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Development of simple solid-phase electrochemiluminescence (ECL) immunosensor with convenient fabrication for high-performance detection of tumor biomarkers is crucial. Herein, a solid-phase ECL immunoassay was constructed based on a bipolar silica nanochannel film (bp-SNA) modified electrode for highly sensitive detection of carbohydrate antigen 125 (CA 125). Inexpensive and readily available indium tin oxide (ITO) electrode was used as the supporting electrode for the growth of bp-SNA. bp-SNA consists of a bilayer SNA film with different functional groups and charge properties, including negatively charged inner layer SNA (n-SNA) and positively charged outer layer SNA (p-SNA). The nanochannels of bp-SNA were used for the immobilization of ECL emitter tris(bipyridine)ruthenium(II), while the outer surface was utilized for constructing the immunorecognition interface. Due to the dual electrostatic interaction composed of electrostatic attraction from n-SNA and electrostatic repulsion from p-SNA, ECL emitter could be stably confined within bp-SNA, providing stable and high ECL signals to the modified electrode. After amino groups on the outer surface of bp-SNA were derivatized with aldehyde groups, recognition antibodies could be covalently immobilized, and an immunosensor was obtained after blocking nonspecific sites. When CA 125 binds to the antibodies on the recognition interface, the formed complex reduces the diffusion of the co-reactant tripropylamine (TPrA) to the supporting electrode, decreasing the ECL signal. Based on this mechanism, the constructed immunosensor can achieve sensitive ECL detection of CA 125. The linear detection range is from 0.01 to 100 U/mL, with a detection limit of 4.7 mU/mL. CA 125 detection in serum is also achieved. The construction immunosensor has advantages including simple and convenient fabrication, high stability of the immobilized emitter, and high selectivity, making it suitable for CA 125 detection. [ABSTRACT FROM AUTHOR]

Sweat is considered the most promising candidate to replace conventional blood samples for noninvasive sensing. There are many tools and optical and electrochemical methods that can be used for detecting sweat biomarkers. Electrochemical methods are known for their simplicity and cost-effectiveness. However, they need to be optimized in terms of selectivity and catalytic activity. Therefore, electrode modifiers such as nanostructures and metal–organic frameworks (MOFs) or combinations of them were examined for boosting the performance of the electrochemical sensors. The MOF structures can be prepared by hydrothermal/solvothermal, sonochemical, microwave synthesis, mechanochemical, and electrochemical methods. Additionally, MOF nanostructures can be prepared by controlling the synthesis conditions or mixing bulk MOFs with nanoparticles (NPs). In this review, we spotlight the previously examined MOF-based nanostructures as well as promising ones for the electrochemical determination of sweat biomarkers. The presence of NPs strongly improves the electrical conductivity of MOF structures, which are known for their poor conductivity. Specifically, Cu-MOF and Co-MOF nanostructures were used for detecting sweat biomarkers with the lowest detection limits. Different electrochemical methods, such as amperometric, voltammetric, and photoelectrochemical, were used for monitoring the signal of sweat biomarkers. Overall, these materials are brilliant electrode modifiers for the determination of sweat biomarkers. [ABSTRACT FROM AUTHOR]

The role of ferroptosis and iron metabolism dysregulation in the pathophysiology of cardiovascular diseases is increasingly recognized. Conditions such as hypertension, cardiomyopathy, atherosclerosis, myocardial ischemia/reperfusion injury, heart failure, and cardiovascular complications associated with COVID-19 have been linked to these processes. Inflammation is central to these conditions, prompting exploration into the inflammatory and immunoregulatory molecular pathways that mediate ferroptosis and its contribution to cardiovascular disease progression. Notably, emerging evidence highlights interleukin-37 as a protective cytokine with the ability to activate the nuclear factor erythroid 2-related factor 2 pathway, inhibit macrophage ferroptosis, and attenuate atherosclerosis progression in murine models. However, a comprehensive review focusing on interleukin-37 and its protective role against ferroptosis in CVD is currently lacking. This review aims to fill this gap by summarizing existing knowledge on interleukin-37, including its regulatory functions and impact on ferroptosis in conditions such as atherosclerosis and myocardial infarction. We also explore experimental strategies and propose that targeting interleukin-37 to modulate ferroptosis presents a promising therapeutic approach for the prevention and treatment of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

In the context of sustainable development and global challenges such as climate change and energy security, this paper conducts a bibliometric analysis of scientific journals on multi-criteria decision-making (MCDM) methods with an emphasis on their applications in environmental and energy engineering. The study used the CiteSpace software program 6.2.R6 Advanced to analyze citation networks and identify key publications, authors, and research topics. The simulations carried out made it possible to identify the main research centers and patterns of international cooperation, pointing to the key countries and institutions involved in MCDM research. The results of the analysis reveal the research areas of greatest interest and the main directions for future research. These results can support scientists, researchers, and policymakers in making more informed and sustainable decisions, contributing to the achievement of the Sustainable Development Goals. [ABSTRACT FROM AUTHOR]

