Interleukin-19 enhances eosinophil infiltration through upregulation of epithelium-derived RANTES expression via the ERK/NF-κB signalling pathway in patients with eosinophilic CRSwNP.

BACKGROUD: The recurrence rate of chronic rhinosinusitis with nasal polyps (CRSwNP) is positively correlated with eosinophil infiltration. Increased interleukin (IL)-19 and eosinophil chemokine RANTES levels have been reported in patients with CRSwNP. This study aimed to clarify the role of IL-19 in mediating RANTES expression and eosinophilic infiltration in eosinophilic CRSwNP (Eos CRSwNP). METHODS: Nasal tissue samples were obtained from patients with CRSwNP and controls. The expression of IL-19, its receptors, ECP, and RANTES in tissues was investigated. Primary human nasal epithelial cells (HNECs) and nasal polyp tissue blocks were cultured, then stimulated by IL-19; ERK phosphorylation, NF-κB pathway activation, RANTES level, eosinophils migration and infiltration were detected using RT-qPCR, ELISA, western blotting, HE, immunohistochemistry, immunofluorescence staining, confocal microscopy, and transwell migration assay. RESULTS: The expression of IL-19 and its receptors (IL-20R1/IL-20R2), eosinophil cationic protein, and RANTES in nasal tissues from patients with Eos CRSwNP was significantly increased compared to that in non-Eos CRSwNP and control subjects. IL-19 co-localized with RANTES in nasal tissues and significantly elevated RANTES expression in HNECs. IL-19-blocking antibody and siRNA knockdown of IL-20R1 ameliorated the effect of IL-19 on RANTES secretion in HNECs. Moreover, IL-19-induced RANTES upregulation was associated with the activation of the ERK and NF-κB pathways. NF-κB activation was mediated by the ERK pathway in IL-19-treated HNECs, and IL-19 enhanced eosinophil infiltration in nasal polyp tissue blocks. CONCLUSIONS: Our findings indicate that IL-19 promotes RANTES expression via the ERK/NF-κB pathway in HNECs and is implicated in eosinophil infiltration in patients with Eos CRSwNP.

Inferring the diagnostic potential of 18F-FDG-PET/CT in post-renal transplantation from a unique case harboring multiple rare complications.

Renal transplantation is undoubtedly an effective treatment for patients with end-stage renal disease, but it is certainly not a cure. Patients require lifelong immunosuppression to maintain optimal allograft function, and post-operative risk complications such as cancer in the transplant recipient cannot be ignored. Besides, infection is a silent complication that follows transplantation. Relatedly, herein, we present a report of a 40-year-old patient who underwent renal transplantation and promptly developed a diffuse large B-cell tumor in the liver and Aspergillus infection in the trachea. In addition, an inflammatory necrotizing granuloma was also observed in the muscles. Of importance, we also described the potential of 18F-FDG-PET/CT, which was instrumental in monitoring and evaluating these relevant post-operative complications in this rare case.

The interaction on HSA and the antibacterial activity from four polyoxometalate hybrids based on berberine.

Four organic-polyoxometalate hybrids BR4[SiW12O40] (BR-SiW), BR3[PMo12O40] (BR-PMo), BR4K[EuSiW11O40]·2H2O (BR-EuSiW) and BR6Na3[EuW10O36] (BR-EuW) were fabricated by the polyoxometalates (POMs) anions and berberine cations (BR) noted for the alkaloids in traditional Chinese herbal medicine. These hybrids have been characterized and confirmed. The interaction between hybrids and human serum albumin (HSA) was investigated in a buffer solution (pH 7.4) using ultraviolet-visible light absorption and fluorescence techniques. The classical Stern-Volmer equation was used to analyze the fluorescence quenching at three temperatures (296, 303 and 310 K), and the static quenching mechanism for interaction was proposed. The Thermodynamic parameters, enthalpy, entropy change, and Gibbs free energy of hybrids interacting on HSA were calculated by Scatchard equation. The results indicated that therewas one binding site on the protein and BR-POMs all showed stronger binding force than that of raw materials. Synchronous fluorescence results showed that the binding sites of BR-POMs and HSA were not effectively affected the surrounding microenvironment. The following antibacterial experiments implied that inhibitory effect of hybrids were synergistic effect from organic active ingredient and POMs but the simple combination. All these data were prepared for further research on biology.

