Serum TLR4 Research Articles

Immunological Strategies in Gastric Cancer: How Toll-like Receptors 2, -3, -4, and -9 on Monocytes and Dendritic Cells Depend on Patient Factors?

(1) Introduction: Toll-like receptors (TLRs) are key in immune response by recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). In gastric cancer (GC), TLR2, TLR3, TLR4, and TLR9 are crucial for modulating immune response and tumor progression. (2) Objective: This study aimed to assess the percentage of dendritic cells and monocytes expressing TLR2, TLR3, TLR4, and TLR9, along with the concentration of their soluble forms in the serum of GC patients compared to healthy volunteers. Factors such as disease stage, tumor type, age, and gender were also analyzed. (3) Materials and Methods: Blood samples from newly diagnosed GC patients and healthy controls were immunophenotyped using flow cytometry to assess TLR expression on dendritic cell subpopulations and monocytes. Serum-soluble TLRs were measured by ELISA. Statistical analysis considered clinical variables such as tumor type, stage, age, and gender. (4) Results: TLR expression was significantly higher in GC patients, except for TLR3 on classical monocytes. Soluble forms of all TLRs were elevated in GC patients, with significant differences based on disease stage but not tumor type, except for serum TLR2, TLR4, and TLR9. (5) Conclusions: Elevated TLR expression and soluble TLR levels in GC patients suggest a role in tumor pathogenesis and progression, offering potential biomarkers and therapeutic targets.

Serum TLR2 and TLR9 in Prostate Cancer Patients in Relation to EBV Status.

The relationship between Toll-like receptors (TLRs) and prostate cancer (PCa) is complex due to the presence of the Epstein-Barr virus (EBV) infection, which has been identified as a predisposing factor for some cancers, including PCa. The present study aims to investigate these complex links by examining the levels of selected TLRs and the potential impact of EBV infection on PCa. Therefore, we examined the serum of patients with PCa. The study compared EBV(+) patients to risk groups, the Gleason score (GS), and the T-trait. Additionally, the correlation between TLR and antibody levels was examined. The results indicated that higher levels of TLR-2 and TLR-9 were observed in more advanced PCa. The findings of this study may contribute to a deeper understanding of the role of viral infections in PCa and provide information on future strategies for the diagnosis, prevention, and treatment of these malignancies.

Correlation analysis of serum TLR4 protein levels and TLR4 gene polymorphisms in gouty arthritis patients.

The Toll-like receptor (TLR) 4-mediated nuclear factor kappa B (NF-κB) signaling pathway regulates the production of inflammatory factors and plays a key role in the pathogenesis of gouty arthritis. The aim of the present study was to investigate the link among TLR4 gene polymorphisms at various loci, protein expression, and gouty arthritis susceptibility. Between 2016 and 2021, a case-control study was used to collect a total of 1207 study subjects, including 317 male patients with gouty arthritis (gout group) and 890 healthy males (control group). The association between gout susceptibility and different genetic models was analyzed by typing three loci of the TLR4 gene (rs2149356, rs2737191, and rs10759932) using a multiplex point mutation rapid assay, and the association between protein expression and gout was confirmed by measuring TLR4 protein concentrations using enzyme-linked immunosorbent assays (ELISAs). In a codominant models AA and AG, the rs2737191 polymorphism in the gout group increased the risk of gout compared to the AA genotype (OR = 2.249, 95%CI 1.010~5.008), and the risk of gout was higher for those carrying the G allele compared to the A allele (OR = 2.227, 95%CI 1.006~4.932). TLR4 protein expression was different between the two groups with different locus genotypes. The differences in TLR4 protein expression between the gout group and control group were statistically significant between the following genotypes: the GG and GT genotypes of the rs2149356 polymorphism; the AA and AG genotypes of the rs2737191 polymorphism; and the TT and TC genotypes of the rs10759932 polymorphism(P<0.05). The TLR4 protein level in the gout group (19.19±3.09 ng/ml) was significantly higher than that in the control group (15.85±4.75 ng/ml). The AG genotype of the TLR4 gene rs2737191 polymorphism may be correlated with the development of gouty arthritis. The level of TLR4 protein expression is significantly higher in patients with gouty arthritis than in controls, and there is a correlation between high TLR4 protein expression and the development of gouty arthritis.

