Systemic Inflammatory Factors Research Articles

The progressive Role of Dyslipidemia and Inflammation in Type 2 Diabetes in Iraqi Patients

Type II diabetes is a complex metabolic disorder that raises the risk of dyslipidemia and obesity. Inflammation is the primary factor in the pathogenesis of this disease and coincides with metabolic dyslipidemia. This work aims to predict the role of dyslipidemia and inflammatory markers in development type II DM by evaluating the levels of lipid profile, TNF-R2, systemic immune inflammatory index (SII) and related biochemical factors in patients with type 2 diabetes. Thirty samples were obtained from diabetic patients and 30 samples from non-diabetic individuals as a control. D10 apparatus (BIO-RAD, USA) used to measure hemoglobin A1c HbA1c, Enzymatic and colorimetric method used to measure biochemical parameter, ELISA technique used to estimate the TNF-R2 levels, and Complete Blood Count determine to calculate SII by the formula (neutrophil *platelet / lymphocyte count) . The results showed significant increase in most of lipid profile levels in patients than control except HDL has the verse results. Also, the results showed that HbA1C was significantly increased in patient compared to healthy group. Furthermore, TNF-R2 and SII appeared higher significant values in patients than control. Furthermore, the results indicated positive correlation between HbA1C and lipid profile (TC, TGs, VLDL and LDL), TNF-R2, SII, and BMI. It can be concluded that dyslipidemia and both TNF-R2 and SII inflammatory parameters have a cardinal role in the development of T2DM and can be served as early diagnostic factors to detect disease progression.

Genetic insights into the association between serum cytokines and frozen shoulder risk: A bidirectional mendelian randomization study

BackgroundAlthough existing studies have indicated a connection between chronic low-grade inflammation and the onset of frozen shoulder (FS), the precise causal relationship between distinct circulating inflammatory factors and FS has yet to be thoroughly evaluated. In this study, we employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between systemic cytokines and FS. MethodsA genome-wide association dataset comprising 41 serum cytokines from 8,293 individuals of Finnish descent was utilized, along with FS data from the UK Biobank included 10,104 FS cases and 451,099 controls. The primary MR method was the inverse variance weighted approach, and four additional MR techniques (MR-Egger, weighted median, simple mode, and weighted mode) were also employed to support and validate the findings. Heterogeneity and horizontal pleiotropy assessments were assessed using Cochrane’s Q and MR-Egger intercept tests. Moreover, a series of sensitivity analyses were conducted to strengthen the accuracy and credibility of these findings. ResultsBased on the IVW method, genetically predicted increasing levels of growth regulated oncogene alpha (GROa) (OR=1.08, 95 % CI 1.02–1.13, P=0.005), interferon gamma-induced protein 10 (IP-10) (OR=1.09, 95 % CI 1.02–1.17, P=0.010), regulated on activation, C–C Motif Chemokine Ligand 5 (CCL5) (OR=1.11, 95 % CI 1.03–1.20, P=0.007) were suggestively associated with an increased risk of FS. Reverse MR analysis revealed no significant causal effect of FS on the 41 systemic inflammatory factors. No heterogeneity or horizontal pleiotropy was observed in our analysis. ConclusionThis study established a causal association between 41 systemic inflammatory factors and FS, indicating that elevated levels of GROa, IP-10 and CCL5 were associated with a higher risk of FS. Further research is warranted to explore the potential of these biomarkers as early predictors and therapeutic targets for FS.

Blocking CTLA-4 promotes pressure overload-induced heart failure via activating Th17 cells.

Targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) with specific antibody offers long-term benefits for cancer immunotherapy but can cause severe adverse effects in the heart. This study aimed to investigate the role of anti-CTLA-4 antibody in pressure overload-induced cardiac remodeling and dysfunction. Transverse aortic constriction (TAC) was used to induce cardiac hypertrophy and heart failure in mice. Two weeks after the TAC treatment, mice received anti-CTLA-4 antibody injection twice a week at a dose of 10 mg/kg body weight. The administration of anti-CTLA-4 antibody exacerbated TAC-induced decline in cardiac function, intensifying myocardial hypertrophy and fibrosis. Further investigation revealed that anti-CTLA-4 antibody significantly elevated systemic inflammatory factors levels and facilitated the differentiation of T helper 17 (Th17) cells in the peripheral blood of TAC-treated mice. Importantly, anti-CTLA-4 mediated differentiation of Th17 cells and hypertrophic phenotype in TAC mice were dramatically alleviated by the inhibition of interleukin-17A (IL-17A) by an anti-IL-17A antibody. Furthermore, the C-X-C motif chemokine receptor 4 (CXCR4) antagonist AMD3100, also reversed anti-CTLA-4-mediated cardiotoxicity in TAC mice. Overall, these results suggest that the administration of anti-CTLA-4 antibody exacerbates pressure overload-induced heart failure by activating and promoting the differentiation of Th17 cells. Targeting the CXCR4/Th17/IL-17A axis could be a potential therapeutic strategy for mitigating immune checkpoint inhibitors-induced cardiotoxicity.

Association of ultraprocessed food consumption with risk of rheumatoid arthritis: a retrospective cohort study in the UK Biobank

BackgroundLimited studies explored the association between consumption of ultraprocessed food (UPF) and rheumatoid arthritis (RA). ObjectivesThis study aimed to examine the association between UPF consumption and RA risk and explore the potential mediating effects of RA-related biomarkers. MethodsThis retrospective cohort study included 207,012 participants without RA at recruitment and completed 24-h dietary recalls. UPF was defined based on the NOVA food classification system. Incident RA was ascertained using the International Classification of Diseases version 10. Cox regression models were used to examine the association between UPF consumption and the incidence of RA. Additionally, mediation analyses were conducted to evaluate the contribution of biomarkers related to the lipid profile, systemic inflammatory factors, serum liver enzymes, and glucose metabolism to the observed associations. ResultsThe participants’ mean (standard deviation [SD]) age at recruitment was 56.08 (7.95) y. During a median follow-up of 12.24 (interquartile range: 11.66–13.03) y, 1869 RA events were recorded. Compared with the lowest quintile of UPF consumption (weight percentage of the UPF), the adjusted hazard ratio (HR) of RA in the highest quintile was 1.17 (95% confidence interval (CI): 1.01, 1.36). There was a 6% elevated risk of RA incidence per SD increase in UPF intake (HR: 1.06; 95% CI: 1.01, 1.11). In the mediation analyses, the biomarkers explained 3.07%–14.80% of the association between UPF intake and RA. ConclusionsHigher UPF consumption was associated with an increased risk of RA, which may be mediated by inflammation, lipids, and liver enzymes. Lower UPF consumption is recommended to reduce RA incidence.

Evaluation of β2-microglobulin in the condition and prognosis of psoriasis patients

Background Numerous studies have linked the inflammatory pathway in psoriasis and metabolic disease, while no specific marker defined it. It is worth exploring the association of β2-microglobulin (β2M) in psoriasis severity and comorbidities. Objectives To investigate the correlation between blood β2M level and psoriasis severity, to explore the inflammatory factors influencing the occurrence of psoriasis comorbidities such as arthritis, diabetes, and hypertension. Methods Ninety-seven psoriasis patients were analyzed in the cohort retrospective study during 12 weeks. Results Significantly higher levels of blood β2M and ESR were observed in the group that patients’ PASI ≥10 than in the group that PASI <10. Blood β2M level had strong significantly positive correlations with the PASI in Pearson’s correlation analysis. In the model that systemic inflammatory factors to find psoriasis comorbidity risk factors, logistic regression analysis showed that blood β2M level was the significant risk factor associated with diabetes and hypertension. High-sensitivity C-reactive protein (hsCRP) was the significant risk factor associated with arthritis. Conclusions Patients with a severer psoriasis tended to have higher blood β2M levels and severer inflammatory state. In the systemic inflammation indexes, the level of blood β2M affected the risk of hypertension and diabetes, and hsCRP affected the risk of arthritis in patients with psoriasis.

