Increase In IL-6 Levels Research Articles

Effects of Inhaled Corticosteroids/Long-Acting Beta-Agonists (ICS/LABA) on Airway Microbial Diversity and IL-8/IL-10 Cytokine Levels in Stable COPD.

Chronic Obstructive Pulmonary Disease (COPD) is a severe respiratory system disorder. In recent years, the combined therapy of inhaled corticosteroids/long-acting beta-agonists (ICS/LABA) has become the primary treatment for stable COPD patients. This study aimed to investigate the effects of ICS/LABA treatment on the airway microbiota and inflammatory profiles in COPD patients. Respiratory samples were collected from 18 individuals, including 2 healthy controls, 4 COPD patients, and 12 COPD patients receiving ICS/LABA treatment. Microbial diversity sequencing was employed to analyze the respiratory microbiota, with both diversity and functional predictions performed. Inflammatory factor levels were assessed using enzyme-linked immunosorbent assay (ELISA). The COPD group exhibited a dysregulated respiratory microbiota compared to the control group. Compared to the COPD group, patients in the ICS/LABA treatment group showed a trend toward decreased α-diversity of bacterial communities in the respiratory tract, while the α- diversity of fungi significantly increased. Post-treatment, the abundance of Streptococcus and Fusicolla decreased, whereas the abundance of Moraxella and Candida increased in the respiratory tract. These findings suggest that ICS/LABA treatment may help maintain a balanced respiratory microbiota. Furthermore, patients in the treatment group exhibited a significant decrease in IL-8 levels and a notable increase in IL-10 levels, indicating that ICS/LABA therapy may modulate cytokine levels by suppressing inflammatory responses and promoting anti-inflammatory reactions. The combined therapy of inhaled corticosteroids/long-acting beta-agonists (ICS/LABA) appears to regulate the gene functions of respiratory tract microbiota and IL-8/IL- 10 levels in stable COPD patients. These findings offer new insights into personalized COPD treatment and microbial interventions.

Proof of Concept: Effects of an Immune-Enhancing Formula on Clinical Markers of Critical Coronavirus Disease 2019 Cases

Background/Objectives: The rapid viral spread observed in coronavirus disease 2019 (COVID-19) is capable of inducing the secretion of excessive inflammatory cytokines. The resulting multi-organ damage is a severe complication that can be attenuated through adequate nutrition. Formulae enhanced with either glutamine or arginine are conditionally essential amino acids that have been proven to improve the condition of hospitalized patients. This retrospective study aimed to investigate the effects of administering an immune-enhancing enteral formula enhanced with arginine and glutamine on the clinical signs and biomarkers of patients with severe COVID-19. Methods: After checking the data of 232 patients enrolled in the biobank for completeness and eligibility, 31 patients with severe COVID-19 in the intensive care unit at Taipei Tzu Chi Hospital were grouped based on the type of enteral formula used: 16 patients received the control formula, and 15 patients received the immune-enhancing formula. Baseline characteristics, clinical signs, and inflammatory markers were analyzed for differences. Results: An increase in IL-10 levels in the intervention group was observed (p = 0.048). Changes in other inflammatory cytokine levels were insignificant. Conclusions: Providing an enteral formula enriched with glutamine and arginine to severe COVID-19 patients may help improve their anti-inflammatory marker levels. Further interventional study utilizing enteral formula enriched with glutamine and arginine is needed to confirm the findings of this study.

Effect of Feeding Frequency on the Growth, Body Composition, and Intestinal Health of Hybrid Grouper (Epinephelus fuscoguttatus♀ × E. lanceolatu♂) Fed a High-Fat Diet

This experiment was to investigate the effects of feeding frequency on the growth performance, body composition, and intestinal health of hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatu ♂). Fifty-six days of feeding with four different feeding frequencies (1 time/day, 2 times/day, 3 times/day, and 4 times/day) were conducted on groupers with an initial body weight of 11.51 ± 0.02 g. The results show the following: (1) Weight gain rate (WGR) and specific growth rate (SGR) of the groupers in the 1 time/day group were significantly lower than in other groups (p < 0.05). (2) Superoxide dismutase (SOD) had the lowest value in the 1 time/day group, significantly lower than the 2 times/day and 4 times/day groups, catalase showed an upward trend, and the 4 times/day group was significantly greater than the other groups (p < 0.05). The total antioxidant capacity (T-AOC) and glutathione peroxidase (GPX) activities in the 1 time/day group were significantly lower than in the other groups (p < 0.05). (3) The increase in feeding frequency led to a significant increase in the expression levels of cat and il-6 (p < 0.05). In summary, appropriate feeding frequency can promote growth and enhance the antioxidant capacity of the fish’s gut. We recommend a best feeding frequency of 2 times/day.

