Association of dietary saturated fatty acid intake with depression: mediating effects of the dietary inflammation index.

Background: Diet and dietary inflammation play an important role in depression. The aim of this study was to assess the association of SFAs with depression risk and the mediating role of DII. Method: Among 22, 478 U.S. adults (≥ 20, years old) according to the National Health and Nutrition Examination Survey (NHANES), univariate logistic regression, and multivariate logistic regression were used to evaluate the association between dietary intake of SFAs and the risk of depression. Dietary inflammation levels were evaluated using the DII. Mediation analysis was used to investigate the risk of DII and depression. The nonlinear relationship between SFAs and depression was assessed using restricted cubic spline (RCS). Results: There was a significant difference in SFA 6.0 dietary intake between depression and non-depression individuals. After adjusting for potential confounders, multifactorial logistic regression results showed that SFA 8.0 (Q3 1.58 (1.09, 2.30), p-value = 0.017; Q4 1.55 (1.00, 2.42), p-value = 0.050) may increase the prevalence factor for depression, SFA 14.0 (Q3 0.67 (0.47, 0.94), p-value = 0.020) may decrease the risk of depression. There were sex and age differences in the effects of different subtypes of SFAs on depression. Dietary intake of SFA 12.0 content showed a nonlinear relationship with the risk of depression (p-value = 0.005). Furthermore, DII was recognized as a mediator of the association between SFAs and the risk of depression. Conclusion: The findings suggest that dietary intake of SFAs is associated with the risk of depression in relation to the chain length of SFAs, and this may be due to the mediating effect of DII.

[Expression and Clinical Significance of Serum sFas/sFasL in Patients with Secondary Hemophagocytic Lymphohistiocytosis].

OBJECTIVE: To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). METHODS: From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve. RESULTS: Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001). CONCLUSION: Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.

Serum Fas levels during first week of sepsis are associated with severity and mortality.

INTRODUCTION: The aim of our study was to explore whether there is an association of serum sFas (cell death apoptosis receptor) concentrations during the first week of sepsis with sepsis severity and sepsis mortality. METHODS: In this observational study, septic patients were recruited. Serum sFas concentrations were determined on days 1, 4, and 8 of sepsis diagnosis. Thirty-day mortality was the outcome variable. RESULTS: Surviving patients (n = 181) compared to non-survivors (n = 101) presented lower serum sFas levels on day 1 (p < 0.001), day 4 (p < 0.001) and day 8 (p < 0.001), and lower SOFA on day 1 (p < 0.001), day 4 (p < 0.001) and day 8 (p < 0.001). Logistic regression analyses showed associations between 30-day mortality and serum sFas levels controlling for SOFA on day 1 (OR = 1.005; 95% CI = 1.003-1.007; p < 0.001), day 4 (OR = 1.044; 95% CI = 1.029-1.060; p < 0.001) and day 8 (OR = 1.012; 95% CI = 1.002-1.022; p = 0.02). CONCLUSIONS: The association of serum sFas concentrations during the first week of sepsis with sepsis severity and sepsis mortality were our new findings.

Comprehensive assessment of markers of apoptosis and cell proliferation during progression of atherosclerosis after surgery in patients with peripheral arterial disease.

Background: Determination of predictors that can affect development of atherosclerosis progression in the postoperative period is an urgent problem in vascular surgery. Objectives: Integrated assessment of markers of apoptosis and cell proliferation in atherosclerotic lesions and their progression after surgery in patients with peripheral arterial diseases. Methods: The investigation included 30 patients with stage IIB-III peripheral arterial disease. All patients have undergone open surgical interventions on the arteries of the aorto-iliac and femoral-popliteal segments. During these interventions, intraoperative specimens were obtained from the vascular wall with atherosclerotic lesions. The following values were evaluated: VEGF А165, PDGF BB, and sFas. Samples of normal vascular wall were obtained from post-mortem donors and used as a control group. Results: The levels of Bax and p53 were increased (p<0.001) in samples from arterial wall with atherosclerotic plaque, while sFas values were reduced (p<0.001), compared to their levels in control samples. Values of PDGF BB and VEGF A165 were 1.9 and 1.7 times higher in atherosclerotic lesion samples (p=0.001), in comparison with the control group. The levels of p53 and Bax were increased against a background of reduced sFas levels in samples with progression of atherosclerosis compared to their baseline values in samples with atherosclerotic plaque (p<0.05). Conclusions: Initially increased values of the Bax marker against a background of reduced sFas values in vascular wall samples from patients with peripheral arterial disease is associated with risk of atherosclerosis progression in the postoperative period.

