Interleukin-6 Levels Research Articles

Levels of IL-6 and IL-8 in complicated versus uncomplicated urinary tract infection

Background: Urinary tract infections (UTIs) are one of the world's most frequent infectious diseases, affecting 150 million people each year and resulting in severe morbidity and high medical expenditures. UTIs can be clinically defined as uncomplicated UTIs (uUTIs) or complicated UTIs (cUTIs) to differentiate infections of benign origin from those with a higher risk of recurrence or progression to severe pathology. The aim of this study was to evaluate interleukin-6 (IL-6) and IL-8 as potential biomarkers in differentiating complicated and uncomplicated Methods: Ninety samples of urine were collected. There were 43 samples from healthy controls and 47 samples from UTI patients, those who have been clinically diagnosed with UTIs by the urologist. The serum IL-6 and IL-8 were measured using an enzyme-linked immunosorbent assay and commercially available kits. Results: The levels of both IL-6 and IL-8 were significantly higher in UTI patient then in control subjects (p=0.001, p=0.001). A significant difference was observed in the mean of level IL-6 between culture positive UTI patients and culture negative UTI patients (p=0.014). In addition, the type of bacterial growth, a significant difference was observed in the mean of serum IL-6 and IL-8 level in UTI caused by gram negative bacteria in comparison with UTI caused by gram positive bacteria. Conclusion: High levels of IL-6 are associated with the growth of gram-negative bacteria, and this indicates that gram-negative bacteria could induce stronger inflammatory responses than gram-positive bacteria. IL-8 levels are higher in UTIs caused by gram-negative bacteria. This result further supported the evidence that gram-negative bacteria are potent inducers of inflammatory responses.

Association between tumor necrosis factor-α gene polymorphism and interleukin-6 level with mortality of neonatal sepsis

Sepsis is a systemic infection that significantly causes morbidity and mortality among neonates, which is associated with immature immune response. Variations in the tumor necrosis factor-alpha gene (TNF-α) -308G/A may be linked to neonatal sepsis mortality by modulating interleukins (ILs) involved in the immune response cascade, such as IL-6. The aim of this study was to investigate the association between TNF-α -308G/A gene variation and IL-6 level with mortality of neonatal sepsis. A cohort of 30 neonates diagnosed with clinical sepsis was recruited. Blood culture was performed for all patients and serum IL-6 levels were examined 24 hours after suspected sepsis. Genetic analysis of TNF-α single nucleotide polymorphisms (SNP) -308G/A was conducted using polymerase chain reaction and DNA sequencing. The association was assessed based on bivariate logistic regression. We found that 12 (40%) of 30 patients had blood culture-proven sepsis. Genotype of TNF-α -308G/A stratified of the patients was 56.7% for GA and 43.3% for GG. There were no AA variations found in this study. There was no significant association between the TNF-α -308 G/A genotype and mortality in neonatal sepsis (p=0.211). Similarly, the allelic model of TNF-α -308 gene had no association with mortality (p=0.325). Additionally, there was no association between serum IL-6 level and mortality in neonatal sepsis (p=0.253). In conclusion, SNP of TNF-α -308 gene and IL-6 level are not associated with mortality in neonatal sepsis.

Anti-inflammatory effects of tiotropium in copd: a randomized double-blind trial

IntroductionChronic Obstructive Pulmonary Disease (COPD) is a major global health issue characterized by respiratory symptoms and exacerbations, significantly impacting mortality and quality of life. Muscarinic antagonists are known to prevent exacerbations, possibly by mitigating airway inflammation. This study evaluated the anti-inflammatory effects of tiotropium in patients with COPD by examining inflammatory protein profiles in sputum and blood, and genome-wide expression in sputum.MethodsWe conducted the prospective, double-blind, randomized-controlled ANTIOFLAM trial. Patients with COPD GOLD II and worse, aged≥40 years and with≥10 smoking pack years were included. After a 4-week wash-out period of inhaled corticosteroids (ICS) and anticholinergics, participants were randomized to 6 weeks of treatment with placebo or tiotropium (soft mist inhaler, 5 µg daily). Our primary endpoint was a decrease of sputum interleukin-6 and interleukin-8 levels in the tiotropium group when compared to the placebo group.ResultsWe evaluated samples of 33 participants (n=17 placebo and n=16 tiotropium). Changes in sputum proteins interleukin-6 and interleukin-8 were significantly higher after treatment with tiotropium when compared to placebo (p<0.05). Differential expression analysis did not reveal gene expression differences including interleukin-6 and −8.ConclusionWe did not find tiotropium to have anti-inflammatory effects in sputum or blood of patients with COPD. In contrast, we found 6 weeks of treatment with tiotropium to increase the concentration of almost all tested sputum inflammatory proteins when compared to placebo, while RNA expression levels did not change.