Comparison of HMGB1, RAGE, TLR4, and NF-κB levels in children and adolescents diagnosed with autism spectrum disorder with healthy controls

Introduction The objective of our study is to clarify the involvement of the HMGB1/RAGE/TLR4/NF-kB axis, a crucial component in inflammation, in the etiopathogenesis of autism spectrum disorder (ASD). Method We analyzed the levels of HMGB1, RAGE, TLR4, and NF-kB in serum from 80 children (40 with ASD and 40 controls). All participants’ sociodemographic characteristics were recorded. In order to determine the severity of the disorder, the Aberrant Behavior Checklist, Childhood Autism Rating Scale, and Autism Behavior Checklist were administered to the ASD group. Result While the soluble TLR4 level was significantly higher in the ASD group (p < 0.001), other parameters examined did not show significant differences between groups. Furthermore, soluble TLR4 serum level was positively correlated with Problem Behavior Checklist hyperactivity subscale scores (p = 0.031), and RAGE serum level was negatively correlated with ABC Stereotype score (p = 0.001). Discussion It was thought that serum TLR4 levels may be important in the etiology of ASD. TLR4 levels are linked to symptoms like hyperactivity in autism, which suggests that this parameter could be used as a clinical guide. Further research is required to substantiate our discoveries and to clarify the involvement of HMGB1, RAGE, TLR4, and NF-kB in the etiopathogenesis of ASD.

Evaluating TLR4 Gene Expression to Monitor Disease Progression in Iraqi Patients with Rheumatoid Arthritis

Background: Toll-like receptors (TLRs) play a significant role in the activation of adaptive immunity and may have an essential role in the development of rheumatoid arthritis (RA). Objectives: To assess the gene expression of TLR4 in individuals with RA compared to healthy individuals. Methods: From July to December 2022. A total of 100 individuals were encompassed in the study, consisting of 50 individuals diagnosed with RA, of whom 42 were females and 8 were males, with an average age of 45.22 years. Additionally, there were 50 healthy control participants, 40 of whom were females and 10 were males, with an average age of 45.64 years. To assess the TLR4 transcript levels, blood samples were collected from each participant, and RNA extraction was performed. cDNA synthesis was carried out, and real-time PCR was utilized for the analysis. The researchers also assessed the clinicopathological characteristics of the patients. Results: The serum TLR4 gene was significantly overexpressed in RA patients (fold change 2.59) compared to the controls (fold change 1.07). The expression level of the TLR4 gene was correlated with the clinicopathological characteristics of the patients, including erythrocyte sedimentation rates (ESR), RF, anti-CCP antibody, and DAS28. Conclusion: TLR4 was overexpressed in RA patients and was correlated with disease activity. It might be a therapeutic target and may contribute to the pathogenesis of RA.