The Role of TRPM2 Channel in Doxorubicin-induced Cell Damage in Laryngeal Squamous Cancer Cells.

Laryngeal squamous cell carcinoma is a common type of head and neck cancer. This study investigated the role of the TRPM2 channel in doxorubicin (DOX)-induced cell damage in human laryngeal squamous cancer cells (Hep-2). Cells were exposed to various DOX concentrations and the appropriate dose was found. Then, TRPM2 antagonist ACA was treated. At the end of the study, cell viability test, Western blot and oxidative stress and inflammatory markers were examined. The results showed that TRPM2 channel expression increased with DOX administration, and DOX incubation in cells caused an increase in ROS, MDA, IL-1β, IL-6, and TNF-α levels, while GSH and GSH-Px levels decreased. Concurrent treatment with ACA attenuated these effects and reduced oxidative stress and inflammation. In addition, DOX-induced apoptosis markers including Casp-3, Casp-8, Casp-9, p53, and Bax were elevated, while Bcl-2 levels were decreased; ACA treatment reversed these changes. The study demonstrated that DOX treatment significantly enhances TRPM2 channel activation and ROS production in Hep-2 cells, thereby initiating apoptotic pathways that lead to cell death. Consequently, targeting the TRPM2 channel may represent a promising therapeutic strategy for treating laryngeal cancer.

Imbalanced VWF-ADAMTS13 axis contributes to the detrimental impact of a preceding respiratory tract infection on stroke.

Respiratory tract infections (RTIs) caused by bacteria or viruses are associated with stroke severity. Recent studies have revealed an imbalance in the von Willebrand factor (VWF)-ADAMTS13 axis in patients with RTIs, including COVID-19. We examined whether this imbalance contributes to RTI-mediated stroke severity. Wild-type (WT), Vwf -/-, or Adamts13-/- mice with respective littermate controls (Vwf +/+, or Adamts13+/+) were infected intranasally with sublethal doses of S. aureus (on days 0, 2, and 5) or mouse-adapted SARS-CoV-2 (on day 0) and subjected to transient (30 or 45 min) cerebral ischemia followed by reperfusion. In S. aureus-infected mice, infarct volumes were assessed on day 2 and functional outcomes on weeks 1 and 4 post-reperfusion. In SARS-CoV-2-infected mice, infarct volumes and functional outcomes (Bederson score) were assessed on day 1 post-reperfusion. We demonstrated that S. aureus or SARS-CoV-2 RTI was accompanied by an imbalance in the VWF-ADAMTS13 axis and an increase in plasma levels of IL-6, CXCL1, and MCP-1, which was associated with larger infarcts and worse functional outcomes (P<0.05 vs. mock-infection). S. aureus- or SARS-CoV-2-infected Vwf -/- mice exhibited reduced infarcts and improved functional outcomes, while infected Adamts13-/- mice displayed greater stroke severity (P<0.05 vs. control). In the models of RTI preceding stroke, VWF contributes to stroke severity, while ADAMTS13 is protective.

Effect of cytotoxic CD8+ T-cells secretory proteins on hypoxic pancreatic cancer cells.