The interplay between systemic inflammatory factors and endometriosis: A bidirectional mendelian randomization study

ObjectiveTo utilize vast genetic data to reveal the interplay between 41 systemic inflammatory factors and endometriosis. DesignBidirectional Mendelian randomization study. Mains outcome measuresThis study obtained believable genetic instrumental variables for systemic inflammatory factors. The effect of systemic inflammatory factors on different endometriosis phenotypes, and the effect of endometriosis on the concentrations of systemic inflammatory factors were investigated. ResultsIn this mendelian randomization study, we found 20 causal relationships involving 18 systemic inflammatory factors and it was shown that Monocyte chemotactic protein-1, Macrophage inflammatory protein-1a, Granulocyte colony-stimulating factor, Macrophage migration inhibitory factor, Interleukin-4, Interleukin-5, Interleukin-8, Interleukin-9, Interleukin-12p70, Interleukin-16, and Interleukin-17 may be the upstream causes of endometriosis (P<0.05). Additionally, if the definition of exposure in the mendelian randomization was endometriosis, it could suggestively cause an increase in Eotaxin, cutaneous T-cell attracting chemokine, and Interferon gamma-induced protein 10 levels, and a decrease in growth-regulated oncogene-alpha, Interleukin-2 receptor, alpha subunit, platelet-derived growth factor BB, and Interleukin-18 (P<0.05). Reverse causality was not observed between a single systemic inflammatory factor and endometriosis. ConclusionsOur findings indicate that several systemic inflammatory factors may act as the initiator at the onset of endometriosis. Additionally, several other inflammatory factors are far more probable to involved downstream during disease development.

Polystyrene nanoplastics exacerbate aflatoxin B1-induced hepatic injuries by modulating the gut−liver axis

Dietary pollution of Aflatoxin B1 (AFB1) poses a great threat to global food safety, which can result in serious hepatic injuries. Following the widespread use of plastic tableware, co-exposure to microplastics and AFB1 has dramatically increased. However, whether microplastics could exert synergistic effects with AFB1 and amplify its hepatotoxicity, and the underlying mechanisms are still unelucidated. Here, mice were orally exposed to 100 nm polystyrene nanoplastics (NPs) and AFB1 to investigate the influences of NPs on AFB1-induced hepatic injuries. We found that exposure to only NPs or AFB1 resulted in colonic inflammation and the impairment of the intestinal barrier, which was exacerbated by combined exposure to NPs and AFB1. Meanwhile, co-exposure to NPs exacerbated AFB1-induced dysbiosis of gut microbiota and remodeling of the fecal metabolome. Moreover, NPs and AFB1 co-exposure exhibited higher levels of systemic inflammatory factors compared to AFB1 exposure. Additionally, NPs co-exposure further exacerbated AFB1-induced hepatic fibrosis and inflammation, which could be associated with the overactivation of the TLR4/MyD88/NF-κB pathway. Notably, Spearman's correlation analysis revealed that the exacerbation of NPs co-exposure was closely associated with microbial dysbiosis. Furthermore, microbiota from NPs-exposed mice (NPsFMT) partly reproduced the exacerbation of NPs on AFB1-induced systemic and hepatic inflammation, but not fibrosis. In summary, our findings indicate that gut microbiota could be involved in the exacerbation of NPs on AFB1-induced hepatic injuries, highlighting the health risks of NPs.

HMGB1: A New Target for Ischemic Stroke and Hemorrhagic Transformation.

Stroke in China is distinguished by its high rates of morbidity, recurrence, disability, and mortality. The ultra-early administration of rtPA is essential for restoring perfusion in acute ischemic stroke, though it concurrently elevates the risk of hemorrhagic transformation. High-mobility group box 1 (HMGB1) emerges as a pivotal player in neuroinflammation after brain ischemia and ischemia-reperfusion. Released passively by necrotic cells and actively secreted, including direct secretion of HMGB1 into the extracellular space and packaging of HMGB1 into intracellular vesicles by immune cells, glial cells, platelets, and endothelial cells, HMGB1 represents a prototypical damage-associated molecular pattern (DAMP). It is intricately involved in the pathogenesis of atherosclerosis, thromboembolism, and detrimental inflammation during the early phases of ischemic stroke. Moreover, HMGB1 significantly contributes to neurovascular remodeling and functional recovery in later stages. Significantly, HMGB1 mediates hemorrhagic transformation by facilitating neuroinflammation, directly compromising the integrity of the blood-brain barrier, and enhancing MMP9 secretion through its interaction with rtPA. As a systemic inflammatory factor, HMGB1 is also implicated in post-stroke depression and an elevated risk of stroke-associated pneumonia. The role of HMGB1 extends to influencing the pathogenesis of ischemia by polarizing various subtypes of immune and glial cells. This includes mediating excitotoxicity due to excitatory amino acids, autophagy, MMP9 release, NET formation, and autocrine trophic pathways. Given its multifaceted role, HMGB1 is recognized as a crucial therapeutic target and prognostic marker for ischemic stroke and hemorrhagic transformation. In this review, we summarize the structure and redox properties, secretion and pathways, regulation of immune cell activity, the role of pathophysiological mechanisms in stroke, and hemorrhage transformation for HMGB1, which will pave the way for developing new neuroprotective drugs, reduction of post-stroke neuroinflammation, and expansion of thrombolysis time window.