Contexto: A determinação de preditores que possam influenciar o desenvolvimento da progressão da aterosclerose no período pós-operatório é um problema urgente em cirurgia vascular. Objetivos: Realizar uma avaliação integral de marcadores de apoptose e proliferação celular nas lesões ateroscleróticas e sua progressão após cirurgia em pacientes com doenças arteriais periféricas. Métodos: A investigação incluiu 30 pacientes com doenças arteriais periféricas de estágio IIB-III. Todos os pacientes foram submetidos a intervenções operatórias abertas nas artérias dos segmentos aorto-ilíaco e fêmoro-poplíteo. Durante a intervenção, foi obtido material intraoperatório da parede vascular com lesões ateroscleróticas. Foram avaliados os seguintes valores: VEGF A165, PDGF BB e sFas. Como grupo controle, amostras de parede vascular normal foram obtidas de doadores post-mortem. Resultados: O nível de Bax e p53 (p < 0,001) em amostras de parede arterial com placa aterosclerótica estava elevado em meio a valores reduzidos de sFas (p < 0,001) em comparação ao grupo controle. Os valores de PDGF BB e VEGF A165 foram 1,9 e 1,7 vezes maiores, respectivamente, nas amostras com lesão aterosclerótica (p = 0,001) do que no grupo controle. O nível de Bax e p53 e Bax estava elevado no contexto de nível reduzido de sFas em amostras com progressão da aterosclerose em comparação com seus valores basais em amostras com placa aterosclerótica (p < 0,05). Conclusões: Níveis inicialmente elevados do marcador Bax no contexto de valores reduzidos de sFas na parede vascular em pacientes com doença arterial periférica estão associados a risco de progressão da aterosclerose no período pós-operatório.

Expression and Clinical Significance of Serum sFas/sFasL in Patients with Secondary Hemophagocytic Lymphohistiocytosis / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH).@*METHODS@#From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve.@*RESULTS@#Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001).@*CONCLUSION@#Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.

Comprehensive assessment of markers of apoptosis and cell proliferation during progression of atherosclerosis after surgery in patients with peripheral arterial disease / Avaliação integral de marcadores de apoptose e proliferação celular na progressão da aterosclerose após cirurgia em pacientes com doença arterial periférica

Abstract Background Determination of predictors that can affect development of atherosclerosis progression in the postoperative period is an urgent problem in vascular surgery. Objectives Integrated assessment of markers of apoptosis and cell proliferation in atherosclerotic lesions and their progression after surgery in patients with peripheral arterial diseases. Methods The investigation included 30 patients with stage IIB-III peripheral arterial disease. All patients have undergone open surgical interventions on the arteries of the aorto-iliac and femoral-popliteal segments. During these interventions, intraoperative specimens were obtained from the vascular wall with atherosclerotic lesions. The following values were evaluated: VEGF А165, PDGF BB, and sFas. Samples of normal vascular wall were obtained from post-mortem donors and used as a control group. Results The levels of Bax and p53 were increased (p<0.001) in samples from arterial wall with atherosclerotic plaque, while sFas values were reduced (p<0.001), compared to their levels in control samples. Values of PDGF BB and VEGF A165 were 1.9 and 1.7 times higher in atherosclerotic lesion samples (p=0.001), in comparison with the control group. The levels of p53 and Bax were increased against a background of reduced sFas levels in samples with progression of atherosclerosis compared to their baseline values in samples with atherosclerotic plaque (p<0.05). Conclusions Initially increased values of the Bax marker against a background of reduced sFas values in vascular wall samples from patients with peripheral arterial disease is associated with risk of atherosclerosis progression in the postoperative period.