Impact of resistance training on salivary interleukin-6 and c-reactive protein – A scoping review

This review examines the impact of resistance training on salivary interleukin-6 (IL-6) and C-reactive protein (CRP). These biomarkers are essential indicators of inflammation and immune response. The study employed a systematic literature review method following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. 20 articles published so far were included in the literature review, sourced from various databases: PubMed, Google Scholar, ERIC, EBSCO, Embase, Medline, Global Health, and Scopus. Keywords including MESH terms “resistance training,” “salivary IL-6,” “salivary CRP,” and “inflammation.” The inclusion criteria were fixed to studies that involved human participants, measured salivary IL-6 and CRP, and incorporated resistance-training protocols. Studies were excluded if they focused on other forms of exercise or used invasive measurement techniques and were not randomized control traits or quasi-experimental trials. The study population in these articles includes a diverse range of patients, such as the general population, adults, elderly adults, individuals with type 2 diabetes, COVID-19 patients with and without diabetes, patients with systemic inflammation and cardiovascular disease, overweight and obese individuals, and men with varying levels of physical fitness. By focusing on salivary measurements, this review emphasizes non-invasive methods for monitoring the physiological effects of resistance training. This review highlights the potential of resistance training to modulate inflammation as measured by salivary biomarkers. It underscores the importance of considering various factors when designing training programs and interpreting their physiological impacts. The variability in findings suggests that the relationship between resistance training and salivary IL-6 and CRP is complex. The reductions in these markers observed in some studies may be attributed to the anti-inflammatory effects of regular exercise. The final remarks from an intense review of the literature have shown resistance training has the potential to influence salivary IL-6 and CRP levels, reflecting changes in systemic inflammatory and immune responses. However, the impact varies based on training protocols and individual differences. Resistance training and biomarkers have practical applications in physiotherapy, such as developing tailored treatment programs, making progressive load adjustments, selecting appropriate exercise modalities, and providing patient feedback and monitoring. Additionally, more focused studies could investigate the underlying mechanisms behind observed outcomes, and new technologies such as advanced imaging and biomarkers could be incorporated to gain deeper insights. Research could also explore the impact of combining resistance training with other therapeutic modalities or investigate the role of individualized treatments in enhancing patient outcomes.

Assessment of Metabolic Syndrome in Patients with Chronic Obstructive Pulmonary Disease: A 6-Month Follow-Up Study

Background/Objectives: The association between chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) is a common one, with long-term therapeutic and prognostic impact. In view of the high pulmonary and cardiovascular morbidity and mortality, self-management contributes to decreasing the risk of an acute cardiac event or pulmonary decompensation. Methods: We conducted a prospective cohort study on 100 patients admitted to Iasi Clinical Rehabilitation Hospital who were divided into two groups according to the presence (67 patients) or absence (33 patients) of MetS. All patients benefited from multidisciplinary counseling sessions on their active role in improving modifiable cardiovascular risk factors and thus increasing quality of life. The aim of this study was to examine the impact of metabolic syndrome on lung function and the role of self-management in a 6-month follow-up period. The demographic, anthropometric, cardiovascular risk factors, and respiratory function were analyzed at baseline and at 6 months. Results: The presence of MetS was associated with higher fasting blood glucose (p = 0.004) and triglycerides (p = 0.003) but not with higher levels of interleukins or TNF-alpha. At the 6-month follow-up, abdominal circumference, forced expiratory volume in one second (FEV1), dyspnea severity, and blood pressure values improved in male patients with COPD. Systolic and diastolic blood pressure decreased in the COPD group as a whole, but especially in male patients with and without associated MetS. BMI was positively correlated with FEV1 (r = 0.389, p = 0.001) and the FEV1/forced vital capacity (FVC) ratio (r = 0.508, p < 0.001) in all COPD patients and in the MetS subgroup. In the COPD group as a whole. the six-minute walk test (6MWT) results (m) were positively correlated with FEV1 and FVC. The correlation remained significant for FVC in COPD patients with and without MetS. An increase in BMI by one unit led to an increase in TG values by 3.358 mg/dL, and the presence of metabolic syndrome led to an increase in TG values by 17.433 mg/dL. Conclusions: In our study, MetS is a common comorbidity in patients with COPD and is associated with higher BMI, fasting glucose, and triglycerides but not with the inflammatory parameters. A mixed pulmonary–cardiovascular rehabilitation intervention leads to improvement in various parameters in both female and male COPD patients.