Hypoxia in tumor cells is linked to increased drug resistance and more aggressive behavior. In pancreatic cancer, the tumor microenvironment is notably hypoxic and exhibits strong immunosuppressive properties. Given that immunotherapy is now approved for pancreatic cancer treatment, further understanding of how pancreatic tumor cell hypoxia influences T-cell cytotoxicityis essential. This study examined how hypoxia affects the interaction between pancreatic tumor cells (PANC-1) and cytotoxic CD8+ T-cells. Pancreatic tumor cells (PANC-1) were exposed to 20 cycles of chronic hypoxic conditions, each for 72 hours, followed by a re-oxygenation period for 24 hours. On cycles 10 and 20, PANC-1 conditioned media (CM) was harvested, and the hypoxic PANC-1 cells were co-cultured with either the activated cytotoxic CD8+ T-cells or with CD8+ T-cells CM. CD8+ T-cells CM was collected after five days of cell activation using anti-CD3/CD28 antibodies and interleukin-2 (IL-2). CD8+ T-cells were activated for 72 hours and then cultured with the hypoxic PANC-1 CM. Hypoxic PANC-1 cells showed significant resistance to the lytic effect of either CD8+ T-cells co-culture or CD8+ T-cells CM treatment compared to normoxic PANC-1 cells. A significant decrease in TNF-α and IFN-γ levels was also detected. Additionally, a significant increase in IL-6, p53 and TNF-α gene expression levels was observed in PANC-1 cells treated with CD8+ T-cells CM. Moreover, IL-6 gene expression level showed a significant difference between hypoxic and normoxic PANC-1 cells. CD8+ T-cell proliferation and cytokines production were significantly higher in cells co-cultured with PANC-1 CM. However, no significant differences were observed after treatment with either hypoxic or normoxic PANC-1 CM. Hypoxia decreases PANC-1 cells' sensitivity to cytotoxic CD8+ T-cells. Reduced tumor cell susceptibility to CD8+ T-cells was associated with increased IL-6 expression and reduced TNF-α and IFN-γ levels. Thus, cytokine dysregulation might contribute to the hypoxia-mediated resistance of pancreatic tumor cells to CD8+ T-cells.

The impact of drug eluting stents on the co-release of interleukin-6 in patients with stable angina

Background: Drug-eluting stents represent an important revolution in the treatment of coronary artery disease. However, the mechanical trauma of stent deployment can trigger vascular injury and inflammatory cytokine cascades, potentially precipitating in-stent restenosis. The release of cytokines is not firmly established in patients with stable angina. Aims: To evaluate the acute effect of drug-eluting stents on the acute inflammatory response in patients with stable angina by quantifying interleukin-6 levels. Methods and materials: A single-centre exploratory study was conducted on 13 patients with stable angina undergoing elective angioplasty. Arterial blood samples were collected before angioplasty and directly after angioplasty. Additionally, venous blood samples were collected 24 hours post-angioplasty. Concentrations of interleukin-6 were analysed to assess changes in the acute inflammatory response. Results: IL-6 concentration significantly increased immediately after stent placement (5.95 ± 0.49 pg/ml, p = &lt;0.05) and 24 hours post-stent placement (8.96 ± 1.16 pg/ml, p= &lt;0.01). Gender-based analysis indicated significant increases in IL-6 levels in males post-stent placement (5.94 ± 0.08 pg/ml, p= &lt; 0.05) and 24 hours post-stent placement (7.27 ± 0.56 pg/ml, p= &lt; 0.01). Statin medication significantly reduced IL-6 expression in patients at baseline (3.27 ± 0.71 pg/ml versus 5.44 ± 0.18 pg/ml, p= &lt; 0.05), but this distinction diminished rapidly after stent insertion, resulting in comparable IL-6 levels at 24 hours post-stent insertion in both groups. Conclusion: Interleukin-6 levels markedly increased immediately after coronary stenting, suggesting its role as an early initiator of the inflammatory response to coronary stenting. While limited by sample size, it lays the groundwork for larger, more comprehensive research to optimize drug-eluting stents outcomes and inflammatory management.

Association of Toxoplasmosis with Serum TGF-β, IL-17, and IL-6 Levels in Individuals with Diabetes

Cytokines play an essential role in regulating the interaction of immune cells in diabetes and infections such as toxoplasmosis. The purpose of this study was to examine the serum levels of interleukin (IL)-6, IL-17, and transforming growth factor-beta (TGF-β) in patients with type 1 and type 2 diabetes mellitus with toxoplasmosis, and to explore their inter-relationship. Forty patients with diabetes mellitus, including 20 with type 1 and 20 with type 2, as well as 20 healthy subjects, voluntarily participated in the study. Each subject provided 5 mL of peripheral blood for enzyme-linked immunosorbent assay. Subjects with type 2 diabetes mellitus who also had toxoplasmosis showed a significant increase in TGF-β levels and a decrease in IL-6 levels. In contrast, patients with type 1 diabetes mellitus displayed a slight increase in IL-6 and IL-17 levels compared to both the patients with type 2 diabetes and the healthy control group. Our findings show an increase in TGF-β and a decrease in IL-6, which may suggest a reduction in inflammation and beta cell destruction in individuals with type 2 diabetes and toxoplasmosis. The elevated serum levels of IL-6 and IL-17 in individuals with type 1 diabetes further support the exacerbation of inflammation.