Resumo Contexto A determinação de preditores que possam influenciar o desenvolvimento da progressão da aterosclerose no período pós-operatório é um problema urgente em cirurgia vascular. Objetivos Realizar uma avaliação integral de marcadores de apoptose e proliferação celular nas lesões ateroscleróticas e sua progressão após cirurgia em pacientes com doenças arteriais periféricas. Métodos A investigação incluiu 30 pacientes com doenças arteriais periféricas de estágio IIB-III. Todos os pacientes foram submetidos a intervenções operatórias abertas nas artérias dos segmentos aorto-ilíaco e fêmoro-poplíteo. Durante a intervenção, foi obtido material intraoperatório da parede vascular com lesões ateroscleróticas. Foram avaliados os seguintes valores: VEGF A165, PDGF BB e sFas. Como grupo controle, amostras de parede vascular normal foram obtidas de doadores post-mortem. Resultados O nível de Bax e p53 (p < 0,001) em amostras de parede arterial com placa aterosclerótica estava elevado em meio a valores reduzidos de sFas (p < 0,001) em comparação ao grupo controle. Os valores de PDGF BB e VEGF A165 foram 1,9 e 1,7 vezes maiores, respectivamente, nas amostras com lesão aterosclerótica (p = 0,001) do que no grupo controle. O nível de Bax e p53 e Bax estava elevado no contexto de nível reduzido de sFas em amostras com progressão da aterosclerose em comparação com seus valores basais em amostras com placa aterosclerótica (p < 0,05). Conclusões Níveis inicialmente elevados do marcador Bax no contexto de valores reduzidos de sFas na parede vascular em pacientes com doença arterial periférica estão associados a risco de progressão da aterosclerose no período pós-operatório.

Physical activity and individual plasma phospholipid SFAs in pregnancy: a longitudinal study in a multiracial/multiethnic cohort in the United States.

BACKGROUND: Circulating individual SFAs in pregnant females are critical for maternal and fetal health. However, research on identifying their modifiable factors is limited. OBJECTIVES: We aimed to examine the associations of total physical activity (PA) and types of PA with circulating individual SFAs during pregnancy in a multiracial/multiethnic cohort of pregnant females in the United States. METHODS: The study included participants in a nested case-control study (n = 321) from the Eunice Kennedy Shriver NICHD Fetal Growth Studies-Singleton Cohort. Sampling weights were applied, so the results represented the entire Fetal Growth Cohort. Plasma phospholipid SFAs were measured at 4 visits [10-14 (visit 1), 15-26 (visit 2), 23-31 (visit 3), and 33-39 (visit 4) weeks of gestation] throughout pregnancy. PA of the previous year at visit 1 and since the previous visit at the subsequent visits was assessed using the validated Pregnancy PA Questionnaire. Time-specific and longitudinal associations were examined using multivariable linear and generalized estimating equation models. RESULTS: Total PA (metabolic equivalent of task-h/wk) was positively associated with circulating heptadecanoic acid (17:0) at visit 1 (ß × 103: 0.07; 95% CI: 0.02, 0.11) and pentadecanoic acid (15:0) at visit 3 (ß × 103: 0.09; 95% CI: 0.03, 0.14) independent of sociodemographic, reproductive, pregnancy, and dietary factors. Across the 4 visits, the positive associations with total PA were consistent for pentadecanoic acid (ß × 103: 0.06; 95% CI: 0.02, 0.10) and heptadecanoic acid (ß × 103: 0.10; 95% CI: 0.06, 0.14). Out of the 4 PA types (i.e., sports/exercise, household/caregiving, transportation, and occupational PA) considered, the magnitude of positive associations was the largest for sports/exercise PA. CONCLUSIONS: Our findings suggest that maternal PA is positively associated with circulating pentadecanoic and heptadecanoic acids. The findings warrant confirmation by future studies.This trial was registered at clinicaltrials.gov as NCT00912132.

Fermented Mangosteen (Garcinia mangostana L.) Supplementation in the Prevention of HPV-Induced Cervical Cancer: From Mechanisms to Clinical Outcomes.