Plastic pollution has become a global environmental problem, and the large number of microorganisms attached to plastic debris in the environment has become a hot topic due to their rapid response to pollutants and environmental changes. In this study, we used high-throughput sequencing to investigate the microbial community structure of and explore the metagenome in the biofilm of two types of plastic debris, polystyrene (PS) and polyethylene terephthalate (PET), and compared them with a water sample collected at the sampling site. The phylum Proteobacteria dominated both the PET and PS samples, at 93.43% and 65.95%, respectively. The metagenome data indicated that the biofilm is enriched with a number of hydrocarbon (petroleum, microplastics, etc.) degrading genes. Our results show that the type of plastic determined the bacterial community structure of the biofilm, while the environment had relatively little effect. [ABSTRACT FROM AUTHOR]

Pesticides have become an integral part of modern agricultural practices, but their widespread use poses a significant threat to human health. As such, there is a pressing need to develop effective methods for detecting pesticides in food and environmental samples. Traditional chromatography methods and common rapid detection methods cannot satisfy accuracy, portability, long storage time, and solution stability at the same time. In recent years, photoelectrochemical (PEC) sensing technology has gained attention as a promising approach for detecting various pesticides due to its salient advantages, including high sensitivity, low cost, simple operation, fast response, and easy miniaturization, thus becoming a competitive candidate for real-time and on-site monitoring of pesticide levels. This review provides an overview of the recent advancements in PEC methods for pesticide detection and their applications in ensuring food and environmental safety, with a focus on the categories of photoactive materials, from single semiconductor to semiconductor–semiconductor heterojunction, and signaling mechanisms of PEC sensing platforms, including oxidation of pesticides, steric hindrance, generation/decrease in sacrificial agents, and introduction/release of photoactive materials. Additionally, this review will offer insights into future prospects and confrontations, thereby contributing novel perspectives to this evolving domain. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have shown that TBX21 (T-Box Transcription Factor 21) plays a vital role in coordinating multiple aspects of the immune response especially type 1 immune response as well as tumor progression. However, the function of TBX21 in colorectal cancer (CRC) remains unclear. Methods: IHC to investigate TBX21 expression in CRC tissues. Cell proliferation and apoptosis assays to validate TBX21 function in vitro and in vivo. RNA-seq assay to explore target genes of TBX21. Human phospho-kinase array assay to explore down-stream signaling of TBX21. Results: We disclosed that the expression of TBX21 was marked decreased in CRC versus normal tissue, and negatively correlated with CRC TNM stages. Surprisingly, we found that the CRC and normal cell lines show no TBX21 expression levels. Ectopic expression of TBX21 inhibited cell proliferation and promoted cell apoptosis in vitro. Moreover, RNA-sequence data first time showed that ARHGAP29 acts as the target gene of TBX21 to mediate down-stream signaling activation. Human phospho-kinase array data first time displayed that ectopic expression of TBX21 reduced kinase RSK and GSK3β activation. In contrast, knocked down the expression of TBX21 or ARHGAP29 alternatively abolished TBX21 mediated cell proliferation suppression, cell apoptosis enhancement and RSK/GSK3β activation. In addition, xenograft model studies demonstrated that TBX21 inhibits colorectal tumor progression via ARHGAP29/ RSK/ GSK3β signaling in vivo. Conclusions: In summary, the aforementioned findings suggest a model of TBX21 in suppressing CRC progression. This may provide a promising target for CRC therapy. [ABSTRACT FROM AUTHOR]

Despite being present in minimal amounts, vitamin B2 (VB2), vitamin C (VC), and vitamin B6 (VB6) each play indispensable roles in human metabolisms. Given that VB2, VC, and VB6 cannot be synthesized by the human body, detections of these three vitamins both in fermentation liquid where vitamins are industrially manufactured and in human serum where vitamin concentrations could be clinically controlled are of significant importance. Here, a nanoporous gold (NPAu) modified screen-printed electrode (NPAu/SPE) was fabricated to detect VB2, VC, and VB6 based on NPAu's electro-oxidation towards vitamins. Owing to the wide separation of peak potentials among VB2, VC, and VB6, the simultaneous detection of these three vitamins was achieved by the NPAu/SPE within a potential range from −0.8 V to 0.8 V. The achieved limits of detection (LOD) for VB2, VC, and VB6 were 0.46, 6.44, and 1.92 μM, with sensitivities of 68.58, 4.77, and 15.94 μA/μM, respectively. Subsequent reliability experiments suggested that the NPAu/SPE exhibited solid anti-interference capability and repeatability. Additionally, the real-sample detection of the NPAu/SPE towards VB2, VC, and VB6 was achieved both in human serum and in fermentation liquid with comparable accuracy (the recovery rates were from 89.8% to 111.7%) as high-performance liquid chromatography (HPLC). Moreover, the portable NPAu/SPE showed comparable performance in terms of the LOD and linear dynamic range when compared to glassy carbon electrodes (GCE) limited to laboratory detection. The proposed NPAu/SPE possesses various advantageous properties including portability, easy fabrication, high sensitivity, and cost-efficiency, making it a potential candidate for clinical and industrial multi-vitamins analysis. [ABSTRACT FROM AUTHOR]