Outcomes and inflammation changes in different types of immunocompromised patients with critically ill COVID-19 admitted to ICU: a national multicenter study

BackgroundImmunocompromised patients face higher risks of Severe Acute Respiratory Syndrome Coronavirus 2 infection and co-infections, leading to a possibility of high disease severity and poor outcomes. Conversely, immunosuppression can mitigate the excessive inflammatory response induced by the virus, potentially reducing disease severity. This study aims to investigate the prognostic differences and early inflammatory response characteristics in various types of immunocompromised patients with severe coronavirus disease 2019 (COVID-19) admitted to intensive care unit (ICU), summarize their clinical features, and explore potential mechanisms.MethodsA retrospective analysis was conducted on critically ill COVID-19 patients admitted to the ICU of 59 medical centers in mainland China during the Omicron outbreak from November 2022 to February 2023. Patients were categorized into two groups based on their immunosuppression status: immunocompromised and immunocompetent. Immunocompromised patients were further subdivided by etiology into cancer patients, solid organ transplant (SOT) patients, and other immunocompromised groups, with immunocompetent patients serving as controls. The mortality rates, respiratory support, complications, and early inflammatory cytokine dynamics upon ICU admission among different populations were analyzed.ResultsA total of 2030 critically ill COVID-19 patients admitted to ICU were included, with 242 in the immunocompromised group and 1788 in the immunocompetent group. Cancer patients had a higher median age of 69 years (IQR 59, 77), while SOT patients were generally younger and had less severe illness upon ICU admission, with a median APACHE II score of 12.0 (IQR 8.0, 20.0). Cancer patients had a twofold increased risk of death (OR = 2.02, 95% CI 1.18–3.46, P = 0.010) compared to immunocompetent patients. SOT and cancer patients exhibited higher C-reactive protein and serum ferritin levels than the immunocompetent group in their early days of ICU admission. The CD8+ T cells dynamics were inversely correlated in cancer and SOT patients, with Interleukin-6 levels consistently lower in the SOT group compared to both immunocompetent and cancer patients.ConclusionCritically ill COVID-19 patients admitted to the ICU exhibit distinct clinical outcomes based on their immunosuppression status, with cancer patients facing the highest mortality rate due to variations in inflammatory responses linked to their immunosuppression mechanisms. Monitoring dynamic changes in inflammatory markers and immune cells, particularly CD8+ T lymphocytes and IL-6, may offer valuable prognostic insights for these patients.

Serum Biomarkers IL-6 and HIF-1α in Rosacea: Assessing Their Significance in Disease Pathogenesis and Telangiectasia Formation

Introduction: Rosacea, a chronic inflammatory disease primarily affecting the central part of the face, is a complex condition whose mechanisms are still not fully understood. However, research has indicated a positive correlation between two molecules: Hypoxia-inducible factor-1α (HIF-1α) and Interleukin-6 (IL-6). The levels of HIF-1α in rosacea patients have yet to be assessed. Objectives: In this study, the aim was to assess the levels of HIF-1α and IL-6 in patients with rosacea in relation to both the severity of the disease and the primary and secondary clinical manifestations of the condition. Methods: The study included patients diagnosed with rosacea and sex-and age-matched healthy volunteers (N: 40, N: 40). Serum HIF-1α and IL-6 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Results: When compared to the control group, serum levels of HIF-1α and IL-6 were significantly elevated in the patient group. A positive correlation was found between the level of HIF-1α and the severity of the disease (r: 0.374, p: 0.017). Furthermore, a significant association was observed between the presence of telangiectasia, one of the primary symptoms, and HIF-1α (r: 2.401, p: 0.016). Conclusion: The significantly elevated levels of IL-6 and HIF-1α in patients with rosacea compared to the control group support the hypothesis that they play roles in the pathogenesis of the disease. The correlation of HIF-1α with the severity of the disease and its significant elevation in patients with telangiectasia suggest its potential involvement in the pathogenesis of the disease, particularly in the formation of telangiectasia.