In the observational clinical study, we identified the oxidative markers of HPV-associated cervical carcinogenesis and the local/circulating ligands of TNF-alpha-induced apoptosis. Cervical biopsies of 196 females infected with low-cancer-risk HPV10/13 or high-cancer-risk HPV16/18 (healthy, pre-cancerous CIN I and CIN II, and CIN III carcinoma) were analysed for OH radical scavenging, catalase, GSH-peroxidase, myeloperoxidase (MPO), nitrate/nitrite, nitrotyrosine, and isoprostane. Ligands of TNF-alpha-dependent apoptosis (TNF-alpha, TRAIL, IL-2, and sFAS) were determined in cervical fluid, biopsies, and serum. Cervical MPO was highly enhanced, while nitrotyrosine decreased in CIN III. Local/circulating TRAIL was remarkably decreased, and higher-than-control serum TNF-alpha and IL-2 levels were found in the CIN I and CIN III groups. Then, 250 females infected with HPV16/18 (healthy and with CIN I and CIN II) were recruited into a placebo-controlled clinical study of supplementation with fermented mangosteen (FM, 28g/day, daily) for three months. Post-trial colposcopy revealed normal patterns in 100% of the FM group versus 62% of the placebo group. Inflammatory cells in cervical fluid were found in 21% of the FM group versus 40% of the placebo group. Locally, FM drastically diminished MPO and NO2/NO3, while it remarkably increased TRAIL. Additionally, FM supplementation normalised serum TRAIL, TNF-alpha, and IL-2.

New evidence for dietary fatty acids in the neutrophil traffic between the bone marrow and the peripheral blood.

Chronic administration of a high-fat diet in mice has been established to influence the generation and trafficking of immune cells such as neutrophils in the bone marrow, the dysregulation of which may contribute to a wide range of diseases. However, no studies have tested the hypothesis that a short-term, high-fat diet could early modulate the neutrophil release from bone marrow at fasting and at postprandial in response to a high-fat meal challenge, and that the predominant type of fatty acids in dietary fats could play a role in both context conditions. Based on these premises, we aimed to establish the effects of different fats [butter, enriched in saturated fatty acids (SFAs), olive oil, enriched in monounsaturated fatty acids (MUFAs), and olive oil supplemented with eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids] on neutrophil navigation from bone marrow to blood in mice. The analysis of cellular models for mechanistic understanding and of postprandial blood samples from healthy volunteers for translational purposes was assessed. The results revealed a powerful effect of dietary SFAs in promotion the neutrophil traffic from bone marrow to blood via the CXCL2-CXCR2 axis. Dietary SFAs, but not MUFAs or EPA and DHA, were also associated with increased neutrophil apoptosis and bone marrow inflammation. Similar dietary fatty-acid-induced postprandial neutrophilia was observed in otherwise healthy humans. Therefore, dietary MUFAs might preserve bone marrow health and proper migration of bone marrow neutrophils early in the course of high-fat diets even after the intake of high-fat meals.

Ionization of semi-fluorinated n-alkanes in controlled atmosphere using flexible micro-tube plasma (FµTP) ionization source with square- and sine-wave voltage.

Non-thermal plasma-based ionization sources have been widely used and shown excellent soft ionization performance in mass spectrometry. Despite their extensive application, the ionization mechanisms of these sources are of great interest for further exploring their full potential. A controlled atmosphere can provide a clean and controllable ionization environment and is beneficial for studying the ionization mechanism. The plasma source itself also has a significant impact on the ionization mechanism of the analyte, and the voltage waveform is one of the key parameters for controlling the plasma source. In this paper, a miniature flexible micro-tube plasma (FµTP) ionization source was sustained using both square and sine-wave voltage. The ionization processes of typical semi-fluorinated n-alkanes (SFAs) were investigated in the controlled atmosphere filled with 80% N2 and 20% O2. The main mass peaks using both square and sine-wave voltages are found to be [M-mH]+ and [M-mH+nO]+ (m = 1, 3; n = 0, 1, 2). However, for the square-wave voltage, the [M-H+O]+ species are the most abundant while [M-H]+ species are dominant for the sine-wave voltage, showing that the plasma generated with sine-wave voltage is somewhat "softer" than the one with square-wave voltage for SFAs. With the assistance of optical spectroscopy, the plasma developments in one discharge cycle for both voltage waveforms were obtained. Only one discharge can be found in each half cycle for square-wave voltage while several for the sine-wave voltage. These would be responsible for the different ionization behaviors in these two cases. This work provides more insight into the ionization mechanism of SFAs and more understanding of plasma-based soft ionization. In addition, the analytical performance was evaluated to be comparable when using these two voltage generators with a big difference in cost, which will benefit the instrumental development.