Sweat, as a biofluid that is easy to extract and contains a variety of biomarkers, can provide various types of physiological information for health monitoring. In recent years, research on wearable sensors for sweat sensing has been emerging continuously. Wearable sweat sensing will probably become an alternative method to traditional chemical analysis. This is due to its advantages of portability, non-invasiveness, comfort, and continuous monitoring. Since the inception of this research field, wearable sweat sensors have achieved significant development in terms of materials, structures, systems, and application directions. Research interests are gradually evolving from single biomarker detection to the pursuit of multi-channel, multi-modal system-level architecture. The analysis of physiological signals has also developed from single signal characterization to omics analysis using multiple physiological information sources. Based on the changes mentioned above, this paper mainly introduces the latest researches of wearable sweat sensors from the aspects of strategy, architecture, material, system, data processing, etc., and tries to summarize the trends of sweat sensors. Finally, this paper analyzes the challenges faced by the sensing platform and possible methods for optimization. [ABSTRACT FROM AUTHOR]

Confined catalytic realms and synergistic catalysis sites were constructed using bimetallic active centers in two-dimensional metal-organic frameworks (MOFs) to achieve highly selective oxygenation of cycloalkanes and alkyl aromatics with oxygen towards partly oxygenated products. Every necessary characterization was carried out for all the two-dimensional MOFs. The selective oxygenation of cycloalkanes and alkyl aromatics with oxygen was accomplished with exceptional catalytic performance using two-dimensional MOF Co-TCPPNi as a catalyst. Employing Co-TCPPNi as a catalyst, both the conversion and selectivity were improved for all the hydrocarbons investigated. Less disordered autoxidation at mild conditions, inhibited free-radical diffusion by confined catalytic realms, and synergistic C–H bond oxygenation catalyzed by second metal center Ni employing oxygenation intermediate R–OOH as oxidant were the factors for the satisfying result of Co-TCPPNi as a catalyst. When homogeneous metalloporphyrin T(4-COOCH3)PPCo was replaced by Co-TCPPNi, the conversion in cyclohexane oxygenation was enhanced from 4.4% to 5.6%, and the selectivity of partly oxygenated products increased from 85.4% to 92.9%. The synergistic catalytic mechanisms were studied using EPR research, and a catalysis model was obtained for the oxygenation of C–H bonds with O2. This research offered a novel and essential reference for both the efficient and selective oxygenation of C–H bonds and other key chemical reactions involving free radicals. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI), heart failure, cardiomyopathy, myocarditis, and myocardial ischemia-reperfusion injury (I/R) are the most common heart diseases, yet there is currently no effective therapy due to their complex pathogenesis. Cardiomyocytes (CMs), fibroblasts (FBs), endothelial cells (ECs), and immune cells are the primary cell types involved in heart disorders, and, thus, targeting a specific cell type for the treatment of heart disease may be more effective. The same interleukin may have various effects on different kinds of cell types in heart disease, yet the exact role of interleukins and their pathophysiological pathways on primary cell types remain largely unexplored. This review will focus on the pathophysiological effects of various interleukins including the IL-1 family (IL-1, IL-18, IL-33, IL-37), IL-2, IL-4, the IL-6 family (IL-6 and IL-11), IL-8, IL-10, IL-17 on primary cell types in common heart disease, which may contribute to the more precise and effective treatment of heart disease. [ABSTRACT FROM AUTHOR]

Signal pathways participate in vital biological processes and regulate complex life activities through protein modifications. Protein modifications in signal pathways are accompanied by electron transfer. The study of electronic behavior helps to explore the physical and chemical processes in signal pathways, receiving extensive attention. There are some excellent reviews that have summarized methods for signal pathway detection, while few discussions are from an electron transfer perspective. This review describes the relationship between signal pathways and electron transfer in protein modification. Subsequently, we summarize the electron transfer-based detection methods, such as electrochemical, photoelectrochemical and electrochemiluminescence methods. Additionally, the applications of signal pathway detection in mechanism study and imaging are also reviewed. Finally, a comprehensive discussion of the summary and outlooks in this field is presented, aiming to provide valuable guidance for the molecular mechanism of life processes and the development of new analytical techniques. [ABSTRACT FROM AUTHOR]

