Biomarkers Interleukin-6 Research Articles

The Effects of 1,8-Cineole Treatment on Benign Prostatic Hyperplasia in Rats.

Benign prostatic hyperplasia is a non-malignant growth of the prostate gland; it's the most common prostatic growth in aging men. 1,8-cineole is a natural compound that is extracted from the essential oil of several aromatic plants including Eucalyptus spp. Recent studies have demonstrated the anti-inflammatory, antioxidant, and anticancer activities of 1,8-cineole. This study aims to investigate the effects of 1,8-cineole treatment on the development of BPH induced by testosterone in rats. Thirty adult male rats were divided into three groups (n=10): a control group, an untreated BPH group that received subcutaneous injections of testosterone (3 mg/kg), and a BPH+cineole group that received 50 mg/kg of cineole intraperitoneally in addition to testosterone for 21 days. Histological changes, serum testosterone, and dihydrotestosterone (DHT) levels, prostatic tissue content of the inflammatory biomarkers interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), oxidative stress biomarkers superoxide dismutase (SOD) and malondialdehyde (MDA), angiogenesis biomarker vascular endothelial growth factor (VEGF-A), cellular proliferation biomarker proliferating cell nuclear antigen (PCNA), transforming growth factor beta-1 (TGF-β1), and pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) genes were analyzed. Cineole treatment led to a reduction in the prostate weight-to-body weight ratio, as well as the restoration of histopathological changes caused by testosterone. Cineole treatment reduced the serum levels of testosterone and DHT, and the prostatic tissue levels of IL-1β, TNF-α, VEGF-A, PCNA, and TGF-β1 compared to those in the BPH group. Additionally, cineole treatment enhanced the SOD activity and decreased the MDA levels in the prostate tissue. Finally, the mRNA expression of the Bax was increased, while the expression of the Bcl-2 was decreased by cineole. Our results highlight the effectiveness of cineole in preventing BPH development in rats. This preventive effect was attributed to the regulation of inflammatory responses, oxidative stress, cellular proliferation, and apoptosis.

Efficacy and safety evaluation of Boswellia serrata and Curcuma longa extract combination in the management of chronic lower back pain: A randomised, double-blind, placebo-controlled clinical study.

Chronic lower back pain (CLBP) is a major condition that leads to disability and reduced quality of life (QoL). This randomised, double-blind, placebo-controlled clinical study evaluated the efficacy and safety of a novel Boswellia serrata and Curcuma longa combination (CL20192) for the treatment of CLBP. Participants with CLBP were randomised to receive either a 300 mg CL20192 capsule (n = 45) or placebo capsule (n = 45) once daily for 90 days. Efficacy was evaluated using the Descriptor Differential Scale and Oswestry Disability Index scores for pain, unpleasantness, and disability. Additionally, the 36-item short form questionnaire was used for QoL evaluation. Frequency of painkiller use, serum levels of inflammatory biomarkers (tumour necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein), and phytoconstituents (total boswellic acids and curcuminoids) were determined. Therapy satisfaction was assessed using the Physician and Patient Global Assessment Scales. All randomised participants completed the study. CL20192 supplementation significantly reduced Descriptor Differential Scale pain, unpleasantness, and Oswestry Disability Index scores compared with the placebo group (p < 0.001 for all parameters). Critical QoL scores greatly improved in the CL20192 group. Serum phytoconstituent levels were elevated in the CL20192-treated group. This group demonstrated a significant reduction in inflammatory biomarker levels (tumour necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein), confirming efficacy in abating CLBP compared with the placebo. Moreover, therapy satisfaction scores were significantly high in the CL20192-treated group, and intervention with CL20192 was well tolerated. Intervention with 300 mg CL20192 capsules, containing a novel combination of Boswellia serrata and Curcuma longa extracts, effectively alleviated pain, unpleasantness, and disability in patients with CLBP compared with the placebo. This outcome was consistent with a decrease in serum inflammatory markers and improved therapy assessment scores.

Inflammation-attenuating effect of carbon dioxide versus room-air environment in a rat laparotomy model.