A Color-Changing Biomimetic Material Closely Resembling the Spectral Characteristics of Vegetation Foliage.

Multispectral/hyperspectral technologies can easily detect man-made objects in vegetation by subtle spectral differences between the object and vegetation, and powerful reconnaissance increases the demand for camouflage materials closely resembling vegetation spectra. However, previous biomimetic materials have only presented static colors that cannot change color, and camouflage in multiple bands is difficult to achieve. To address this challenge, inspiration is drawn from the color change of foliage, and a color-change model is proposed with active and static pigments embedded in a matrix medium. The color of a composite material is dominated by the colored active pigment, which conceals the color of the static pigments and the color is revealed when the active pigment fades. A color-changing biomimetic material (CCBM) is developed with a solution casting method by adopting microcapsuled thermochromic pigments and chrome titanate yellow pigments as fillers in a base film with polyvinyl alcohol and lithium chloride. A Kubelka-Munk four-flux model is constructed to optimize the component proportions of the CCBM. The material has a reversible color change, closely resembles the foliage spectrum in UV-vis-NIR ranges, and imitates the thermal behavior of natural foliage in the mid-infrared regime. These results provide a novel approach to multispectral and hyperspectral camouflage.

Exploring causal mechanisms and essential factors in the prevention and control of chlamydia in Guangdong, Southern China: a study protocol.

BACKGROUND: Chlamydia Trachomatis (CT) is among the most prevalent sexually transmitted diseases (STDs) globally. According to the World Health Organization, more than 131 million people get infected with CT annually. CT is usually transmitted via sexual contact or perinatal exposure and can result in severe long-term complications. In developing nations, particularly, the prevention and control of CT is challenging. Hence, this study will explore the feedback mechanisms of chlamydia prevention and control, as well as identify the essential factors affecting the control and prevention of this infection in China. METHODS: Our study will employ a mixed-methods research design that encompasses both qualitative and quantitative methods. Firstly, we will develop a causal loop diagram (CLD) based on the literature review and optimize it via in-depth interviews with stakeholders. Additionally, we will utilize a quantitative method called MICMAC(Impact Matrix Cross-Reference Multiplication Applied to a Classification tool) to obtain consensus among different stakeholders and pinpoint the key information. Next, the CLD will be transformed into a system dynamics model (SDM) to evaluate the feedback mechanisms within the CLD. The causality in the CLD will be modeled using mathematical equations, which facilitate the transformation into an SDM. As such, we will be able to analyze the dynamic behavior of the system and its response to different decisions. DISCUSSION: Our study offers a systematic perspective on the control and prevention of chlamydia infection through system dynamics modeling, examining the dynamic properties and background factors of the system. The creation of the CLD affords stakeholders the chance to comprehend the functionality of their relationships and improve cooperation. Consequently, by evaluating the outcomes of these simulations, it will be possible to analyze and determine potential interventions and their effects on chlamydia infections. This modeling approach can help us gain insight into the dynamic characteristics of the system, evaluate the potential outcomes of different decisions, and design control strategies to either stabilize the system or adjust its behavior.

Improving eye care quality through brief verbal intervention on optometry service provider by using unannounced standardized patient with refractive error: study protocol for a randomized controlled trial.

BACKGROUND: Improper refractive correction can be harmful to eye health, aggravating the burden of vision impairment. During most optometry clinical consultations, practitioner-patient interactions play a key role. Maybe it is feasible for patients themselves to do something to get high-quality optometry. But the present empirical research on the quality improvement of eye care needs to be strengthened. The study aims to test the effect of the brief verbal intervention (BVI) through patients on the quality of optometry service. METHODS: This study will take unannounced standardized patient (USP) with refractive error as the core research tool, both in measurement and intervention. The USP case and the checklist will be developed through a standard protocol and assessed for validity and reliability before its full use. USP will be trained to provide standardized responses during optical visits and receive baseline refraction by the skilled study optometrist who will be recruited within each site. A multi-arm parallel-group randomized trial will be used, with one common control and three intervention groups. The study will be performed in four cities, Guangzhou and three cities in Inner Mongolia, China. A total of 480 optometry service providers (OSPs) will be stratified and randomly selected and divided into four groups. The common control group will receive USP usual visits (without intervention), and three intervention groups will separately receive USP visits with three kinds of BVI on the patient side. A detailed outcome evaluation will include the optometry accuracy, optometry process, patient satisfaction, cost information and service time. Descriptive analysis will be performed for the survey results, and the difference in outcomes between interventions and control providers will be compared and statistically tested using generalized linear models (GLMs). DISCUSSION: This research will help policymakers understand the current situation and influencing factors of refractive error care quality, and then implement precise policies; at the same time, explore short and easy interventions for patients to improve the quality of optometry service. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200062819. Registered on August 19, 2022.

