Detection of serum Aspergillus-specific IgM and IgG antibody levels for the diagnosis of chronic pulmonary aspergillosis developed in patients with tuberculosis.

Chronic pulmonary aspergillosis (CPA) is common among individuals with underlying lung diseases. The clinical manifestations of CPA include systemic symptoms (e.g., weight loss, fatigue, fever), chronic productive cough, chest discomfort, and occasional haemoptysis, which are similar to the manifestations of pulmonary tuberculosis (PTB) and are often misdiagnosed as PTB. Considering the striking similarities between CPA and PTB in clinical manifestations and imaging features, more specific microbiological and serological detections are needed for a definitive diagnosis. This study aimed to explore the clinical characteristics of CPA in TB as well as the diagnostic significance of Aspergillus-specific IgG and Aspergillus-specific IgM.A total of 140 patients diagnosed with TB by culture between December 2017 and February 2019 were included. Enrolled patients were categorized into two groups (CPA group and non-CPA group) according to CPA diagnostic criteria. All collected specimens were subjected to Aspergillus-specific IgG and IgM detection testing.The median concentration of Aspergillus-specific IgG in the CPA group (211.04 AU/ml) was significantly higher than that in the non-CPA group (77.88 AU/ml) (Z value - 6.397, P < 0.001). The sensitivity and specificity of Aspergillus-specific IgG for CPA diagnosis were 81.82% and 72.97%, respectively. In the chronic cavitary pulmonary aspergillosis (CCPA) group, the IgG positivity rate (≥ 120 AU/ml) was 96.2%, which was 21.4% in the non-CCPA patients (P < 0.001).The detection of Aspergillus-specific IgG serological changes is feasible and facilitates reliable differentiation between Aspergillus and Mycobacterium tuberculosis infection. However, Aspergillus-specific IgM has limited diagnostic value, with unsatisfactory sensitivity results.

Arbuscular Mycorrhizal Fungi Compete Asymmetrically for Amino Acids with Native and Invasive Solidago.

Arbuscular mycorrhizal fungi (AMF) and soil amino acids both affect plant performance. However, little is known about how AMF compete for amino acids with native and invasive congeners. We conducted a factorial experiment (inoculation, native and invasive species, and amino acids) to examine the competition for amino acids between soil microbes and both native and invasive congeners. The competition for amino acids between AMF and invasive Solidago canadensis was weaker than that observed between AMF and native S. decurrens. This asymmetric competition increased the growth advantage of S. canadensis over S. decurrens. The efficacy (biomass production per unit of nitrogen supply) of amino acids compared to ammonium was smaller in S. canadensis than in S. decurrens when both species were grown without inoculation, but the opposite was the case when both species were grown with AMF. AMF and all microbes differentially altered four phenotypic traits (plant height, leaf chlorophyll content, leaf number, and root biomass allocation) and the pathways determining the effects of amino acids on growth advantages. These findings suggest that AMF could enhance plant invasiveness through asymmetric competition for amino acids and that amino acid-driven invasiveness might be differentially regulated by different microbial guilds.

Interleukin-17A up-regulates thymic stromal lymphopoietin production by nasal fibroblasts from patients with allergic rhinitis.