The mechanism by which laparoscopic operations induce lower post-operative inflammatory response compared to open surgery was investigated with regard to the effect of the type of gas environment. Rats were subjected to midline laparotomy at either CO2 (group CO2) or room-air environment (group Air) or to anesthesia only (group Control) under atmospheric pressure conditions. At various timepoints after surgery (1, 3, 6, 24, or 48h), the expression of inflammation biomarkers interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), and nuclear factor-κΒ (NFκΒ) were assessed immunohistochemically in tissue samples excised from the liver, intestine, and kidneys, accompanied by histopathologic analysis, and their levels were measured by ELISA in blood samples. Tissue expression of IL-6, TNFα, and NFκΒ was downregulated in the liver and intestine in group CO2 compared to group Air and in the kidneys in group Air compared to group CO2. However, no differences were noted among groups regarding the histopathologic score of organ tissues and the blood serum levels of inflammation biomarkers. Post-operative local inflammatory response was lower in intra-peritoneal organs of rats subjected to laparotomy at CO2 rather than room-air environment under atmospheric pressure conditions.

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

Rosacea, a chronic inflammatory disease primarily affecting the central area 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. The aim of this study 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. The study included patients diagnosed with rosacea and sex-and age-matched healthy controls (N=40, N=40). Serum HIF-1α and IL-6 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Compared to the control group, the patient group had significantly elevated serum levels of HIF-1α and IL-6. 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 manifestations, and HIF-1α (z=2.401, P=0.016). The significantly elevated levels of IL-6 and HIF-1α in patients with rosacea compared to the control group support the hypothesis that these molecules play a role in the pathogenesis of the disease. The correlation between HIF-1α and 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.

Prognostic utility of mid-regional pro-adrenomedullin and growth differentiation factor 15 in patients undergoing transfemoral transcatheter aortic valve implantation.

Risk prediction in patients with severe, symptomatic aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) remains an unsolved issue. In addition to classical risk scoring systems, novel circulating biomarkers like mid-regional pro-adrenomedullin (MR-proADM) and growth differentiation factor 15 (GDF-15) may be of value in assessing risk. Consecutive patients undergoing elective transfemoral TAVI were included in this prospective observational study. Baseline information, imaging findings, blood samples, and clinical outcomes were collected. Blood levels of the classical biomarkers interleukin-6 (IL-6) and high-sensitivity C-reactive peptide (hsCRP) and of the novel biomarkers MR-proADM and GDF-15 were measured and their predictive utility for mortality assessed. The study cohort consisted of 92 patients undergoing TAVI. The median age was 80.7years [IQR 77.2;83.3], and 48 (52.2%) were male. Analysis of the area under the curve (AUC) of the receiver-operating characteristics showed that the hsCRP levels discriminated poorly (AUC 0.66, 95% CI [0.52;0.8], p = 0.027), whereas all other biomarkers reached a higher level of discrimination (IL-6: AUC 0.76, 95% CI [0.66;0.86], p < 0.001; MR-proADM: AUC 0.73, 95% CI [0.61;0.85], p = 0.002; GDF-15: AUC 0.73, 95% CI [0.61;0.85], p = 0.002). Kaplan-Meier analysis in conjunction with Youden J-statistics yielded the optimal cutoff points for each biomarker to predict survival: IL-6 4.65pg/mL, hsCRP 12.9mg/L, MR-proADM 1.02nmol/L, and GDF-15 2400.1pg/mL. Novel circulating biomarkers like MR-proADM and GDF-15 may provide additional value in predicting survival after TAVI.

Flexible, Electrochemical Skin-Like Platform for Inflammatory Biomarker Monitoring.

Addressing global challenges in wound management has greatly encouraged the emergence of home diagnosis and monitoring devices. This technological shift has accelerated the development of new skin patch sensors for continuous health monitoring. A key requirement is the creation of flexible platforms capable of mimicking human skin features. Here, for the first time, an innovative, highly adaptable electrochemical biosensor with molecularly imprinted polymers (MIPs) is customized for the detection of the inflammatory biomarker interleukin-6 (IL-6). The 3-electrode gold pattern is geometrically standardized onto a 6µm thick polyimide flexible membrane, an optically transparent, and biocompatible polymeric substrate. Subsequently, a biomimetic sensing layer specifically designed for the detection of IL-6 target is produced on these transducers. The obtained MIP biosensor shows a good linear response within the concentration range 50pgmL-1-50ngmL-1, with a low limit of detection (8pgmL-1). X-ray photoelectron spectroscopy, scanning electron microscopy, and Fourier transform infrared spectroscopy characterizations confirm the modifications of the flexible gold transducer. After optimization, the biosensing device shows remarkable potential in terms of sensitivity, selectivity, and reproducibility. Overall, the integration of a low-cost electrochemical sensor on biocompatible flexible polymers opens the way for a new generation of monitoring tools with higher accuracy, less invasiveness, and greater patient comfort.

The Levels of Biomarkers Interleukin 1 (IL-1) and Brain-Derived Neurotrophic Factor (BDNF) in Non-Invasive Conventional Rehabilitation and Robotic Rehabilitation Among Brain Injury Patients: A Narrative Review.