Aging is characterized by declines in physiological function that increase risk of age-associated diseases and limit healthspan, mediated in part by chronic low-grade inflammation. Interleukin (IL)-37 suppresses inflammation in pathophysiological states but has not been studied in the context of aging in otherwise healthy humans. Thus, we investigated associations between IL-37 and markers of healthspan in 271 young (18–39 years; n = 41), middle-aged (40–64 years; n = 162), and older (65 + years; n = 68) adults free of overt clinical disease. After conducting a thorough validation of AdipoGen's IL-37 ELISA, we found that plasma IL-37 is lower in older adults (young: 339 ± 240, middle-aged: 345 ± 234; older: 258 ± 175 pg/mL; P = 0.048), despite elevations in pro-inflammatory markers. As such, the ratios of circulating IL-37 to pro-inflammatory markers were considerably lower in older adults (e.g., IL-37 to C-reactive protein: young, 888 ± 918 vs. older, 337 ± 293; P = 0.02), indicating impaired IL-37 responsiveness to a pro-inflammatory state with aging and consistent with the notion of immunosenescence. These ratios were related to multiple indicators of healthspan, including positively to cardiorespiratory fitness (P < 0.01) and negatively to markers of adiposity, blood pressure, and blood glucose (all P < 0.05). Lastly, we correlated single-nucleotide polymorphisms (SNPs) in the IL37 and ILR8 (the co-receptor for IL-37) genes and found that variants in IL37 SNPs tended to be associated with blood pressure and adiposity (P = 0.08–0.09) but did not explain inter-individual variability in circulating IL-37 concentrations across age (P ≥ 0.23). Overall, our findings provide novel insights into a possible role of IL-37 in biological aging in humans. [ABSTRACT FROM AUTHOR]

The IL-1 superfamily of cytokines is a central regulator of immunity and inflammation. The family is composed of 11 cytokines (with agonist, antagonist, and anti-inflammatory properties) and 10 receptors, all tightly regulated through decoy receptor, receptor antagonists, and signaling inhibitors. Inflammation not only is an important physiological response against infection and injury but also plays a central role in atherosclerosis development. Several clinical association studies along with experimental studies have implicated the IL-1 superfamily of cytokines and its receptors in the pathogenesis of cardiovascular disease. Here, we summarize the key features of the IL-1 family, its role in immunity and disease, and how it helps shape the development of atherosclerosis. [ABSTRACT FROM AUTHOR]

While we previously revealed RSK4 as a therapeutic target in lung and bladder cancers, the wider role of this kinase in other cancers remains controversial. Indeed, other reports instead proposed RSK4 as a tumour suppressor in colorectal and gastric cancers and are contradictory in breast malignancies. One explanation for these discrepancies may be the expression of different RSK4 isoforms across cancers. Four RNAs are produced from the RSK4 gene, with two being protein-coding. Here, we analysed the expression of the latter across 30 normal and 33 cancer tissue types from the combined GTEx/TCGA dataset and correlated it with clinical features. This revealed the expression of RSK4 isoforms 1 and 2 to be independent prognostic factors for patient survival, pathological stage, cancer metastasis, recurrence, and immune infiltration in brain, stomach, cervical, and kidney cancers. However, we found that upregulation of either isoform can equally be associated with good or bad prognosis depending on the cancer type, and changes in the expression ratio of isoforms fail to predict clinical outcome. Hence, differential isoform expression alone cannot explain the contradictory roles of RSK4 in cancers, and further research is needed to highlight the underlying mechanisms for the context-dependent function of this kinase. [ABSTRACT FROM AUTHOR]