Evaluation of the Activity of Olibanum Oil as an Immune Booster in Rats

The applications of herbal medicine have recently acquired growing interest in range of the prophylaxis and treatment of diseases. Olibanum has been used since ancient eras and several reports studied the pharmacological characteristics of boswellic acid, particularly their effect on the inflammatory response, analgesic properties, and anti-arthritic activity mostly in cell lines, but new approaches include animal models to assess these natural derivatives effects taking into consideration of being safer than synthetic preparations. The impact of olibanum oil on several parameters was studied in rats during this study. These included white blood cell (WBC) count, lactate dehydrogenase (LDH), and C reactive protein (CRP), as well as other pro-inflammatory cytokines like tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), and the cytokine interleukin -10 (IL-10) that is anti-inflammatory. Total WBCs in addition to IL-10 levels significantly increased in the oil-treated group in comparison with the control one, while the rats treated with olibanum oil revealed a significant reduced level of LDH, CRP, IL-6 and TNF- α compared with the controls (p < 0.05). These outcomes indicate that olibanum oil treatment are manifested by cytokine changes, it can improve the anti-inflammatory response and down-regulate the pro-inflammatory cytokines. So, the promising impact of olibanum oils as an immunomodulator could be used in alternative therapies.

The Effect of Intermittent Pneumatic Compression Device Combined with Low-Molecular-Weight Heparin on the Prevention of Deep Vein Thrombosis in Elderly Patients after Femoral Neck Fracture Surgery.

Aims/Background Femoral neck fractures in elderly patients carry a high risk of developing deep vein thrombosis (DVT) due to prolonged immobilization and surgical intervention. This study examines the effectiveness of combining intermittent pneumatic compression (IPC) with low-molecular-weight heparin (LMWH) for preventing DVT in elderly patients following femoral neck fracture surgery. Methods A total of 150 elderly patients with femoral neck fractures, admitted between January 2022 and January 2024, were retrospectively selected, and their clinical data were analyzed. Based on the treatment methods, the patients were divided into a control group (n = 71) and a study group (n = 79). The control group received LMWH treatment, while the study group received a combination of LMWH and IPC. The incidence of DVT, surgical outcomes, hip joint function, coagulation function indicators, hemodynamic indicators, and serum pro-inflammatory factors were compared between the two groups. Results The results showed that the incidence of DVT in the study group was lower than in the control group (p = 0.017). There were no significant differences between the two groups in terms of intraoperative blood loss, postoperative drainage volume, or Harris scores (p > 0.05). After the intervention, the study group demonstrated higher levels of average velocity (Va), peak blood flow velocity (Vp), and blood flow (BF) compared to the control group (p < 0.05). Additionally, the activated partial thromboplastin time (APTT) and prothrombin time (PT) were longer, while the D-dimer (D-D) level was lower in the study group (p < 0.05). The study group also exhibited lower levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) (p < 0.05). Conclusion The results indicate that combining IPC with LMWH effectively reduces the incidence of postoperative DVT in elderly patients with femoral neck fractures, improves venous blood flow in the lower limbs, reduces vascular inflammation, and ensures safety.

Revisiting the markers interleukin-6 and glucagon-like peptide-1 for targeting low-grade inflammation in type 2 diabetes: a meta-analysis and our lab experience.

Type 2 diabetes (T2DM) manifests as pancreatic disorder as a consequence of low-grade systemic inflammation, attributed to upregulated levels of interleukin-6 (IL-6). This in turn is associated with a reduced incretin effect with lower circulatory GLP-1 levels. Therefore, its important to monitor the circulating IL-6 and GLP-1 levels for better management and outcomes in T2DM patients. Limited studies being available in literature on circulating concentrations of GLP-1 and IL-6 in T2DM patients, a meta-analysis was conducted by identifying 1558 studies from 3 databases. As per inclusion and exclusion criteria, the studies were screened for the 2-markers.Forest plots were drawn for standardized mean differences and median values were deduced from the datasets. In parallel, analysis was conducted to ascertain the expression levels of the markers by ELISA (n = 52 T2DM patients) in real time. The meta-analysis showed a significant (p < 0.01) standardized mean difference of 3.82 and 1.04 for IL-6 and GLP-1 respectively. The median values obtained from analysis for IL-6 were 26.50 pg/ml which were higher than the controls downregulated levels of GLP-1(8.77 pg/ml) were noted. The above findings are corroborated by the results of our experimental analysis with IL-6 concentrations at 11.603pg/ml and GLP-1 at 13.05pg/ml. The study highlights that systemic concentrations of IL-6 and GLP-1 correspond to a persistent low-grade inflammation and decreased incretin effect in T2DM patients which manifest as pancreatic β-cell dysfunction. The expression of the markers is inversely correlated and monitoring their levels is clinically important for targeting them through their potential antagonists thus reducing the risk of complications, thereby improving the quality of life of the patients.