IL-21 induces pyroptosis of Treg cells via Akt-mTOR-NLRP3-caspase 1 axis in eosinophilic chronic rhinosinusitis.

BACKGROUND: Regulatory T (Treg) cells, which prevent inflammation-induced eosinophil infiltration, are deficient in nasal polyps (NPs) in patients with eosinophilic chronic rhinosinusitis (ECRS). It is concomitant with loss of Foxp3 after certain inflammatory stimuli. OBJECTIVE: We sought to determine the inflammatory cytokines involved in inducing the loss of Treg cells in NPs. METHODS: The abundance of cytokines in ECRS patients or mice were tested using ELISA, immunochemistry, immunofluorescence, quantitative reverse transcription PCR (qPCR), and/or flow cytometry. Expression of eosinophil cationic protein (ECP), CD4+ T cells, IL-4, and IL-17A and eosinophils in nasal mucosa of mouse model was investigated by immunochemistry, immunofluorescence, and hematoxylin and eosin staining. The percentage and death of induced Treg (iTreg) cells, source of IL-21 in NPs from ECRS and non-ECRS patients, and abundance of different systemic phenotypes of CD4+ T cells in a mouse model were studied by flow cytometry. Western blot analysis, scanning, and transmission electronic microscopy were used to detect pyroptosis of iTreg cells. RESULTS: IL-21 was highly expressed in nasal mucosa of ECRS patients and mice, causing pyroptosis and preventing development of iTreg cells in vitro. The elevated IL-21 in NPs from ECRS patients was mainly produced by CD3+ T cells, including T follicular helper, T peripheral helper, TH2, and TH17 cells and CD3+CD4- T cells. T peripheral helper cells and CD3+CD4- T cells were the predominant source of IL-21 in NPs from non-ECRS patients. Blocking IL-21/IL-21R signaling significantly reduced the number of eosinophils and CD4+ T cells along with ECP, IL-4, and IL-17A expression in the nasal mucosa of ECRS mice. It also increased Treg cell percentage and systemically decreased TH2 and TH17 ratios. Akt-mTOR inhibition prevented IL-21-induced pyroptosis in human and mouse iTreg cells. CONCLUSION: Elevated IL-21 drives pyroptosis and prevents Treg cell development in ECRS patients. IL-21 induced pyroptosis via activating Akt-mTOR-NLRP3-caspase 1 signaling.

Effect of Buffalo Breed on the Detailed Milk Composition in Guangxi, China.

Buffalo is the second source of milk in the world, and its milk is rich in nutritive components. It is well-known that breed influences milk composition. This work aimed to compare the detailed milk composition of three buffalo breeds (Murrah, Nili-Ravi, and Mediterranean) housed under the same environmental conditions. Mediterranean buffalo milk showed a significantly higher content of fat, protein, and some fatty acids. Moreover, the milk from the Mediterranean breed was characterized by the highest content of sphingomyelin (SM), cholesterol, and lanosterol. However, the Murrah buffalo milk contained the highest amount of total unsaturated fatty acids, phosphatidylinositol, and whey proteins. Furthermore, the Nili-Ravi buffalo milk was characterized by the highest content of total saturated fatty acids, phosphatidylglycerol, squalene, lathosterol, stigmasterol, beta-sitosterol, and casein fractions. Nevertheless, the lactose and amino acid profiles of the milk remained almost similar across the three buffalo breeds. The generated results in this study enable a comprehensive understanding of the milk constituent variability that is linked to buffalo breeds, which may support the acquirement of essential scientific knowledge on milk ingredient-processing interactions that will offer a foundation of knowledge for Chinese dairy processors in terms of milk processability and innovation.

