Interleukin-6 Concentrations Research Articles

Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia

BACKGROUND Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS). AIM To investigate the relationship between serum IL-6 concentration and the clinical features of EOS. METHODS We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls (F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups (P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group (F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score (r = -0.389, P = 0.032) and avolition/asociality subscore (r = -0.387, P = 0.026). CONCLUSION Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

Associations Between Biomarkers of Myocardial Injury and Systemic Inflammation and Risk of Incident Ventricular Arrhythmia

BackgroundCardiac troponins (cTns) and biomarkers of inflammation are elevated in heart failure (HF) and predict cardiovascular risk. Whether these biomarkers associate with risk of ventricular arrhythmias (VAs) is unclear. ObjectivesThis study sought to assess whether cTnT, growth differentiation factor 15 (GDF-15), interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations are associated with incident VA. MethodsIn a prospective, observational study of patients treated with implantable cardioverter-defibrillator, cTnT, GDF-15, IL-6, and CRP were measured at baseline and after 1.4 ± 0.5 years and were associated with implantable cardioverter-defibrillator–detected incident VA, HF hospitalizations, and mortality. ResultsThis study included 489 patients aged 66 ± 12 years and 83% were men. Median concentrations of cTnT were 15 (Q1-Q3: 9-25) ng/L at inclusion, and higher concentrations were associated with higher age, male sex, diabetes mellitus, coronary artery disease, and HF. During 3.1 ± 0.7 years of follow-up, 137 patients (28%) had ≥1 VA. cTnT concentrations were associated with an increased VA risk (per log-unit, HR: 1.63; 95% CI: 1.31-2.01; P < 0.001), also after adjustment for age, sex, body mass index, coronary artery disease, HF, renal function, and left ventricular ejection fraction (P < 0.001). GDF-15, IL-6, and CRP concentrations were not associated with incident VA, but all (including cTnT) were associated with HF hospitalization and mortality. Changes in cTnT, GDF-15, IL-6, and CRP from baseline to 1.4 years were not associated with subsequent VA. ConclusionsHigher concentrations of cTnT, GDF-15, IL-6, and CRP associate with HF hospitalization and death, but only cTnT predict incident VA. These findings suggest that myocardial injury rather than inflammation may play a pathophysiological role in VA and sudden cardiac death.

Early Enteral Nutrition Does Not Cause Excessive Inflammatory Response in Veno-Arterial Extracorporeal Membrane Oxygenation Patients

Background: To evaluate the safety between early enteral nutrition (EN) and parenteral nutrition (PN) by observing changes in inflammatory cytokines and gastrointestinal hormones in veno-arterial extracorporeal membrane oxygenation (VA ECMO) patients. Methods: This study was a prospective, observational study that enrolled patients receiving VA ECMO treatment from 1 January 2020 to 31 December 2023. Patients were enrolled in an EN group or a PN group according to the inclusion criteria. The concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor α (TNF-α) on the first five days of VA ECMO treatement were tested in both groups. Serum concentrations of Motilin (MOT), Gastrin (GAS), Cholecystokinin (CCK), and Calcitonin gene-related peptide (CGRP) were measured for the EN group. Student t test or Fisher test was used to compare the difference between the two groups. Results: 28 patients were enrolled in this study; 16 in the EN group and 12 in the PN group. The baseline characteristics were comparable between the two groups. The concentration of IL-1β in the EN group was significantly lower than that of the PN group on day 3 and day 4 (day 3: 0.65 ± 0.17 pg/mL vs. 0.93 ± 0.09 pg/mL, p &lt; 0.01, day 4: 0.52 ± 0.16 pg/mL vs. 0.74 ± 0.12 pg/mL, p &lt; 0.01). The concentration of IL-6 and TNF-α in the EN group were also significantly lower than in the PN group on day 3 and day 4. There was no statistical difference in IL-10 serum concentration between the EN group and the PN group from day 1 to day 5. On day 3, the concentration of MOT, GAS and CCK reached the highest level and then gradually decreased. Conclusions: Implementation of early EN in patients receiving VA ECMO does not cause significant elevation of pro-inflammatory cytokines with an excessive inflammatory response.