Considering the limitations associated with existing methods for the detection of trace amounts of trichlorfon, this paper proposes a novel molecularly imprinted electrochemiluminescence (ECL) sensor for the detection of trichlorfon by utilizing the double enhancement effect of trichlorfon and Ag nanoparticles supported by multi-walled carbon nanotubes (MWCNTs/Ag NPs) in a luminol–H2O2 ECL system. Here, trichlorfon was electropolymerized on the surface of the MWCNT/Ag NP–modified gold nanoelectrode with o-phenylenediamine to prepare the molecularly imprinted polymer-based sensor. After eluting the trichlorfon, imprinted holes for the identification of trichlorfon were retained on the sensor, which were used as signal switches to obtain different ECL intensities through the adsorption of different concentrations of trichlorfon. The ECL signal of the sensitized luminol–H2O2 was doubly enhanced by the MWCNTs/Ag and trichlorfon, improving the sensitivity of the sensor. The trichlorfon concentration was positively correlated with the enhanced ECL intensity of the sensor in the range 5.0 × 10−8–5.0 × 10−11 mol L−1, and the detection limit of trichlorfon was 3.9 × 10−12 mol L−1. Moreover, the proposed sensor was successfully applied to the detection of trichlorfon residues in real samples, and the recovery ranged between 91.8 and 109%. A molecularly imprinted electrochemiluminescence sensor for trichlorfon detection by utilizing the double enhancement effect of trichlorfon and Ag nanoparticles supported by multi-walled carbon nanotubes in a luminol–H2O2 ECL system. The dual enhancement of the ECL signal improved the sensitivity of the sensor. [ABSTRACT FROM AUTHOR]

BACKGROUND: Dynamin 2 (DNM2) involved in tumor progression in various malignancies. OBJECTIVE: For the first time, we evaluated DNM2 expression pattern, its association with clinicopathological characteristics and survival outcomes in RCC subtypes. METHODS: We evaluated the DNM2 expression pattern in RCC tissues as well as adjacent normal tissue using immunohistochemistry on tissue microarray (TMA) slides. RESULTS: Our findings revealed increased DNM2 expression in RCC samples rather than in adjacent normal tissues. The results indicated that there was a statistically significant difference between cytoplasmic expression of DNM2 among subtypes of RCC in terms of intensity of staining, percentage of positive tumor cells, and H-score (P = 0.024, 0.049, and 0.009, respectively). The analysis revealed that increased cytoplasmic expression of DNM2 in ccRCC is associated with worse OS (log rank: P = 0.045), DSS (P = 0.049), and PFS (P = 0.041). Furthermore, cytoplasmic expression of DNM2 was found as an independent prognostic factor affecting DSS and PFS in multivariate analysis. CONCLUSIONS: Our results indicated that DNM2 cytoplasmic expression is associated with tumor aggressiveness and poor outcomes. DNM2 could serve as a promising prognostic biomarker and therapeutic target in patients with ccRCC. [ABSTRACT FROM AUTHOR]

Aim: High‐grade vaginal intraepithelial neoplasia (VAIN) is considered to be a premalignant lesion. We conducted a 20‐year retrospective observational single‐center study on the effectiveness of vaginal stripping (local excision procedure) as a treatment for high‐grade VAIN. Methods: Women diagnosed with VAIN and treated with vaginal stripping performed from 1998 to 2017 at our unit were identified using the hospital computer database. Vaginal stripping was performed for high‐grade VAIN after being diagnosed by colposcopy‐directed biopsies. The patients were followed every 3–6 months afterward via cytology monitoring and vaginal smear. Colposcopy‐guided biopsy was repeated for high‐grade abnormal cytology or persistent low‐grade abnormality. The residual disease and recurrence rates were determined. Risk factors for margin positivity and residual and recurrent disease were identified. The association between margin positivity and recurrence was evaluated. Results: Excluding three women whose final histology were malignant, the follow‐up smears and histology (if any) were traced in the remaining 111 women. The median follow‐up time was 76 months. Twenty‐one of them had persistent abnormal smears (14 high‐grade lesions and seven low‐grade lesions) during the year following the vaginal stripping. The residual disease rate was 18.9% (21/111). The recurrence rate was 7.2%. There were five women (4%) with procedure‐related complications. History of hysterectomy was identified as a risk factor for recurrence. Conclusions: Vaginal stripping is a valid treatment option for VAIN. High‐grade VAIN post treatment recurred up to 5 years post treatment. Regular long‐term surveillance is needed. [ABSTRACT FROM AUTHOR]

Synthetic molecules that mimic the function of natural enzymes or molecules have untapped potential for use in the next generation of drugs. Cyclic compounds that contain aromatic rings are macrocyclic cyclophanes, and when they coordinate iron ions are of particular interest due to their antioxidant and biomimetic properties. However, little is known about the molecular responses at the cellular level. This study aims to evaluate the changes in immune gene expression in human cells exposed to the cyclophanes Fe2PO and Fe2PC. Confluent human embryonic kidney cells were exposed to either the cyclophane Fe2PO or Fe2PC before extraction of RNA. The expression of a panel of innate and adaptive immune genes was analyzed by quantitative real-time PCR. Evidence was found for an inflammatory response elicited by the cyclophane exposures. After 8 h of exposure, the cells increased the relative expression of inflammatory mediators such as interleukin 1; IRAK, which transduces signals between interleukin 1 receptors and the NFκB pathway; and the LPS pattern recognition receptor CD14. After 24 h of exposure, regulatory genes begin to counter the inflammation, as some genes involved in oxidative stress, apoptosis and non-inflammatory immune responses come into play. Both Fe2PO and Fe2PC induced similar immunogenetic changes in transcription profiles, but equal molar doses of Fe2PC resulted in more robust responses. These data suggest that further work in whole animal models may provide more insights into the extent of systemic physiological changes induced by these cyclophanes. [ABSTRACT FROM AUTHOR]