Trajectories of neutrophil-to-lymphocyte ratios during neoadjuvant chemotherapy correlate with short- and long-term outcomes in gastric cancer: a group-based trajectory analysis

BackgroundSystemic inflammatory factors can predict the survival prognosis of gastric cancer (GC) patients after neoadjuvant chemotherapy (NACT). However, whether longitudinal changes in systemic inflammatory factors are associated with short - and long-term outcomes has not been reported.MethodsThis study is a retrospective analysis of 216 patients with advanced gastric cancer who received NACT between January 2011 and June 2019, comparing receiver operating characteristic (ROC) curves for screening suitable inflammatory markers. Group-based trajectory modeling (GBTM) was used to analyze longitudinal changes in inflammatory markers during NACT to identify different potential subgroups and to compare postoperative complications, recurrence-free survival (RFS), and overall survival (OS) among subgroups.ResultsUltimately, neutrophil-lymphocyte ratio (NLR) had the highest area under the curve (AUC) value in predicting prognosis was included in the GBTM analysis. Three trajectories of NLR were obtained: Stable group (SG) (n = 89), Ascent-descend group (ADG) (n = 80) and Continuous descend group (CDG) (n = 47). Compared with SG, ADG and CDG are associated with an increased risk of postoperative recurrence and death. The median time of RFS and OS of SG was longer than that of ADG and CDG (median RFS 81 vs. 44 and 22 months; median OS 69 vs. 41 and 30 months). In addition, CDG had significantly higher postoperative serious complications than SG and ADG (17 (36.2%) vs. 17 (19.1%) and 12 (15.0%); p = 0.005).ConclusionThere were different trajectories of NLR during NACT, and these potential trajectories were significantly associated with severe postoperative complications, recurrence, and mortality in patients with GC.

Denervation-Induced Sarcopenia Model.

Rheumatoid arthritis (RA) is an important risk factor for sarcopenia. Physical inactivity, systemic inflammatory factors, and medication directly or indirectly induce skeletal muscle loss in RA patients. The sarcopenia-induced systemic or local proinflammatory microenvironment also contributes to the onset and progression of autoimmune disease. Accumulated evidence suggests the importance of treatment and management of sarcopenia in patients with RA to improve their long-term prognosis. To elucidate the relationship between skeletal muscle and systemic immune homeostasis, a denervation-induced skeletal muscle-losing mouse model is introduced in this chapter. By developing local amyotrophy in the sciatic nerve-dominant area in a RA model, the underlying mechanism of sarcopenia in RA could be assessed. Also, an examination of the efficacy of anti-rheumatic regents on sarcopenia and the influence of sarcopenia management on RA improvement is also achievable.

Guanidinoacetic acid ameliorates hepatic steatosis and inflammation and promotes white adipose tissue browning in middle-aged mice with high-fat-diet-induced obesity.