PURPOSE: Emerging evidence has shown that interleukin (IL)-17A is implicated in the pathogenesis of allergic rhinitis (AR). Thymic stromal lymphopoietin (TSLP) orchestrates the immune response toward a Th2 phenotype. Although increased TSLP is found in AR, the contribution of IL-17A in TSLP production by nasal fibroblasts is not well understood. We aimed to investigate the effect and mechanism of IL-17A on TSLP production by human nasal fibroblasts (HNFs) from AR patients. METHODS: HNFs from AR patients were cultured and stimulated with IL-17A in the absence or presence of a Janus kinase (JAK) 2 or JAK1/3 inhibitor. Western blotting was used to assay phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and nuclear factor-kappa B (NF-κB) p65 in HNFs. The TSLP expression in the cells and culture supernatants was evaluated by real-time polymerase chain reaction and enzyme-linked immunoassay. RESULTS: Stimulation with IL-17A induced STAT3 phosphorylation, which was inhibited by the pretreatment with JAK2 inhibitor AZD1480 or JAK1/3 inhibitor tofacitinib. IL-17A promoted the nuclear translocation of NF-κBp65 protein, leading to increased TSLP production, while the pre-incubation with AZD1480 prior to IL-17A attenuated these effects. However, the pre-incubation with tofacitinib before IL-17A stimulation had no impact on the expression of NF-κBp65 and TSLP. CONCLUSIONS: IL-17A up-regulated TSLP production by HNFs through JAK2/NF-κB pathway. Although IL-17A induced STAT3 activation through JAK1/2/3, IL-17A-mediated TSLP expression was not dependent on STAT3 signaling. These observations would provide mechanistic insight into therapeutic strategies to improve the immune and inflammation associated with Th17A in the management of AR.

Rational design of the carbonyl reductase EbSDR8 for efficient biosynthesis of enantiopure (R)-3-chloro-1-phenyl-1-propanol.

(R)-3-Chloro-1-phenyl-1-propanol ((R)-CPPO) is an important chiral intermediate for antidepressants. For its efficient biosynthesis, the carbonyl reductase EbSDR8 was engineered to asymmetrically reduce the unnatural substrate 3-chloro-1-phenyl-1-propanone (3-CPP) at high concentrations. Molecular docking and molecular dynamics simulations of the resulting mutants suggested enlarged substrate binding pocket and more reasonable interactions between the enzyme and the substrate or cofactor as the reasons for the enhanced catalytic activity and thus the remarkably improved conversion of high-concentration 3-CPP. Using the best mutant EbSDR8G94A/L153I/Y188A/Y202M as the whole-cell biocatalyst, reduction of 3-CPP (1.0 M) was conducted using 100% isopropanol as both the solvent and co-substrate for NADH regeneration, delivering (R)-CPPO with ˃ 99% eep and 95.5% conversion. This result suggests EbSDR8G94A/L153I/Y188A/Y202M as a potential biocatalyst for green production of (R)-CPPO at the industrial scale. KEY POINTS: • Rational design of EbSDR8 by modulating steric hindrance and molecular interactions; • Non-aqueous biocatalysis using isopropanol as both the solvent and co-substrate; • Whole-cell catalyzed production of 161 g/L enantiopure (R)-CPPO from 1.0 M of 3-CPP. Graphical Abstract.

Efficacy of path-oriented psychological self-help interventions to improve mental health of empty-nest older adults in the Community of China.

BACKGROUND: China has the world's largest aging population and the number of empty-nest older adults is on the rise. In comparison to the aging population in general, empty-nest older adults have a lower level of subjective well-being and poorer mental health status due to a lack of emotional support from their children. The aim of this study is to conduct an empirical study to evaluate the efficacy of the 'Path-oriented Psychological Self-help Intervention' (P-oPSI) led by nurses on the mental health of empty-nest older adults in the community, to provide a scientific foundation for improving their quality of life. METHODS: A Quasi-Experimental controlled intervention study was conducted from 2015 to 2017. A total of 76 empty-nest older adults from 2 districts were recruited using a convenience sampling and assigned to 2 groups based on their residential communities in the city of Chifeng in the Inner Mongolia Autonomous Region, China. The wait list control group participated in a mental health lecture to gain knowledge and learn techniques of mental health promotion. The intervention group additionally received 1 month of training in a nurse-led 'P-oPSI' for a month. Both groups were followed-up for 3 months. Mental health status, coping styles, and psychological self-help ability of the participating empty nest older adults were assessed at the baseline, 1 month, and 3-months follow up, respectively. Two-way analysis of variance and a simple effect test were used to analyse the differences of the two groups. RESULTS: The P-oPSI yielded a greater benefit for the mental health status, coping styles, and psychological self-help ability of the participants in the intervention group. Combined with a simple effect test, the scores of the mental health status, positive coping style, and psychological self-help ability of those in the intervention group significantly increased at 1 month after the baseline (F mental health status = 7.59, F positive coping style = 7.24, F psychological self-help ability = 7.07); and the sustainable effect of this program lasted for 3 months after the intervention (F mental health status = 13.24, F positive coping style = 10.42, F psychological self-help ability = 10.45), which reached statistical significance (P < 0.01). CONCLUSIONS: The P-oPSI program significantly improved the level of mental health of empty-nest older adults in China. This intervention provides a new approach of self-management to improve mental health of older adults in community settings. TRIAL REGISTRATION: chictr.org.cn: ChiCTR1900025552. Retrospectively registered 1 September 2019.

