Optical Aptamer-Based Cytokine Nanosensor Detects Macrophage Activation by Bacterial Toxins.

Overactive or dysregulated cytokine expression is a hallmark of many acute and chronic inflammatory diseases. This is true for acute or chronic infections, neurodegenerative diseases, autoimmune diseases, cardiovascular diseases, cancer, and others. Cytokines such as interleukin-6 (IL-6) are known therapeutic targets and biomarkers for such inflammatory diseases. Platforms for cytokine detection are, therefore, desirable tools for both research and clinical applications. Single-walled carbon nanotubes (SWCNT) are versatile nanomaterials with near-infrared fluorescence that can serve as transducers for optical sensors. When functionalized with an analyte-specific recognition element, SWCNT emission may become sensitive and selective toward the desired target. SWCNT-aptamer sensors are easily assembled, inexpensive, and biocompatible. In this work, we introduced a nanosensor design based on SWCNT and a DNA aptamer specific to IL-6. We first evaluated several SWCNT-aptamer constructs based on this simple direct complexation method, wherein the aptamer both solubilizes the SWCNT and confers sensitivity to IL-6. The sensor limit of detection, 105 ng/mL, lies in the relevant range for pathological IL-6 levels. Upon investigation of sensor kinetics, we found rapid response within seconds of antigen addition which continued over the course of 3 h. We found that this sensor construct is stable and the aptamer is not displaced from the nanotube surface during IL-6 detection. Finally, we investigated the ability of this sensor construct to detect macrophage activation caused by bacterial lipopolysaccharides (LPS) in an in vitro model of disease, finding rapid and sensitive detection of macrophage-expressed IL-6. We are confident that further development of this sensor will have novel implications for diagnosis of acute and chronic inflammatory diseases, in addition to contributing to the understanding of the role of cytokines in these diseases.

An optical aptamer-based cytokine nanosensor detects macrophage activation by bacterial toxins.

Overactive or dysregulated cytokine expression is hallmark of many acute and chronic inflammatory diseases. This is true for acute or chronic infection, neurodegenerative diseases, autoimmune diseases, cardiovascular disease, cancer, and others. Cytokines such as interleukin-6 (IL-6) are known therapeutic targets and biomarkers for such inflammatory diseases. Platforms for cytokine detection are therefore desirable tools for both research and clinical applications. Single-walled carbon nanotubes (SWCNT) are versatile nanomaterials with near-infrared fluorescence that can serve as transducers for optical sensors. When functionalized with an analyte-specific recognition element, SWCNT emission may become sensitive and selective towards the desired target. SWCNT-aptamer sensors are easily assembled, inexpensive, and biocompatible. In this work, we introduced a nanosensor design based on SWCNT and a DNA aptamer specific to IL-6. We first evaluated several SWCNT-aptamer constructs based on this simple direct complexation method, wherein the aptamer both solubilizes the SWCNT and confers sensitivity to IL-6. The sensor limit of detection, 105 ng/mL, lies in the relevant range for pathological IL-6 levels. Upon investigation of sensor kinetics, we found rapid response within seconds of antigen addition which continued over the course of three hours. We found that this sensor construct is stable, and the aptamer is not displaced from the nanotube surface during IL-6 detection. Finally, we investigated the ability of this sensor construct to detect macrophage activation caused by bacterial lipopolysaccharides (LPS) in an in vitro model of disease, finding rapid and sensitive detection of macrophage-expressed IL-6. We are confident further development of this sensor will have novel implications for diagnosis of acute and chronic inflammatory diseases, in addition to contributing to the understanding of the role of cytokines in these diseases.

Central sensitisation in pelvic pain: A cohort study.

BACKGROUND: Central sensitisation (CS) leads to pain amplification and impacts on the management of pelvic pain (PP). Identification of CS in patients with PP may provide additional treatment pathways and improve patient outcomes. AIMS: The aims are to quantify the prevalence of questionnaire-predicted CS (QPCS) in patients presenting with PP and investigate associations between QPCS and clinical variables. MATERIALS AND METHODS: This was an observational, cross-sectional study. Subjects with PP completed a questionnaire comprising four validated tools: the Central Sensitisation Inventory (CSI) for QPCS, Pain Catastrophising Scale for Catastrophising Trait, Bladder Pain/Interstitial Cystitis Symptom Score for bladder pain syndrome (BPS) and the Rome IV criteria for irritable bowel syndrome (IBS). RESULTS: One hundred and eleven women were enrolled in the study; 74.8% (n = 83) had a CSI score of >40, indicating the presence of QPCS. Subjects with QPCS were more likely to screen positive for catastrophising trait (odds ratio (OR) 3.57, 95% CI 1.19-10.76, P = 0.02), BPS (OR 11.77, 95% CI 2.13-64.89, P = 0.005) and IBS (OR 2.6, 95% CI 1.05-6.43, P = 0.04). They were more likely to experience pain for more than two years (OR 4.98, 95% CI 1.94-12.82, P = 0.001) and other pain symptoms involving bladder (OR 9.87, 95% CI 2.52-38.67, P = 0.001), bowel (OR 3.13, 95% CI 1.31-7.48, P = 0.01), back (OR 4.17, 95% CI 1.66-10.51, P = 0.002) and vulva (OR 3.61, 95% CI 1.21-10.82, P = 0.02). They also had higher previous diagnoses of mental health disorder (OR 3.5, 95% CI 1.5-8.4, P = 0.005) or IBS (OR 8.9, 95% CI 1.6-49.1, P = 0.01). CONCLUSIONS: QPCS occurs frequently in patients with PP, and subjects with QPCS experience more prolonged and complex pain.