Protective Effect of Oyaksoongi-San against Asthma Induced by Ovalbumin in a Mouse Model

Oyaksoongi-San (OYSGS), which is a combination of 11 herbal ingredients, has long been used in Asia to relieve symptoms of various diseases conditions, including vomiting and diarrhea. In this study, we assessed the protective efficacy of OYSGS in a murine model of asthma induced by ovalbumin (OVA) and explored potential molecular mechanisms. Male C57BL/6 mice were sensitized with OVA and airway challenged with OVA (1% w/v in PBS) for 1 h. OYSGS (100, 300, and 500 mg/kg once daily) was administered for 6 days by oral gavage. Our results revealed that OYSGS significantly decreased the number of inflammatory cells and reduced the concentrations of interleukin (IL)-5 and IL-13 in bronchoalveolar lavage fluid (BALF). Histological analyses showed that OYSGS substantially decreased inflammation and mucus hypersecretion in the airway. Further analyses revealed that OYSGS effectively reduced oxidative stress, as shown by downregulation of malondialdehyde (MDA) and upregulation of total glutathione (GSSG/GSH), and markedly suppressed the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). Together, these results suggest that OYSGS effectively inhibits the airway inflammatory responses, mucus secretion, and oxidative stress induced by OVA.

Ranolazine ameliorates T1DM-induced testicular dysfunction in rats; role of NF-κB/TXNIP/GSDMD-N/IL-18/Beclin-1 signaling pathway

Approximately 90% of diabetic males have varying degrees of testicular dysfunction. The current study investigates the possible beneficial consequences of ranolazine against T1DM-induced testicular dysfunction in rats. Thirty-two male Sprague Dawley rats were assorted into 4 groups; normal, diabetic (single 50 mg/kg STZ, I.P.) and ranolazine (40 and 80 mg/kg, orally). The present investigation revealed that the hypoglycemic impact of ranolazine significantly improved the testicular weight and body weight of the final rats, as well as the concentration of blood testosterone, sperm count, and viability, all of which were associated with STZ-induced testicular dysfunction. Furthermore, as demonstrated by elevated reduced glutathione (GSH) activity and lowered malondialdehyde (MDA) levels, diabetic rats administered ranolazine showed a noteworthy improvement in the oxidant/antioxidant ratio. Furthermore, a substantial rise in beclin-1 concentration was seen in conjunction with a significant decrease in thioredoxin-interacting protein (TXNIP) and interleukin-18 (IL-18) concentrations when ranolazine was administered. Although ranolazine exhibited a reduction in inflammation as seen by lower expression of nuclear factor-κB (NF-κB) and cluster of differentiation (CD68) in the testicles, these biochemical findings were validated by improvements in the morphological and histopathological outcomes of both the pancreatic and testicular tissues. In conclusion, daily oral administration of ranolazine (40 and 80 mg/kg) for 8 weeks could be a promising therapy for T1DM-induced testicular dysfunction through its dose-dependent anti-oxidant and anti-inflammatory effects.

Effect of Adding Yeast Cultures to High-Grain Conditions on Production Performance, Rumen Fermentation Profile, Microbial Abundance, and Immunity in Goats.