Guanidinoacetic acid (GAA) is a naturally occurring amino acid derivative that plays a critical role in energy metabolism. In recent years, a growing body of evidence has emerged supporting the importance of GAA in metabolic dysfunction. Hence, we aimed to investigate the effects of GAA on hepatic and adipose tissue metabolism, as well as systemic inflammatory responses in obese middle-aged mice models and attempted to explore the underlying mechanism. We found that dietary supplementation of GAA inhibited inguinal white adipose tissue (iWAT) hypertrophy in high-fat diet (HFD)-fed mice. In addition, GAA supplementation observably decreased the levels of some systemic inflammatory factors, including IL-4, TNF-α, IL-1β, and IL-6. Intriguingly, GAA supplementation ameliorated hepatic steatosis and lipid deposition in HFD-fed mice, which was revealed by decreased levels of TG, TC, LDL-C, PPARγ, SREBP-1c, FASN, ACC, FABP1, and APOB and increased levels of HDL-C in the liver. Moreover, GAA supplementation increased the expression of browning markers and mitochondrial-related genes in the iWAT. Further investigation showed that dietary GAA promoted the browning of the iWAT via activating the AMPK/Sirt1 signaling pathway and might be associated with futile creatine cycling in obese mice. These results indicate that GAA has the potential to be used as an effective ingredient in dietary interventions and thus may play an important role in ameliorating and preventing HFD-induced obesity and related metabolic diseases.

ROLE OF MICROGLIA IN SEPSIS-ASSOCIATED ENCEPHALOPATHY PATHOGENESIS: AN UPDATE.

Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis, which is characterized by cognitive dysfunction, a poor prognosis, and high incidences of morbidity and mortality. Substantial levels of systemic inflammatory factors induce neuroinflammatory responses during sepsis, ultimately disrupting the central nervous system's (CNS) homeostasis. This disruption results in brain dysfunction through various underlying mechanisms, contributing further to SAE's development. Microglia, the most important macrophage in the CNS, can induce neuroinflammatory responses, brain tissue injury, and neuronal dysregulation, resulting in brain dysfunction. They serve an important regulatory role in CNS homeostasis and can be activated through multiple pathways. Consequently, activated microglia are involved in several pathogenic mechanisms related to SAE and play a crucial role in its development. This article discusses the role of microglia in neuroinflammation, dysfunction of neurotransmitters, disruption of the blood-brain barrier, abnormal control of cerebral blood flow, mitochondrial dysfunction, and reduction in the number of good bacteria in the gut as main pathogenic mechanisms of SAE and focuses on studies targeting microglia to ameliorate SAE to provide a theoretical basis for targeted microglial therapy for SAE.

Estrogen deficiency induces bone loss through the gut microbiota

Postmenopausal osteoporosis is a common bone metabolic disease, and gut microbiota (GM) imbalance plays an important role in the development of metabolic bone disease. Here, we show that ovariectomized mice had high levels of lipopolysaccharide in serum and gut microbiota dysbiosis through increases in luminal Firmicutes:Bacteroidetes ratio. We depleted the GM through antibiotic treatment and observed improvements in bone mass, bone microstructure, and bone strength in ovariectomized mice. Conversely, transplantation of GM adapted to ovariectomy induced bone loss. However, GM depletion reversed ovariectomy-induced gene expression in the tibia and increased periosteal bone formation. Furthermore, bioinformatics analysis revealed that the G-protein-coupled bile acid receptor (TGR5) and systemic inflammatory factors play key roles in bone metabolism. Silencing TGR5 expression through small interfering RNA (siRNA) in the local tibia and knockout of TGR5 attenuated the effects of GM depletion in ovariectomized mice, confirming these findings. Thus, this study highlights the critical role of the GM in inducing bone loss in ovariectomized mice and suggests that targeting TGR5 within the GM may have therapeutic potential for postmenopausal osteoporosis.

What can traditional plant therapy do in the face of Covid-19? Examples from traditional Chinese medicine.

