scholarly journals Serum Metabolomic Profiling Reveals the Amelioration Effect of Methotrexate on Imiquimod-Induced Psoriasis in Mouse

2020 ◽  
Vol 11 ◽  
Author(s):  
Jiaxin Zong ◽  
Jieyi Cheng ◽  
Yuanfeng Fu ◽  
Jing Song ◽  
Weisong Pan ◽  
...  

Background:The imiquimod (IMQ)-induced psoriasis mouse model has been used as a model for pathogenic mechanism research, and methotrexate (MTX) is widely employed to treat various clinical manifestations of psoriasis. We explored the underlying pathogenesis of psoriasis and the treatment mechanism of the conventional drugs from the metabolic perspective of the psoriasis mouse model.Methods:Male BALB/c mice were smeared IMQ for 7 days to induce treatment-resistant psoriasis and intragastrically administered 1 mg/kg MTX. We evaluated inflammation of psoriasis-like lesions and therapeutic effects of MTX based on histological changes and immunohistochemistry. Based on gas chromatography-mass spectrometer detection of serum samples, a comprehensive metabolomics analysis was carried out to identify alterations of metabolites.Results:It was found that MTX ameliorated psoriatic lesions (representative erythema, scaling, and thickening) by inhibiting proliferation and differentiation of keratinocytes. Using multivariate statistical analysis to process metabolomics data, the results displayed alterations in serum metabolites among mice of the control group, IMQ group, and MTX group. Compared with group, psoriasis mice had the higher level of d-galactose and lower expression of myo-inositol, 9,12-octadecadienoic acid, and cholesterol. In contrast with the model set, serum levels of glycine, pyrrolidone carboxylic acid, d-galactose, and d-mannose were significantly decreased in the MTX group.Conclusion:The differential metabolites, reflecting the perturbation in the pathways of inositol phosphate metabolism; galactose metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and glutathione metabolism, may lead to the pathogenesis of psoriasis, and they are also related to the pharmacological treatment effect of MTX on psoriasis. This study established the foundation for further research on the mechanism and therapeutic targets of psoriasis.

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Andréa Tavares Dantas ◽  
Sayonara Maria Calado Gonçalves ◽  
Anderson Rodrigues de Almeida ◽  
Rafaela Silva Guimarães Gonçalves ◽  
Maria Clara Pinheiro Duarte Sampaio ◽  
...  

Objective. To determine active TGF-β1 (aTGF-β1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients.Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR.Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p< 0.0001). Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p= 0.02), digital ulcers (p= 0.02), lung fibrosis (p< 0.0001), positive antitopoisomerase I (p= 0.03), and higher modified Rodnan score (p= 0.046). Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin.Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 47.2-47
Author(s):  
C. Gioia ◽  
B. Lucchino ◽  
C. Iannuccelli ◽  
G. Dolcini ◽  
M. DI Franco

Background:Fibromyalgia (FM) is a common rheumatic disease characterized by chronic widespread pain, sleep and mood disorders. A higher prevalence of FM in women compared with men is well known, although the specific differences in clinical manifestations related to gender are still poorly defined. Brain-Derived Neurotrophic Factor (BDNF) is an endogenous growth factor that gained attention for its potential as biomarker of several diseases, including FM and depression.Objectives:The aims of this study were to investigate gender-related difference among males and females affected by FM in clinical manifestations, depressive features and BDNF serum level, evaluating also the diagnostic potential of the latter.Methods:We consecutively enrolled adult patients affected by FM (ACR 2016) referring to our out-patient clinic. Each subject underwent clinical and answered to questionnaires for the severity of FM symptoms (Revised Fibromyalgia Impact Questionnaire, R-FIQ) and depressive symptoms (Beck Depression Inventory-II, BDI-II). We collected blood samples from a subgroup of patients of both sexes, matched for age, for BDNF serum level dosage through ELISA. BDNF levels were assessed also in a control group, matched for sex and age.Results:The cohort was composed by 201 FM patients (172 F, 29 M), mean age 49.13. Females showed higher values of R-FIQ total score (p=0,0005) as well the specific items of the R-FIQ for pain (p=0,013), fatigue (p=0,014), memory problems (p=0,007), tenderness to touch (p<0,0001), balance problems (p<0,0001) and sensitivity to environmental stimuli (p=0,012) when compared with males (fig. 1). There was no difference in BDI-II between males and females, but notably male patients reported a significantly higher frequency of coexisting depressive disorder (p=0,038) (fig. 2). Serum BDNF levels were evaluated in 40 FM patients and 40 healthy controls (HC) (F:M 1:1). BDNF levels were significantly lower in FM patients compared with HC (p<0,0001). Among FM patients, BDNF levels were lower in males compared with females (p<0,0001) (fig.3). BDNF did not correlate with any clinical and clinimetric parameter. BDNF showed a good diagnostic performance (AUC=0,89, CI95%=0,82-0,9630, p<0,0001) (fig. 4). At a cut-off value <6,47 ng/dl, BDNF showed a specificity of 75% and a sensibility of 92,31%,(CI 95%=79,68-97.35) for FM identification (LR=3,692).Conclusion:FM clinical manifestations are strongly dependant from gender. While females present a more severe disease and a higher burden of symptoms, mood disorders tend to be a major characteristic of males with FM. Reduced BDNF serum levels have been reported as typical of depressive disorders. Our findings of lower BDNF levels in male FM patients compared to females support this hypothesis. BDNF have potential as biomarker of the disease and should be validated in larger cohorts.References:[1]Sarzi-Puttini et al. Nature Reviews 2020[2]Colucci-D’Amato et al. Int J Molecular Sciences 2020[3]Nugraha et al. Rheumatol Int 2012[4]Schmitt et al. Ann Med 2016[5]Melchior et al. Neuroscience 2016[6]Stefani et al. Neuroscience Letters 2012Disclosure of Interests:None declared