It is a common practice among farmers to utilize high-grain diets with the intention of promoting ruminant growth. However, this approach bears the risk of inducing rumen disorders and nutrient metabolism diseases. Yeast culture (YC) showed advantages in ruminant applications. The objective of this study was to evaluate the effects of adding two different types of YC to high-grain conditions on production performance, rumen fermentation profile, microbial abundance, and immunity in goats. A total of 30 male goats with similar body condition were randomly distributed into 3 dietary treatments with 10 replicates per treatment as follows: basic diet group (CON); basic diet + 0.5% yeast culture 1 (YC1) group; basic diet + 0.5% yeast culture 2 (YC2) group. The trial lasted for 36 days. The results demonstrated that dietary YC supplementation led to an increase in the average daily gain and a reduction in feed intake and weight gain ratio in goats. It increased the apparent digestibility of crude protein, NDF, and ADF (p < 0.05). The serum concentrations of interleukin (IL)-1β, IL-6, and Tumor Necrosis Factor-α in the control group were significantly higher than those of the YC groups (p < 0.05). The serum concentrations of Immunoglobulin (Ig)A and IgG in the control group were significantly lower than those in the YC groups (p < 0.05). The rumen concentration of microbial protein (MCP) in the control group was significantly lower than that in the YC groups (p < 0.05). There was a negative correlation between the concentration of IL-10 and Bacteroidota, Spirochaetota, and Succinivibrio, while there was a positive correlation between concentrations of IL-10 and Firmicutes. Nevertheless, discrepancies were observed in the impact of the two different types of YC on the physiological and biochemical indicators of the animals. The concentration of triglyceride in the YC1 group was significantly higher than that of the CON and YC2 groups, while the concentration of urea in the YC2 group was significantly higher than that of the CON and YC1 groups (p < 0.05). At the phylum level, the addition of YC2 to the diet significantly increased the relative abundance of Bacteroidota and Fibrobacterota and significantly decreased Firmicutes compared to the control. At the genus level, the addition of YC1 to the HGD significantly reduced the relative abundance of Rikenellaceae_RC9_gut_group, while the addition of YC2 to the HGD significantly increased the relative abundance of Prevotellace-ae_UCG-001, Fibrobacter, and Prevotellaceae_UCG-003 (p < 0.05). The addition of YC significantly improved growth performance, increased nutrient digestibility, beneficially manipulated ruminal fermentation and microbial diversity, and improved immune function. The choice of yeast cultures can be customized according to specific production conditions.

Inflammatory biomarker detection in saliva samples by printed graphene immunosensors

Herein, we present the design and fabrication of a portable biochemical sensor based on the Screen Printed Electrode (SPE) concept and applied for detecting interleukin-6 (IL-6), a key player in the complex process of inflammation, in real human saliva. The sensing mechanism relies on the antigen-antibody binding between the IL-6 molecule and its antibody immobilized over a surface of a Thermally Exfoliated Graphene Oxide (TEGO) layer. TEGO, deposited by Aerosol Jet Printing (AJP), provides advantages in terms of a time/cost consumingfast, easy and efficient biofunctionalization. The biosensor shows a dynamic range comprising IL-6 concentrations falling within the normal IL-6 levels in saliva. An extensive analysis of device performance, focused on the assessment of the sensor Limit of Detection (LoD) by two modes (i.e. from the lin-log calibration curve and from blank measurements), provides a best value of about 1 × 10−2 pg/ml of IL-6 in saliva. Our work aims at providing a contribution toward applications in real environment, going beyond a proof of concept or prototyping at lab scale. Hence, the characterization of the sensor was finalized to find a reliable device-to-device reproducibility and calibration through the introduction of a measurement protocol based on comparative measurements between saliva samples without (blank) and with IL-6 spiked in it, in place of the standard addition method used in daily laboratory practice. Device-to-device reproducibility has been accordingly tested by acquiring multiple experimental points along the calibration curve using different individual devices for each point.

Olokizumab in patients with inflammatory phenotype of osteoarthritis, treatment experience

Objective: to investigate the efficacy and safety of olokizumab (OKZ) in patients with knee osteoarthritis (OA) with synovitis, persistent pain and ineffectiveness of previous conservative therapy. Material and methods. The study included 15 patients with stage II–III knee OA who fulfilled the ACR criteria and had pain ≥50 mm on a visual analogue scale (VAS), synovitis and treatment failure. The age of patients ranged from 54 to 75 years; the duration of the disease was from 1 to 23 years. The duration of the study was 12 weeks, during which the patients received 3 subcutaneous injections of OKZ at a dose of 64 mg. The effectiveness of the treatment was assessed by the dynamics of pain intensity according to VAS, WOMAC and KOOS indices, the values of the DN4 questionnaire and the quality of life according to EQ-5D. In addition, the general assessment of the patient's health (GHA) according to VAS, the assessment of treatment efficacy by doctor and patient and the need for non-steroidal anti-inflammatory drugs (NSAIDs) were considered. All patients underwent laboratory testing. Results and discussion. During treatment, there was a significant decrease in pain intensity according to VAS, a statistically significant improvement in the KOOS and WOMAC indices (p&lt;0.05), quality of life according to the EQ-5D questionnaire and GHA. Patients and doctors rated the treatment results very positively: an improvement or significant improvement was observed in 92.3% of cases. Adverse events were identified in 4 patients, which in 2 cases served as the reason for discontinuation of OKZ treatment and termination of participation in the study. During treatment with OKZ, a statistically significant decrease in CRP and ESR values, an increase in the concentration of interleukin 6 (p = 0.003), COMP (p = 0.03) and PIINP (p = 0.01) were observed. Conclusion. The results obtained suggest a significant symptomatic and anti-inflammatory effect of OKZ in patients with the inflammatory phenotype of OA.

