were only seen at baseline. BAFF, TWEAK, and sCD163 levels were analyzed with bead-based multiplexed immunoassay. Arginase activity was measured with Chinard's method. BAFF (p < .001) and sCD163 (p = .003) levels and arginase activity (p < .015) were higher in periodontitis patients compared to healthy controls. BAFF levels (p < .001) and arginase activity (p < .001) of periodontitis patients were reduced at 2 weeks posttreatment and continued to decrease up to 6 (p = .038) and 12 weeks (p = .024), respectively. The reduction of sCD163 levels became significant (p = .003) at 24 weeks posttreatment. The decrease in salivary BAFF levels 2 weeks after periodontal treatment indicates a change in cell signaling toward limited B-cell activation. Decreasing arginase activity similarly reflects a significant reduction in inflammatory response. The reduction in sCD163 levels that are observed at 24 weeks may reflect a longstanding anti-inflammatory macrophage activation, given their multiple functions in immune response, inflammation, and healing.

Immune phenotype of the endometrium in patients with recurrent implantation failures after the transfer of genetically tested embryos in assisted reproductive technology programs

Recurrent implantation failures (RIF) in assisted reproduction programs are one of the most challenging problems. Among the factors that can adversely affect implantation, endometrial immune structural disorders may be one of the leading causes. The aim of our work was to study the immune features of the endometrium in women with RIF after genetically tested embryo transfer in comparison with fertile gestational carriers. Immune cells in endometrial samples were studied by flow cytometry and RNA expression of IL (interleukin)15, IL18, fibroblast growth factor-inducible 14 receptor (Fn14), and tumor necrosis factor-like weak inducer of apoptosis (TWEAK) by reverse polymerase chain reaction. In one-third of the cases, a unique immune profile of the endometrium, which we called the not transformed endometrial immune phenotype, was found. It is characterized by a combination of features, such as high expression of HLA-DR on natural killers (NK), increased fraction of CD16 + , and a decreased fraction of CD56bright endometrial NK. In addition, when compared to gestational carriers, patients with RIF had a greater discrepancy between IL18 mRNA expression data, reduced mean TWEAK and Fn14 levels, and increased IL18/TWEAK and IL15/Fn14 ratios. Immune abnormalities that were found in more than half of the patients (66.7 %) may be the cause of implantation failures in genetically tested embryo transfer programs.

Monitoring of Serum TWEAK Level Guides Glucocorticoid Dosages in the Treatment of Systemic Lupus Erythematosus

Objective: Accurate assessment of systemic lupus erythematosus (SLE) disease activity is critical. This study explored the relationship between the serum level of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score as well as the role of TWEAK in guiding the glucocorticoid dosage in SLE treatment. Methods: This study involved 131 patients with SLE, 34 with subacute cutaneous lupus erythematosus (SCLE), 22 with discoid lupus erythematosus (DLE), and 32 healthy volunteers. The serum and urinary TWEAK levels were determined. Monomeric C-reactive protein (mCRP), anti-dsDNA IgG, antinuclear antibody (ANA), complements in serum and urinary albumin level were measured. The SLEDAI 2000 (SLEDAI-2K) was used to evaluate disease activity. The correlation of the SLEDAI-2K score with all biomarkers was determined. Methylprednisolone was orally administered to patients with SLE depending on the serum level of TWEAK. Results: TWEAK levels were higher in patients with SLE or SCLE than in patients with DLE or healthy controls. The serum TWEAK level was positively correlated with the SLEDAI-2K score in patients with SLE (P &lt; 0.001), and was more strongly correlated with the SLEDAI-2K score than other parameters (P &lt; 0.001). Moreover, TWEAK-based glucocorticoid therapy was associated with lower SLEDAI-2K scores, better tapering of glucocorticoid doses, and fewer lupus flares in patients with SLE. Conclusions: Serum TWEAK is a useful biomarker reflecting SLE disease activity. Monitoring of the serum TWEAK level can improve the outcomes of glucocorticoid therapy in patients with SLE.

Platelet‑related parameters as potential biomarkers for the prognosis of sepsis.