Exploring the links between celebrity worship, body dissatisfaction, and disordered eating among young adult celebrity worshippers in China.

Considerable evidence exists on the associations of celebrity worship with body dissatisfaction and disordered eating. However, relevant findings are confined to Western contexts and thinness-oriented body dissatisfaction and disordered eating. Consequently, the relationships of celebrity worship with muscularity-oriented body dissatisfaction and disordered eating are largely underexplored, especially in non-Western countries. Thus, the present study aimed to examine the relationships of celebrity worship with body dissatisfaction and disordered eating in China. A total of 593 young adult celebrity worshippers in China were recruited online. Correlation and mediation analyses were conducted. In contrast to previous findings, celebrity worship was not associated with thinness-oriented body dissatisfaction. However, significant associations were identified between celebrity worship and muscularity-oriented body dissatisfaction for men (r = 0.32, p < .001) and women (r = 0.26, p < .001), thinness-oriented disordered eating for men (r = 0.31, p < .001) and women (r = 0.37, p < .001), and muscularity-oriented disordered eating for men (r = 0.58, p < .001). Body image inflexibility mediated the associations between celebrity worship and disordered eating in men and women. Findings indicate that celebrity worship correlates positively with body dissatisfaction and disordered eating in Chinese young adults.

Morphology, Solid Structure and Antioxidant Activity in Vitro of Angelica sinensis Polysaccharide-Ce(IV).

Angelica Sinensis polysaccharide cerium (ASP-Ce) was prepared by Angelica Sinensis polysaccharide (ASP) and cerium ammonium nitrate (NH4 )2 Ce(NO3 )6 . and its morphology, and solid structure was investigated. The antioxidant activity of the ASP-Ce complex in vitro was evaluated. The antioxidant activity of ASP-Ce complex in vitro was evaluated by the scavenging activity of 2,2-diphenyl-1-picrylhyrazyl radical (DPPH), hydroxyl radical (⋅OH) and superoxide anion radical ( O 2 - ${{{\rm O}}_{2}^{-}}$ ⋅). The results showed that the ASP-Ce had the more ordered structure for inserting the Ce4+ into the polymer chain of ASP and there was little change in the conformation of the polysaccharide from Ce4+ . Three free radical scavenging experiments proved that ASP-Ce had better antioxidant capacity than of ASP, especially on DPPH, and then on O 2 - ${{{\rm O}}_{2}^{-}}$ ⋅. The scavenging rate of ASP-Ce at 1.0 mg/mL on DPPH reached 71.6 %. Therefore, these results provide references for the further development and utilization of rare earth-polysaccharide.

Interleukin-19 upregulates fibronectin and collagen I expression via the NF-κB-Smad2/3 pathway in fibroblasts of patients with chronic rhinosinusitis.

BACKGROUND: Tissue remodeling is a prominent characteristic of chronic rhinosinusitis (CRS). Excess deposition of fibronectin (FN) and collagen (Col) I by fibroblasts is crucial for the pathologic tissue remodeling in CRS without nasal polyps (CRSsNP). Increased interleukin (IL)-19 level in patients with CRS had been demonstrated in our previous studies. Here, we aimed to evaluate the role of IL-19 in mediating FN and Col I expression in CRS. METHODS: Nasal mucosal tissue samples were collected from patients with CRS with nasal polyps (CRSwNP), CRSsNP, and controls. The expression of IL-19, vimentin, FN, and Col I were detected using immunohistochemistry and immunofluorescence. Primary human nasal fibroblasts were treated with IL-19, then the activation of Smad2/3, NF-κB and relevant pathways, and the expression of FN and Col I were measured. RESULTS: Expression levels of vimentin, FN, and Col I were significantly increased in nasal tissues from patients with CRSsNP compared with CRSwNP and control subjects. Moreover, IL-19 co-localized with FN and Col Ι in nasal tissues. IL-19-treated fibroblasts had increased production of FN and Col I, which was associated with the activated Smad2/3 and NF-κB pathways. Moreover, Smad2/3 activation was mediated by the NF-κB pathway in IL-19-treated fibroblasts. CONCLUSIONS: IL-19 promotes FN and Col I production via the activated NF-κB-Smad2/3 pathway in fibroblasts, leading to fibrosis and collagen deposition in patients with CRS.