CLINICAL AND LABORATORY CHANGES IN POSTSURGICAL PAIN MARKERS IN CHILDREN

Pos toperative pain in children remains a signifi cant problem in pediatric intensive care, possibly related to an imperfectalgorithm for its management. Prolonged postoperative pain delays recovery and rehabilitation, increases treatment costs,and prolongs opioid use. Inadequate perioperative pain management can lead to a variety of postoperative complications, the prediction of which remains elusive despite the use of commonly accepted clinical, laboratory, and instrumental indicators. The aim of this study was to evaluate clinical and laboratory changes in children after abdominal surgery and their correlation with acute pain scales.Material and Methods. The study included 83 children aged 7-18 years who underwent abdominal surgery under opioid anesthesia. Inclusion criteria: age 7-18 years; indication for surgery for acute appendicitis; American Society of Anesthesiologists (ASA) Anesthesia Risk Score I and II; parental consent for the children to participate in the study.Acute pain intensity was measured using the Visual Analog Scale (VAS) and the Face, Legs, Activity, Cry, Consolability(FLACC) scale. Key vital signs assessed included heart rate, respiratory rate, systolic and diastolic blood pressure, and oxygen saturation (SpO2). In addition, laboratory indicators including leukocyte count, blood glucose level, erythrocyte sedimentation rate, and TLR-4 and CD40L levels were determined. All clinical and laboratory studies were conducted in accordance with the World Medical Association Declaration of Helsinki«Ethical Principles for Medical Research Involving Human Subjects» (Minutes of the Ethics Committee No. 2, dated February 24, 2002). Statistical analysis was performed on a personal computer using Statistica 10 software, using parametric and nonparametric statistical methods. The study is a part of the research project of the Department of Children’s Diseases of the Postgraduate Medical Education Faculty of the Ivano- Frankivsk National Medical University «Health Status and Adaptation of Children from the Precarpathian Region with Somatic Diseases, Their Prevention» 2021-2026, state registration number 0121U111129; the author is a co-researcher.Results. The mean age of the children was 13.8±0.23 years, while the mean body weight was 40.9±1.6 kg. Gender assessment showed no diff erences between boys and girls (55.4 % and 44.6 %, respectively, р&gt;0.05).The study showed very strong positive correlations (r=0.9-1.0) between acute pain assessment scores on the VAS and FLACCscale and heart rate, blood glucose levels; strong positive correlations (r=0.7-0. 9) with total leukocyte count and erythrocytesedimentation rate; moderate positive correlations (r=0.5-0.7) with serum TLR4 and CD40L levels; weak positive correlations(r&lt;0.5) with diastolic blood pressure, SpO2, and opioid and non-opioid analgesic administration.Conclusions. The observed positive correlations between acute pain scores on the VAS and FLACC scale and proinflammatory indicators may support the theory of involvement of these markers in the generation of acute pain in pediatricpatients. However, further research is needed to investigate the mechanisms of acute postoperative pain generation, to identify markers related to nociception in chronic pain, and to develop preventive strategies for these conditions in children.

Retracted: Effects of Modified Duhuo Jisheng Decoction Combined with Arthroscopic Surgery on Bone Metabolism, Oxidative Stress, and Serum TLR4 and TGF-β1 in Patients with Knee Osteoarthritis.

[This retracts the article DOI: 10.1155/2022/1933504.].

Investigation of the expression level and clinical significance of HMGB1, β1 globulin and TLR-4 in serum of children with rheumatoid arthritis.

Investigation of the expression level and clinical significance of HMGB1, β1 globulin and TLR-4 in serum of children with rheumatoid arthritis.

Toll-like receptor 2-mediated downstream cytokine levels as determinant of malaria pathogenesis.

Toll-like receptors (TLRs) are transmembrane proteins that recognize specific molecular patterns and activate downstream cytokine production usually for the eradication of invading pathogens. The objective of this study was to evaluate the genetic polymorphism of TLR2 Arg753Gln (rs 5743708) and soluble cytokines and TLR2 expression levels in malaria disease cases. The study included prospectively collected 2 ml blood samples from 153 individuals clinically suspected for malaria and confirmed by microscopy and RDT from Assam. Stratification of the study groups was done as healthy control (HC, n=150), uncomplicated malaria (UC-M, n=128) and severe malaria (SM, n=25). The PCR-restriction fragment length polymorphism (RFLP) method was applied for the analysis of TLR2 Arg753Gln polymorphism and following the ELISA for soluble serum TLR2 (sTLR2) and its associated downstream cytokines, viz. tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels. Variation in TLR2 Arg753Gln gene showed no association with the susceptibility and the severity of malarial infection. Soluble TLR2 expression was significantly higher in uncomplicated malaria (UC-M) cases compared to healthy controls (P=0.045) and in terms of SM cases, the expression was also found to be higher in UC-M cases (P=0.078). The TNF-α expression was significantly higher in SM cases compared to both UC-M and control (P=0.003 and P=0.004). Similarly, significantly elevated expression of IFN-γ was noted in SM cases compared to both UC-M (P=0.001) and healthy controls (P<0.001). The present study suggests the association of deregulated TLR2 pathway that leads to the deleterious downstream immune response in the development of malarial pathogenicity.

