Sodium-iodide symporter and its related solute carriers in thyroid cancer.

The solute carrier (SLC) family is a large group of membrane transport proteins. Their dysfunction plays an important role in the pathogenesis of thyroid cancer. The most well-known SLC is the sodium-iodide symporter (NIS), also known as sodium/iodide co-transporter or solute carrier family 5 member 5 (SLC5A5) in thyroid cancer. The dysregulation of NIS in thyroid cancer is well documented. The role of NIS in the uptake of iodide is critical in the treatment of thyroid cancer, radioactive iodide (RAI) therapy in particular. In addition to NIS, other SLC members may affect the autophagy, proliferation, and apoptosis of thyroid cancer cells, indicating that an alteration in SLC members may affect different cellular events in the evolution of thyroid cancer. The expression of the SLC members may impact the uptake of chemicals by the thyroid, suggesting that targeting SLC members may be a promising therapeutic strategy in thyroid cancer.

Targeting Nrf2 to treat thyroid cancer.

Oxidative stress (OS) is recognized as a contributing factor in the development and progression of thyroid cancer. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal transcription factor involved in against OS generated by excessive reactive oxygen species (ROS). It governs the expression of a wide array of genes implicated in detoxification and antioxidant pathways. However, studies have demonstrated that the sustained activation of Nrf2 can contribute to tumor progression and drug resistance in cancers. The expression of Nrf2 was notably elevated in papillary thyroid cancer tissues compared to normal tissues, indicating that Nrf2 may play an oncogenic role in the development of papillary thyroid cancer. Nrf2 and its downstream targets are involved in the progression of thyroid cancer by impacting the prognosis and ferroptosis. Furthermore, the inhibition of Nrf2 can increase the sensitivity of target therapy in thyroid cancer. Therefore, Nrf2 appears to be a potential therapeutic target for the treatment of thyroid cancer. This review summarized current data on Nrf2 expression in thyroid cancer, discussed the function of Nrf2 in thyroid cancer, and analyzed various strategies to inhibit Nrf2.

Constructing a noble-metal-free 0D/2D CdS/SnS2heterojunction for efficient visible-light-driven photocatalytic pollutant degradation and hydrogen generation.

Semiconductor photocatalysis has attracted the attention of a wide audience for its outstanding capabilities in water purification and energy conversion. Herein, a noble-metal-free nanoheterojunction is created by planting zero-dimensional (0D) CdS nanograins, of 10-20 nm in size, on the surface of 2D SnS2nanosheets (NSs) using anin situchemical bathing deposition process, where SnS2NSs have an average diameter of 400 nm and thicknesses of less than 20 nm. The possible formation mechanism of the CdS/SnS2(CS/SS) heterogeneous nanostructure is elaborated upon. The catalytic activities over CS/SS nanocomposites for the photodegradation of organic dye and hydrogen evolution from photolysis water splitting are examined under visible light irradiation. The apparent rate constant (k) of the optimal CS/SS-3 composite in the decontamination of methylene blue (MB) is up to 3.34 and 1.87 times as high as that of pristine SnS2and pure CdS counterparts, respectively. The optimized CS/SS-3 sample consistently achieves the highest photocatalytic hydrogen production rate, at 10.3 and 5.7 folds higher than that of solo SnS2and CdS panels, respectively. The boosted photocatalytic capacities of CdS/SnS2heterostructures are essentially attributed to the formation of the closely interfacial incorporation of CdS and SnS2semiconductors, resulting in the effective charge transportation and spatial separation of the photoinduced electron-hole pairs. Furthermore, the traditional type-II charge transfer pathway is proposed based on the perfect band structure and the free radical experiment results.

Autophagy regulates anti-angiogenic property of lenvatinib in thyroid cancer.