Until June 2022, more than 540.9 million people had been diagnosed with COVID-19, and the pandemic had claimed more than six million lives worldwide. Two years after fighting the virus, we faced a more uncertain position. SARS-CoV-2 is constantly mutating and reappears regularly, particularly with Omicron variants showing high genetic variation and immune escape mechanisms. The efficacy and duration of protection of existing vaccines against new variants of SARS-CoV-2 remains uncertain. The world needs time to develop new variant-specific drugs, including monoclonal topics, vaccines, and other antiviral drugs, to fight the epidemic. The aim of this study was to illustrate the scientific, effective and systematic nature of three classical prescriptions of traditional Chinese medicine (TCM) for the treatment of COVID-19 through comparison of disease symptoms, diagnostic process, and treatment methods and evidence-based and pharmacological studies. We analysed the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia" (Version 9) made by China, "WHO-2019-nCoV-therapeutics", "Therapeutic Guidelines" published by Australian Therapeutic Guidelines Limited, "Shanghan Lun (Treatise on Febrile Diseases)", "Jinkui Yaolue (Golden Chamber Synopsis), and "Wenyi Lun (The Epidemic Febrile Disease)". We manually retrieved the dictionary of traditional Chinese medicine (Version II). In addition, we searched the Wiley online library, National Center for Biotechnology Information (NCBI), VIP, WHO website, and China National Knowledge Infrastructure (CNKI) for relevant literature from 2001 to 2022. We searched the original plants, ingredients, pharmacology, functions and indications, usage and dosage, drug efficacy, literature sources, and conduct an evidence-based studies. We quantified the strength of pharmacological action to show the pertinence of disease development. We found that the diagnosis and treatment of pulmonary infection caused by epidemic disease in TCM classics is consistent with the diagnostic process of modern medical therapeutic guidelines. The three classic prescriptions have significant symptomatic therapeutic effects on the respiratory, gastrointestinal, urinary and hematological symptoms of the clinical manifestations of COVID-19. It was found that the herbal functional group of Houpo (Cortex Magnoliae Officinalis), Chaihu (Radix Bupleuri), Cangzhu (Rhizoma Atractylodis), Qianghuo (Notopterygii Rhizoma et Radix), etc showed strong anti-inflammatory activity and had a positive effect on treating and preventing the outbreaks of systemic inflammatory factors. TCM can obtain obvious curative effect in symptomatic treatment, has strong anti-inflammatory effect, and can effectively reduce symptoms and patients' pain.

Role of systemic inflammatory factors in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT): From biology to theragnosis

AimSystemic inflammatory factors have been validated as indicators of ongoing systemic inflammation that could be predictive markers of poor prognosis for oncological outcomes. However, the prognostic impact of systemic inflammation markers is unknown in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT). MethodsWe conducted an observational, retrospective, multicentric study of 40 patients with GEP or unknown origin NETs treated with PRRT between 2016 and 2020. The systemic inflammatory markers were calculated as follows: neutrophil to lymphocyte ratio (NLR)=neutrophil count/lymphocyte count, monocyte to lymphocyte ratio (MLR)=monocyte count/lymphocyte count, platelet to lymphocyte ratio (PLR)=platelet count/lymphocyte count, albumin to lymphocyte ratio (ALR)=albumin levels/lymphocyte count and derived Neutrophil to Lymphocyte ratio (dNLR)=neutrophil count/(leucocytes count – neutrophils count). Baseline analysis and after the second dose were used for the calculation of different ratios. ResultsThe median age was 63 years (range 41–85), 55% were male. The baseline cut-off values for NLR were 2.61, for MLR 0.31, for PLR 110.14, for ALR 2.39 and for dNLR 1.71. The cut-off values after the 2° dose were, for NLR 2.3, for MLR 0.3, for PLR 131.61, ALR 4.16, and dNLR 1.48. Median progression-free survival (PFS) was 21.7 months (95% CI 10.7–32.8 months) and overall survival (OS) was 32.1 months (95% CI 19.6–44.7 months), PFS was shorter in patients with elevated NLR (p=0.001), ALR (0.03), and dNLR (p=0.001) in baseline analysis. DCR was 81% and ORR 18%. ConclusionsIn GEP or unknown origin NETs treated with PRRT, we have identified the predictive and prognostic impact of baseline systemic inflammatory factors.

Casein Hydrolysate Alleviates Adipose Chronic Inflammation in High Fat-Diet Induced Obese C57BL/6J Mice through MAPK Pathway.