Early-life IL-4 administration induces long-term changes in microglia in the cerebellum and prefrontal cortex.

Microglia are crucial for brain development and their function can be impacted by postnatal insults, such as early-life allergies. These are characterized by an upregulation of interleukin (IL)-4 levels. Allergies share a strong comorbidity with Autism Spectrum Disorders (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). We previously showed that early-life allergic asthma induces hyperactive and impulsive behaviors in mice. This phenotype was reproduced in animals administered with IL-4 in the second postnatal week. Mechanistically, elevated IL-4 levels prevented microglia-mediated engulfment of neurons in the cerebellum, resulting in a surplus of granule cells and consequent dysfunction in cerebellar connectivity. Here, we aimed to further understand the impact of early IL-4 administration in microglia of the cerebellum and the prefrontal cortex (PFC), two brain regions with protracted developmental programs and susceptible to immune system malfunction after birth. While IL-4 administration induced differential short-term effects on microglia in the cerebellum and PFC, both regions presented similar microglial features in adult mice. Although Sholl analysis did not reveal significant alterations in overall microglia morphology at postnatal day (P)10, the density of microglia was decreased in the cerebellum at this age, especially in the granular layer (GL), but remained unaltered in the PFC. Interestingly, the presence of microglia with phagocytic cups, morphological features important for whole-cell engulfment, was decreased in both regions. When assessing the long-term consequences of IL-4 administration, cerebellar and PFC microglia were hypo-ramified and exhibited increased overall density. Importantly, microglia alterations were exclusive to the GL of the cerebellum and the infralimbic region of the PFC. Our results show that postnatal elevated levels of IL-4 impair the percentage of microglia engaged in cell clearing in two brain regions with protracted developmental programs. Interestingly, IL-4-exposed microglia adapt a similar phenotype in the adult cerebellum and PFC. Our data suggest that this early-life increase in IL-4 levels is sufficient to elicit long-lasting alterations in microglia, potentially increasing cell susceptibility to later insults.

Efficacy and Mechanisms of Qianghuo Shengshi Tang in Rheumatoid Arthritis: A Network Pharmacology and Experimental Study

Objective This study assesses the anti-inflammatory and therapeutic effects of Qianghuo Shengshi Tang (QHSST) on rheumatoid arthritis (RA) through network pharmacology and experimental validation and explore the underlying mechanisms. Methods Complete composition analysis of QHSST using UPLC-Q-Orbitrap-MS. And collection potential targets using relevant databases. Protein–protein interaction (PPI) networks were constructed and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were conducted. Anti-inflammatory activity of QHSST was evaluated in RAW264.7 cells by assessing apoptosis, NO, interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α). In rats with wind-cold-dampness paralysis-RA, efficacy of QHSST was confirmed by evaluating foot volumes, arthritis scoring index (AI), blood routine, rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibody, and hematoxylin and eosin (H&amp;E) staining and inflammatory factors. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to examine protein expression in the ankle joints to elucidate the mechanism of QHSST action. Results We identified 44 compounds using UPLC-Q-Orbitrap-MS. Additionally, network pharmacology revealed five active ingredients and seven key targets. GO and KEGG analyses highlighted the involvement of PI3K-Akt signaling and tyrosine kinase inhibitor resistance pathways. Cell studies showed that QHSST reduced apoptosis, NO, IL-6, and TNF-α levels, while increasing IL-10 level in the dexamethasone and 3.125 µg/mL groups, indicating its anti-inflammatory effects. Animal experiments revealed that QHSST and methotrexate significantly decreased AI scores, foot volumes, and blood routine. H&amp;E staining revealed varying degrees of joint harm, accompanied by a decrease in RF, anti-CCP antibody, IL-6, and TNF-α levels, and an increase in IL-10 level, underscoring the efficacy of QHSST in treating RA. ELISA and immunohistochemistry suggest that QHSST may exerts its effects by modulating the EGFR/SRC/PI3 K/AKT/NF-κB pathway. Conclusion Our findings provide a scientific foundation for therapeutic benefits of QHSST in alleviating RA by confirming the anti-inflammatory and RA-relieving properties of the supplement.