Acquired brain injury (ABI) is becoming increasingly common in Malaysia as a result of a rise in both strokes and accidents. The present review aims to explore the levels of serum inflammatory markers of interleukin-1 (IL-1) and brain-derived neurotrophic factor (BDNF) following conventional and robotic rehabilitation regimes among ABI patients and the association between serum biomarkers with the Medical Research Council (MRC) scale for muscle strength. Online databases, namely ScienceDirect, PubMed, and Google Scholar were utilized by using search terms such as 'Definition of brain injury', 'Epidemiology of brain injury', 'Interleukin-1 in stroke', 'BDNF in stroke', 'Interleukin-1 in traumatic brain injury', 'BDNF in traumatic brain injury', 'Interleukin-1 level and robotic rehabilitation', 'BDNF and robotic rehabilitation', 'Interleukin-1 level and neurorehabilitation', and 'BDNF and neurorehabilitation'. All types of articles with different levels of evidence were included along with other relevant review articles. Articles that were not in English and were not available in the full text were excluded. The review identifies similar and no significant improvement in the treatment between conventional rehabilitation and robotic rehabilitation concerning serum biomarkers IL-1and BDNF. This review also identifies that muscle strength and endurance training improved the levelof serum BDNF in brain injury patients. Therefore, this review provides evidence of the levels of IL-1 and BDNF in non-invasiveconventionalrehabilitation and robotic rehabilitation among brain injury patients, as well as their relation with the MRC scale, to give a good functional outcome that will enhance the quality of life of these groups of individuals.

Hemoglobin homeostasis in abdominal aortic aneurysm: diagnostic and prognostic potential of hemoglobin/heme and scavenger molecules

BackgroundThere is increasing evidence implicating hemoglobin/heme and their scavengers in oxidative stress-mediated pathologies, but information is limited in abdominal aortic aneurysm (AAA).Methods and resultsIn this case-control study, we assessed heme/heme-related markers in 142 men with AAA and 279 men with a normal aortic diameter consecutively recruited from an ultrasound screening program in Sweden. Enzyme-linked immunosorbent assays (ELISAs) were used to measure heme oxygenase-1 (HO-1) and hemopexin (Hpx) plasma levels, colorimetric assays for cell-free heme and whole blood hemoglobin (Hb) levels, and droplet digital PCR (ddPCR) and real-time PCR to determine haptoglobin (Hp) (pheno)type and genotype, respectively. Hpx and heme plasma levels at baseline were elevated, while HO-1 levels were lower in men with AAA (p < 0.001) and were significantly associated with AAA prevalence independently of potential confounders. A combination of heme and HO-1 showed the best diagnostic potential based on the area under the curve (AUC): 0.76, sensitivity: 80%, specificity: 48%. Additionally, when previously described inflammatory biomarker interleukin-6 (IL-6), was added to our model it significantly improved the diagnostic value (AUC: 0.87, sensitivity: 80%, specificity: 79%) compared to IL-6 alone (AUC: 0.73, sensitivity: 80%, specificity: 49%). Finally, Hb (positively) and Hpx (negatively) levels at baseline were associated with AAA growth rate (mm/year), and their combination showed the best prognostic value for discriminating fast and slow-growing AAA (AUC: 0.76, sensitivity: 80%, specificity: 62%).ConclusionsThis study reports the distinct disruption of heme and related markers in both the development and progression of AAA, underscoring their potential in aiding risk stratification and therapeutic strategies.

Longitudinal Tracking of Calprotectin and Interleukin-6 in Sweat and Saliva Using a Sweat Wearable Device