Obesity-induced adipose chronic inflammation is closely related to the development of insulin resistance and T2DM. Tripeptides l-valyl-l-prolyl-l-proline (VPP) and l-isoleucyl-l-prolyl-L-proline (IPP) derived from bovine casein have been reported to prevent inflammatory changes and mitigate insulin resistance in adipocytes. In this study, we aimed to investigate the influence of casein hydrolysates (CH) containing VPP and IPP on a high fat diet (HFD)-induced obese mice and cytokine TNF-α-induced adipocytes. Our data showed that CH alleviated chronic inflammation both in vivo and in vitro. 4% CH suppressed HFD-induced systemic inflammatory factors, hypertrophic white adipocytes, and macrophage infiltration. More importantly, CH was able to improve adipocyte dysfunction induced by TNF-α by increasing the expression of CCAAT/enhancer binding protein α (C/EBP-α) rather than peroxisome proliferator-activated receptor γ (PPAR-γ). Furthermore, CH also dose-dependently suppressed mitogen-activated protein kinase (MAPK)-c-Jun N-terminal kinase (JNK) phosphorylation and enhanced the phosphorylation of Erk 1/2, but not nuclear factor-kappa B (NF-κB) p65 phosphorylation, in TNF-α-induced 3T3-L1 cells. These results indicated that CH could ameliorate adipose chronic inflammation through the MAPK pathway. Altogether, our findings suggested that 4% CH supplementation for 6 weeks exerted a protective role in preventing obesity-related inflammation and adipose dysfunction.

Systemic inflammation factors influence on the risk of detecting signs of cardiovascular calcification in a patient with stage 5D chronic kidney disease

BACKGROUND. Chronic kidney disease (CKD) is a common pathology influencing mortality risk in the world population. Calcification of aorta and heart structures (valves, coronary arteries) is a risk factor for cardiovascular complications. The influence of cytokines, integrin proinflammatory indices, acute phase proteins and other inflammatory factors on the risk of extravasal calcification is promising. THE AIM: to study the effect of cytokines, integrative proinflammatory indices, acute phase proteins and other inflammatory factors on the risk of extra-osseous calcification. PATIENTS AND METHODS. A one-stage, cohort study of 85 patients with CKD 5D treated with programmed hemodialysis was conducted. General clinical examination was carried out according to the protocol. Blood levels of C-reactive protein (CRP) were determined by immunoturbodimetry. A Glasgow Prognostic Score (GPS) risk index for systemic inflammation was calculated using CRP and plasma albumin concentrations. Interleukin-6 (IL-6), interleukin-3 (IL-3) were assessed by enzyme immunoassay. Blood leukocyte shift index (BLI) was calculated. Echocardioscopy was performed using Doppler mode. The presence of cardiac valve calcification (CAC) was registered, its severity was assessed. To estimate the abdominal aortic calcification, the abdominal radiography was carried out in the left lateral projection. The severity of manifestations of aortic calcification was assessed using the L.I. Kauppilla Calcification Scale. Statistical analysis was performed using STATISTICA 12.6. toolkit (StatSoft, USA). RESULTS. Systemic inflammatory factors negatively affected the severity of cardiovascular calcification. An increased GPS value was found to correlate with the severity of CAC and CSA. In the case of calcification severity analysis considering IL-3 and IL-6 values, it was also shown that high levels of these pro-inflammatory cytokines are associated with severe manifestations of anterior aortic wall calcification and aortic calcification at the L3 level. Inclusion of ISLC in the analysis had no effect on the severity of calcification of the aortic wall and no effect on the intensity of cardiac valve calcification in general, the aortic valve and the mitral valve in particular.

Systemic inflammatory regulators and proliferative diabetic retinopathy: A bidirectional Mendelian randomization study.

Increasing evidence shows that systemic inflammation is an embedded mechanism of proliferative diabetic retinopathy (PDR). However, the specific systemic inflammatory factors involved in this process remained obscure. The study aimed to identify the upstream and downstream systemic regulators of PDR by using Mendelian randomization (MR) analyses. We performed a bidirectional two-sample MR analysis implementing the results from genome-wide association studies for 41 serum cytokines from 8,293 Finnish individuals, and PDR from FinnGen consortium (2,025 cases vs. 284,826 controls) and eight cohorts of European ancestry (398 cases vs. 2,848 controls), respectively. The inverse-variance-weighted method was adopted as the main MR method, and four additional MR methods (MR-Egger, weighted-median, MR-pleiotropy residual sum and outlier (MR-PRESSO), and MR-Steiger filtering methods) were used for the sensitivity analyses. Results from FinnGen and eight cohorts were pooled into a meta-analysis. Our results showed that genetically predicted higher stem cell growth factor-β (SCGFb) and interleukin-8 were positively associated with an elevated risk of PDR, with a combined effect of one standard deviation (SD) increase in SCGFb and interleukin-8 causing 11.8% [95% confidence interval (CI): 0.6%, 24.2%]) and 21.4% [95% CI: 3.8%, 41.9%]) higher risk of PDR, respectively. In contrast, genetically predisposition to PDR showed a positive association with the increased levels of growth-regulated oncogene-α (GROa), stromal cell-derived factor-1 alpha (SDF1a), monocyte chemotactic protein-3 (MCP3), granulocyte colony-stimulating factor (GCSF), interleukin-12p70, and interleukin-2 receptor subunit alpha (IL-2ra). Our MR study identified two upstream regulators and six downstream effectors of PDR, providing opportunities for new therapeutic exploitation of PDR onset. Nonetheless, these nominal associations of systemic inflammatory regulators and PDR require validation in larger cohorts.