Oral administration of liposome-encapsulated thymol could alleviate the inflammatory parameters in serum and hippocampus in a rat model of Alzheimer's disease

BackgroundNeuroinflammation is closely related to Alzheimer's Disease (AD) pathology, hence supplements with anti-inflammatory property could help attenuate the progression of AD. This study was conducted to evaluate the potential anti-inflammatory effects of liposome encapsulated thymol (LET), administered orally, in prevention of Alzheimer in a rat model by anti-inflammatory mechanisms. MethodsThe rats were grouped into six groups (n = 10 animals per group), including Control healthy (Con), Alzheimer's disease (AD) model, AD model treated with free thymol in 40 and 80 mg/kg body weight (TH40 and TH80), AD model treated with LET in 40 and 80 mg/kg of body weight (LET40 and LET80). The behavioral response of step through latency (Passive Avoidance Test), concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) were assessed in serum and hippocampus. ResultsThe results showed that significant increase in concentrations of IL-1β (P = 0.001), IL-6 (P = 0.001), TNF-α (P = 0.001) and COX-2 (P = 0.001) in AD group compared with healthy control rats. AD induction significantly reduced step through latency and revealed deficits in passive avoidance performance. The results also showed the treatment with free thymol especially in higher concentrations and also LTE could decrease serum concentrations of IL-1β (P < 0.05), IL-6 (P < 0.05), TNF-α (P < 0.05), and COX-2 (P < 0.05) and increase BDNF (P < 0.05) compared with control Alzheimer rats in hippocampus and serum. There were also significant correlations between serum and hippocampus concentrations of IL-1β (r2 = 0.369, P = 0.001), IL-6 (r2 = 0.386, P = 0.001), TNF-α (r2 = 0.412, P = 0.001), and COX-2 (r2 = 0.357, P = 0.001). It means a closed and positive relation between serum and hippocampus concentrations of IL-1β, IL-6, TNF-α, and COX-2. ConclusionsLET demonstrates its ability to attenuate neuroinflammatory reaction in AD model through suppression of IL-1β, IL-6, and TNF-α and COX-2 indicators. Hence, it can ameliorate AD pathogenesis by declining inflammatory reaction.

Electrochemical Biosensor for Point-of-Care Testing of Low-Abundance Biomarkers of Neurological Diseases.

The neurofilament protein light chain (NEFL) is a potential biomarker of neurodegenerative diseases, and interleukin-6 (IL-6) is also closely related to neuroinflammation. Especially, NEFL and IL-6 are the two most low-abundance known protein markers of neurological diseases, making their detection very important for the early diagnosis and prognosis prediction of such kinds of diseases. Nevertheless, quantitative detection of low concentrations of NEFL and IL-6 in serum remains quite difficult, especially in the point-of-care test (POCT). Herein, we developed a portable, sensitive electrochemical biosensor combined with smartphones that can be applied to multiple scenarios for the quantitative detection of NEFL and IL-6, meeting the need of the POCT. We used a double-antibody sandwich configuration combined with polyenzyme-catalyzed signal amplification to improve the sensitivity of the biosensor for the detection of NEFL and IL-6 in sera. We could detect NEFL as low as 5.22 pg/mL and IL-6 as low as 3.69 pg/mL of 6 μL of serum within 2 h, demonstrating that this electrochemical biosensor worked well with serum systems. Results also showed its superior detection capabilities over those of high-sensitivity ELISA for serum samples. Importantly, by detecting NEFL and IL-6 in sera, the biosensor showed its potential for the POCT model detection of all known biomarkers of neurological diseases, making it possible for the mass screening of patients with neurodegenerative diseases.