Immunological Study of Orthodontically Treated Patients Recovering from COVID-19 in Babylon Province, Iraq

Background and Objectives: This study aimed to examine the levels of the toll-like receptors TLR4 and TLR2 in the blood and saliva of patients with coronavirus disease-2019 (COVID-19) receiving orthodontic care in Babylon Province. Materials and Methods: Sixty serum and saliva samples were collected and divided into three groups of 20 patients: patients with COVID-19 who did not receive orthodontic treatment (group 1); patients with COVID-19 who received orthodontic treatment (group 2); and patients with COVID-19 who received orthodontic treatment and recovered (group 3). Thirty samples of serum and saliva from healthy outpatient clinics comprised the control group. Enzyme-linked immunosorbent assay was used to determine the result. Results: TLR4 levels in saliva increased in all experimental groups (1–3) as compared with the control group. However, only COVID-19 patients and orthodontic patients in group 2 had elevated blood levels of TLR4, whereas the levels were reduced in the other two groups (1 and 3). All experimental groups showed an increase in TLR2 levels in saliva relative to the control group. In the first and second experimental groups, serum TLR2 concentrations increased dramatically, whereas they declined in the third group. There was no correlation between TLR4 and TLR2 in either group of patients. The concentrations of TLR4 and TLR2 in saliva were higher in the experimental groups than in the control group.

MicroRNAs and cytokines as potential predictive biomarkers for COVID-19 disease progression

Host microRNAs can influence the cytokine storm associated SARS-CoV-2 infection and proposed as biomarkers for COVID-19 disease. In the present study, serum MiRNA-106a and miRNA-20a were quantified by real time-PCR in 50 COVID-19 patients hospitalized at Minia university hospital and 30 healthy volunteers. Profiles of serum inflammatory cytokines (TNF-α, IFN-γ, and IL-10) and TLR4 were analyzed by Eliza in patients and controls. A highly significant decrease (P value = 0.0001) in the expressions of miRNA-106a and miRNA-20a was reported in COVID-19 patients compared to controls. A significant decrease in the levels of miRNA-20a was also reported in patients with lymphopenia, patients having chest CT severity score (CSS) > 19 and in patients having O2 saturation less than 90%. Significantly higher levels of TNF-α, IFN-γ, IL-10 and TLR4 were reported in patients compared to controls. IL-10 and TLR4 levels were significantly higher in patients having lymphopenia. TLR-4 level was higher in patients with CSS > 19 and in patients with hypoxia. Using univariate logistic regression analysis, miRNA-106a, miRNA-20a, TNF-α, IFN-γ, IL-10 and TLR4 were identified as good predictors of disease. Receiver operating curve showed that the downregulation of miRNA-20a in patients having lymphopenia, patients with CSS > 19 and patients with hypoxia could be a potential biomarker with AUC = 0.68 ± 0.08, AUC = 0.73 ± 0.07 and AUC = 0.68 ± 0.07 respectively. Also, ROC curve showed accurate association between the increase of serum IL-10 and TLR-4 and lymphopenia among COVID-19 patients with AUC = 0.66 ± 0.08 and AUC = 0.73 ± 0.07 respectively. ROC curve showed also that serum TLR-4 could be a potential marker for high CSS with AUC = 0.78 ± 0.06. A negative correlation was detected between miRNA-20a with TLR-4 (r = − 0.30, P value = 0.03). We concluded that, miR-20a, is a potential biomarker of COVID-19 severity and blockade of IL-10 and TLR4 may constitute a novel therapy for COVID-19 patients.

Changes in the content of Puerarin-PLGA nanoparticles in mice under the influence of alcohol and analysis of their antialcoholism.

To observe the metabolic changes and antialcoholic effect of Puerarin-PLGA nanoparticles (PUE-NP) in mice. PUE-NP was prepared and characterized by particle size distribution and morphology. The mouse models with acute alcoholism were established to observe their behavioral changes after alcohol poisoning. The expressions of biologically active enzymes such as CRE, BUN, AST, ALT in serum and SOD and TLR4 in liver of mice in each group were detected, and the pathological changes in liver and kidney tissues were observed by HE staining. The PUE-NP metabolism in mice was determined by in vitro release assay and HPLC. PUE-NP nanoparticles had good morphology and structure, and the mouse models with alcohol poisoning were established successfully. Compared with alcohol group, puerarin and PUE-NP increased the disappearance latency time of righting reflex, and the recovery time of righting reflex was significantly shortened. Water maze results showed that Puerarin and PUE-NP had inhibitory effect on impaired memory. HPLC results showed that PUE-NP reached its peak in mice after 1 h, and the content percentage was twice that of puerarin preparation alone, and the distribution time of puerarin concentration in vivo was prolonged, indicating that PLGA nanoparticles had a loading and slow-release effect on puerarin and increased the bioavailability of puerarin in mice. In addition, compared with the alcohol group, Puerarin and PUE-NP improved serum ALT, AST, CRE, and BUN levels in mice, enhanced SOD activity in liver, and inhibited TLR4 expression. The effect was better in the PUE-NP group than in the Puerarin group. PUE-NP delayed the release and metabolism of Puerarin and had better effect in the treatment of the alcoholic liver and kidney injury.