Chinese Guideline on Allergen Immunotherapy for Allergic Rhinitis: The 2022 Update.

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.

Application of 18F-FDG PET/CT in Langerhans Cell Histiocytosis.

Purpose: This study aims to explore the application value of the 18F-FDG PET/CT imaging in diagnosing, staging, and typing Langerhans cell histiocytosis (LCH) via the morphological and metabolic analyses of the 18F-FDG PET/CT images. Methods: We retrospectively analyzed the 18F-FDG PET/CT images and clinical data of nineteen patients with LCH. The shape, size, density, distribution, and 18F-FDG uptake of all lesions were documented. In addition, the SUVmax of the lesions, liver, and blood pool was measured prior to calculating the lesion-to-liver and lesion-to-blood pool ratios. Results: Among the 19 analyzed patients, the positive rate of the PET/CT image was 94.7% (18/19), with 1 false negative (5.3%, 1/19) case occurring in the cutaneous LCH. Among the 76 lesions, 69 were FDG-avid lesions (69/76, 90.8%). Additionally, we observed no FDG uptake in 7 lesions (7/76, 9.2%). In contrast, 59 lesions (59/76, 77.6%) were abnormal on diagnostic CT scan, but 17 lesions (17/76, 22.4%) were undetected. The 18F-FDG PET/CT image revealed additional 6 lesions in the bone, 4 in the lymph node, 3 in the spleen, and 3 occult lesions, which CT scan did not detect. Additionally, there were 6 cases with single-system LCH. The remaining 13 cases were multisystem LCH. Our 18F-FDG PET/CT image analyses altered the typing of 4 LCH patients. In the case of all lesions, the mean SUVmax of the 18F-FDG-avid lesions was 5.4 ± 5.1 (range, 0.8∼26.2), and the mean lesion-to-liver SUVmax ratio was 3.1 ± 2.52 (range, 0.7∼11.9), and the mean lesion-to-blood pool SUVmax ratio was 4.6 ± 3.4 (range 0.7∼17.5). Conclusion: The 18F-FDG PET/CT image plays an essential role in LCH diagnosis, primary staging, and typing. It can accurately evaluate the distribution, range, and metabolic information of LCH, providing a vital imaging basis for the clinical evaluation of disease conditions, selection of treatment schemes, and determining patient prognosis.

Analysis of misdiagnosis and 18F-FDG PET/CT findings of lymph node tuberculosis.

OBJECTIVE: To investigate 18F-FDG PET/CT findings of tuberculous lymphadenitis and analyze the causes of misdiagnosis. METHOD: Between 2013 and 2021, a retrospective review was conducted on 22 patients at Jiangxi Provincial People's Hospital Affiliated with Nanchang University who had lymph node tuberculosis confirmed by histology or clinical investigation. Subjective judgment and quantitative analysis were adopted. RESULTS: Out of 22 patients, 14 are male and 8 are female. The average age was 55.5 years (55.5±12.4). The most common site of lymph node tuberculosis (LNTB) is the mediastinum (41.5%), followed by the neck (24.4%) and the abdominal cavity (21.9%). Half of the patients have more than one site affected. More than half of LNTB patients (54.5%) are concurrent with other types of TB, especially PTB. Among the 41 biggest affected lymph nodes, the average maximum diameter, minimum diameter, SUVmax and the lesion SUVmax/SUVmean liver ratio are 22.04±8.39, 16.93±6.75, 9.72±5.04 and 6.72±3.60, respectively. There is a poor correlation coefficient of 0.236 between the FDG uptake and the size of the biggest affected lymph node. Patients who are concurrent with no other TB have the significantly higher FDG uptake than patients who are concurrent with other TB (12.42 vs 8.02) (p = 0.005). Among these cases, 6 cases (27.3%) are accurately diagnosed with LNTB, all of which have pulmonary tuberculosis as a complication. However, 16 cases (72.7%) are misdiagnosed as lymphoma (50%), sarcoidosis (13.6%), and lymph node metastasis (9%). CONCLUSIONS: This study demonstrates that 18F-FDG PET/CT is very useful in detecting LNTB because tuberculous granulomas show significant levels of glucose uptake. It proves to be an effective method for revealing lesion extent and discovering additional lesions that morphological imaging is missed. However, 18F-FDG PET/CT is not able to reliably distinguish LNTB from lymphoma, sarcoidosis, and metastatic lymph nodes. Nonetheless, 18F-FDG PET/CT allows for the selection of the most optimal biopsy location, and thus has potential to detect early treatment response and distinguish between active and inactive lesions.