Celecoxib as an adjuvant to chemotherapy for patients with metastatic colorectal cancer: A randomized controlled clinical study.

OBJECTIVES: To investigate the anti-tumor activity and tolerability of celecoxib as an adjuvant therapy for patients with metastatic colorectal cancer (CRC). METHODS: In this randomized controlled study, 54 patients with metastatic CRC were randomized into 2 groups; the control group (n=28) which received 6 cycles of folinic acid, fluorouracil and irinotecan (FOLFIRI) regimen (5-flourouracil, leucovorin, irinotecan), and the celecoxib group (n=26) which received 6 cycles of FOLFIRI regimen plus celecoxib 200 mg twice daily. The study duration was 3 months. Patients were assessed at baseline and at the end of intervention through the Response Evaluation Criteria in Solid Tumors objective response rate (ORR) and through evaluating the serum concentrations of vascular endothelial growth factor (VEGF), soluble factor-related apoptosis (sFAS), sFAS ligand (sFASL), and epithelial neutrophil-activating peptide -78 (ENA-78/CXCL5). Common Terminology Criteria for Adverse Events version 6.0 was used for evaluating drug-related toxicity. RESULTS: After intervention, celecoxib/FOLFIRI arm showed significant elevation in ORR as compared to FOLFIRI arm (p=0.001). As compared to FOLFIRI arm, celecoxib/FOLFIRI arm showed significantly lower VEGF (p<0.001), CXCL5 (p<0.001), and sFASL (p<0.001) serum levels and significantly higher sFAS serum level and sFAS/FASL ratio (p<0.001). Furthermore, celecoxib/FOLFIRI arm showed significantly higher progression-free survival and one-year overall survival when compared to FOLFIRI arm. CONCLUSION: Celecoxib plus chemotherapy may represent an effective and safe synergetic protocol for patients with metastatic CRC.Clinicaltrial.gov ID:NCT03645187.

Plasma Levels of sFas-sFasL and FASL Gene Expression Are Associated with Tuberculosis.

Apoptosis of macrophages infected by Mycobacterium tuberculosis via Fas-FasL is an important immune mechanism against infection. This study investigated the association of tuberculosis (TB) with the presence of the polymorphisms FAS -670A/G and FASL -124A/G, the levels of sFas and sFasL, and the gene expression of FASL and cytokines. Samples of 200 individuals diagnosed with TB and 200 healthy controls were evaluated. Real-time PCR (genotyping and gene expression) and ELISA (dosages of sFas, sFasL, IFN-γ, and IL-10) tests were performed. There was no association of FAS -670A/G and FASL -124A/G polymorphisms with TB. The TB group exhibited high plasma levels of sFas and reduced plasma levels of sFasL (p < 0.05). The correlation analysis between these markers revealed a positive correlation between the levels of sFas and sFasL, sFasL and FASL expression, and between sFas and FASL expression (p < 0.05). In the TB group, there was a positive correlation between FASL expression and IFN-γ levels and higher levels of IL-10 compared to IFN-γ (p < 0.05). High levels of sFas and reduced levels of sFasL and FASL expression may contribute to the inhibition of apoptosis in infected cells and represent a possible bacterial resistance resource to maintain the infection.

Blood soluble Fas concentrations and ischemic stroke patient mortality.

BACKGROUND: Fas is a major receptor for cell death by apoptosis. Higher blood concentrations of soluble Fas (sFas) have been reported in patients with ischemic stroke compared to control subjects. The aim of this study was to explore the existence or not of an association between blood sFas concentrations and mortality in patients with ischemic stroke. METHODS: This study included patients admitted to Intensive Care Units with severe and malignant middle cerebral artery infarction (MCAI), defined as acute infarction, in more than 50% of this territory on computed tomography and less than 9 points on the Glasgow Coma Scale (GCS). Serum sFas levels were determined at the time of diagnosis of MMCAI. RESULTS: Non-surviving severe MMCAI patients (n = 27) showed lower platelet count (p = 0.004), higher serum sFas (p < 0.001), and lower GCS (p = 0.001) compared to surviving patients (n = 27). Multiple logistic regression found an association of serum sFas levels and mortality at 30 days (OR = 1.015; 95% CI = 1.002-1.027; p = 0.02) after control for CGS and platelet count. CONCLUSIONS: The main novelty of our study was the existence of an association between high blood sFas concentrations and mortality in patients with ischemic stroke.