Retracted: Application Value of Serum Hcy, TLR4, and CRP in the Diagnosis of Cerebral Small Vessel Disease.

[This retracts the article DOI: 10.1155/2022/4025965.].

Pattern recognition receptor CD14 gene polymorphisms in alcohol use disorder patients and its Influence on liver disease susceptibility.

BackgroundAlcohol use disorders (AUDs) leading to liver disease is major concern over other spectrum of disorder. Excessive alcohol consumption resulting in leaky gut syndrome is attributed to alcohol-induced liver injury through portal translocation of bacterial endotoxin. Susceptibility to alcoholic liver disease (ALD) in AUD patients could be dependent upon genes responsible for inflammation and alcohol metabolism. The pattern recognition receptor CD14 gene is a major player in endotoxin-mediated inflammation and susceptibility to ALD. This study investigated the genetic association of CD14 polymorphisms and other mechanisms relevant to altered inflammatory responses leading to ALD.MethodsPatients with alcohol use disorder with ALD (n = 128) and without liver disease (ALC, n = 184) and controls without alcohol use disorder (NALC, n = 152) from North India were enrolled. The CD4 gene polymorphisms in the North Indian population were evaluated by RFLP and sequencing. Secretory CD14 (sCD14), LBP, TLR4, MD2, TNFα, IL1b, IFNγ, IL6, IL10, and IL4 levels in serum were measured by ELISA among groups. The influence of polymorphisms on CD14 gene promoter activity and circulatory bacterial DNA level was determined.ResultsThe CD14 gene promoter and exonic region SNPs were found to be monomorphic, except for SNP rs2569190 for the North Indian population. The genetic association of SNP rs2569190(C/T) with the risk of developing ALD was found significant for TT genotype [ORTT, 95% CI = 2.19, 1.16–4.13 for ALD vs. ALC and OR, 2.09, 1.18–3.72 for ALD vs. NALC]. An increased sCD14 level was observed in AUD patients compared to NALC control. Increased levels of LBP, TLR4, TNFα, IL1β, IFNγ, and IL6 and reduced levels of MD2, IL10, and IL4 were observed among the ALD patients compared to the other two control groups. Elevated levels of pro-inflammatory and reduced levels of anti-inflammatory cytokines were observed in the risk genotype TT groups of ALD patients and the ALC group compared to NALC. Promoter activity was observed in the intronic region flanking SNPs and risk genotype can influence reporter activity, indicating CD14 gene expression.ConclusionEnhanced CD14 expression associated with inflammatory responses increases susceptibility to ALD in the TT genotype of AUD patients.