Histamine H4 receptor regulates Th2-cytokine profile through thymic stromal lymphopoietin in allergic rhinitis.

PURPOSE: Epithelial thymic stromal lymphopoietin (TSLP) promotes Th2 inflammatory responses through induction of OX40 ligand (OX40L) on dendritic cells in allergic rhinitis (AR). Emerging evidence supports the important role of histamine H4 receptor (H4R) in allergic inflammation. This study aimed to investigate the effects of H4R in Th2-cytokine profile mediated by TSLP in AR. METHODS: Human nasal epithelial cells (HNECs) from AR patients were stimulated with histamine in the presence or absence of H4R agonist (4-methylhistamine, 4-MH) and antagonist (NJ7777120, JNJ) or H1R agonist (2-pyridylethylamine). TSLP protein was measured by Western blotting and ELISA. To further elucidate the role of H4R in the in vivo situation of experimental AR, rats were sensitized and treated with JNJ or 4-MH. TSLP and OX40 ligand (OX40L) in the nasal mucosa were assayed by Western blotting. Th2 cytokines including interleukin-4, 5 and 13 in nasal lavage fluids were detected by ELISA. RESULTS: Histamine alone did not induce TSLP production by HNECs. The pre-incubation with 4-MH prior to histamine promoted TSLP expression, which was inhibited by the stimulation with JNJ prior to histamine and 4-MH. The pre-incubation with 2-pyridylethylamine before histamine stimulation had no impact on TSLP production. In AR rats, the levels of TSLP and OX40L protein were increased as well as Th2 cytokines, which was further up-regulated by 4-MH treatment, while JNJ treatment attenuated these effects. CONCLUSIONS: H4R activation induced TSLP production by HNECs, which up-regulated OX40L expression in the nasal mucosa of sensitized rats. These factors promoted Th2-cytokine profile in AR.

Simple strategy for sensitive detection of dopamine using CdTe QDs modified glassy carbon electrode.

BACKGROUND: Cellular and brain metabolism of dopamine can be correlated with a number of neurodegenerative disorders, our study was to explore a simple and efficient method to detect dopamine in real samples. METHODS: A new quantum dots (CdTe QDs) could be prepared using the hydrothermal method, the electrochemical biosensor was established by dropping CdTe QDs on the surface of glassy carbon electrode (GCE). RESULTS: The CdTe QDs/GCE exhibited the excellent electrochemical catalytic activity toward dopamine (DA) with good stability and high sensitivity in presence of interfering substances. The detection limit of DA was calculated by differential pulse voltammetry (DPV) as low as 0.3 µmol L-1 with a linear dynamic range of 1 µmol L-1 to 400 µmol L-1 . CONCLUSION: In this paper, the proposed electrochemical biosensor could be effectively used for the direct and rapid detection of DA in human serum and urine samples.

Preparation of quantum dots CdTe decorated graphene composite for sensitive detection of uric acid and dopamine.

The assembly of quantum dots (QDs) in a simply method opens up opportunities to obtain access to the full potential of assembled QDs by virtue of the collective properties of the ensembles. In this study, quantum dots CdTe and graphene (Gr) nanocomposite was constructed for the simultaneous determination of uric acid (UA) and dopamine (DA). The CdTe QDs-Gr nanocomposite was prepared by ultrasonication and was characterized with microscopic techniques. The nanocomposite modified electrode was characterized by cyclicvoltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Due to the synergistic effects between CdTe QDs and Gr, the fabricated electrode exhibited excellent electrochemical catalytic activities, good biological compatibility and high sensitivity toward the oxidation of UA and DA. Under optimum conditions, in the co-existence system the linear calibration plots for UA and DA were obtained over the range of 3-600 µM and 1-500 µM with detection limits of 1.0 µM and 0.33 µM. The fabricated biosensor also exhibits the excellent repeatability, reproducibility, storage stability along with acceptable selectivity.