As a novel anti-inflammatory cytokine of the interleukin (IL)-1 family, IL-37 protects the human body from diseases characterized by excessive inflammation. The pathologic process of hyperhomocysteinemia (hHcy) is accompanied by persistent inflammation. However, little is known regarding the role of IL-37 in hHcy. In the present study, the levels of cytokines including IL-37, IL-1β, IL-6 and tumor necrosis factor-α in the supernatant were detected by ELISA. mRNA and protein expression were detected by Reverse transcription-quantitative PCR and western blotting, respectively. LDH level was determined by ELISA and the cell viability was detected through CCK-8 kit. In the present study, mean serum IL-37 levels of patients with hHcy were 32.3% lower than those of controls (P<0.01). In peripheral blood mononuclear cells (PBMCs) from patients with hHcy, mean IL-37 mRNA expression was 73.5% lower (P<0.01) and IL-37 protein expression was 77.7% lower compared with that of healthy controls (P<0.01). Furthermore, the results demonstrated that exogenous homocysteine (Hcy) stimulation markedly downregulated the mRNA and protein expression levels of IL-37 in PBMCs in vitro. In 293T cells, overexpression of IL-37 restored the cell viability impaired by Hcy, and reduced the release of lactate dehydrogenase and the proinflammatory cytokines IL-1β, IL-6 and tumor necrosis factor-α. In conclusion, IL-37 was downregulated by Hcy in vivo and in vitro, and IL-37 exhibited a protective role against cell injury induced by Hcy. [ABSTRACT FROM AUTHOR]

IL-37, the anti-inflammatory cytokine of the IL-1 family, plays several key roles in the regulation of autoimmune diseases. Yet, its role in Hashimoto's thyroiditis (HT) is not clear. In the present study, we found that, in tissues from HT patients, most of the follicular epithelial cells were positive for both IL-37 and single Ig IL-1-related receptor (SIGIRR) by immunohistochemical staining, while the infiltrating lymphocytes and other inflammatory cells hardly expressed any. Meanwhile, mRNA expression levels of IL-37 in peripheral blood mononuclear cells (PBMC) of HT patients were significantly higher than those in normal controls measured by quantitative real-time PCR. Finally, we studied the possible role of IL-37 in IFN-γ-stimulated rat FRTL-5 cells. The results showed that IL-1β, TNF-α, and MCP-1 mRNA levels were significantly decreased, while the expression of IL-4 mRNA was dramatically up-regulated in IFN-γ-stimulated rat thyroid cell line FRTL-5 pre-treated with IL-37. The current study, for the first time, demonstrated that the IL-37 network is involved in Hashimoto's thyroiditis, and IL-37 signaling pathway may ameliorate the excessive autoimmune responses in this chronic lymphocytic thyroiditis. [ABSTRACT FROM AUTHOR]

Background. Interleukin-37 (IL-37) acts as an inhibitor of innate and adaptive immunity. However, the exact role of IL-37 in the patients with acute coronary syndrome (ACS) remains to be elucidated. Methods. Patients were classified into 4 groups: normal coronary artery (NCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). The circulating Treg, Th1, and Th17 frequencies were measured. The effect of IL-37 on stimulated peripheral blood mononuclear cells (PBMCs) and the influence of IL-37 on DCs were explored. In addition, the role of IL-37-treated tDCs on Treg cell expansion and the stability of these tDCs were also tested. Results. Our results showed that the circulating Treg frequencies were decreased, while Th1 and Th17 frequencies were increased in ACS patients, and that IL-37 expanded Tregs but suppressed Th1 and Th17 cells in activated PBMCs derived from ACS patients. Of note, IL-37-treated human DCs obtained a tolerogenic phenotype, and such tDCs promoted expansion of Tregs and decreased the Th1 and Th17 populations when cocultured with CD4+ T cells. Interestingly, IL-37-treated DCs from patients with ACS are phenotypically and functionally comparable to IL-37-treated DCs from NCA patients, and tolerogenic properties of IL-37-treated DCs were highly stable. Conclusion. In conclusion, our results reveal a beneficial role of IL-37 in the patients with ACS and suggest that autologous IL-37-treated tDCs may be a novel therapeutic strategy for the patients with ACS. [ABSTRACT FROM AUTHOR]