Changes in Whey Proteome between Mediterranean and Murrah Buffalo Colostrum and Mature Milk Reflect Their Pharmaceutical and Medicinal Value.

Milk represents an integrated meal for newborns; its whey protein is rich in many health beneficial components and proteins. The current study aimed to investigate the differences between colostrum and mature milk from Mediterranean and Murrah buffaloes using labeled proteomics and bioinformatics tools. In the current work, LC-MS/MS analysis led to identification of 780 proteins from which 638 were shared among three independent TMT experiments. The significantly changed proteins between the studied types were analyzed using gene ontology enrichment and KEGG pathways, and their interactions were generated using STRING database. Results indicated that immunological, muscular development and function, blood coagulation, heme related, neuronal, translation, metabolic process, and binding proteins were the main terms. Overall, colostrum showed higher levels of immunoglobulins, myosins, actin, neurofascin, syntaxins, thyroglobulins, and RNA-binding proteins, reflecting its importance in the development and activity of immunological, muscular, cardiac, neuronal, and thyroid systems, while lactoferrin and ferritin were increased in mature milk, highlighting its role in iron storage and hemoglobin formation.

IL-17A mediates pyroptosis via the ERK pathway and contributes to steroid resistance in CRSwNP.

BACKGROUND: Pyroptosis is closely related to inflammation. However, the molecular mechanisms and pathologic contributions of pyroptotic epithelial cell are not yet fully understood. OBJECTIVE: This study aimed to explore the function and molecular mechanisms of IL-17A on human nasal epithelial cell (hNEC) pyroptosis. METHODS: The expression of pyroptosis-related biomarkers and IL-17A was assessed in sinonasal mucosa from control individuals, patients with chronic rhinosinusitis without nasal polyps, and patients with chronic rhinosinusitis with nasal polyps (CRSwNP) by using quantitative RT-PCR. Their localization was analyzed via immunohistochemistry and immunofluorescence. The ultrastructural characteristics of IL-17A-induced pyroptosis in hNECs were visualized by using electron microscopy. IL-17A functional assays were performed on hNECs and airway epithelial cell lines. Cytokine levels were quantified via ELISA. The signaling pathways involved in IL-17A-induced pyroptosis were studied via unbiased RNA sequencing and Western blotting. RESULTS: The expression of IL-17A and the pyroptotic biomarkers NOD-like receptor family, pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D, and IL-1ß was increased in nasal mucosa from patients with CRSwNP compared with in those with chronic rhinosinusitis without nasal polyps and the control subjects. IL-17A was positively correlated and colocalized with the pyroptotic biomarkers. IL-17A treatment induced pyroptosis in the hNECs and cell lines analyzed, primarily through the extracellular signal-regulated kinase (ERK)-NLRP3/caspase-1 signaling pathway, and increased IL-1ß and IL-18 secretion in hNECs. Moreover, IL-17A-induced pyroptosis contributed to steroid resistance by affecting glucocorticoid receptor-α and glucocorticoid receptor-ß expression, and the inhibition of pyroptotic proteins partially abolished IL-17A-induced steroid resistance in hNECs. CONCLUSION: Elevated IL-17A level promotes pyroptosis in hNECs through the ERK-NLRP3/caspase-1 signaling pathway and contributes to glucocorticoid resistance by affecting glucocorticoid receptor homeostasis in patients with CRSwNP.

IL-19 induced by IL-13/IL-17A in the nasal epithelium of patients with chronic rhinosinusitis upregulates MMP-9 expression via ERK/NF-κB signaling pathway.