Effect of Mirabilite and Rhubarb in Gynecological Laparoscopy

Recently, traditional Chinese medicine (TCM) nursing intervention has been proven to have advantages in the nursing of various diseases. Among these interventions, TCM external treatments are commonly employed in TCM nursing intervention. In this study, we aim to investigate the clinical efficacy of the external application of mirabilite and rhubarb in the perioperative nursing of gynecological laparoscopic surgery. This study included a total of 92 patients who underwent gynecological laparoscopic surgery from January 2022 to January 2023 as the study objects. They were randomly assigned into two groups, namely the conventional (Con) group (n = 46) and the TCM group (n = 46). The Con group received routine perioperative nursing care for laparoscopy, while the TCM group received topical application of rhubarb and mirabilite in conjunction with routine nursing care. We found that the combination of routine nursing and external treatment with mirabilite and rhubarb significantly reduces the ambulation time, gastrointestinal function recovery time, first defecation time, and length of hospital stay for patients undergoing gynecological laparoscopic surgery (P &lt; 0.05). The external application of mirabilite and rhubarb effectively alleviates postoperative pain in patients (P &lt;0.05). Furthermore, there was a significant increase in IL-6 and IL-17 levels after surgery in both groups (P &lt;0.05); However, after receiving external treatment, patients experienced relief from their inflammatory state to some extent (P &lt;0.05). These findings demonstrate that the perioperative nursing method involving the external application of mirabilite and rhubarb can enhance recovery in patients with gynecological diseases after laparoscopic surgery.

Prognostic significance of serum interleukin-6 in severe/critical COVID-19 patients treated with tocilizumab: a detailed observational study analysis

Baseline IL-6 levels have been found to be non-predictive of subsequent outcomes following tocilizumab treatment, highlighting the need for more reliable predictive markers. To address this, a retrospective analysis was conducted on the clinical profiles, diagnostic tests, and follow-up prognoses of 60 patients with severe or critical COVID-19, all of whom were identified as experiencing a cytokine storm and subsequently received tocilizumab treatment. Among the patients, the overall survival rate during follow-up was 80%, with further analysis revealing that advanced age was an independent risk factor for adverse outcomes. Following tocilizumab administration, a statistically significant increase in IL-6 and D-dimer levels was observed, while markers such as C-reactive protein (CRP), procalcitonin (PCT), and fibrinogen demonstrated reductions compared to pre-treatment values. Specifically, IL-6 levels initially surged briefly after tocilizumab intervention before gradually diminishing. To assess the prognostic utility of IL-6, the Receiver Operating Characteristic (ROC) curve was employed, which yielded an area under the curve (AUC) of 0.812, indicating strong predictive capability, with a sensitivity of 100% and a specificity of 53.49%. The optimal cut-off value for IL-6 was identified at 147.79 pg/mL. In conclusion, IL-6 levels tend to rise transiently following tocilizumab therapy, before gradually declining. These post-treatment IL-6 measurements may serve as a valuable biomarker for assessing prognosis in patients undergoing this treatment.

Synergistic Inhibition of Nasopharyngeal Carcinoma by Biyan Qingdu Granule and Micro-Radiation: An Experimental Study

Objective: To investigate the role of Biyan Qingdu Granule combined with micro-radiation in suppressing nasopharyngeal carcinoma and to explore its mechanism of action. Methods: FAT cells of nasopharyngeal carcinoma were injected into the hind limb axilla of F344 rats to establish a rat nasopharyngeal carcinoma tumor model. X-ray radiation was applied to the oral cavity of the rats, delivering a micro-dose of radiation to the distant hind limb axilla tumor. The general condition of the rats, including oral mucosal inflammation, the size of the nasopharyngeal tumor mass, pathological changes in the tumor tissue, and the levels of TNF-α, IL-1β, IL-6, IL-18, IL-12, ICAM-1, and VCAM-1 in the tumor tissue, were assessed. Results: Oral administration of Biyan Qingdu Granule improved the rats’ overall condition and reduced oral mucosal inflammation. Pathological examination revealed tumor cell degeneration and necrosis. ELISA analysis of tumor tissue showed significant reductions in TNF-α, IL-1β, IL-6, ICAM-1, and VCAM-1 levels, along with a notable increase in IL-18 levels. Conclusion: Biyan Qingdu Granule, when combined with micro-radiation, can inhibit tumor growth and reduce tumor volume. Its mechanism of action may involve enhancing immune function and suppressing inflammatory factors.