Spinal cord stimulation attenuates paclitaxel-induced gait impairment and mechanical hypersensitivity via peripheral neuroprotective mechanisms in tumor-bearing rats

BackgroundTaxanes such as paclitaxel (PTX) induce dose-dependent chemotherapy-induced peripheral neuropathy (CIPN), which is associated with debilitating chronic pain and gait impairment. Increased macrophage-related proinflammatory activities have been reported to mediate...

Effects of resistance exercise and whey protein supplementation on cognitive function in older men: secondary analysis of a randomised, double-blind, placebo-controlled trial

PurposeAgeing is associated with cognitive decline. This study investigated the individual and combined effects of resistance exercise (RE) and whey protein supplementation (PRO) on cognitive function in older men. MethodsIn a pooled-groups analysis, 36 older men (age: 67 ± 4 years) were randomised to either RE (2 x/week; n = 18) or no exercise (NE; n = 18), and either PRO (2 × 25 g/d whey protein isolate; n = 18) or control (CON, 2 × 23.75 g maltodextrin/d; n = 18). A sub-analysis was also conducted between RE + CON (n = 9) and RE + PRO (n = 9). At baseline and 12 weeks, participants completed a battery of neuropsychological tests (CANTAB; Cambridge Cognition, UK) and neurobiological, inflammatory, salivary cortisol and insulin sensitivity biomarkers were quantified. ResultsPRO improved executive function z-score (+0.31 ± 0.08) greater than CON (+0.06 ± 0.08, P = 0.03) and there was a trend towards improved global cognitive function (P = 0.053). RE and RE + PRO did not improve any cognitive function domains (p ≥ 0.07). RE decreased tumor necrosis factor-alpha (P = 0.02) and interleukin-6 (P = 0.048) concentrations compared to NE, but changes in biomarkers did not correlate with changes in cognitive domains. Muscle strength (r = 0.34, P = 0.045) and physical function (ρ = 0.35–0.51, P < 0.05) outcomes positively correlated with cognitive function domains at baseline, but only Δskeletal muscle index correlated with Δepisodic memory (r = 0.34, P = 0.046) following the intervention. ConclusionIn older men, PRO improved cognitive function, most notably executive functioning. RE did not improve any cognitive function domains but did decrease biomarkers of systemic inflammation. No synergistic effects were observed.

An Examination into the Effects of a Nutraceutical Supplement on Cognition, Stress, Eye Health, and Skin Satisfaction in Adults with Self-Reported Cognitive Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Dietary quality and the consumption of antioxidant-rich foods have been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. Methods: In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. Results: Compared to the placebo, nutritional supplementation was associated with larger improvements in one primary outcome measure comprising episodic memory (p = 0.037), but not for working memory (p = 0.418) or verbal learning (p = 0.841). Findings from secondary and exploratory outcomes demonstrated that the nutraceutical intake was associated with larger improvements in the Everyday Memory Questionnaire (p = 0.022), increased plasma brain-derived neurotrophic factor (p = 0.030), decreased plasma malondialdehyde (p = 0.040), and increased skin carotenoid concentrations (p = 0.006). However, there were no group differences in changes in the remaining outcome measures. Conclusions: Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings.

Endometrial microbial dysbiosis and metabolic alteration promote the development of endometrial cancer.