Author(s):  
Rahin Sh Hamad ◽  
Bushra H. Shnawa ◽  
Shereen J. Al-Ali

Colorectal cancer (CRC) is classified as one of the most prevalent cancer types worldwide, with high morbidity and mortality rates. Patients of CRC have been shown to express a detectable cytokine in serum which contributes to cancer pathogenesis. Therefore, the serum interleukin 10 (IL-10) level in CRC patients was investigated in this study. Patients' medical records with CRC admitted to the Rizgary and Nanakali hospitals, Erbil, Iraq was analyzed as the study group compared to the healthy volunteers' control group. Seventy-one serum samples were collected, thirty-one from diagnosed CRC patients and forty from healthy controls. The concentrations of IL-10 in the sera were assessed by enzyme-linked immunosorbent assay (ELISA). The present finding showed that IL-10 Was significantly elevated in CRC patients' sera compared to the control group, suggesting confirmation of its usefulness for detecting CRC patients' prognosis. A non-significant Pearson correlation was detected between IL-10 serum levels and the CRC group's age, gender, and body mass index. Herein is the first study on the evaluation of IL-10 levels in CRC patients in Kurdistan, Iraq.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Jirak ◽  
M Lichtenauer ◽  
B Wernly ◽  
V Paar ◽  
C Jung ◽  
...  

Abstract Background Soluble (s) ST-2 has been recently evaluated as a monitoring parameter in heart failure (HF). Besides being a marker for cardiac strain and hemodynamic stress, studies also found an influence of ST2 on the immune system, above all mediated through its Janus-Face ligand IL-33, an alarmin released under stress conditions or by cellular death. In contrast to sST2, the role of IL-33 in HF is yet unknown. Objective In this project, we aimed for an analysis of the ST2/IL33 pathway in patients with heart failure with reduced ejection fraction (HFrEF). Methods In total, 200 patients were included in the study: 59 with ischemic (ICM), 65 with dilated (DCM) cardiomyopathy (mean LVEF 38%), as well as 76 control patients without coronary artery disease or signs of heart failure. Serum samples were analyzed by use of ELISA after informed consent. Results sST2 showed a significant elevation in all HF patients (p<0.0001) compared to the control group. No significant differences in levels of sST2 were observed between ICM and DCM patients. In contrast to sST2, no differences between HF patients and control group were observed for IL-33. Furthermore, sST2 showed a significant correlation with CRP (p<0.001, r=0.28), NT-pro-BNP (p<0.0001, r=0.40) and an inverse correlation with ejection fraction (p<0.0001, r=−0.40). Additionally, sST2 showed a significant elevation in patients in NYHA stages I-II (p=0.030) and NYHA stages III-IV (p<0.01). Again, no significant correlations were observed between IL-33 and parameters mentioned above. Analysis of sST2 in heart failure Conclusions We observed a significant increase and correlation with disease severity of sST2 in chronic HFrEF patients of both ischemic and non-ischemic origin, but contrary to our expectations, no significant changes in serum levels of IL-33. Thus, a mechanism independent of ST2/IL33 axis could be responsible of sST2 secretion in HF. Further studies including acute decompensated patients could provide a better understanding of the IL-33 role in HF.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Vinod Umare ◽  
Vandana Pradhan ◽  
Milind Nadkar ◽  
Anjali Rajadhyaksha ◽  
Manisha Patwardhan ◽  
...  