Abstract A034: Addressing the challenge of pre-analytical variables in circulating protein biomarker analysis for liquid biopsy

Abstract While liquid biopsy using plasma proteins is a promising avenue for early cancer detection, diagnosis, prognosis, and disease monitoring, the clinical translation of plasma proteomics has been limited due to the complexity of the proteome and the impact of pre-analytical variation on its integrity. In recent years, advancements in plasma proteomic technologies, such as Olink, have helped address the challenge of proteome complexity. However, challenges with pre- analytical variables have persisted. During blood collection and whole blood storage, ex vivo blood cell activation and lysis can occur, releasing proteins into the plasma and obscuring relevant in vivo abundances. This is especially true for cancer where many key biomarkers are expressed in white blood cells and platelets. To address these issues, Streck developed Protein Plus BCT, which stabilizes blood cells and minimizes plasma proteome changes following prolonged whole blood storage. To demonstrate its functionality and compatibility with Olink assays, blood was collected from 5 donors into EDTA, ACD-A, and Protein Plus BCT. Plasma was isolated at draw time (&amp;lt; 2 hours) and following 24, 72, and 120 hours of ambient whole blood storage using a double spin protocol (per Instructions for Use). Plasma samples were analyzed using an Olink Explore 384-plex panel. After just 24 hours of whole blood storage, plasma isolated from EDTA or ACD-A had 4.2 and 2.2 times more proteins that are significantly elevated in abundance relative to draw time, respectively, than plasma isolated from Protein Plus BCT. For the key cancer biomarker IL-8, which is associated with worse clinical outcomes and poor response to immunotherapy, Protein Plus BCT maintains draw-time levels such that the mean NPX difference relative to draw time never exceeds -0.18, or a 0.88-fold change for up to 120 hours. Comparatively, samples collected into EDTA and ACD-A show dramatic increases in IL-8 levels with mean NPX differences of 6.34 and 6.62, respectively, corresponding to 80.1- and 98.3-fold increases after 120 hours of whole blood storage. For Galectin-3, an inflammatory biomarker elevated in many cancer types (i.e., lung, breast, and ovarian), the mean NPX difference relative to draw time for samples drawn into EDTA is 1.46 after 24 hours and increases to 2.27 after 120 hours of whole blood storage (a 2.75-fold and 4.8-fold increase, respectively). In samples collected into Protein Plus BCT, the mean NPX difference, relative to draw time, for Galectin-3 never exceeds 0.05 (a 1.04-fold increase) even after 120 hours of whole blood storage. Taken together, these data suggest that Protein Plus BCT extends the storage of whole blood at ambient temperature without compromising the integrity of the sample or the proteomic results, providing researchers and assay developers valuable flexibility in the transport, storage, and processing of their samples. Protein Plus BCT is for Research Use Only. Not for use in diagnostic procedures. Protein Plus BCT should only be used for research or the development of new assays. Citation Format: Rachel M Miller, Jing Li. Addressing the challenge of pre-analytical variables in circulating protein biomarker analysis for liquid biopsy [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A034.

Immune checkpoints PD1/PDL1, TIM3/GAL9 and key immune mediators landscape reveal differential expression dynamics on imatinib response in chronic myeloid leukemia.