Emerging evidence suggests that the endometrial microbiome plays important roles in the development of endometrial cancer (EC). Here, we evaluate stage-specific roles of microbial dysbiosis and metabolic disorders in patients with EC, patients with endometrial hyperplasia (EH), and patients afflicted with benign uterine conditions (CK). This prospective cohort study included 33 women with EC, 15 women with endometrial EH, and 15 women with benign uterine conditions (CK) from November 2022 to September 2023. Different typical endometrial samples were imaged with a scanning electron microscope and a transmission electron microscope. The endometrial microbiome was assessed by sequencing the V3-V4 region of the 16S rRNA gene and the ITS1 to fill the gap in relation to the study of the uterine fungal microbiome. Moreover, liquid chromatography-mass spectrometry-based metabolomics was used to identify and quantify metabolic changes among these groups. The endometrial microbiome revealed that there is a structural microbiome shift and an increase in the α-diversity in the EC and EH cases, distinguishable from the benign cases, especially the fungal community structure. The fungal microbiome from patients with EC and EH was altered relative to controls and dominated by Penicillium sp. By contrast, Sarocladium was more abundant in controls. Significant differences were observed in the composition and content of compounds between benign cases and EC, especially estradiol-like metabolism-related substances. Altered microbiota was correlated with the concentrations of interleukin-6 (IL-6), IL-11, transforming growth factor-beta, and β-glucuronidase activity especially the relative abundance increase of Penicillium sp. This study suggested that the endometrial microbiome is complicit in modulating the development of EC such as estrogen activity and a pro-inflammatory response. Our work provides a new insight into the endometrial microbiome from a perspective of stages, which opens up new avenues for EC prognosis and therapy.

Benefits of maternal pectin supplementation in gestation diet on vaginal microbiota of sows and intestinal health of newborn piglets.

Pectin is a proven prebiotic and widely used in human health products. This study aims to assess the impact of dietary pectin supplementation during gestation on sow vaginal microbiota and the offspring's intestinal composition. Thirty sows were randomly allocated to two groups and fed a standard diet (CON) or a standard diet supplemented with 3 g/kg pectin (PEC). Blood, feces, and vaginal swab samples from the sows and blood, intestines issue, and colonic content samples from the offspring were collected and analyzed. The results indicate that the relative abundance of vaginal Lactobacillus was notably enhanced in the PEC group and fecal β-glucuronidase (β-G) activity and plasma 17β-estradiol (E2) concentration were also significantly increased in the PEC group. Newborn piglets were found to host different microbial communities as well. At the phylum level, Proteobacteria dominated in the CON group, and Firmicutes was predominant in the PEC group. Newborn piglets in the PEC group had a lower interleukin-6 (IL-6) concentration in their plasma. The expression of intestinal cytokines of offspring was improved as well. Villus height and villus height/crypt depth (V/C) in the PEC group were extremely higher than those in the CON group. In conclusion, dietary pectin supplementation can be of benefit to both sows and newborn piglets.

Tracking the Levels of Adiponectin and Interleukin-18 for Assessing the Efficiency of Chemotherapy in Suppressing Breast Cancer Progression

Breast cancer is a genetically and clinically heterogeneous disease. Cancerous cells multiplying abnormally in the breast, eventually spreading to the rest of the body if untreated. Breast cancer almost exclusively occurs in women. Cancer is a major public health problem worldwide with millions of new cancer patients diagnosed each year and many deaths resulting from this disease. Worldwide, female breast cancer has now surpassed lung cancer as the most commonly diagnosed cancer. SUBJECTS: Ninety two females were included in the current study, they were classified into three groups, depending on their health status (patients and healthy women) and the type of tumor suffered by the study patients: 32 female patients with cancerous breast tumors before receiving chemotherapy, 30 female patients with benign breast tumors (the pathological control group) and 30 females, who were included as a healthy control group. METHODS: Sandwich-ELISA method was applied to evaluate adiponectin and interleukin-18 concentrations in the sera of the study participants. RESULTS: Assessment of the adiponectin revealed a significant increase in the samples of malignant breast tumors group when compared with those of benign breast tumors (p=0.000) and healthy individuals (p=0.002). Interleukin-18 levels in the malignancy tumor group were significantly lower than their levels in the pathological (p=0.007) as well as healthy (p=0.000) controls groups. This study shows apparent slight decrease of adiponectin concentrations in cancerous patients group after getting approximately three consecutive doses of chemotherapy in comparison with its levels pretreatment, while non-significant difference was noted when comparing interleukin-18 levels after receiving the last dose of chemotherapy with its level before starting treatment. Although the levels of interleukin-18 increased after the end of the recommended course of chemotherapy, it did not rise to the levels of this protein in the healthy control group. The individual efficiency (sensitivity) of the evaluated criteria in the current study for distinguishing between cancerous and benign breast tumors was convergent. While the study recorded the highest specificity (93%) for adiponectin while the lowest specificity (40%) was recorded in interleukin-18. Adiponectin and interleukin-18 were able to distinguish 28 out of 32 breast cancer samples (88%).