Introduction: This work demonstrates an electrochemical sensor for the application of continuous, noninvasive measurement of inflammation in sweat and saliva through the biomarkers Calprotectin and Interleukin-6 (IL-6), respectively. Calprotectin and IL-6 play a part in the systemic inflammation inherent to chronic inflammatory conditions, such as Inflammatory Bowel Disease (IBD), rheumatoid arthritis, cystic fibrosis, etc. Sweat and saliva represent comparable external mediums through which inflammation can be tracked continuously and noninvasively. Materials and Methods: Calprotectin and IL-6 were measured in sweat and saliva for 2 chronically inflamed subjects and 10 healthy subjects over a two-day period. Sweat measurements were performed using a wearable, skin-based electrochemical sensor utilizing electrochemical impedance spectroscopy (EIS) to quantify Calprotectin and IL-6 concentrations continuously in passively expressed sweat. Calprotectin and IL-6 levels were measured in real time and transmitted to a wireless device application. Figure 1 illustrates the sensor and wearable device design and composition alongside an application interface displaying the wearer's Calprotectin levels measured in real time. Synchronously collected saliva was measured for Calprotectin and IL-6 to characterize the relationship between sweat and saliva expression, establish the relationship between Calprotectin and IL-6 expression as markers of chronic inflammation, and investigate the sweat and salivary diurnal patterns of marker expression for inflamed and healthy subjects. In addition, we tracked sweat Calprotectin over a 40-hour period for chronically inflamed and healthy subjects with varying levels of inflammation and treatments. Results and Discussion: Between sweat and saliva, Calprotectin and IL-6 demonstrated a strong linear relationship (R2>0.7), and strong to moderate linear relationships between Calprotectin and IL-6 in sweat and saliva, respectively. Bland-Altman analysis and Deming regression analysis determined a low incidence of outliers and similar ranges of Calprotectin and IL-6 expression between sweat and saliva. Diurnal analysis exhibited significantly higher sweat Calprotectin and higher median Calprotectin measured in the morning-afternoon than measured in the evening among chronically inflamed and healthy subjects, respectively. Among sweat IL-6 measured in the morning-afternoon and evening, chronically inflamed individuals expressed higher median sweat IL-6 in the morning-afternoon, while healthy individuals expressed higher median IL-6 in the evening. Temporal results of 40-hour tracking of sweat Calprotectin demonstrated higher basal Calprotectin in a medicated over unmedicated inflamed subject, and higher basal Calprotectin of inflamed subjects over a healthy subject. Conclusion: Calprotectin and IL-6 demonstrated strong positive linear relationships between saliva and sweat expression of each marker and strong to moderate linear relationships between the markers in sweat and saliva, along with a low incidence of outliers and a similar range of expression between sweat and saliva. Diurnal patterns were characterized for chronically inflamed and healthy individuals for Calprotectin and IL-6 in sweat, and continuous tracking of inflammation in sweat was demonstrated with the wearable sensor device. Figure 1

Estimation of interleukin-6 level and atherogenic indices as predictors of severity of rheumatoid arthritis in Iraqi patients

Background &amp; Objective: Rheumatoid Arthritis (RA) is an inflammatory illness that causes joint degeneration and inflammation of the synovial membrane, leading to significant disability over time. Interleukin-6 (IL-6) is a widely distributed pro-inflammatory cytokine that has a variety of roles in several pathophysiologic systems, most notably in the RA development. The purpose of this study was to assess the blood levels of IL-6 and the severity and activity of RA in patients, and to assess the association of atherogenic indices with IL-6 as a predictor of severity in RA disease. Methodology: This study was a case control observational study involving 300 participants diagnosed with RA by the rheumatologists in accordance with American College of Rheumatologists (ACR)/ European League Against Rheumatism (EULAR) 2010 criteria. Serum levels of IL-6, CRP, RF and ACPA were measured by using ELISA technique. While, lipid profile was determined with spectrophotometry. Receiver operating curve (ROC) was used to study the opportunity of using atherogenic indices and IL-6 as diagnostic tools for RA. Results: The results indicated a higher IL-6 level in RA patients in comparison to the control group, e.g., 28.55 (18.76-41.07) pg/mLvs 10.19 (6.11-12.50) pg/ml. High atherogenic index of plasma (AIP) risk &gt; 0.24 in RA patients parameters (GDF-15, IL-6), the lipid profile parameters and atherogenic indices (TC, TG, VLDL-C, LDL-C, CRI-I, CRI-II, AIP, and AC) were compared with moderate atherogenic risk (AIP &lt; 0.24) in RA patients. While a significant decrease was recorded in the HDL-C and BMI levels, it had significantly high atherogenic risk (AIP &gt; 0.24) compared with moderate atherogenic risk (AIP &lt; 0.24) in RA patients. The ROC results analysis showed that the top 5 highly sensitive predictors for RA, e.g., CRI-I, AC, AIP, CRI-II followed by IL-6, have a relatively good sensitivity and specificities for predictors for RA. Conclusion: Increase in interleukin-6 may indicate the activity and severity of the disease. This biomarker could be helpful for early disease detection. The results showed a higher IL-6 in RA patients as well as increased dyslipidemia and atherogenicity in RA patients. Elevation of serum IL-6 and atherogenic indices are the best predictors for RA patients with a higher risk of atherosclerosis than other biomarkers. There is an important correlation between atherogenic indices parameters and the immunological biomarkers IL-6 indicating a significant role of the inflammation in the incidence of atherogenic indices in RA. Abbreviations: AUC- Area Under Curve; ACPA - Anti Cyclic Citrullinated Peptide Antibodies; CRP- C-Reactive Protein; ESR- Erythrocyte Sedimentation Rate; RF- Rheumatoid Factor; BMI- Body Mass Index; GDF-15 -Growth Differentiation Factor-15; DAS28-CRP- Disease Activity Score-28-C-Reactive Protein; TC- Total Cholesterol; TG- Triglyceride; HDL-C -High Density Lipoprotein Cholesterol; LDL-C -Low Density Lipoprotein Cholesterol; VLDL-C-Very Low Density Lipoprotein Cholesterol; AC-Atherogenic Coefficient; AIP-Atherogenic Index of Plasma; CR-I, CR-II- Castelli’s Risk Indexes. Keywords: Rheumatoid Arthritis, Interleukin-6, Atherogenic Indices. Citation: Abdulridha GAO, Hussein MA, Majeed SR. Estimation of interleukin-6 level and atherogenic indices as predictors of severity of rheumatoid arthritis in Iraqi patients. Anaesth. pain intensive care 2024;28(4):700−705; DOI: 10.35975/apic.v28i4.2400. Received: February 26, 2024; Reviewed: April 16, 2024; Accepted: July 09, 2024