BACKGROUND: Tissue remodeling is a crucial characteristic of chronic rhinosinusitis (CRS). Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is crucial for the pathologic tissue remodeling in CRS. Elevation of interleukin (IL)-19 or MMP-9 levels in patients with CRS had been proven in previous studies. Here, we aimed to investigate the role of IL-19 in mediating MMP-9 expression in CRS. METHODS: Nasal tissue samples were collected from 45 individuals having chronic rhinosinusitis with nasal polyps (CRSwNP), 24 CRS without nasal polyps (CRSsNP), and 17 controls. Expression of IL-19, its receptors (IL-20R1/IL-20R2), and MMP-9 were investigated using RT-qPCR and Immunofluorescence (IF). Human nasal epithelial cells (HNECs) were stimulated by IL-19; ERK phosphorylation, nuclear factor-κB (NF-κB) pathway activation, and MMP-9 level were detected by RT-qPCR, enzyme-linked immunosorbent assay, western blot, and IF. We also explored the effect of type1/2/3 cytokines on IL-19 production by RT-qPCR, and western blot. RESULTS: Expression levels of IL-19, its receptors (IL-20R1/IL-20R2), and MMP-9 were increased in nasal tissues from individuals with CRSwNP compared to those with CRSsNP as well as the controls. IL-19 significantly elevated the production of MMP-9 in HNECs. Furthermore, IL-19 could activate the ERK and NF-κB pathways, accompanied by increased MMP-9 production in HNECs. Conversely, both ERK and NF-κB inhibitors significantly attenuated the role of IL-19 in MMP-9 production. siRNA knockdown of IL-20R1 suppressed ERK and NF-κB pathway activation, thereby decreasing MMP-9 expression. IL-13 and IL-17A were found to stimulate IL-19 production in HNECs. CONCLUSION: IL-19, promoted by IL-13 and IL-17A, contributes to the upregulation of secretion of the tissue remodeling factor MMP-9 in patients with CRS.

Development of a Multifunction Set Yogurt Using Rubus suavissimus S. Lee (Chinese Sweet Tea) Extract.

Rubus suavissimus S. Lee leaves, also known as Chinese sweet tea or Tiancha, are used in folk medicine in southern China. This study evaluated the impact of the addition of Chinese sweet tea extract (0.25%, 0.5%, and 1%) on the chemical composition, organoleptic properties, yogurt culture viability, and biological activities (i.e., antioxidant, anticancer, and antihypertensive activities) of yogurt. Seven phenolic compounds were reported in Chinese sweet tea for the first time. The numbers of the yogurt culture were similar across all yogurt treatments. The yogurt supernatant with 0.25%, 0.5%, and 1% Chinese sweet tea extract had a total phenolic content that was 3.6-, 6.1-, and 11.2-fold higher, respectively, than that of the control yogurt. The biological activities were significantly increased by the addition of Chinese sweet tea extract: Yogurt with the addition of 1% Chinese sweet tea extract had the highest biological activities in terms of the antioxidant activity (92.43%), antihypertensive activity (82.03%), and inhibition of the Caco-2 cell line (67.46%). Yogurt with the addition of 0.5% Chinese sweet tea extract received the highest aroma and overall acceptability scores. Overall, Chinese sweet tea extract is a promising food ingredient for producing functional yogurt products that may substantially contribute to reducing the risk of developing chronic diseases such as cancer and cardiovascular disease.

Redefining Cardiac Biomarkers in Predicting Mortality of Inpatients With COVID-19.

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.12 ([95% CI, 4.60-11.03] P<0.001), (NT-pro)BNP (N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide) was 5.11 ([95% CI, 3.50-7.47] P<0.001), CK (creatine phosphokinase)-MB was 4.86 ([95% CI, 3.33-7.09] P<0.001), MYO (myoglobin) was 4.50 ([95% CI, 3.18-6.36] P<0.001), and CK was 3.56 ([95% CI, 2.53-5.02] P<0.001). The cutoffs of those cardiac biomarkers for effective prognosis of 28-day mortality of COVID-19 were found to be much lower than for regular heart disease at about 19%-50% of the currently recommended thresholds. Patients with elevated cardiac injury markers above the newly established cutoffs were associated with significantly increased risk of COVID-19 death. In conclusion, cardiac biomarker elevations are significantly associated with 28-day death in patients with COVID-19. The prognostic cutoff values of these biomarkers might be much lower than the current reference standards. These findings can assist in better management of COVID-19 patients to improve outcomes. Importantly, the newly established cutoff levels of COVID-19-associated cardiac biomarkers may serve as useful criteria for the future prospective studies and clinical trials.