Association of serum soluble Fas concentrations and mortality of septic patients / Asociación de concentraciones séricas de soluble Fas y mortalidad de pacientes sépticos

Introduction: Scarce data on Fas, one of the main receptors that activates the apoptosis extrinsic pathway, in septic patients exists. Higher blood soluble Fas (sFas) concentrations in non-survivor septic patients compared with survivors have been found in small studies; however, the association of blood sFas concentrations with mortality controlling for sepsis severity has not been stablished due to this small sample size in those studies. Thus, our main objective study was to determine whether an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists. Methods: We included septic patients in this observational and prospective study carried out in three Spanish Intensive Care Units. We obtained serum samples at sepsis diagnosis sepsis for sFas levels determination. Results: Thirty-day non-surviving patients (n=85) compared to surviving patients (n=151) had higher serum sFas levels (p<0.001). We found in multiple logistic regression analysis an association of serum sFas levels with mortality controlling for age and SOFA (OR=1.004; 95% CI=1.002–1.006; p<0.001), and for age and APACHE-II (OR=1.004; 95% CI=1.002–1.006; p<0.001). Serum sFas levels showed and area under the curve for mortality prediction of 71% (95% CI=65–71%; p<0.001). Kaplan–Meier analysis showed higher mortality rate in patients with serum sFas levels>83.5ng/mL (Hazard ratio=3.2; 95% CI=2.1–5.0; p<0.001). Conclusions: That an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists was our main new finding study.(AU)

Introducción: Existen pocos datos sobre Fas, uno de los principales receptores que activan la vía extrínseca de la apoptosis, en pacientes septicos. En estudios de pequeño tamaño muestral se han encontrado altas concentraciones sanguíneas de soluble Fas (sFas) en pacientes sépticos fallecidos en comparación con supervivientes; sin embargo, no ha sido establecida la asociación de concentraciones sanguíneas de sFas con mortalidad controlando por la gravedad de la sepsis. Por lo tanto, el principal objetivo de nuestro estudio fue determinar si existe una asociación entre concentraciones sanguíneas de sFas y la mortalidad en sepsis controlando por la gravedad. Métodos: Incluímos pacientes sépticos en este estudio observacional y prospectivo realizado en tres Unidades de Cuidados Intensivos españolas. Obtuvimos muestras de suero en el momento del diagnóstico de la sepsis para la determinación de concentraciones de sFas. Resultados: Los pacientes fallecidos durante los primeros treinta días (n=85) comparados con los supervivientes (n=151) tuvieron mayores concentraciones séricas de sFas (p<0,001). Se encontró una asociación de concentraciones séricas de sFas con mortalidad controlando por edad y SOFA (OR=1,004; 95% IC=1,002-1,006; p < 0,001), y por edad y APACHE-II (OR=1,004; 95% IC=1,002-1,006; p < 0,001). Las concentraciones séricas de sFas mostraron un área bajo la curva para la predicción de mortalidad del 71% (IC 95%=65%-71%; p < 0,001). El análisis Kaplan-Meier mostró una mayor mortalidad en los pacientes con concentraciones séricas de sFas > 83,5 ng/mL (Hazard ratio=3,2; 95% IC=2,1-5,0; p < 0,001). Conclusiones: La asociación entre concentraciones sanguíneas de sFas y la mortalidad en sepsis controlando por la gravedad fue el principal nuevo hallazgo de nuestro estudio.(AU)

Association of serum soluble Fas concentrations and mortality of septic patients.