Telehealth Parenting Program and Salivary Epigenetic Biomarkers in Preschool Children With Developmental Delay

Children with developmental delays are at a heightened risk of experiencing mental health challenges, and this risk is exacerbated among racially minoritized children who face disproportionate adversity. Understanding the impact of parenting interventions on biological markers associated with these risks is crucial for mitigating long-term health disparities. To examine the effect of 20 weeks of an internet-based parent-child interaction training (iPCIT) program on biomarkers associated with aging and chronic inflammation among preschoolers with developmental delay at 12-month follow-up. An observational secondary analysis of data from a randomized clinical trial conducted from March 17, 2016, to December 15, 2020, to assess changes in salivary DNA methylation (DNAm)-derived biomarkers following iPCIT intervention. Participants were recruited from 3 Part C early intervention sites in a large southeastern US city. Eligible participants included children recruited within 3 months of their third birthday who had a Child Behavior Checklist Externalizing Problems T score greater than 60 and provided saliva in at least 1 study wave. Data analysis was conducted May 2023 to April 2024. Participants received either iPCIT (a telehealth therapeutic intervention focused on enhancing the parent-child relationship and addressing behavioral challenges in young children) or referrals as usual. DNAm at the 12-month follow-up was assessed using the Infinium HumanMethylationEPIC Bead Chip Assay to derive biomarkers DunedinPACE, C-reactive protein (CRP), and interleukin-6 (IL-6). Analyses were intent-to-treat and used path analysis. A total of 71 children (mean [SD] age, 36.27 [0.61] months 51 male [71.8%] and 20 female [28.2%]) were analyzed, of whom 34 received iPCIT and 37 received referrals as usual. The iPCIT group had a slower pace of aging (β = 0.26; 95% CI, 0.06 to 0.50; P = .03) and less DNAm-derived CRP (β = 0.27; 95% CI, 0.05 to 0.49; P = .01) relative to the control condition at the 12-month follow-up. These associations remained significant after accounting for baseline DNAm score, child demographics, and symptom severity, and were independent of predicted buccal epithelial cell proportion for both DunedinPACE and CRP. There was no association with DNAm-derived IL-6 (β = 0.14; 95% CI, -0.08 to 0.36; P = .21). In this study of a parenting intervention, iPCIT, the association of intervention with decreased molecular markers of inflammation and biological aging suggests their potential to modify aspects of the biological embedding of stress. Understanding the systemic biological impact of such interventions offers insights into addressing health disparities and promoting resilience among vulnerable populations. ClinicalTrials.gov Identifier: NCT03260816.

The dichloromethane fraction from Calotropis gigantea (L.) dryand. Stem bark extract prevents liver cancer in SDT rats with insulin-independent diabetes mellitus