Markers of chronic low-grade inflammation and serum cytokine levels in patients with type 1 diabetes: associations with time in ranges and glucose variability

BACKGROUND: Increased glucose variability is recognized as a risk factor for vascular diabetic complications. It is assumed that deteriorating effect of GV on blood vessels can be realized through the activation of inflammatory signaling pathways.AIM: to determine associations of low-grade inflammation markers and serum cytokines with time in ranges and GV parameters derived from continuous glucose monitoring (CGM) in patients with type 1 diabetes (T1D).MATERIALS AND METHODS: In 470 adult patients with T1D, high-sensitivity C-reactive protein (hsCRP) and fibrinogen was measured, neutrophil-lymphocyte ratio (NLR) and the Systemic Immune-inflammation Index (SII) were calculated. In a sample of 130 patients and 20 healthy individuals (control), serum concentrations of interleukins (IL-1β, IL-4, IL-6, sIL-6Rα, IL-19, IL-20, IL-22, IL-26, IL-27, IL-28A, IL-29, IL-32, IL-34, IL-35) were assessed by multiplex analysis. Time in the ranges and GV parameters: Coefficient of Variability (CV), Mean Amplitude of Glycemic Excursions (MAGE), and Mean Absolute Glucose rate of changes (MAG) were derived from CGM data.RESULTS: Patients with Time In Range (TIR) &lt;70% had higher concentrations of hs-CRP and fibrinogen, higher SII values, and demonstrated a trend toward higher TIR compared with those with TIR ≥70% (p=0.018, p=0.026, p=0.037, p=0.101, respectively). Patients with T1D, when compared to control, demonstrated increased concentrations of IL-1β (p&lt;0.0001), IL-6 (p&lt;0.0001), decreased levels of IL-4 (p=0.002), and a tendency to decrease IL-22 and IL-29 (p=0.1). Patients with TIR&gt;70% had higher levels of IL-4 (p=0.02) as well as lower concentrations of IL-1β (p=0.0003) and IL-6 (p=0.007) than patients with TIR≤70%. In a multivariate stepwise regression analysis including clinical data and CGM parameters as independent variables, body mass index was positive predictor of hsCRP and fibrinogen levels, TIR was negatively associated with IL-20 and IL-34, time above range was associated positively with IL-1β, MAGE showed positive association with SII, IL-26 and IL28A, while MAG was positively associated with IL-29.CONCLUSION: T1D patients with non-target TIR (&lt;70%) have higher levels of low-intensity inflammatory markers and serum pro-inflammatory cytokines than patients with TIR&gt;70%. Both hyperglycemia and increased GV are associated with intensity of low-grade inflammation in T1D.

Mutations in Genes Producing Nitric Oxide and Hydrogen Sulfide and Their Connection With Apoptotic Genes in Chronic Myeloid Leukemia.

Background Despite advances in chronic myeloid leukemia (CML) genetics, the role of nitric oxide (NO) and hydrogen sulfide (H2S) gene mutations and their relationship to apoptotic genes is unclear. Therefore, this study investigated NO- and H2S-producing genes' mutations and their interactions with apoptotic genes using Sanger sequencing and next-generation sequencing (NGS). Methodology A complete blood count (CBC) was carried out to measure the total number of white blood cells, while IL-6 levels were assessed in both control and CML patients using an ELISA technique.Sanger sequencing was used to analyzemutations in the CTH and NOS3 genes, whereas NGS was applied to examine mutations on all chromosomes. Results White blood cell (WBC) and granulocyte counts were significantly higher in CML patients compared to controls (p<0.0001), and monocyte counts were similarly higher (p<0.05). Interleukin-6 (IL-6) levels were significantly elevated in CML patients thancontrols (p<0.0001), indicating a possible link to CML etiology or progression. Multiple mutations have been identified in both genes, notably in CTH exon 12 and the NOS3genes VNTR, T786C, and G894T. This study also measured IL-6 concentrations using IL-6 assays, identifying its potential as a CML prognostic diagnostic. WBC counts, granulocyte counts, and mid-range absolute counts, or MID counts, were significantly higher in CML patients than in normal control individuals. NGS identified 1643 somatic and sex chromosomal abnormalities and 439 actively expressed genes in CML patients. The findings imply a genomic landscape beyond the BCR-ABL1 mutation in CML development compared to other databases. Conclusion In conclusion, this study advances the understanding of the genetic characteristics of CML by identifying mutations in the NO- and H2S-producing genes and their complex connections with genes involved in apoptosis. The comprehensive genetic profile obtained by Sanger sequencing and NGS provides possibilities for identifying novel targets for therapy and personalized treatments for CML, therefore contributing to developments in hematological diseases.