Visualization of Protein in Peanut Using Hyperspectral Image with Chemometrics.

The study aims to explore the potential of hyperspectral imaging (HSI) with chemometrics for rapidly and non-invasively visualizing the spatial distribution of protein content which can affect the quality of peanut products as a critical component of peanut. Spectral data contained in the region of interest (ROI) of the corrected hyperspectral images of peanut were extracted and protein contents were measured with conventional chemical method. By comparing different pretreatments and modeling algorithms, the second-order derivatives (2nd-der) on spectra is optimal pretreatment, and partial ceast square (PLS) is the best regression method. Based on the pretreatment spectra and the measured protein content model, a good performance model (RC=0.91, SEC=0.86; RP=0.86, SEP=0.69) was built with full wavelengths. The fourteen optimal wavelengths were carried out based on the regression coefficients (RC) of the established PLS model. Then, using optimal wavelengths built RC-PLS model which show resembling performance (RC=0.86, SEC=1.03; RP=0.80, SEP=0.77). At last, an imaging processing algorithm was developed to transfer each pixel in peanut to protein content with the 2nd-der-RC-PLS model. There was no significant difference between Kjeldahl and HSI method by the paired test. The result demonstrated the capacity of HSI in combination with chemometrics for fast and non- destructively determining protein content in peanut.

[Research Process on Hyperspectral Imaging Detection Technology for the Quality and Safety of Grain and Oils].

The quality and safety of grain and oils are related to the national nutrition and health safety of the public. Owing to the difficulties in operation, destruction, high cost, reagent pollution and other shortcomings, conventional detection method cannot meet the fast, non-destructive, efficient and pollution-free requirements, which pose great difficulties in integrating with Industry 4.0. With the development of chemometrics, hyperspectral imaging (HSI) technology integrates the advantages of spectroscopy and image technology to overcome the defects of conventional detection method, which has become the developingt trend of grain and oils quality testing technology. Based on many interrelated research papers, this paper reviews the principles of HSI and the existing research in quality (component determination, germination test, variety classification) and safety (fungal detection, pest detection) of grain and oils. Meanwhile, in order to promote the application and development of hyperspectral imaging technology in the field of grain and oils, we specially analyze the aspect of HSI including spectral range, chemometrics, equipment and the accuracy of model, pointing out the current problems and prospecting the direction and priority.

Apelin-13 upregulates Egr-1 expression in rat vascular smooth muscle cells through the PI3K/Akt and PKC signaling pathways.

Previous studies have shown that Apelin-13 upregulates early growth response factor-1 (Egr-1) via the extracellular signal-regulated protein kinase (ERK) signaling pathway. Apelin-13 induces proliferation and migration of vascular smooth muscle cells (VSMCs) as well as the upregulation of osteopontin (OPN) via the upregulation of Egr-1. This study was designed to further explore the activity of Apelin-13 in VSMCs by investigating members of the mitogen-activated protein kinase (MAPK) family, in particular Jun kinase (JNK) and p38 mitogen-activated protein kinase (P38). We also examined whether the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) and protein kinase C (PKC) signaling pathways were involved in the regulation of Egr-1 by Apelin-13. We treated rat aortic VSMCs with Apelin-13 and examined the expression of JNK, p-JNK, P38, and p-P38 to investigate whether Apelin-13-mediated increases in Egr-1 occurred through the JNK and P38 signaling pathways. We then pretreated VSMCs with the Gi protein inhibitor pertussis toxin (PTX) and the Gq inhibitor YM254890, added Apelin-13 and looked for changes in Egr-1 expression. Finally, we pretreated with the PI3K inhibitor LY294002 and the PKC inhibitor GF109203X, and treated with Apelin-13. Our results showed that JNK and P38 did not participate in Apelin-13-mediated increase in Egr-1. Instead, Apelin-13 upregulation of Egr-1 was mediated by a PTX-sensitive Gi protein. Apelin-13 did increase ERK phosphorylation through the PI3K/Akt and PKC signaling pathways, resulting in changes in Egr-1 expression. These data provide important targets for future studies to modulate vascular remodeling.