Systemic lupus erythematosus (SLE) is an inflammatory rheumatic disease characterized by production of autoantibodies and organ damage. Elevated levels of cytokines have been reported in SLE patients. In this study we have investigated the effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β) on clinical manifestations in 145 Indian SLE patients. One hundred and forty-five healthy controls of the same ethnicity served as a control group. Clinical disease activity was scored according to SLEDAI score. Accordingly, 110 patients had active disease and 35 patients had inactive disease. Mean levels of IL-6, TNF-α, and IL-1βwere found to be significantly higher in SLE patients than healthy controls (P<0.001). Mean level of IL-6 for patients with active disease (70.45±68.32 pg/mL) was significantly higher (P=0.0430) than those of inactive disease patients (43.85±63.36 pg/mL). Mean level of TNF-αwas44.76±68.32 pg/mL for patients with active disease while it was25.97±22.03 pg/mL for those with inactive disease and this difference was statistically significant (P=0.0161). Similar results were obtained for IL-1β(P=0.0002). Correlation between IL-6, TNF-α, and IL-1βserum levels and SLEDAI score was observed (r=0.20,r=0.27, andr=0.38, resp.). This study supports the role of these proinflammatory cytokines as inflammatory mediators in active stage of disease.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5312-5312
Author(s):  
Eline Zijtregtop ◽  
Waichu Wong ◽  
Friederike Meyer- Wentrup ◽  
Martha Lopez-Yurda ◽  
Raoull Hoogendijk ◽  
...  

Abstract Background Pediatric classical Hodgkin lymphoma (cHL) is a clonal disorder in an inflammatory background, also known as the microenvironment. This microenvironment is of major importance for growth and survival of the malignant Hodgkin/Reed Sternberg (HRS) cells. HRS cells and the microenvironment communicate through chemo- and cytokines. Blood biomarkers result from this active crosstalk, and may be a surrogate for lymphoma viability (Steidl et al, JCC 2011). Blood biomarkers are important because they hold the promise to be easily available and cost-effective. One promising biomarker in adult patients with cHL is the "Thymus and Activation-Regulated Chemokine, TARC (Plattell et al, Haematologica 2012). Elevated TARC levels are also described in patients with atopic dermatitis (Hijnen et al, J All Clin Immunol 2004). In adult cHL patients about 85% of patients have significantly elevated levels of TARC in pre-treatment serum or plasma compared to healthy controls (Plattell et al). So far nothing is known about TARC in pediatric cHL patients. To define its value as a diagnostic marker in pediatric cHL patients, we compared TARC levels of pediatric cHL patients with control patients. This study was IRB-approved and registered under Dutch Trial registry number 6876. Methods After providing informed consent, plasma and serum samples were collected of newly diagnosed cHL patients before start of treatment. To define normal values of TARC in children, samples were collected from non-cHL randomly selected patients from the hematology, endocrinology and oncology outpatient clinic. Baseline characteristics including history of atopic dermatitis were collected. These control patients were divided in three age groups (0-9,10-14 and 15-18 years). TARC levels were measured by enzyme-linked immunosorbent assay (R&D systems, Human CCL17/TARC Quantikine ELISA Kit). TARC levels of the cHL patients were compared to the control group to obtain ROC curves and calculate the AUC, cross-validated sensitivity and specificity and accuracy of TARC as a diagnostic marker. We hypothesized that pediatric cHL patients had elevated pretreatment TARC levels in both serum and plasma. Analyses were done using SAS V9.4. Results Fourteen cHL patients were included with a median age of 14 (range 11-17) years. Ten (71.4%) were female. Eighty patients were included in the control group with a median age of 12 (range 10 months-18) years. Twenty-nine patients (36.3%) were included in age group 0-9, 25 (31.2%) in age group 10-14 and 26 (32.5%) in age group 15-18. Thirty-nine (48.8%) were female. Patients of the control group had a median TARC value of 71 (range 18-762) pg/ml for plasma and 318 (range 27-1300) pg/ml for serum. TARC plasma and serum levels decreased with age (Spearman correlation -0.26, 2-tailed p=0.0204), but there were no statistically significant pairwise comparisons found between the pre-specified age groups. In the eight control patients (10%) with atopic dermatitis no significantly higher plasma and serum levels were found (plasma median with eczema 97 versus 70 pg/ml without eczema (p=0.71) and serum median with eczema 643 versus 317 pg/ml (p=0.71)). Plasma was collected in 14 cHL patients, and all had elevated TARC levels, with a median plasma level of 18449 (range 1635-55821) pg/mL. Serum samples were collected in 8/14 cHL patients and all had elevated serum TARC levels. Median serum level: 46703 (range 12817-149739) pg/ml. The plasma TARC levels of cHL patients were significantly higher than those of the control group patients (p<0.001). With a cut-off of level of of 898.70 pg/ml, we obtained 100% (95% CI 73% - 100%) sensitivity and 100% (95% 94% - 100%) specificity. Serum TARC levels also were significantly higher than those of the control group patients (p<0.001), with a cut-off level of 10283.57 pg/ml, sensitivity and specificity will be 100% (95% CI 60% - 100% for sensitivity and 95% CI 94% - 100% for specificity). Conclusion All classical cHL patients had significantly higher TARC levels compared to the 80 control patients. Despite the small sample size of cHL patients, TARC was found to be a sensitive and specific diagnostic marker for pediatric cHL in both plasma and serum. Further research with a bigger sample of cHL patients is necessary to improve the accuracy of the sensitivity, as well as to investigate whether TARC is also a valuable marker for disease response during treatment in pediatric patients with cHL. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Author(s):  
Belén G Sánchez ◽  
Jose M Gasalla ◽  
Manuel Sanchez-Chapado ◽  
Alicia Bort ◽  
Ines Diaz-Laviada