PI-10: DIETARY IRON RESTRICTION PROTECTS AGAINST VASO-OCCLUSION AND ORGAN DAMAGE IN SICKLE CELL DISEASE

Purpose: Sickle cell disease (SCD) is the most commonly inherited monogenic hemoglobinopathy and results from a mutation in the β-globin gene (HbS), leading to red blood cell (RBC) sickling, vaso-occlusive episodes (VOE), and organ damage. Chronic hemolysis, inflammation, and repeated red blood cell transfusions in SCD can disrupt iron homeostasis. Patients who receive multiple blood transfusions develop iron-overload, and another subpopulation of SCD patients manifest iron deficiency. SCD mice exhibit increased iron absorption via upregulation of the intestinal transcription factor hypoxia inducible factor-2a(HIF-2a) leading to the development of iron overload. Disruption of intestinal HIF-2a or limiting iron intake by dietary iron restriction in SCD mice, significantly reduced systemic iron overload, lowered cellular sickle hemoglobin as reflected by reduced RBC mean corpuscular hemoglobin concentration (MCHC), and consequently improved hemolysis and ameliorated anemia. Understanding iron homeostasis is therefore critical to SCD pathogenesis and holds the promise for identifying novel approaches to treat SCD. Materials and methods: SCD mice were generated by transplanting bone marrow cells from Berkeley SCD (Tg[Hu-miniLCRα1GγAγδβS]Hba−/− Hbb−/−) mice into 8-week old, lethally-irradiated C57BL/6J mice. Immediately after transplantation, SCD mice were fed either a regular-iron diet (Ctrl) containing 185 parts per million (ppm) iron or an otherwise identical iron-restricted diet (IRD) containing 3 ppm iron. VOE and organ damage analysis were done 3-4 months after treatments. Results: IRD resulted in a reduced organ iron concentration (Fig-1A) in SCD compared to Ctrl group, confirming that dietary iron restriction ameliorates organ iron deposition in SCD mice. SCD mice treated with IRD exhibited reduced MCHC (Fig-1B) and serum indirect bilirubin(IDBILC) (Fig-1C) indicating a decrease in cellular sickle hemoglobin and hemolysis. Furthermore, IRD reduced the fraction of aged neutrophils by >50% in SCD mice (Fig-1D), which corresponded with improved VOE parameters. Specifically, intravital microscopy (IVM) demonstrated elevated mean centerline RBC velocity and blood flow rate and decreased leukocyte adhesion in IRD compared to Ctrl mice (Fig-1E-G). Importantly, IRD led to prolonged survival after TNF-a challenge in SCD mice (Fig-1H). IRD resulted in a dramatic reduction in lung leukocyte infiltration, indicating significantly reduced lung inflammation in SCD mice (Fig-2A). Compared to Ctrl liver samples, IRD resulted in significantly less liver necrosis, leukocyte infiltration and fibrosis (Fig-2B,C), decreased serum liver enzymes (ALT, AST; Fig-2D), and reduced levels of total and direct bilirubin (TBILC, DBILC; Fig-2D).We further hypothesized that, in addition to reducing iron concentration in organs, IRD ameliorates organ damage by preventing translocation of microbial compounds.IRD inhibits translocation of FITC-Dextran by 5-fold compared to Ctrl suggesting functionally improved gut permeability (Fig-2E). We detected significantly decreased TLR2 ligands in serum of IRD mice (Fig-2F) suggesting ligands from gram-positive bacteria (TLR2 agonists) may play a role in triggering SCD complications. Conclusion: Our study demonstrates for the first time that dietary iron restriction reduces VOE severity and alleviates chronic organ damage in SCD mice. Novel approaches that target iron availability/absorption in the gut, the gut microbiome and aged neutrophil crosstalk and gut barrier integrity, provide an important area of further investigation with the potential of improving hemolysis, VOE, and organ damage in SCD patients.(A)The bone-marrow/spleen/liver Non-heme iron content. (B)MCHC, (C)IDBILC,(D)aged neutrophils percentage in Ctrl/IRD SCD mice. IVM parameters (E) (Vrbc) (F) blood flow rate (J) the number of adherent leukocytes and (J) survival rate after TNF-a injection(A)Leukocyte infiltration in lung and (B)liver tissue. (C)Liver necrosis, leukocyte infiltration, and fibrosis. (D)Liver ALT and AST, TBILC, and DBILC from sera. (E)serum FITC-Dextran and (F) TLR2 ligands activity in Ctrl/IRD SCD mice The authors do not declare any conflict of interest

The comparison of changes in fecal and mucosal microbiome in metabolic endotoxemia induced by a high-fat diet