Trastuzumab Potentiates Antitumor Activity of Thiopyrano[2,3-d]Thiazole Derivative in AGS Gastric Cancer Cells

Gastric cancer remains a significant therapeutic challenge, highlighting the need for new strategies to improve treatment efficacy. This study investigates the potential of combined therapy with the novel Thiopyrano[2,3-d]Thiazole derivative LES-6400 and the anti-HER2 antibody trastuzumab in AGS gastric cancer cells. The antitumor effects of the combined therapy were evaluated using various techniques, including the MTT assay for cell viability, [3H]-thymidine incorporation for DNA synthesis, and flow cytometry to assess apoptosis (Annexin V-FITC/PI staining), mitochondrial membrane potential (MMP), and inflammatory cytokine levels. ELISA was employed to measure the levels of IL-6, p53, and cytochrome C. The combination of LES-6400 (1 µM) and trastuzumab (10 µg/mL) demonstrated superior antitumor activity compared to monotherapy with either agent in AGS gastric cancer cells. The combination therapy enhanced apoptosis, presumably by inducing oxidative stress in the cells and disrupting mitochondrial membrane potential. Additionally, a significant increase in p53 protein levels and modulation of interleukin levels, including a marked reduction in IL-6 levels, were observed, suggesting an impact on apoptotic and inflammatory responses. These findings indicate that the combined use of LES-6400 and trastuzumab is a promising therapeutic strategy for gastric cancer, warranting further investigation into the mechanisms of action and potential clinical applications of this combined approach.

Human Amniotic Epithelial Stem Cells Promote Functional Recovery After Spinal Cord Injury In Rats By Regulating The Polarization Of Macrophages.

Spinal cord injury (SCI) is a catastrophic nerve injury caused by extremelysevere damage to thespinalcord, for which effective treatments are currently unavailable. Human amniotic epithelial stem cells (hAESCs) are considered promising candidates for transplantation in various clinical and preclinical applications, due to their lack of limitations such as ethical barriers, immune rejection, tumorigenicity, or cell origin. Nevertheless, the effectiveness and mechanism by which hAESCs treat SCI remain elusive.To assess the motor function recovery process following SCI in rats, the Basso Beattie Bresnahan (BBB) behavior test, inclined plate scale and motor evoked potential (MEP) analysis were used in this study after transplantation of hAESCs at different doses. And the underlying mechanism was investigated by histological and molecular methods. The transplantation of hAESCs can significantly promote the recovery of motor function in SCI group, and the higher the dose, the better the effect. Compared with SCI group, hAESCs group had reduced tissue damage, significantly increased the number of neurons, neurofilaments and myelin sheath, and significantly reduced syringomyelia and glial scars. In addition, hAESCs inhibited the Levels of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) and increased the expression of the interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13), and promoted the shift of M1-polarized macrophages to M2-polarized macrophages. Our results demonstrate that hAESCs promoted the recovery of motor function after SCI by promoting M2 polarization of macrophages and reducing neuroinflammation.These findings may provide novel therapeutic strategies for SCI.

Noncontact 3D Bioprinting of Proteinaceous Microarrays for Highly Sensitive Immunofluorescence Detection within Clinical Samples.

Immunofluorescence assays are extensively used for the detection of disease-associated biomarkers within patient samples for direct diagnosis. Unfortunately, these 2D microarrays suffer from low repeatability and fail to attain the low limits of detection (LODs) required to accurately discern disease progression for clinical monitoring. While three-dimensional microarrays with increased biorecognition molecule density stand to circumvent these limitations, their viscous component materials are not compatible with current microarray fabrication protocols. Herein, we introduce a platform for 3D microarray bioprinting, wherein a two-step printing approach enables the high-throughput fabrication of immunosorbent hydrogels. The hydrogels are composed entirely of cross-linked proteins decorated with clinically relevant capture antibodies. Compared to two-dimensional microarrays, these proteinaceous microarrays offer 3-fold increases in signal intensity. When tested with clinically relevant biomarkers, ultrasensitive single-plex and multiplex detection of interleukin-6 (LOD 0.3 pg/mL) and tumor necrosis factor receptor 1 (LOD 1 pg/mL) is observed. When challenged with clinical samples, these hydrogel microarrays consistently discern elevated levels of interleukin-6 in blood plasma derived from patients with systemic blood infections. Given their easy-to-implement, high-throughput fabrication, and ultrasensitive detection, these three-dimensional microarrays will enable better clinical monitoring of disease progression, yielding improved patient outcomes.