Interleukin-37 (IL-37) is unique in the IL-1 family since it broadly suppresses innate immunity and elevates in humans with inflammatory and autoimmune diseases. IL-37 shows definite groups and transcripts for human IL37 gene, but it is still not completely understood the effect and mechanisms of inflammatory response in endothelial cells. It is well accepted that endothelial dysfunction caused by inflammation is a key initiating event in atherosclerotic plaque formation, which leads to the occurrence and development of the cardiovascular adverse events in clinical since the inflammatory responses of endothelial cells could induce and enhance the deposition of extensive lipid and the formation of atherosclerotic plaque in the intima. Thus, it is essential to investigate the role and potential mechanisms in endothelial inflammatory response to prevent the formation and development of many cardiovascular diseases including atherosclerosis. So far, the recent studies have revealed that IL-37 is able to inhibit inflammatory response by suppressing the TLR2-NF-κB-ICAM-1 pathway intracellularly in human coronary artery endothelial cells (HCAECs). Further, the role of IL-37 may be related to the IL-18 pathway extracellularly and involved in the adhesion and transmigration of neutrophils in HCAECs. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-37, a new IL-1 family member, has received increasing attention in recent years. In the past decade, it has been determined that IL-37 is expressed in various normal cells and tissues and is regulated by inflammatory stimuli and pro-cytokines via different signal transduction pathways. Recently, it has been found that IL-37 is expressed in a variety of cancers, chronic inflammatory and autoimmune disorders, and exerts anti-inflammatory effects. Moreover, a growing body of literature demonstrates that IL-37 plays a vital role in inhibiting both innate and adaptive immune responses as well as inflammatory reactions. In addition, IL-37 may prove to be a new and potentially useful target for effective cytokine therapy. Further evidence is needed to clarify in more detail the effects of IL-37 in experimental and clinical studies. Based on an extensive summary of published data, the aim of this review is to outline the current knowledge of IL-37, including the location, structure, expression, regulation and function, as well as the potential clinical applications of this cytokine. [ABSTRACT FROM AUTHOR]

Interleukin-37 (IL-37) is an IL-1 family cytokine discovered in recent years and has 5 different isoforms. As an immunosuppressive factor, IL-37 can suppress excessive immune response. IL-37 plays a role in protecting the body against endotoxin shock, ischemia-reperfusion injury, autoimmune diseases, and cardiovascular diseases. In addition, IL-37 has a potential antitumor effect. IL-37 and its receptors may serve as novel targets for the study, diagnosis, and treatment of immune-related diseases and tumors. [ABSTRACT FROM AUTHOR]

Background/Aims: Recently, studies have shown that interleukin-37 (IL-37) is involved in atherosclerosis-related diseases. However, the regulatory mechanisms of IL-37 in atherosclerosis remain unknown. This study aims to determine the role of IL-37 in atherosclerosis and to investigate the underlying mechanisms involved. Methods: IL-37 expression in human atherosclerotic plaques was detected by immunohistochemical staining and real-time reverse transcription polymerase chain reaction (RT-PCR). Oil Red O staining was used to measure the size of plaques. Cell apoptosis in vitro and in vivo was tested by flow cytometric analysis and terminal deoxynucleotidyl-transferase mediated dUTP nick-end labeling (TUNEL) staining, respectively. Protein expression levels of IL-37, IL-18Rα and p-Smad3 were measured by Weston blotting. Results: Immunohistochemical staining revealed that IL-37 was highly expressed in human atherosclerotic plaques. Intracellular cytokine staining revealed that infiltrated CD4+ T lymphocytes and vascular smooth muscle cells (VSMCs), but not macrophages, were the major sources of IL-37. Mice that overexpressed IL-37 exhibited significant improvements in their atherosclerotic burden, as demonstrated by reduced plaque size, increased collagen levels, and reduced numbers of apoptotic cells in vivo. Subsequently, mechanistic studies showed that IL-37 played an anti-atherosclerotic role, at least partially, through reducing inflammation by promoting the differentiation of the T helper cell anti-inflammatory phenotype, and through increasing plaque stability by decreasing matrix metalloproteinase (MMP)-2/13-mediated degradation of collagen and inhibiting VSMCs apoptosis. Conclusion: IL-37 may be a novel potential therapeutic target in patients with atherosclerotic heart disease. [ABSTRACT FROM AUTHOR]