The aim of this study was to compare the mucosal and fecal microbiota in a high fat diet-induced metabolic endotoxemia (ME) model and to identify potential species that represent dysbiosis and might mediate the inflammatory process. Fourteen male wistar albino rats were fed a standard diet (n = 7) and a high-fat diet (HFD) (n = 7). The standard diet (2600 kcal/kg) contained 3% of energy from fat and HFD (6740 kcal/kg) contained 67% beef tallow. After feeding for 12 weeks, all rats were sacrificed after fasting for 12 h and blood samples were collected. Fresh faecal samples and descending colon samples of rats were collected in sterile plastic tubes using a clean technique, immediately snap-frozen in liquid nitrogen, and then stored at −80 °C until used for analysis. Serum glucose, TRG, TLR4, LPS, and fecal LPS increased in the HFD group. On the contrary, HDL was higher and statistically significant in the CD group. The levels of IL-6 and TNF-α in the colon tissue of the HFD group were significant. The HFD group caused a significant increase in LPS levels in serum and feces. In addition, the gut and mucosal microbiome were positively/negatively correlated with the ME markers (IL-6, TNF-α, LPS). The results showed that gut and mucosal microbiome changes were associated with HFD. These changes were dense at species levels. The current study demonstrated changes in gut and mucosal microbiota in HFD-induced metabolic endotoxemia.

Correlation Analysis of Umbilical Cord Blood Metabolic Phenotype and Inflammation in Patients with Gestational Diabetes Mellitus Complicated with Overweight and Obesity.

Background Gestational diabetes mellitus (GDM) is a common metabolic disorder in pregnancy. The incidence rate is increasing year by year, which seriously threatens the safety of maternal and infant. Obesity is a vital factor in inducing GDM. Pregnant women with GDM account for a large proportion of overweight and obese pregnant women. Our study aimed to explore the potential mechanism of differential metabolites on inflammation and find the intervention and management methods for GDM in overweight and obese pregnant women. Methods Umbilical cord blood samples and placenta were collected from normal weight pregnant women with GDM (control group) and overweight and obese pregnant women with GDM (obesity group) for a comparative study. Serum inflammatory factors IL-10, TNF-α, IL-6, lipopolysaccharide (LPS), and TLR4 expression were detected by ELISA. The expression levels of BCL-2 and caspase-3 were measured by Western blot. TUNEL staining was used to observe the apoptosis of placental villi. KEGG combined with metabolomics was used to compare the differences of metabolic maps between the two groups. Results Compared with the control group, the level of anti-inflammatory factor IL-10 in the cord blood was decreased in the obesity group, while the levels of proinflammatory factors TNF-α, IL-6, and LPS were increased. In the placental tissues, the obesity group had higher concentrations of LPS, TLR4, and caspase-3 and lower concentration of BCL-2. Placental villi in the obesity group were more likely to undergo apoptosis than the control group. Correlation analysis showed that the above metabolite concentrations were negatively correlated with TNF-α or LPS. Conclusion Metabolites could control obesity in the process of controlling the occurrence and development of inflammation.

Correlation between innate and adaptive immunity response in TB children post BCG vaccination. Is it effective or not?: Cross-sectional study

BackgroundHow far the role of innate immunity and adaptive immunity do in children who have been BCG vaccinated in controlling the course and the severity of the TB disease has not been completely known. Mycobacterium tuberculosis entry to the body will be recognized by Toll-like receptors found on macrophages, neutrophils, and dendritic cells as part of the innate immune response, after which the dendritic cells will then present the antigen to lymphocyte T0 cells and initiate the adaptive immune response (of which CD4 T cells have an important role in). Was one or were both of these immune responses function well or not in a BCG Vaccinated Children with TB? ObjectiveThis study aim to find a better understanding of the role of innate immune response assessed by TLR2/TLR4 mRNA gene expression and serum TLR2/TLR4 levels, while the role of adaptive immune response is assessed by analyzing serum CD4 level in children with TB who have had BCG vaccination. MethodsThis cross-sectional study was conducted among children with TB at the outpatient and inpatient wards at Bhakti Medicare and Jakarta Islamic Hospital. Expression of mRNA gene was measured using the Boom method and protein serum levels were measured using the ELISA method. The results were analyzed by using the SPSS v.23 program. ResultsSixty-nine children were recruited as subjects. In this study, 68.1% of whom had BCG scars. TLR4 mRNA gene expression was found to be higher than TLR2 mRNA gene expression. Serum CD4 level was found to be highest out of TLR2 and TLR4 level, but serum TLR2 level was higher than TLR4 level. TLR2/TLR4 mRNA gene expression, serum TLR2/TLR4 levels, and CD4 levels in subjects with BCG scar were also found to be significantly higher than in subjects without BCG scar (p < 0.001). There was a significant positive correlation between TLR2/TLR4 mRNA gene expression and serum TLR2/TLR4 levels (r = 0.860; r = 0.864; p < 0.001) and between serum levels TLR2/TLR4 with serum CD4 levels (r = 0.822; r = 0.832 p < 0.001). ConclusionAs early as possible, BCG vaccine administration is needed in endemic countries, but it must be ensured that scars can be formed. It is also important to control Latent TB Infection (LTBI) to prevent transmission and relapse of disease.