Associations between circulating interleukin-18 levels and adult-onset Still’s disease: a meta-analysis

Associations between circulating interleukin-18 levels and adult-onset Still’s disease: a meta-analysis

Interleukin-6 levels in atrium and onset of spontaneous atrial fibrillation: is there a causal relationship

Abstract Background Cumulative evidence suggests that atrial interleukin-6 (IL-6) may play a significant role in the development of spontaneous postoperative atrial fibrillation (sPOAF) in coronary artery bypass grafting (CABG) patients. Our previous studies found that the IL-6 produced by the atrium is positively related to the development of sPOAF. However, the causal relationship between IL-6 and sPOAF is not established. Purpose This study aims to explore the potential causality between atrial IL-6 and spontaneous AF(sAF), alongside assessing the impact of IL-6 on the electrophysiological properties of atrial myocytes (AM). Methods To determine the causal link between IL-6 and sAF, mice were randomly divided into eight groups: seven receiving injections of varying doses of recombinant IL-6 protein groups (15ng/kg to180ng/kg) into the left atrial wall, and one control group (vehicle). Mice were monitored for sAF for 7 days using implanted telemetry device. At 48 hrs post-injection, the left atrial appendages of another set of mice were collected for analyzing levels of IL-6, Myeloperoxidase (MPO), Transforming Growth Factor-β1 (TGF-β1), and Tumor Necrosis Factor-α (TNF-α). To assess the effect of IL-6 on the electrophysiological characteristics of AM, AMs were isolated from the hearts of 12-week-old mice and divided into experimental and control groups for electrophysiological testing. The experimental group was perfused with extracellular solutions containing 100 ng/mL of IL-6 while the control group was perfused with standard extracellular solutions. The measurements focused on action potential (AP), transient outward potassium current (Ito), and inward rectifier potassium current (Ik1) after a 30-minute perfusion. Results As depicted in Fig. 1A, a dose-response relationship between IL-6 levels and sAF occurrence was observed, with incidence increasing from 0% at 15 ng/kg to 75% at 180 ng/kg (χ²= 16.691, P = 0.005). The injection of IL-6 also induced the production of MPO, TGF-β1, and TNF-α with a dose-dependent effects (Fig. 2). In comparison to control, the AP duration at 90% (APD90) and APD50 of repolarization of atrial myocytes were significantly shortened in IL-6 group (Fig. 1B). For voltages from -10mV to +70mV, atrial myocytes in the IL-6 group showed significantly lower Ito current density than those in the control (Fig. 1C). No significant alterations were observed in the impact of IL-6 on Ik1 current density in atrial myocytes (Fig.1D). Conclusion To the best of our knowledge, this is the first study that experimentally tested the causal relation between IL-6 and sAF. The injection of IL-6 could cause the onset of sAF and produce MPO, TGF-β1, and TNF-α with a significant dose-dependent effect. The effect of IL-6 on inducing sAF might be through its effect on reducing APD and Ito current density in mouse atrial myocytes. This suggests that inhibition of atrial IL-6 might be a potential novel sPOAF prevention strategy.

Co-frequency or contrary? The effects of Qiwei Baizhu Powder and its bioactive compounds on mucosa-associated microbiota of mice with antibiotic-associated diarrhea

Qiwei Baizhu Powder (QWBZP) has been proven effective in treating antibiotic-associated diarrhea (AAD), and the mechanism is associated with regulating the gut microbiota. However, the role of the bioactive compounds of QWBZP in regulating the gut microbiota is still unclear. In this study, 24 mice were divided into a normal control group (N), a model group (R), a QWBZP decoction group (TW), and a QWBZP-TG group (TG). AAD mouse models were established by mixed antibiotic administration. After modeling, mice in the TW group and TG group were treated with QWBZP decoction and QWBZP-TG, respectively. Mice in the N group and R group were gavaged with sterile water. 16S rRNA gene sequencing was used to investigate the changes of mucosa-associated microbiota (MAM) in the small intestine of mice. Moreover, the levels of diamine oxidase (DAO), D-Lactate, secretory immunoglobulin A (sIgA), interleukin 6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay (ELISA) kits. The results showed that QWBZP-TG significantly altered the diversity, structure, and abundance of MAM in the AAD mice. QWBZP-TG exerted a stronger suppression effect on Escherichia and Clostridium compared with QWBZP decoction. Meanwhile, QWBZP-TG downregulated the abundance of Lactobacillus, which elicited an opposite effect to QWBZP decoction. Prevotella was the signature bacteria that responded to the QWBZP-TG intervention. Furthermore, both QWBZP decoction and QWBZP-TG decreased the levels of DAO, D-Lactate, sIgA, IL-6, and TNF-α in the AAD mice. The role of glycosides is to help QWBZP ameliorate diarrhea symptoms by inhibiting the proliferation of diarrhea-associated bacteria, reducing inflammation and regulating immunity.