Singlet oxygen (1O2) is the excited state of ground, triplet state, molecular oxygen (O2). Photosensitized 1O2 has been extensively studied as one of the reactive oxygen species (ROS), responsible for damage of cellular components (protein, DNA, lipids). On the other hand, its generation has been exploited in organic synthesis, as well as in photodynamic therapy for the treatment of various forms of cancer. The aim of this review is to highlight the versatility of 1O2, discussing the main bioorganic applications reported over the past decades, which rely on its production. After a brief introduction on the photosensitized production of 1O2, we will describe the main aspects involving the biologically relevant damage that can accompany an uncontrolled, aspecific generation of this ROS. We then discuss in more detail a series of biological applications featuring 1O2 generation, including protein and DNA labelling, cross-linking and biosensing. Finally, we will highlight the methodologies available to tailor 1O2 generation, in order to accomplish the proposed bioorganic transformations while avoiding, at the same time, collateral damage related to an untamed production of this reactive species. [ABSTRACT FROM AUTHOR]

Interleukin-37 (IL-37) has been reported to be closely linked to vascular diseases, including atherosclerosis and aortic calcification. The present study aimed to assess the expression levels of IL-37 in patients with hypertension. Blood samples were collected from control subjects (n=20) and patients with hypertension (n=45). Subsequently, macrophages, lymphocytes and dendritic cells were individually isolated and the mRNA expression of IL-37 was measured. In addition, the circulating IL-37 levels in control subjects (n=30) and patients with hypertension (n=334) were assessed. Furthermore, all patients who were subjected to detection of circulating IL-37 underwent ambulatory blood pressure monitoring. The results suggested that the mRNA levels of IL-37 in macrophages, but not in lymphocytes and dendritic cells, isolated from patients with hypertension were markedly elevated compared with those in cells isolated from control subjects. Circulating IL-37 levels were increased in patients with hypertension compared with those in control subjects and positively correlated with systolic and diastolic blood pressure in patients with hypertension. No differences were observed between patients with dipper hypertension and patients with non-dipper hypertension. In addition, patients with hypertension with a smoking habit, type 2 diabetes mellitus and carotid atherosclerotic plaque (CAP) exhibited higher IL-37 levels. IL-37 levels were positively correlated with creatinine, C-reactive protein and homocysteine levels. Furthermore, the results of a linear regression analysis suggested that IL-37 levels were independently associated with the presence of CAP. In conclusion, IL-37 levels are increased in patients with hypertension and may be associated with the onset of CAP. [ABSTRACT FROM AUTHOR]

Interleukin 37 (IL-37) is an anti-inflammatory cytokine expressed in foam cells located in the atherosclerosis plaques. The present study aimed to evaluate the association of the IL-37 polymorphisms with premature coronary artery disease (pCAD), cardiovascular risk factors, metabolic parameters, and levels of liver enzymes. Three IL-37 polymorphisms (rs6717710, rs2708961, and rs2708947) were determined in 1161 patients with pCAD and 951 healthy controls. IL-37 polymorphisms were not associated with the presence of pCAD. The association of the polymorphisms with cardiovascular risk factors, metabolic parameters, and levels of liver enzymes was evaluated independently in pCAD and healthy controls. In pCAD patients, under different models, the rs6717710 was associated with low risk of having elevated alkaline phosphatase (ALP) (padditive = 0.020; pdominant = 0.02; pheterozygous = 0.04; pcodominant1 = 0.040). On the other hand, in healthy controls, the rs6717710 was associated with low risk of having elevated levels of alanine aminotransferase (ALT) (padditive = 0.04, precessive = 0.01, pcodominant2 = 0.01) and aspartate aminotransferase (AST) (padditive = 0.02, pdominant = 0.02). The IL-37 polymorphisms were not associated with the risk of pCAD. In pCAD patients, the rs6717710 was associated with low risk of having elevated ALP levels, whereas in controls was associated with low risk of having elevated ALT and AST levels. [ABSTRACT FROM AUTHOR]

Virtually all types of cardiovascular diseases are associated with pathological activation of the innate immune system. The NACHT, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome is a protein complex that functions as a platform for rapid induction of the inflammatory response to infection or sterile injury. NLRP3 is an intracellular sensor that is sensitive to danger signals, such as ischemia and extracellular or intracellular alarmins during tissue injury. The NLRP3 inflammasome is regulated by the presence of damage-associated molecular patterns and initiates or amplifies inflammatory response through the production of interleukin-1β (IL-1β) and/or IL-18. NLRP3 activation regulates cell survival through the activity of caspase-1 and gasdermin-D. The development of NLRP3 inflammasome inhibitors has opened the possibility to targeting the deleterious effects of NLRP3. Here, we examine the scientific evidence supporting a role for NLRP3 and the effects of inhibitors in cardiovascular diseases. [ABSTRACT FROM AUTHOR]