Early diagnosis and accurate prognosis are key for reducing the fatality rate and medical expenses associated with sepsis. Platelets are involved in the delayed tissue injury that occurs during sepsis. Therefore, the aim of the present study was to investigate the usefulness of platelets and associated parameters as prognostic markers of sepsis. The present study collected patient samples based on The Third International Consensus Definitions for Sepsis and Septic Shock criteria. Platelet-associated parameters were detected by flow cytometry and their correlation with clinical scores and prognoses was analyzed. Considering the association between endothelial cells and platelet activation, levels of plasma tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and angiopoietin-2 (Ang-2) were analyzed by ELISA. The results showed significant differences in platelet P-selectin expression and phosphatidylserine exposure, mitochondrial membrane potential (Mmp)-Index values and plasma levels of TWEAK and Ang-2 between patients and healthy controls (P<0.05). Except for P-selectin and TWEAK levels, all parameters were correlated with clinical scores (acute physiology and chronic health evaluation II and sequential/sepsis-related organ failure assessment). Additionally, platelet Mmp-Index between admission and the end of therapy was only different in non-survivors (P<0.001) and platelet phosphatidylserine exposure was significantly lower in survivors (P=0.006). Therefore, of the parameters tested, the dynamic monitoring of phosphatidylserine exposure, platelet Mmp-Index values and plasma Ang-2 levels had the most potential for the assessment of disease severity and clinical outcomes.

The Effect of Coenzyme Q10 on Oxidative Stress and Endoplasmic Reticulum Stress in an Experimental Diabetes Model

Diabetes is the 8th leading cause of death worldwide. The greatest increase in rates has been seen in low and middle-income countries. Urbanization and lifestyle changes such as an increase in sedentary lifestyles, increase in the intake of foods with high energy but poor nutrition levels have caused a high incidence of the disease worldwide. Treating the mechanisms involved in the pathogenesis of diabetes with nutrients such as antioxidants can reduce further complications of the disease. This study tests whether hyperglycemia triggers endoplasmic reticulum stress in the liver and brain tissues of rats and the possible role of oxidative stress in this pathway. We investigated the relationship between oxidative and endoplasmic reticulum stress via the TWEAK pathway, and how the coenzyme Q10 affects further diabetic complications. We examined oxidative stress markers (Oxidized Glutathione, Reduced Glutathione) in the liver and brain tissues of rats in the control, diabetic, and diabetic antioxidant groups by ELISA method. We also determined endoplasmic reticulum stress markers (PERK, ATF6, GRP78) and the TWEAK molecule by the Western Blott method in the same experimental groups. Our results underlined that coenzyme Q10 had a significant and positive effect on oxidative and endoplasmic reticulum stress parameters, and TWEAK levels. We also found a more robust positive correlation between oxidative and endoplasmic reticulum stress parameters for the liver compared to the brain. However, a significant positive correlation was also seen between TWEAK and endoplasmic reticulum stress of the brain.

The Relationship between Serum TWEAK Levels and Carotid Intima-media Thickness in Patients with Fabry Disease.

Fabry disease (FD) is associated with inflammation, proteinuria, and chronic kidney disease. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) plays an important role in inflammation in diabetic nephropathy and lupus nephritis. Since there is a close relationship linking serum TWEAK (sTWEAK), inflammation, and carotid intima-media thickness (CIMT) in various kidney diseases, we aimed to determine the relationship between sTWEAK levels and CIMT in subjects with and without proteinuria in a cross-sectional study involving 15 FD patients (seven females, eight males) and seven healthy controls (four females, three males). There were no differences in age, sex, estimated glomerular filtration rate, and biochemical parameters (serum glucose, albumin, creatinine, uric acid, C-reactive protein (CRP), low-density lipoprotein, and high-density lipoprotein) between FD patients and healthy controls. The spot urine protein-creatinine ratios of healthy controls and FD patients were 90 mg/g and 185 mg/g, respectively (P = 0.022). STWEAK levels were higher in FD patients than in healthy controls (P = 0.007). The CIMT of FD patients and healthy controls was 0.55 ± 0.14 mm and 0.42 ± 0.04 mm, respectively (P = 0.007). STWEAK was positively correlated with CRP and CIMT, and negatively with proteinuria (P = 0.005, P = 0.013, and P = 0.018, respectively). In the multivariate analysis, only sTWEAK was an independent variable of increased CIMT. We demonstrated that sTWEAK and CIMT were increased in FD patients. STWEAK might have a role in the pathogenesis of subclinical atherosclerosis in FD.