Abstract BackgroundThis study has been undertaken with the urgent need for exploring reliable biomarkers for early infection of SARS-CoV-2. We performed a retrospective study analyzing the serum levels of the cardiovascular biomarkers N-terminal pro-B natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), Ischemia Modified Albumin (IMA) and pregnancy associated plasma protein A (PAPP-A), in 84 patients with COVID-19. MethodsPatients were divided in three groups according to their RT-qPCR and IgG values in acute infection (n=35), early infection (n=25) or control subjects (n=24). Levels of biomarkers were analyzed in patient’s serum samples by commercially available ELISA kits.ResultsMultivariate analysis and Receiver Operating Characteristic (ROC) curve showed that IMA and PAPP-A, had an excellent discrimination value for the early stage of COVID-19. Serum levels of IMA in early SARS-CoV-2 infected patients were significantly higher than in the control group with an area under the ROC curve (AUC) value of 0.94 (95% confidence interval (CI): 0.881- 0.999). Likewise, the serum level of PAPP-A was significantly higher in patients with early infection than in controls [AUC = 0.801 (95% CI: 0.673–0.929)]. The combined use of IMA and PAPP-A enhanced the sensitivity for total SARS-CoV-2 infected patients to 93%. ConclusionsThese results suggest that the levels of PAPP-A and IMA might be used as efficient biomarkers for the early stage of COVID-19 with high sensitivity and specificity. Importantly, when monitoring pregnancy and cardiovascular diseases by PAPP-A or IMA levels, an infection by SARS-CoV-2 should be discarded for proper interpretation of the results.


2020 ◽  
Author(s):  
RongBin Pan ◽  
Kok Suen Cheng ◽  
Yanjuan Chen ◽  
Xingwang Zhu ◽  
Wenting Zhao ◽  
...  

Abstract BackgroundGancao Nurish Yin (GCNY) decoction has been applied to clinical rheumatoid arthritis (RA) patients and it had shown effectiveness not only in disease activity controlling but also on improving patients’ physical status. However, its mechanism of function has not been investigated. Metabolic perturbations have been associated with RA and targeting the metabolic profile is one of the ways to manage the disease. The aim of this study was to observe the effect of GCNY on metabolic changes of human tumor necrosis factor alpha (hTNF-α) transgenic arthritic mouse model. MethodshTNF-α transgenic arthritic model mice were divided into control and GCNY groups with 6 mice in each group. After 8 weeks of treatment, liver tissues of mice in both groups were obtained for liquid chromatography-mass spectrometry (LC/MS) analysis. Significantly regulated metabolites by GCNY treatment were first identified, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and network analysis.ResultsOf the 126 metabolites detected in the liver, 17 metabolites were with significantly altered between control group mice and mice treated with GCNY. Specifically, thiamine, gamma-L-Glutamyl-L-valine, pantothenic acid, pyridoxal (Vitamin B6), succinic acid, uridine 5'-diphospho-glucuronic acid (UDP-D-Glucuronate), uridine, allantoic acid, N-Acetyl-D-glucosamine, nicotinamide ribotide and N2,N2-Dimethylguanosine were down-regulated by GCNY treatment whereas isobutyrylglycine, N-Acetylcadaverine, N-Carbamoyl-L-aspartic acid, L-Anserine, creatinine and cis-4-Hydroxy-D-proline were up-regulated. Six metabolic pathways were significantly altered including the alanine, aspartate and glutamate metabolism, pyrimidine metabolism, thiamine metabolism, amino sugar and nucleotide sugar metabolism, pantothenate and CoA biosynthesis and citrate cycle (TCA cycle). Integrative metabolic network analysis suggested the possibility of GCNY having both positive and negative effects on RA through the suppression of angiogenesis and promotion of leukocyte extravasation into the synovium, respectively. ConclusionsGCNY can induce a change in the metabolic profiles of hTNF-α transgenic arthritic mouse model. Further optimization of this decoction may lead to better therapeutic effects on RA patients.