The immune system of chronic myeloid leukemia (CML) patients is severely impaired, hampering anti-tumor responses, and maximal immune recovery occurs after achieving deep molecular responses to tyrosine kinase inhibitors. This study aimed to discern the expression patterns of NCR2, IL2, IL4, EOMES, FOXP3, GATA3, RORGT, PD1/PDL1 and TIM3/GAL9, expanding our previous dataset up to 19 key immune mediators, during the initial year on imatinib. Gene expression dynamics were evaluated in 171 peripheral blood samples from 89 CML patients, including 43 longitudinally monitored individuals, and 52 healthy donors. Univariate and unsupervised analyses confirmed diminished expression of most studied immune mediators, except for TNF, ARG1 and IL4, differentiating between baseline and 3-month samples. Most of the studied mediators normalized along treatment, with a transient increase of TNF and IL6 levels at 3-months, especially in optimal responders (BCR::ABL1 < 0.1%). Univariate and multivariate analyses showed heightened ARG1 levels and a transition from PD1/PDL1 dominance at 3 months to TIM3/GAL9 at 12 months in non-optimal responders (BCR::ABL1 ≥ 0.1%). Our longitudinal design offers a deeper exploration of immune gene expression dynamics in CML patients on imatinib, highlighting its potential implications for therapy outcomes.

Chronic exposure to low concentration of diflubenzuron and pyriproxyfen induces brain oxidative stress and inflammation and alters locomotion in zebrafish (Danio rerio)

Diflubenzuron (DFB1) and pyriproxyfen (PPF) are pesticides widely used in agriculture and urban environments to control insect actions. The aim of this study was to evaluate the effects of chronic 30-day exposure to DFB (0.025 and 0.125 mg/L) and PPF (0.379 and 0.758 mg/L) on the behavior of juvenile zebrafish (Danio rerio). Fish were exposed to insecticides from early stage (4 h post fertilization) to 30 days post fertilization (dpf). At 45 dpf, fish were evaluated in the novel tank test, social behavior test, and mirror aggressive test. Brain gene expression related to oxidative stress and inflammation was also evaluated. DFB reduced locomotor parameters in the novel tank and aggression tests, while it induced to hyperactivity in the social behavior test. PPF reduced anxiety-like behavior, measured by the time spent in risky areas of the novel tank, and reduced aggression against the mirror image. There was a significant reduction in mRNA levels of the nfe2l2 gene (∼0.54 fold downregulated) and increase in levels of cat (PPF ∼1.8 fold change), gsr (PPF ∼1.5 fold change), gpx1a (PPF ∼1.6 and DFB 1.1 fold change), tnf-α (PPF 1.9 and DFB 2.2 fold change), and il-6 (PPF ∼1.2 and DFB 2.3 fold change). These endpoints are indicative of the threatening effects of insecticides to aquatic organisms and the need for alternative methods to control pests by using less harmful and safer substances for animal and human well-being, as well as for the environment.

Different levels of lipids, Hb1Ac and cytokines among patients with coronary artery disease

BackgroundDifferent risk factors are responsible for the occurrence of coronary artery disease (CAD). Among these, the main factors are dyslipidemia, dysglycaemia, and endothelial inflammation. The aim of the study was to analyze the levels of lipids, glucose, and cytokine in patients with different coronary heart diseases. MethodsA total of 2147 patients diagnosed with coronary atherosclerosis, stable angina, unstable angina, acute non-ST-segment elevation infarction (NSTEMI) and acute ST-segment-elevation myocardial infarction (STEMI) at the Cardiovascular Center of Beijing Tongren Hospital from February 2022 to April 2023. The data were gathered from the medical record system.Nonparametric Wilcoxon test was used for statistical analysis of continuous variables, and chi-square test was used for statistical analysis of categorical variables among multiple groups. ResultsCompared with coronary atherosclerosis group, acute myocardial infarction group showed a significant increase in IL-6 level (p < 0.001). Compared with stable angina group, acute myocardial infarction group showed a significant increase in IL-6 and decrease in INF-γlevels (p < 0.001). Compared with unstable angina group, acute myocardial infarction group showed a significant increase in IL-6 level and decrease in IL-17, as well as INF-γlevels (p < 0.001). Compared with NSTEMI group, the proportion of younger, males, glycemic-lowering drugs, as well as the levels of TC, LDL-C in STEMI group increased significantly, while the proportion of hypertension, IFG/IGT/DM, hyperlipidemia and Hb1Ac level decreased significantly. STEMI group showed a significant increase in IL-2 and IL-6 levels (p < 0.05). ConclusionsThe levels of lipids, Hb1Ac, IL-2 and IL-6 were varying in patients with different stages of coronary heart diseases.The data would contribute to a deeper understanding of the roles of lipids, glucose, and inflammation in the occurrence and development of CAD.