Partial deletion of the Akap1 gene promotes abnormalities in gut barrier function, gut microbiota composition and cardiac function during cardiovascular aging in mice

Abstract Background Cardiovascular aging is characterized by mitochondrial dysfunction, changes in intestinal permeability and microbiota composition. Mitochondria-targeted A-kinase anchoring proteins (mitoAKAPs) are a group of structurally diverse proteins binding the regulatory subunits of protein kinase A (PKA), and targeting PKA at discrete intracellular locations. We analyzed the effects of global partial genetic deletion of Akap1 on intestinal barrier permeability, microbiota composition, inflammation, and cardiac function during aging in mice. Purpose The proposal of this study was to determine the role of mitoAKAPs in the gut-heart axis during cardiovascular aging. Methods Young (4-6-month) and old (18-24-month) genetically modified Akap1+/+ and Akap1+/− mice of either sex underwent evaluation of cardiac function by transthoracic echocardiography. To evaluate gut barrier integrity, we analyzed expression levels of intestinal junction proteins occludin (Ocln), zonulin (Tjp1) in colonic samples and FITC-dextran permeability in vivo, circulating levels of Tumor Necrosis Factor-alpha (TNF-alpha), Lipopolysaccharide (LPS), Interleukin-1 (IL-1) and Interleukin-10 (IL-10). Fecal microbial composition was evaluated by Illumina Mi-Seq, Gut microbiota differences based on 16S rDNA sequencing at genus and species taxonomic levels were identified using linear discriminant analysis (LDA) combined with effect size (LEfSe) algorithm. Finally, faecal microbiota transplantation (FMT) was performed for five weeks to test whether modification of gut microbiota composition can affect cardiac function. Results A reduction in % left ventricular shortening (FS%) was observed in young and old Akap1+/- mice compared to Akap1+/+ mice. This finding was associated to increased intestinal permeability, as indicated by reduced mRNA levels of Ocln and Tjp1, increased LPS traslocation across intestinal epitelium into blood in 24m Akap1+/- mice compared to Akap1+/+. Through the analysis of the microbial signature, we observed the different bacterial species present in the microbiota of the experimental groups. FMT of bacteria species from old Akap1+/− to young Akap1+/+ mice induced gut abnormalities and cardiac dysfunction, while FMT from young Akap1+/+ donors ameliorated cardiac dysfunction in old Akap1+/+ mice. Conclusions MitoAKAPs play a crucial role in the maintenance of intestinal barrier function, gut microbiota composition and cardiac function during aging. Modulation of the composition of the intestinal microbiota influences intestinal permeability and cardiac function. MitoAKAPs could represent an important diagnostic and therapeutic target for cardiac and intestinal dysfunction.

Mizhuo Guanchangye enema delays the decline of renal function in rats with chronic kidney disease by intervening in the TLR4/MyD88/NF-κB pathway

BackgroundChronic kidney disease (CKD) is a prevalent chronic condition that poses a significant threat to human health. There is a close connection between the gut and kidneys, jointly influencing the onset and progression of CKD through the “gut-kidney axis.” Traditional Chinese medicine has shown potential in CKD treatment, but the specific mechanisms require further investigation.ObjectivesThis study aims to explore the protective effects of Mizhuo Enema (MZGCY) on kidney function in CKD rats by regulating the TLR4/MyD88/NF-κB signaling pathway.MethodsThe researcher employed a CKD rat model, which was divided into four groups: Control, Model, half-dose Mizhuo Guanchangye (1/2 MZGCY), and full-dose Mizhuo Guanchangye (MZGCY). Post enema administration, assessments were conducted on kidney function indicators, which included blood urea nitrogen (BUN), serum creatinine (SCR), and 24-h urinary protein. Additionally, measurements were taken for intestinal toxic substances such as indoxyl sulfate (IS) and lipopolysaccharide (LPS), as well as inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Examinations of pathological changes in both the intestines and kidneys were also performed. During this process, immunofluorescence was utilized to detect the expression levels of proteins toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor kappa B (NF-κB) in the intestinal tissues.ResultsIt was found that after enema treatment, the BUN, SCR, and 24-h urinary protein levels in the MZGCY and 1/2 MZGCY groups significantly decreased, indicating notable improvement in kidney function. Compared to the model group, the IS, LPS, IL-6, and TNF-α levels in the MZGCY and 1/2 MZGCY groups were significantly reduced. Immunofluorescence showed a marked decrease in the expression of TLR4, MyD88, and NF-κB proteins in the intestines of the MZGCY group.ConclusionMZGCY significantly reduces the levels of intestinal toxins and inflammatory factors in the serum of CKD rats by interfering with the TLR4/MyD88/NF-κB signaling pathway, thereby improving intestinal and renal pathological changes and delaying CKD progression. This study demonstrates that MZGCY has significant renal protective effects, providing a new potential approach for CKD treatment.