INTRODUCTION: Scarce data on Fas, one of the main receptors that activates the apoptosis extrinsic pathway, in septic patients exists. Higher blood soluble Fas (sFas) concentrations in non-survivor septic patients compared with survivors have been found in small studies; however, the association of blood sFas concentrations with mortality controlling for sepsis severity has not been stablished due to this small sample size in those studies. Thus, our main objective study was to determine whether an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists. METHODS: We included septic patients in this observational and prospective study carried out in three Spanish Intensive Care Units. We obtained serum samples at sepsis diagnosis sepsis for sFas levels determination. RESULTS: Thirty-day non-surviving patients (n=85) compared to surviving patients (n=151) had higher serum sFas levels (p<0.001). We found in multiple logistic regression analysis an association of serum sFas levels with mortality controlling for age and SOFA (OR=1.004; 95% CI=1.002-1.006; p<0.001), and for age and APACHE-II (OR=1.004; 95% CI=1.002-1.006; p<0.001). Serum sFas levels showed and area under the curve for mortality prediction of 71% (95% CI=65-71%; p<0.001). Kaplan-Meier analysis showed higher mortality rate in patients with serum sFas levels>83.5ng/mL (Hazard ratio=3.2; 95% CI=2.1-5.0; p<0.001). CONCLUSIONS: That an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists was our main new finding study.

Appetite Regulation of TLR4-Induced Inflammatory Signaling.

Appetite is the basis for obtaining food and maintaining normal metabolism. Toll-like receptor 4 (TLR4) is an important receptor expressed in the brain that induces inflammatory signaling after activation. Inflammation is considered to affect the homeostatic and non-homeostatic systems of appetite, which are dominated by hypothalamic and mesolimbic dopamine signaling. Although the pathological features of many types of inflammation are known, their physiological functions in appetite are largely unknown. This review mainly addresses several key issues, including the structures of the homeostatic and non-homeostatic systems. In addition, the mechanism by which TLR4-induced inflammatory signaling contributes to these two systems to regulate appetite is also discussed. This review will provide potential opportunities to develop new therapeutic interventions that control appetite under inflammatory conditions.

Blood concentrations of proapoptotic sFas and antiapoptotic Bcl2 and COVID-19 patient mortality.

Background: There are no data on circulating concentrations of sFas (proapoptotic protein of extrinsic pathway) and Bcl2 (antiapoptotic protein of intrinsic pathway) in COVID-19 patients. Thus, our objective study was to determine whether an association exists between serum concentrations of sFas and Bcl2 and COVID-19 patient mortality.Methods: This observational and prospective study of COVID-19 patients was performed in eight Intensive Care Units (ICU) from Canary Islands (Spain). Serum levels of sFas and Bcl2 at ICU admission were determined. Mortality at 30 days was the end-point study.Results: Surviving patients (n = 42) compared to non-surviving (n = 11) had lower APACHE-II (p < 0.001), lower SOFA (p = 0.004), lower serum sFas levels (p = 0.001) and higher serum Bcl2 levels (p < 0.001). Logistic regression showed an association between high serum sFas levels and mortality after controlling for APACHE-II (OR = 1.004; 95% CI = 1.101-1.007; p = 0.01) or SOFA (OR = 1.003; 95% CI = 1.101-1.106; p = 0.004), and between low serum Bcl2 levels and mortality after controlling for APACHE-II (OR = 0.927; 95% CI = 0.873-0.984; p = 0.01) or SOFA (OR = 0.949; 95% CI = 0.913-0.987; p = 0.01).Conclusions: Thus, to the best of our knowledge, this is the first study reporting blood levels of sFas and Bcl2 in COVID-19 patients and its association with mortality.

Serum Levels of Soluble Fas and Fas Ligand in Iranian Women with Pre-eclampsia.

BACKGROUND: The precise responsible mechanism of pre-eclampsia remains controversial however, recent data suggest a main role of the abnormal activation of the adaptive immune system and Apoptosis. In this study, we have measured serum levels of Fas/Fasl as two important members of extrinsic apoptotic pathway in patient with pre-eclampsia. METHODS: 207 participants including 99 pre-eclampsia patients and 108 age and sex-matched normal pregnant women were involved in the case-control study. Plasma sample from each participant was collected and stored at -20 °C until batch processing.Serum levels of Fas and Fas ligand were measured by ELISA for each participant including 99 pre-eclampsia patients and 108 normal pregnant women. Following a test of statistical normality, nonparametric data were analyzed by Mann-Whitney. RESULTS: sFas levels in case group was significantly higher than controls; 584 (397-892) pg/ml in cases opposed to 341 (213-602) pg/ml in controls (p value< 0.01). sFasL in pre-eclampsia women was a little lower than controls; 255 (173-318) pg/ml and in case group compared to 265.5 (184-381.5) pg/ml in controls. CONCLUSION: We have found the increased levels of sFas in patients with pre-eclampsia in compare with the healthy pregnant women. It seems that abnormality in sFAS is related with pre-eclampsia.