A Highly Sensitive Oligonucleotide Hybridization Assay for Klebsiella pneumoniae Carbapenemase with the Probes on a Gold Nanoparticles Modified Glassy Carbon Electrode.

To develop a new electrochemical DNA biosensor for determination of Klebsiella pneumoniae carbapenemase, a highly sensitive and selective electrochemical biosensor for DNA detection was constructed based on a glassy carbon electrode (GCE) modified with gold nanoparticles (Au-nano). The Au-nano/GCE was characterized by scanning electromicroscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The hybridization detection was measured by differential pulse voltammetry using methylene blue as the hybridization indicator. The dynamic range of detection of the sensor for the target DNA sequences was from 1 × 10(-11) to 1 × 10(-8) M, with an LOD of 1 × 10(-12) M. The DNA biosensor had excellent specificity for distinguishing complementary DNA sequence in the presence of non-complementary and mismatched DNA sequence. The Au-nano/GCE showed significant improvement in electrochemical characteristics, and this biosensor was successfully applied for determination of K. pneumoniae.

An example of enzymatic promiscuity: the Baylis-Hillman reaction catalyzed by a biotin esterase (BioH) from Escherichia coli.

Ten lipases and esterases have been examined to catalyse the reaction between p-nitrobenzaldehyde and methyl vinyl ketone, the Baylis-Hillman reaction, to form 3-[hydroxyl-(4-nitrophenyl)-methyl]-but-3-en-2-one. Among these enzymes, Escherichia coli BioH esterase had the best activity. Optimal conditions for this reaction were: 0.1 mmol aldehyde, 0.1 mmol activated alkene, 30 mg E. coli BioH, 1 ml acetonitrile at 30 °C for 96 h. In addition to the named substrates, four other aldehydes and three activated alkenes were also investigated to determine the substrate range of the enzyme. The structures of nine products were confirmed by NMR and yields of the corresponding products ranged from 21 to 46 %.

Ileum intussusception secondary to submucosal liposarcoma in adult：A case report.

Intussusception in adults is a rare surgical emergency. Unlike in children, most adult intussusceptions arise from a pathological lead point. Ileal intussusception caused by a submucosal liposarcoma is a particularly rare phenomenon. This report describes the diagnosis and management of adult ileal intussusception secondary to submucosal liposarcoma in adult to provide a reference for future clinical work. A 64-year-old female presented to the emergency department with worsening abdominal pain associated with an 8 h history of intermittent vomiting. Based on physical examination, laboratory investigations, and computed tomography, the most likely diagnosis was ileal intussusception secondary to liposarcoma. Thus, emergency laparotomy was performed. During exploration, an ileal invagination was visualised approximately 30 cm from the ileocecal valve, and a flexible polypoid mass was palpable at the lead point of the intussusception. Subsequently, the patient underwent radical resection of pathological tissues with a primary end-to-end ileal anastomosis. Histopathological examination revealed a well-differentiated submucosal liposarcoma. Postoperatively, the patient recovered uneventfully and was doing well at the 6-month follow-up in the outpatient clinic. Thus, clinicians should consider the origin of submucosal liposarcomas in adult with intussusception. Once ileal intussusception secondary to submucosal liposarcoma is diagnosed, timely radical resection is recommended.

Transcription Factor Pdr3p Promotes Carotenoid Biosynthesis by Activating GAL Promoters in Saccharomyces cerevisiae.