2020 ◽  
Author(s):  
Zhixiong Li ◽  
Yaqiu Lin ◽  
Mao Yuan ◽  
Xiaosong Jiang ◽  
Chaowu Yang ◽  
...  

Abstract Background Myogenic miRNAs (myomiRs) which dramatically increased during myogenesis have been shown to play critical roles in many aspects of muscle function. As a myomiR, miR-499-5p, has been identified to be highly expressed in cardiac and skeletal muscle. The study focused on the effects of miR-499-5p on muscle metabolism in broiler chicken. Methods In the current study, we assigned 16 broiler chicks to control group and treatment group and then monitored the effects using metabolomics. Chicks were fed basal diets without or with miR-499-5p delivery. Muscle samples were collected and analyzed by ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). Results Our findings revealed that miR-499-5p injection altered the concentrations of a variety of metabolites in the muscle. Thereinto, a total of 46 metabolites were identified at higher (P < 0.05) concentrations and 30 metabolites were identified at lower (P < 0.05) concentrations in the treatment group as compared with the control group. These metabolites were primarily involved with the regulation of lipid and carbohydrate metabolism. Further metabolic pathway analysis revealed that fructose and mannose metabolism, galactose metabolism, inositol phosphate metabolism and terpenoid backbone biosynthesis were the most important and critical pathway which may partially interpret the effects of miR-499-5p. Conclusions To our knowledge, this research is the first report of metabolic signatures and related metabolic pathways in the skeletal muscle for miR-499-5p injection and provide new insight into the effect of miRNA on growth performance.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jun Ma ◽  
Yanting Zhang ◽  
Zhuowei Huang ◽  
Xuebing Liu ◽  
Luxian Lv ◽  
...  

Background: A growing body of evidence shows that immune system disorders are one of the important etiological factors of schizophrenia. Inflammatory cytokines play a very critical role in the pathogenesis and treatment of schizophrenia. However, in the actual clinical practice, there is still a lack of confirmed biological indicators that can be used to evaluate the therapeutic effect of antipsychotics.Methods: In this study, 82 male patients with first-episode schizophrenia and 30 healthy controls were included. The Positive and Negative Syndrome Scale (PANSS) scores were evaluated, and the serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 17 (IL-17), and transforming growth factor β1 (TGF-β1) were detected, both at baseline and 4 weeks later. The patients were divided into two groups, the effective group and the ineffective group, according to the reduction rate of PANSS.Results: In the case group, the levels of hs-CRP were significantly elevated (p = 0.00), whereas IL-1β, IL-6, and IL-17 were significantly reduced as compared to the baseline (p = 0.01, 0.02, and 0.00, respectively). Importantly, the baseline levels of the five inflammatory factors were significantly higher in the case group as compared to the control group (p = 0.00, 0.00, 0.00, 0.00, and 0.00, respectively). Post-treatment, the serum levels for IL-1β, IL-6, and IL-17 were significantly higher in the effective group than in the ineffective group (p = 0.00, 0.00, and 0.01, respectively). For every increase in the amount of IL-1β, the risk of ineffectiveness increased by 7% (OR = 0.93 [0.86–1.00]; p = 0.04), whereas for every increase in the amount of IL-17, the risk of ineffectiveness increased by 5% (OR = 0.95 [0.90–0.99]; p = 0.03).Conclusion: The results of the study showed that the levels of inflammatory factors in patients with different therapeutic effects were different, and the changes in the amounts of IL-1β and IL-17 acted as predictors of poor efficacy.


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