Effect of Statins on Serum Levels of TNF-alpha and Interleukin-6 in Patients with Kidney Disease: A Meta-analysis of Randomized Clinical Trials.

Some clinical trials have indicated the beneficial effects of statins in patients with kidney disease, while others have reported no positive effect of statins in these patients. We conducted this meta-analysis to identify the effects of statins on serum levels of interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α) in patients with kidney disease. A systematic literature search was performed using PubMed, Scopus, and Web of Science databases to identify all studies published from inception to August, 2022. The major outcome variable was the Weighted Mean Difference (WMD). Eligible studies were stratified based on target population, intervention duration, dosage and type of statins, and solubility of statins. Meta-analysis performed on seven publications (8 studies), including 213 patients with kidney disease and 188 control individuals, indicated that the concentration of IL-6 was marginally decreased in patients with kidney disease following statin therapy disease (WMD = -1.15 pg/mL; 95% CI = -2.33 to 0.04, P = 0.05, I2 = 68.5%). The findings of subgroup analysis based on the dosage of statins showed that neither highintensity nor moderate/low-intensity statin treatment could significantly influence the serum level of IL-6. Lipophilic statins were more effective than hydrophilic statins, and they marginally decreased the levels of IL-6 (WMD = -1.21 pg/mL; 95% CI = -2.43 to 0, P = 0.05, I2 = 55.7%). Meta-analysis of four publications (five studies) with 157 patients with kidney disease and 132 control subjects showed that statins reduced the serum levels of TNF-α in patients with kidney disease when compared with control individuals (WMD= -2.66 pg/mL; 95% CI = -4.26 to -1.06, P < 0.001, I2 = 63%). Statins only marginally decreased the concentration of IL-6 in patients with kidney disease, but neither high-intensity nor moderate/low-intensity statin treatment could significantly influence the level of IL-6. However, statins reduced serum levels of TNF-α in patients with kidney disease.

Titanium particle-induced inflammasome in human gingival epithelial cells

Background/purposePeri-implantitis remains a substantial challenge. This study investigated the effect of titanium particles on human oral epithelial cells, focusing on the nucleotide-binding domain and leucine-rich repeat protein (NLRP) 3 inflammasome. Materials and methodsThe Ca9-22 human gingival epithelial cell line was subjected to incubation with titanium particles. To evaluate cell viability, the MTT assay was employed. Total RNA was extracted, and messenger RNA (mRNA) expressions of COX2, TGF-β1, NLRP1, NLPR3, CASP1, and AIM2 were analyzed. The concentration of interleukin (IL)1β in cell supernatants was quantified through enzyme-linked immunosorbent assay. Intracellular reactive oxygen species (ROS) were visualized using an ROS assay Kit. ResultsCa9-22 cells treated with titanium particles showed >75% cell viability across all concentrations tested, with consistent results. mRNA expressions of inflammation-related genes (COX2 and TGF-β1) significantly increased in a dose-dependent manner. The mRNA expression of NLRP3 and CASP1, as well as the secretion of IL1β, increased after 6-h incubation with titanium particles. Moreover, the ROS assay results showed increased production of ROS after treatment with titanium particles, whereas NLRP3 expression and IL1β secretion reduced after treatment with N-acetyl-l-cysteine (ROS scavenger). ConclusionOur findings indicate that titanium particles possess a distinct ability to trigger the NLRP3 inflammasome, partly by producing ROS.