Pleiotropic drug resistance (PDR) family proteins have been extensively studied for their roles in transporting hydrophobic substances, including carotenoids. Overexpression of the PDR family regulator Pdr3p was recently found to boost the biosynthesis of carotenoids, which could not be explained by enhanced product secretion due to the meager extracellular proportions. To provide insights into the possible mechanism, comparative transcriptomics, reverse metabolic engineering, and electrophoretic mobility shift assay (EMSA) were conducted. Transcriptomic data suggested an unexpected correlation between Pdr3p overexpression and the transcriptional levels of GAL promoter-driven genes. This assumption was verified using mCherry and the lycopene synthetic pathway as the reporters. qRT-PCR and EMSA provided further evidence for the activation of GAL promoters by Pdr3p binding to their upstream activation sequences (UASs). This work gives insight into the mechanism of Pdr3p-promoted carotenoid production and highlights the complicated metabolic networking between transcriptional factors and promoters in yeast.

Apelin-13-induced proliferation and migration induced of rat vascular smooth muscle cells is mediated by the upregulation of Egr-1.

Apelin-13 plays an important role in the migration and proliferation of vascular smooth muscle cells (VSMCs); however, the underlying mechanisms are still unclear. Egr-1 is a nuclear transcription factor, which is considered to be the critical initiating factor of the processes of VSMC proliferation and migration. Egr-1 is known to regulate the expression of osteopontin (OPN), which is a marker of the phenotypic modulation that is a necessary condition of VSMC proliferation and migration. We hypothesized that the role of Apelin-13 is mediated via upregulation of Egr-1. To test this hypothesis, we analyzed the effects of Apelin-13 treatment on Egr-1 mRNA and protein expression in A10 rat aortic VSMCs by RT-PCR and Western blotting, respectively. Results showed that, Apelin-13 upregulated the expression of Egr-1. Furthermore, treatment with the extracellular-regulated protein kinase (ERK) inhibitor, PD98059, inhibited the upregulation of Egr-1 by Apelin-13. In addition, this upregulation was inhibited by treatment of VSMCs with the Egr-1 specific deoxyribozyme ED5 (DNAenzyme/10-23 DRz). Furthermore, ED5 treatment was found to significantly inhibit Apelin-13-induced migration and proliferation of VSMCs using transwell and MTT assays, respectively. The evaluation of OPN mRNA and protein expression levels by RT-PCR and Western blot analyses revealed that ED5 treatment also inhibited Apelin-13-induced OPN upregulation. The results of this study indicated that Apelin-13 upregulates Egr-1 via ERK. Furthermore, Apelin-13 induced the proliferation and migration of VSMCs as well as the upregulation of OPN via the upregulation of Egr-1. These results will provide an important theoretical and experimental basis for the control of inappropriate remodeling of vessel walls, and will hopefully lead to the prevention and treatment of vascular remodeling diseases.

Assessment of myocardial bridge and mural coronary artery using ECG-gated 256-slice CT angiography: a retrospective study.

Recent clinical reports have indicated that myocardial bridge and mural coronary artery complex (MB-MCA) might cause major adverse cardiac events. 256-slice CT angiography (256-slice CTA) is a newly developed CT system with faster scanning and lower radiation dose compared with other CT systems. The objective of this study is to evaluate the morphological features of MB-MCA and determine its changes from diastole to systole phase using 256-slice CTA. The imaging data of 2462 patients were collected retrospectively. Two independent radiologists reviewed the collected images and the diagnosis of MB-MCA was confirmed when consistency was obtained. The length, diameter, and thickness of MB-MCA in diastole and systole phases were recorded, and changes of MB-MCA were calculated. Our results showed that among the 2462 patients examined, 336 have one or multiple MB-MCA (13.6%). Out of 389 MB-MCA segments, 235 sites were located in LAD2 (60.41%). The average diameter change of MCA in LAD2 from systole phase to diastole phase was 1.1 ± 0.4 mm, and 34.9% of MCA have more than 50% diameter stenosis in systole phase. This study suggested that 256-slice CTA multiple-phase reconstruction technique is a reliable method to determine the changes of MB-MCA from diastole to systole phase.

Metabolic Engineering of Yarrowia lipolytica for Terpenoid Production: Tools and Strategies.