Exercise-induced inflammatory and thrombotic acute phase response in hypertensive patients

Abstract Background/Introduction Vigorous physical activity may acutely trigger the onset of an acute coronary syndrome especially in sedentary persons with established cardiovascular risk factors such as arterial hypertension. The rupture of an inflamed coronary plaque and the activation of the coagulation cascade are the main underlying mechanisms. Purpose The present study aimed to determine the effect of acute exercise on the inflammatory and thrombotic response in patients with arterial hypertension as compared to normotensive peers. Methods After excluding patients with any inflammatory or/and coronary artery disease, a total of 60 non-treated hypertensive patients and 65 normotensive individuals underwent a maximal treadmill exercise testing. Βlood samples were drawn at rest and immediately after peak exercise. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cell (WBC), interleukin-6 (IL-6), and total fibrinogen (TF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity were measured. Results All biomarkers increased with exercise, except PAI-1, which decreased (P&amp;lt;0.05 for the change between resting and peak exercise for all biomarkers). The normotensive group had less marked (P&amp;lt;0.05) exercise-induced changes than the hypertensive group in hsCRP (7.7 vs. 8.6%), SAA (5.6 vs. 11.9%), WBC (45.0 vs. 51.7%), and PAI-1 (-17.3 vs. -20.1%) and a similar (P=NS) change in IL-6 (23.8 vs. 23.0%) and TF (8.5 vs. 8.5%) (see also Figure). Conclusion(s) In conclusion, the exercise-induced inflammatory and thrombotic acute phase response seems to be more pronounced in non-treated hypertensive patients than in normotensive controls. The effect of blood-pressure lowering treatment on the exercise-induced acute phase response remains to be elucidated.Figure

Evaluation of aortic inflammation in marfan syndrome patients with 18-fluorodeoxyglucose positron emission and computed tomography

Abstract Background The role of inflammation in Marfan Syndrome (MS) has been well studied in current research. These studies have investigated the role of serum Interleukin 6 (IL-6), Transforming Growth Factor-b (TGF-b) and Macrophage Colony Stimulating Factor (MCSF) as biomarkers of disease severity and progression. Surgical repair is the recommended treatment of aortic aneurysms when aortic diameter reaches the indication threshold. It has been observed however that dissection may occur even before this threshold is reached. 18-fluorodeoxyglucose (18 F-FDG) positron emission tomography / computed tomography (PET/CT) is the gold standard imaging modality to noninvasively assess vascular inflammation. Purpose Our aim was to investigate whether MS patients have increased aortic wall inflammation as assessed by 18F-FDG PET/CT, and the relationship between aortic wall inflammation with serum levels of IL-6, TGF-b and MCSF. Methods The study population consisted of fifteen MS patients and seventeen sex and age matched controls. In all subjects, serum levels of circulating IL-6, TGF-b and MCSF were measured. In PET/CT, the arterial target-to-background ratio (TBR) was calculated for aortic root (AR), ascending aorta(As), aortic arch (AA) and descending aorta (DA). Also, all patients were assessed with transthoracic echocardiography where the diameters of AR, As, AA, and DA were estimated at baseline and were reexamined at the end of the follow up period. Results TBR for MS vs. controls was 2.17±0.75 vs 2.01±0.36, p=0.75 at AR; 2.15±0.67 vs 1.84±0.35, p=0.040 at As; 2.16±0.64 vs 1.70±0.25, p=0.03 at AA and 1.97±0.52 vs 1.83±0.42, p=0.23 at DA respectively. Additionally, Marfan patients had increased levels of serum biomarkers. However, this difference was statistically significant (SS) only for IL-6 serum levels; 2.17±0.46 vs 1.08±0.12 p=0.011 and IL-6 was SS associated with AR TBR (rho=0.572, p=0.033), As TBR (rho=0.604, p=0.022) and DA TBR (rho=0.714, p=0.004). Two of our patients were operated due to severe dilatation of the aortic root and the surgical specimens showed aortic wall inflammation of moderate severity along with fibrosis. Conclusion MS patients have increased of aortic wall inflammation as assessed by 18F-FDG PET/CT, a finding that highlights the role of inflammation in the pathway of disturbed TGF signaling. Further research is needed to determine its prognostic role and value in identifying patients with an indication for early intervention.