Association between TNF-α & IL-6 level changes and remission from depression with duloxetine treatment

Purpose/Aim of the study The pathophysiology of major depressive disorder (MDD) involves multiple factors, including inflammatory processes. This study investigated the relationship between changes in the levels of cytokines and remission in patients with MDD following duloxetine treatment. Materials and methods MDD patients were administered duloxetine for 16 weeks. Clinical evaluation and immunological monitoring were performed every 4 weeks. Results Our results indicated that changes in serum levels of TNF-α and IL-6 were associated with remission following duloxetine treatment in MDD patients. There was a slight increase in TNF-α levels in the first four weeks following duloxetine treatment, which correlated significantly with patients who were in remission. Furthermore, patients in remission exhibited an initial increase in IL-6 levels in the first four weeks, followed by a decrease at 16 weeks. Conclusions These results suggest an important relationship between changes in cytokine levels and remission in patients with major depression after duloxetine treatment.

The potential role of interleukin-6 in the association between inflammation and cognitive performance in obstructive sleep apnea

BackgroundInterleukin-6 (IL-6) represents one of the main molecules involved in inflammatory responses, which can be altered in either patients with cognitive impairment or obstructive sleep apnea (OSA). The present study aimed to evaluate serum IL-6 levels and cognitive performance in patients with severe OSA (Apnea-Hypopnea Index - AHI >30/h). MethodsThirty patients with severe OSA were compared to 15 controls similar in age, sex, and Body Mass Index. All patients underwent a sleep medicine interview, including the Epworth Sleepiness Scale (ESS), a polygraphic cardiorespiratory recording, the Montreal Cognitive Assessment (MoCA), and a blood sample for serum IL-6 assessment. ResultsOSA patients presented higher IL-6 serum levels (Md = 7.38) than controls (Md = 2.20, p < 0.001). Moreover, OSA patients showed lower MoCA (Md = 27.00) and higher ESS scores (Md = 8.00) than controls (Md = 30.00, p < 0.001; Md = 4.00, p = 0.004, respectively). Higher IL-6 serum levels were associated with lower oxygen saturation parameters and MoCA scores. ConclusionsThis study documented an association between inflammation, featured by higher IL-6 serum levels, and both nocturnal hypoxemia and cognitive impairment in OSA patients. Therefore, the increase in IL-6 levels may represent the result of vascular damage and neuroinflammation due to intermittent nocturnal hypoxia and further causing neurocognitive dysfunction in OSA.

Cytokine profile of oral fluid in case of traumatic fractures of the lower jaw and the presence of third molars in patients` oral cavity

Objective. To analyze the level of cytokines in the oral fluid of patients with traumatic fractures of the mandible in the presence of third molars, to establish the influence of the latter on the oral cavity homeostasis, to determine the most informative indicators. Materials and methods. 82 people aged 18–60 years took part in the study, they were divided into 3 groups. Group 1 contained 43 patients with mandibular fracture and having more than two third molars. Group 2 consisted of 18 patients with mandibular fracture, without third molars. Group 3 included 21 people without a fracture of the mandible, who had more than two-thirds of the molars. Group 4 (control) contained the data of somatically and dentally healthy individuals, borrowed from special literature. The levels of IL-1β, IL-6, IL-8, and TNF-a in OF were determined using standard enzyme immunoassay kits. The data were processed statistically. Results. A comparison of the indicators of groups 1 and 3 revealed a significant increase in the level of IL-6 z = 4.15 (H = 20.43; p = 0.0001) and the level of IL-8 z = 3.08 (H = 12.29; p = 0.0064) in patients with a jaw fracture. A considerable increase in IL-8 levels was determined in the individuals from group 2 compared with group 3 – z = 2.74 (H = 12.29; p = 0.0064). The comparison of groups 1 and 4 in terms of TNF-a showed a tendency to a significant difference of z = 1.60 (H = 4.65; p = 0.19), and the data of group 2 in comparison with group 4 were significantly higher than z = 1.97 (H = 4.65; p = 0.19). Comparing the results of groups 3 and 4 with each other we revealed a considerable difference of z = 1.75 (H = 4.65; p = 0.19). Conclusion. The profile of cytokines level in the OF indicates that the presence of third molars in the oral cavity in mandibular fractures affects the homeostasis of the oral cavity negatively, which is the reason for expanding the indications for their removal in order to prevent infectious and inflammatory complications.