Ethnopharmacological relevanceCalotropis gigantea (L.) Dryand. (C. gigantea) is a traditional medicinal plant, recognized for its effectiveness in managing diabetes, along with its notable antioxidant, anti-inflammatory, and anticancer properties. Type II diabetes mellitus (T2DM) is characterized by chronic metabolic disorders associated with an elevated risk of hepatocellular carcinoma (HCC) due to hyperglycemia and impaired insulin response. The scientific validation of C. gigantea's ethnopharmacological efficacy offers advantages in alleviating cancer progression in T2DM complications, enriching existing knowledge and potentially aiding future clinical cancer treatments. AimThis study aimed to investigate the preventive potential of the dichloromethane fraction of C. gigantea stem bark extract (CGDCM) against diethylnitrosamine (DEN)-induced HCC in T2DM rats, aiming to reduce cancer incidence associated with diabetes while validating C. gigantea's ethnopharmacological efficacy. Materials and methodsSpontaneously Diabetic Torii (SDT) rats were administered DEN to induce HCC (SDT-DEN-VEH), followed by treatment with CGDCM. Metformin was used as a positive control (SDT-DEN-MET). All the treatments were administered for 10 weeks after the initial DEN injection. Diabetes-related parameters, including serum levels of glucose, insulin, and glycosylated hemoglobin (HbA1c), as well as liver function enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase), were quantified. Serum inflammation biomarkers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated. Liver tissue samples were analyzed for inflammation protein expression (IL-6, TNF-α, transforming growth factor-β1 (TGF-β1), and α-smooth muscle actin (α-SMA)). Histopathological evaluation was performed to assess hepatic necrosis, inflammation, and fibrosis. Liver cell proliferation was determined using immunohistochemistry for Ki-67 expression. ResultsRats with SDT-DEN-induced HCC treated with CGDCM exhibited reduced serum glucose levels, elevated insulin levels, and decreased HbA1c levels. CGDCM treatment also reduced elevated hepatic IL-6, TNF-α, TGF-β1, and α-SMA levels in SDT-DEN-VEH rats. Additionally, CGDCM treatment prevented hepatocyte damage, fibrosis, and cell proliferation. No adverse effects on normal organs were observed with CGDCM treatment, suggesting its safety for the treatment of HCC complications associated with diabetes. Additionally, the absence of adverse effects in SD rats treated with CGDCM at 2.5 mg/kg further supports the notion of its safe usage. ConclusionsThese findings suggest that C. gigantea stem bark extract exerts preventive effects against the development of HCC complications in patients with T2DM, expanding the potential benefits of its ethnopharmacological advantages.

A unified metric of human immune health.

Immunological health has been challenging to characterize but could be defined as the absence of immune pathology. While shared features of some immune diseases and the concept of immunologic resilience based on age-independent adaptation to antigenic stimulation have been developed, general metrics of immune health and its utility for assessing clinically healthy individuals remain ill defined. Here we integrated transcriptomics, serum protein, peripheral immune cell frequency and clinical data from 228 patients with 22 monogenic conditions impacting key immunological pathways together with 42 age- and sex-matched healthy controls. Despite the high penetrance of monogenic lesions, differences between individuals in diverse immune parameters tended to dominate over those attributable to disease conditions or medication use. Unsupervised or supervised machine learning independently identified a score that distinguished healthy participants from patients with monogenic diseases, thus suggesting a quantitative immune health metric (IHM). In ten independent datasets, the IHM discriminated healthy from polygenic autoimmune and inflammatory disease states, marked aging in clinically healthy individuals, tracked disease activities and treatment responses in both immunological and nonimmunological diseases, and predicted age-dependent antibody responses to immunizations with different vaccines. This discriminatory power goes beyond that of the classical inflammatory biomarkers C-reactive protein and interleukin-6. Thus, deviations from health in diverse conditions, including aging, have shared systemic immune consequences, and we provide a web platform for calculating the IHM for other datasets, which could empower precision medicine.

Rapid identification of early infections in febrile patients after CD19 target CAR-T cell therapy for B-cell malignancies