Treatment of NAFLD with intermittent calorie restriction or low-carb high-fat diet - a randomised controlled trial.

BACKGROUND & AIMS: The first-line treatment for non-alcoholic fatty liver disease (NAFLD) is weight reduction. Several diets have been proposed, with various effects specifically on liver steatosis. This trial compared the effects of intermittent calorie restriction (the 5:2 diet) and a low-carb high-fat diet (LCHF) on reduction of hepatic steatosis. METHODS: We conducted an open-label randomised controlled trial that included 74 patients with NAFLD randomised in a 1:1:1 ratio to 12 weeks' treatment with either a LCHF or 5:2 diet, or general lifestyle advice from a hepatologist (standard of care; SoC). The primary outcome was reduction of hepatic steatosis as measured by magnetic resonance spectroscopy. Secondary outcomes included transient elastography, insulin resistance, blood lipids, and anthropometrics. RESULTS: The LCHF and 5:2 diets were both superior to SoC treatment in reducing steatosis (absolute reduction: LCHF: -7.2% [95% CI = -9.3 to -5.1], 5:2: -6.1% [95% CI = -8.1 to -4.2], SoC: -3.6% [95% CI = -5.8 to -1.5]) and body weight (LCHF: -7.3 kg [95% CI = -9.6 to -5.0]; 5:2: -7.4 kg [95% CI = -8.7 to -6.0]; SoC: -2.5 kg [95% CI =-3.5 to -1.5]. There was no difference between 5:2 and LCHF (p = 0.41 for steatosis and 0.78 for weight). Liver stiffness improved in the 5:2 and SoC but not in the LCHF group. The 5:2 diet was associated with reduced LDL levels and was tolerated to a higher degree than LCHF. CONCLUSIONS: The LCHF and 5:2 diets were more effective in reducing steatosis and body weight in patients with NAFLD than SoC, suggesting dietary advice can be tailored to meet individual preferences. LAY SUMMARY: For a person with obesity who suffers from fatty liver, weight loss through diet can be an effective treatment to improve the condition of the liver. Many popular diets that are recommended for weight reduction, such as high-fat diets and diets based on intermittent fasting, have not had their effects on the liver directly evaluated. This study shows that both a low-carb high-fat and the 5:2 diet are effective in treating fatty liver caused by obesity. CLINICAL TRIALS REGISTRATION: This study is registered at Clinicaltrials.gov (NCT03118310).

Serum Soluble Fibrinogen-Like Protein 2 Represents a Novel Biomarker for Differentiation Between Acute and Chronic Egyptian Hepatitis B Virus-Infected Patients.

Hepatitis B virus (HBV) infection is considered as one of the most serious public health problems worldwide including Egypt. Soluble fibrinogen-like protein 2 (sFGL2) is a well-known immunomodulator that is produced by the T cells and has a strong inhibitory effect on the proliferation of T cells and maturation of dendritic cells (DC). In the current study, serum levels of sFGL2 were assessed utilizing enzyme-linked immunosorbent assay (ELISA) technique among 20 acute HBV-infected patients, 55 chronic HBV-infected patients and 15 healthy individuals. In addition, serum levels of soluble FAS ligand (sFASL), soluble FAS receptor (sFAS) as well as interferon-γ (IFN-γ) were assessed and correlated to the levels of sFGL2. According to our results, serum levels of sFGL2 were significantly higher in the acute HBV-infected patients than in the chronic HBV-infected patients and healthy individuals. On the other hand, the serum levels of sFASL, sFAS and IFN-γ were significantly higher in the chronic than in acute HBV-infected patients. Also, serum sFGL2 levels were negatively correlated with the serum levels of sFASL, sFAS, IFN-γ and albumin as well as hemoglobin concentration. Furthermore, serum sFGL2 levels were positively correlated with the activities of ALT and AST and total bilirubin levels in serum. Thus, the current work highlights the possibility of utilizing serum sFGL2 level as a novel biomarker for the differentiation between acute and chronic Egyptian HBV-infected patients.