Inflammation in the blood: what's behind it?

Inflammation is the body's defensive response to mostly harmful stimuli, usually in response to pathogens or toxic substances. However, the immune response in chronic inflammation is usually directed against harmless antigens, such as allergens, or commensal pathogens, such as herpes viruses, or against the body's own structures, as in autoimmune diseases. The body reacts to the respective stimulating factors with arelatively uniform inflammatory response. Besides the initial reaction of the innate immune system, the activation of immune cells and the release of pro-inflammatory cytokines are in the foreground. Accordingly, inflammatory changes that can be detected in the blood usually do not arise in the blood itself, but in aspecific tissue or organ system. In the case of long-term or chronic inflammation, the inflammatory response can be detected in the blood by means of various factors, and both general inflammatory parameters as well as specific parameters can be used for diagnostic purposes. However, the long-term systemic inflammatory response itself also affects the patients suffering from chronic inflammation. This article provides an overview of systemic inflammatory factors relevant for laboratory diagnostics, of how they contribute to specific diseases, and of the systemic effects induced by chronic inflammation.

NCR, an Inflammation and Nutrition Related Blood-Based Marker in Colon Cancer Patients: A New Promising Biomarker to Predict Outcome.

Background: Colorectal carcinoma (CRC) is a heterogeneous disease, and differences in outcomes have been reported among patients diagnosed with the same disease stage. Prognostic and predictive biomarkers provide information for patient risk stratification and guide treatment selection. Although numerous studies have analyzed the effects of systemic inflammatory factors on CRC outcomes, clinical significance remains to be elucidated. In particular, the treatment strategy of colon cancer patients is different from that of rectal cancer due to outcome and recurrence differences. The identification of patients with a poor prognosis who might benefit from intensive treatment approaches is clinically necessary. Methods: This study aimed to evaluate the value of different blood-based markers and assess the significance of our newly developed inflammatory-nutrition-related biomarker (NCR = BMI × albumin/CRP) in patients with colon cancer. A two-stage design was used with 212 patients with colon cancer (CC) in the discovery cohort (n = 159) and in an external validation cohort (n = 53). Results: A lower preoperative NCR level was significantly correlated with a worse prognosis, sidedness, undifferentiated histology, nodal involvement, and advanced UICC stage. We compared the NCR with other established prognostic indices and showed that the NCR is a more reliable indicator of a poor prognosis for patients with CC. Patients with low NCR levels experienced a significantly shorter Overall Survival (OS) than patients with high levels. Multivariate analysis confirmed preoperative NCR levels as an independent predictor for overall survival with a hazard ratio of 3.3 (95% confidence interval 1.628−6.709, p < 0.001). Finally, we confirmed the predictive value of the NCR in an independent validation cohort and confirmed NCR as an independent prognostic factor for OS. Conclusion: Taken together, we discovered a new prognostic index (NCR) based on BMI, albumin, and CRP levels as an independent prognostic predictor of OS in patients with colon cancer. In all UICC stages, our newly developed NCR marker is able to distinguish patients with better and worse prognoses. We, therefore, propose that NCR may serve as a supplement to the TNM staging system to optimize the risk stratification in CC patients towards personalized oncology. In particular, NCR can be used in clinical trials to stratify patients with UICC II and III tumors and help better select patients who might benefit from adjuvant treatment.