BackgroundCD19-targeted chimeric antigen receptor T (CAR-T) cell therapy stands out as a revolutionary intervention, exhibiting remarkable remission rates in patients with refractory/relapsed (R/R) B-cell malignancies. However, the potential side effects of therapy, particularly cytokine release syndrome (CRS) and infections, pose significant challenges due to their overlapping clinical features. Promptly distinguishing between CRS and infection post CD19 target CAR-T cell infusion (CTI) remains a clinical dilemma. Our study aimed to analyze the incidence of infections and identify key indicators for early infection detection in febrile patients within 30 days post-CTI for B-cell malignancies.MethodsIn this retrospective cohort study, a cohort of 104 consecutive patients with R/R B-cell malignancies who underwent CAR-T therapy was reviewed. Clinical data including age, gender, CRS, ICANS, treatment history, infection incidence, and treatment responses were collected. Serum biomarkers procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were analyzed using chemiluminescent assays. Statistical analyses employed Pearson’s Chi-square test, t-test, Mann–Whitney U-test, Kaplan–Meier survival analysis, Cox proportional hazards regression model, Spearman rank correlation, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic accuracy and develop predictive models through multivariate logistic regression.ResultsIn this study, 38 patients (36.5%) experienced infections (30 bacterial, 5 fungal, and 3 viral) within the first 30 days of CAR T-cell infusion. In general, bacterial, fungal, and viral infections were detected at a median of 7, 8, and 9 days, respectively, after CAR T-cell infusion. Prior allogeneic hematopoietic cell transplantation (HCT) was an independent risk factor for infection (Hazard Ratio [HR]: 4.432 [1.262–15.565], P = 0.020). Furthermore, CRS was an independent risk factor for both infection ((HR: 2.903 [1.577–5.345], P < 0.001) and severe infection (9.040 [2.256–36.232], P < 0.001). Serum PCT, IL-6, and CRP were valuable in early infection prediction post-CAR-T therapy, particularly PCT with the highest area under the ROC curve (AUC) of 0.897. A diagnostic model incorporating PCT and CRP demonstrated an AUC of 0.903 with sensitivity and specificity above 83%. For severe infections, a model including CRS severity and PCT showed an exceptional AUC of 0.991 with perfect sensitivity and high specificity. Based on the aforementioned analysis, we proposed a workflow for the rapid identification of early infection during CAR-T cell therapy.ConclusionsCRS and prior allogeneic HCT are independent infection risk factors post-CTI in febrile B-cell malignancy patients. Our identification of novel models using PCT and CRP for predicting infection, and PCT and CRS for predicting severe infection, offers potential to guide therapeutic decisions and enhance the efficacy of CAR-T cell therapy in the future.

Evaluation of salivary biomarker interleukin-6 in oral squamous cell carcinoma and oral potentially malignant disorders − A comparative cross-sectional South Indian study

Abstract Background: Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of oral malignancies and represents a major global health care problem. It is often preceded by oral potentially malignant disorders (OPMD). Although regular clinical examination forms the backbone for oral cancer screening, subtle lesions go unnoticed and there is a need for more sensitive and specific molecular biomarkers in mass screening of population. Salivary proteomics offer an attractive alternative to serum and tissue testing. Aims: To find the diagnostic utility of salivary interleukin-6 (IL-6) in the differential diagnosis of OSCC, OPMD from healthy controls. Study Design: In vivo study. Methods: After approval from the Institutional Review Board, unstimulated whole saliva was collected from 90 subjects, 30 in each group of OSCC, OPMD and controls after ethical clearance. Salivary IL-6 was measured by ELISA, and the results were statistically analysed. Results: Significant difference in salivary IL-6 was seen between OSCC, OPMD and controls. Receiver operating characteristic curve analysis showed the highest area under a curve of 0.982 in distinguishing OSCC from controls. It showed a sensitivity of 71% and specificity of 100% at a cut-off value of 33.4 pg/mL (P = 0.000). Moderately differentiated OSCC (MDSCC) showed a significant increase in salivary IL-6 concentration compared to well-differentiated OSCC (WDSCC). Conclusion: Results of the present study showed strong predictive power of salivary IL-6 in distinguishing OSCC from controls. Its levels also increased with tumor aggressiveness from WDSCC to MDSCC. Thus, salivary IL-6 could have a diagnostic and/or prognostic significance in identifying high-risk groups in mass screening of the population.

Establishment of a human nasal epithelium model of histamine-induced inflammation to assess the activity of fexofenadine as an inverse agonist and its link to clinical benefit.

Fexofenadine (FEX) is an antihistamine that acts as an inverse agonist against histamine (HIS) receptor 1 (H1R), which mediates the allergic reaction. Inverse agonists may be more potent than neutral antagonists, as they bind the same receptor as the agonist (HIS) but stabilize the inactive form and induce an opposite pharmacological response, suppressing the basal activity of H1R and preventing HIS from binding. This study aims to establish and validate a model of HIS-induced inflammation based on fully reconstituted human nasal epithelial tissue to assess the activity of FEX as an inverse agonist in this model and explore its link to clinical benefit. The model was developed using nasal MucilAir™ (Epithelix) in vitro epithelium challenged by HIS. Two conditions were assessed in a side-by-side comparison: tissue was exposed to HIS + FEX with or without FEX pre-treatment (one-hour prior to HIS challenge). Tissue functionality, cytotoxicity, H1R gene expression, and inflammatory cytokines were assessed. HIS at 100µM induced significant 3.1-fold and 2.2-fold increases for inflammatory biomarkers interleukin (IL)-8 and IL-6, respectively (p < 0.0001), as well as rapid upregulation of H1R mRNA. Inflammatory biomarkers were inhibited by FEX and H1R expression was significantly reduced (p < 0.0001). FEX alone decreased H1R expression at all doses tested. With one-hour FEX pre-treatment, there was significantly higher downregulation of IL-8 (p < 0.05) and further downregulation of H1R expression and IL-6 versus without FEX pre-treatment; the effects of FEX were improved from 22% to 40%. A model of HIS-induced airway inflammation was established based on IL-8, IL-6 and H1R gene expression and was validated with FEX. FEX works as an inverse agonist, with a higher effect when used before+during versus only during the HIS challenge. Taking FEX before+during allergen exposure, or when symptoms first occur, may reduce basal activity and H1R gene expression, providing stronger protection against the worsening of symptoms upon allergen exposure.