Terpenoids are a diverse group of compounds with isoprene units as basic building blocks. They are widely used in the food, feed, pharmaceutical, and cosmetic industries due to their diverse biological functions such as antioxidant, anticancer, and immune enhancement. With an increase in understanding the biosynthetic pathways of terpenoids and advances in synthetic biology techniques, microbial cell factories have been built for the heterologous production of terpenoids, with the oleaginous yeast Yarrowia lipolytica emerging as an outstanding chassis. In this paper, recent progress in the development of Y. lipolytica cell factories for terpenoid production with a focus on the advances in novel synbio tools and metabolic engineering strategies toward enhanced terpenoid biosynthesis is reviewed.

TSLP Induces Epithelial-Mesenchymal Transition in Nasal Epithelial Cells From Allergic Rhinitis Patients Through TGF-ß1/Smad2/3 Signaling.

BACKGROUND: Airway remodeling is demonstrated in Asian patients with allergic rhinitis (AR). The epithelial-mesenchymal transition (EMT) is one of the key mechanisms underlying airway remodeling. Thymic stromal lymphopoietin (TSLP) is an important contributor to airway remodeling. Although increased TSLP is found in AR, little is known about whether TSLP is involved in airway remodeling through induction of the EMT. OBJECTIVE: We investigated the effect of TSLP on the EMT in human nasal epithelial cells (HNECs) from AR patients. METHODS: Human nasal epithelial cells from AR patients were stimulated with TSLP in the absence or presence of the preincubation with a selective inhibitor of transforming growth factor beta 1 (TGF-ß1) receptor (SB431542). The expression of TGF-ß1 in the cells was evaluated by using real-time polymerase chain reaction, Western blotting, and immunocytochemistry. Western blotting and immunocytochemistry were used to assay EMT markers including vimentin, fibroblast-specific protein 1 (FSP1) and E-cadherin, small mothers against decapentaplegic homolog2/3 (Smad2/3), and phosphorylated Smad2/3 in the cells. The levels of extracellular matrix components such as collagens I and III in supernatants were measured by enzyme-linked immunoassay. Morphological changes of the cells were observed under inverted phase-contrast microscope. RESULTS: A concentration-dependent increase of TGF-ß1 mRNA and protein was observed following stimulation with TSLP. Furthermore, TSLP decreased the expression of E-cadherin protein, but upregulated the production of FSP1 and vimentin proteins along with increased levels of collagens I and III, and the morphology of the cells was transformed into fibroblast-like shape. Additionally, a significant increase was found in phosphorylation of Smad2/3 protein. However, these effects were reversed by SB431542 preincubation. CONCLUSION: TSLP-induced HNECs to undergo the EMT process via TGF-ß1-mediated Smad2/3 activation. TSLP is an activator of the EMT in HNECs and might be a potential target for inhibiting EMT and reducing airway remodeling in AR.

Hyaluronic Acid-Based Nanocarriers for Anticancer Drug Delivery.

Hyaluronic acid (HA), a main component of the extracellular matrix, is widely utilized to deliver anticancer drugs due to its biocompatibility, biodegradability, non-toxicity, non-immunogenicity and numerous modification sites, such as carboxyl and hydroxyl groups. Moreover, HA serves as a natural ligand for tumor-targeted drug delivery systems, as it contains the endocytic HA receptor, CD44, which is overexpressed in many cancer cells. Therefore, HA-based nanocarriers have been developed to improve drug delivery efficiency and distinguish between healthy and cancerous tissues, resulting in reduced residual toxicity and off-target accumulation. This article comprehensively reviews the fabrication of anticancer drug nanocarriers based on HA in the context of prodrugs, organic carrier materials (micelles, liposomes, nanoparticles, microbubbles and hydrogels) and inorganic composite nanocarriers (gold nanoparticles, quantum dots, carbon nanotubes and silicon dioxide). Additionally, the progress achieved in the design and optimization of these nanocarriers and their effects on cancer therapy are discussed. Finally, the review provides a summary of the perspectives, the lessons learned so far and the outlook towards further developments in this field.