Increased serum levels of tumour necrosis factor-like weak inducer of apoptosis in children with autism spectrum disorder

Introduction: A previous study has evaluated the association between serum tumour necrosis factor-like weak apoptosis inducer (TWEAK) levels and autism spectrum disorder (ASD). In line with this investigation, the present study aimed to measure serum TWEAK levels to determine whether their eventual alteration might have etiopathogenetic significance in children with ASD. Methods: A total of 40 treatment-naive children with ASD and 40 healthy children as controls were included in the present study. The Schedule for Affective Disorders and Schizophrenia for School-Aged Children—Present and Lifetime Version, DSM-5 was used by a psychiatrist to screen the healthy controls for psychiatric disorders after a physical examination by a paediatrician. The clinical severity of the ASD symptoms was assessed by the Childhood Autism Rating Scale. Venous blood samples were collected, and serum TWEAK levels were measured. Results: This study included 80 children in total, with 40 (50.0%) in the patient group and 40 (50.0%) in the healthy control group. Thirty four (85.0%) of the participants in the patient group, and 31 (77.5%) in the healthy control group, were male, and the remainder were female. The distribution of the gender ratio was statistically similar between groups (p = 0.568). The volunteers were between 36 and 59 months old. The average age in the patient group was 46.0 ± 6.5, while that in the healthy control group was 45.2 ± 6.7. The ages were also statistically similar between groups (p = 0.615). The TWEAK values of the patient group were found to be statistically higher than those of the healthy control group (p < 0.001). Discussion: This study examined whether serum TWEAK levels were related to ASD in childhood. Our findings indicate that children with ASD have higher TWEAK levels when compared to other children. The findings further indicate that serum TWEAK levels could be related to ASD etiopathogenesis independent of ASD symptom severity.

Evaluation of serum TWEAK, TRAIL, and oxidative stress markers in rosacea patients.

Rosacea is a chronic inflammatory skin disease of unknown pathogenesis. TWEAK and TRAIL are two cytokines thought to have a role in the pathogenesis of some inflammatory and autoimmune diseases. The purpose of this study was to examine TWEAK and TRAIL serum levels and oxidative stress markers in patients with rosacea. Forty rosacea patients and 40 sex- and age-matched healthy controls were involved in the study. Serum TWEAK and TRAIL levels were evaluated with ELISA kits. Serum total antioxidant status, total oxidant status, total thiol, native thiol, disulfide levels were evaluated, and oxidative stress index was computed. Serum levels of TWEAK, TRAIL, and oxidative stress markers did not differ statistically in the patients and controls. Both TWEAK and TRAIL levels in the patients were detected to be statistically higher in male than in female. TWEAK and TRAIL may not have a systemic effect in rosacea, unlike other inflammatory diseases. More studies are needed to investigate the role of TWEAK and TRAIL in rosacea.

Baseline interleukin-10, CD163, and tumor necrosis factor-like weak inducer of apoptosis (TWEAK) gingival tissue levels in relation to clinical periodontal treatment outcomes: A 12-week follow-up study.

The aim of this study was to examine the relationship between healing response after non-surgical periodontal treatment and baseline gingival tissue levels of M2 macrophage activation-related proteins CD163, interleukin (IL)-10, interferon (IFN)-γ, and tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and the CD163/TWEAK ratio. Eighty-eight gingival tissue samples from 44 Stage III/IV, Grade C periodontitis patients (18 smokers) and 41 tissue samples from 41 periodontally healthy participants (18 smokers) were evaluated. Clinical parameters were recorded in periodontally healthy individuals at baseline and in periodontitis patients at pre-treatment and 2, 6, and 12weeks following therapy. IL-10, IFN-γ, CD163, and TWEAK levels were analyzed with Luminex technique. Tissue levels (median, 1st -3rd quartile) of IL-10 (pg/ng protein), CD163 (pg/μg protein) and TWEAK (pg/μg protein) were as follows: IL-10 periodontitis: 2.08, 0.86-5.32 and periodontally healthy: 5.22, 3.20-10.25; CD163 periodontitis: 8.85, 4.92-14.06 and periodontally healthy: 18.36, 12.51-34.02; TWEAK periodontitis: 0.08, 0.05-0.11 and periodontally healthy: 0.16, 0.12-0.21. IL-10, CD163, and TWEAK levels were higher (P<0.001) in periodontally healthy tissues than in periodontitis tissues. Pocket closure at 12weeks was associated with elevated baseline gingival CD163 levels (P =0.047) and CD163/TWEAK ratio (P =0.001). Elevated baseline gingival CD163/TWEAK ratio was associated with pocket reduction at 6 (P =0.022) and 12weeks (P =0.002). Associations of pocket closure with pre-treatment gingival tissue CD163 levels and CD163/TWEAK ratio indicate that baseline M2 macrophage activation profile may play a role in periodontal wound healing.