IP-10, MIP1α, IL-6, and IL-1β as Biomarkers Associated with Disease Severity of COVID-19

Background: The factors responsible for the progression of COVID-19 from a mild illness to a severe and often lethal condition, characterized by respiratory failure and multiple organ involvement, remain unclear. The identification of biomarkers capable of predicting disease progression is of the highest importance. Objectives: This study sought to assess laboratory measurements of interferon-gamma inducible protein-10 (IP-10), macrophage inflammatory protein 1-alpha (MIP1α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) to achieve this objective. Methods: We measured IP-10 and MIP1α by qRT-PCR and IL-6 and IL-1β using an enzyme-linked immunosorbent assay in 120 serum samples. We analyzed differences between patients with moderate, severe, and recovered COVID-19. Results: The number of positive cases for biomarkers IP-10, MIP1α, IL-6, and IL-1β were significantly different between groups. The expression levels of IP-10 and MIP1α were significantly higher in patients with severe COVID-19 compared to those who had recovered. A strong positive association was observed between IP-10 and MIP1α in severe infection cases. Additionally, these biomarkers were relatively independent predictors of disease severity. Conclusions: The results suggest that IP-10, MIP1α, IL-6, and IL-1β are promising research candidates for understanding the severity of COVID-19 and for investigating possible pathophysiological mechanisms of the disease.

Novel point-of-care cytokine biomarker lateral flow test for the screening for sexually transmitted infections and bacterial vaginosis: study protocol of a multicentre multidisciplinary prospective observational clinical study to evaluate the performance and feasibility of the Genital InFlammation Test (GIFT)

IntroductionA prototype lateral flow device detecting cytokine biomarkers interleukin (IL)-1α and IL-1β has been developed as a point-of-care test—called the Genital InFlammation Test (GIFT)—for detecting genital inflammation associated with sexually...

Correlation of Inflammatory Biomarkers (Interleukin-6, Interleukin-8, and Tumor Necrosis Factor-alpha) with Severity of Acute Pancreatitis

Abstract Background: Early assessment of severity of acute pancreatitis is very essential for the selection of patients who will require intensive care to prevent local complications and organ dysfunction. Several scoring systems have been developed, but these require large number of clinical and biochemical parameters, making them overly complicated and cumbersome. There is a need to develop simple clinical investigations which would help in assessing the severity of acute pancreatitis. Hence, the present study is undertaken to evaluate the role of inflammatory biomarkers (interleukin-6 [IL-6], IL-8, and tumor necrosis factor-alpha [TNF-α]) in the assessment of severity in acute pancreatitis. Materials and Methods: This cross-sectional study was conducted at a tertiary care teaching hospital in North India and enrolled 50 patients with acute pancreatitis. Serum levels of IL-6, IL-8, and TNF-α were measured within 24 h of admission. Results: The levels of IL-6, IL-8, and TNF-α were found to be significantly higher in patients with severe pancreatitis as compared to mild disease. With a cutoff level of &gt;46.379 pg/ml, IL-6 had a sensitivity of 96.15%, specificity of 95.83%, and diagnostic accuracy of 96% for predicting progression to severe acute pancreatitis. Similarly, IL-8 &gt;39.54 pg/mL had a sensitivity of 92.31%, specificity of 91.67%, and diagnostic accuracy of 92%. TNF-α &gt;11.80 pg/mL had a sensitivity of 53.85%, specificity of 95.83%, and diagnostic accuracy of 74%. Conclusion: The current study results suggests that IL-6 and IL-8 levels measured within 24 h of admission can be used for predicting progression to severe acute pancreatitis.

Inflammation biomarkers in the intracranial blood are associated with outcome in patients with ischemic stroke

BackgroundPerforming endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) allows a port of entry for intracranial biological sampling.ObjectiveTo test the hypothesis that specific immune players are molecular contributors...