PRETREATMENT WITH ERYTHROPOIETIN ALLEVIATES THE RENAL DAMAGE INDUCED BY ISCHEMIA REPERFUSION VIA REPRESSION OF INFLAMMATORY RESPONSE.

The aim: This study aimed to examine the anti-inflammatory, and antiapoptotic effects of erythropoietin against kidney injury inducted by ischemia reperfusion in experimental model. Materials and methods: 20 male Sprague Dawley rats were randomly divided into 4 equal groups: sham (subject to median laparotomy only), control (subject to 30 minutes ischemia and 2hours reperfusion), vehicle (injected by distilled water and subjected to the same procedure of ischemia reperfusion), erythropoietin group (as in vehicle group but the rats pretreated with 1000 U/kg of erythropoietin). The left kidney and blood specimen were collected. The blood utilized to assess serum creatinine. While kidneys utilized to assessed MCP-1, TLR2, and caspase-3 in addition to histopathological evaluation. Results: Control and vehicle samples showed that a significant elevation in serum creatinine, TLR2, caspase-3, and MCP-1 as compared with sham group. The histological eval¬uation showed a significant rise in kidney injury scores. Kidneys and blood samples of erythropoietin pretreated rats established histopathological and functional improvement as evidenced via reduced kidney injury scores in addition to the reduction in serum creatinine, as well as there were a significant diminished in caspase-3, MCP-1, and TLR2 levels when compared with control and vehicle groups. Conclusions: Erythropoietin has renoprotective effect against ischemia and reperfusion, which achieved by decrease the inflammatory response as well as antiapoptotic effect.

The effect of Borago officinalis on the signaling pathway of the NLRP3 inflammasome complex, TLR4 and some inflammatory cytokines in type II diabetic patients with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in which the lungs become severely inflamed, causing the alveoli to constrict or fill with fluid, which prevents the lungs from functioning properly. This disease becomes more dangerous when it occurs in patients with diabetes. Because of the clinical condition of these patients, it is not possible to treat them with usual medicines. One of the best options for treating these people is to use herbs. Borage (Borago officinalis) is a medicinal herb that, in addition to its anti-inflammatory properties, is also able to control blood sugar. Therefore, in the current study, the effect of borage oil was considered on the signaling pathway of the NLRP3 inflammasome complex, TLR4, and serum levels of inflammatory cytokines (IL-1? and IL-18) in type II diabetic patients with ARDS. For this purpose, 25 diabetic type II patients with ARDS were divided into three groups by ARDS Berlin Definition. Then, after providing the demographic and clinical characteristics of the patients, they were treated with 30 mg/day borage oil for seven days. The expression of NLRP3 and TLR4 genes (by Real-time PCR technique) and serum levels of IL-1? and IL-18 (by ELISA test) were evaluated before and after treatment with borage oil through blood samples taken from patients. The results showed that serum levels of inflammatory cytokines (IL-1? and IL-18), NLRP3 gene, and TLR4 gene were significantly decreased in diabetic type II patients with mild ARDS by treating with borage oil. IL-1? serum level and TLR4 were significantly decreased in diabetic type II patients with moderate ARDS. But there was not any significant decrease or increase in IL-1?, IL-18, NLRP3 gene, and TLR4 gene in diabetic type II patients with severe ARDS after 7 days of treatment with borage oil. According to the obtained results, borage oil can act as a double-edged blade. Thus, in the early and middle stages of ARDS, borage oil can be effective in reducing the inflammasome pathway of inflammation and also reduce blood sugar levels in these diabetic patients. But in the severe stage of ARDS, it not only does not help to treat the ARDS; it also increases systolic and diastolic blood pressure in diabetic patients.