We aimed to explore the role of lenvatinib-mediated autophagy in papillary thyroid cancer (PTC). K1 and BCPAP, were tested for cell viability, proliferation, and apoptosis after treatment with lenvatinib or chloroquine (CQ) or both. The levels of angiogenesis vascular endothelial growth factor A (VEGFA) were measured by ELISA. Transwell and wound-healing assays were performed using endothelial HUVECs cells. The dynamics of microvessels were detected by tubular formation assay. Western blotting was used to determine the expression of LC3-I/II and Atg-7 and alterations in the PI3K/Akt/mTOR and MEK/ERK pathways. In vivo tumor growth assay and immunohistochemical staining (IHC) was also performed. The results showed that lenvatinib inhibited the viability of K1 and BCPAP cells and caused apoptosis. We further showed that lenvatinib also upregulated autophagy levels in thyroid cancer cells in a dose-dependent manner through the PI3K/Akt/mTOR and MEK/ERK pathways. Co-administration of lenvatinib with CQ resulted in a greater decrease of VEGFA in the tumor supernatant than with either lenvatinib or CQ alone. Autophagy inhibition enhanced the cytotoxicity and anti-angiogenic ability of lenvatinib, which was supported by the HUVECs migration, wound healing, and tube formation assays. Inhibiting autophagy chemically or genetically enhanced lenvatinib's cytotoxic effects and anti-angiogenic efficacy in thyroid cancer cells in vitro and in vivo. In conclusion, lenvatinib inhibited cell viability and induced apoptosis and autophagy in human PTC cells. Significantly, the combination of lenvatinib and autophagy inhibition may represent a novel and effective treatment option for PTC, which may be able to overcome drug resistance.

De-Ammonium Ba0.18V2O4.95/NH4V4O10 Film Electrodes as High-Performance Cathode Materials for Magnesium-Ion Batteries.

Magnesium-ion batteries (MIBs) have been pushed into the research boom in the post-lithium-ion batteries era due to their low cost, no dendrite hazard, and high capacity. However, finding suitable cathode materials to improve the slow kinetics of Mg2+ is an ongoing challenge. In this work, Ba0.18V2O4.95/NH4V4O10 film electrodes were grown in one step on indium tin oxide (ITO) conductive glass using a low-temperature liquid-phase deposition method. Temperature was used as the probe condition, and it was concluded that the films annealed at 400 °C had suitable crystallinity and de-ammonium lattice space. At lower current density, with 0.5 M Mg(ClO4)2/PC as the electrolyte, it exhibited an initial discharge capacity of 130.99 mA h m-2 at 210 mA m-2 and 106.52% capacity retention after 100 cycles. In addition, it exhibited excellent electrochemical performance in long-term cycling (92.98% capacity retention after 300 cycles at 600 mA m-2). According to the results of ex situ X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and high-resolution transmission electron microscopy (HRTEM), the removal of NH4+ created more lattice space, assisting Ba0.18V2O4.95 to increase the transfer channels of Mg2+, providing more active sites to promote diffusion kinetics (the average DMg2+ was 2.07 × 10-12 cm2 s-1) and specific capacity. Therefore, these film electrodes for scalable Mg2+ storage are promising MIB cathode candidates that exhibit good performance advantages in storage applications.

Synthesis and Electrochemical Performance of V6O13 Nanosheets Film Cathodes for LIBs.

V6O13 thin films were deposited on indium-doped tin oxide (ITO) conductive glass by a concise low-temperature liquid-phase deposition method and through heat treatment. The obtained films were directly used as electrodes without adding any other media. The results indicate that the film annealed at 400 °C exhibited an excellent cycling performance, which remained at 82.7% of capacity after 100 cycles. The film annealed at 400 °C with diffusion coefficients of 6.08 × 10-12 cm2·s-1 (Li+ insertion) and 5.46 × 10-12 cm2·s-1 (Li+ extraction) in the V6O13 film electrode. The high diffusion coefficients could be ascribed to the porous morphology composed of ultrathin nanosheets. Moreover, the film endured phase transitions during electrochemical cycling, the V6O13 partially transformed to Li0.6V1.67O3.67, Li3VO4, and VO2 with the insertion of Li+ into the lattice, and Li0.6V1.67O3.67, Li3VO4, and VO2 partially reversibly transformed backwards to V6O13 with the extraction of Li+ from the lattice. The phase transition can be attributed to the unique structure and morphology with enough active sites and ions diffusion channels during cycles. Such findings reveal a bright idea to prepare high-performance cathode materials for LIBs.

The Isoforms of Estrogen Receptor Alpha and Beta in Thyroid Cancer.

The incidence of thyroid cancer was predominant in women, indicating that the sex hormone may have a role in thyroid cancer development. Generally, the sex hormone exerts its function by binding to the correspondent nuclear receptors. Therefore, aberrant of these receptors may be involved in the development of thyroid cancer. Estrogen receptor alpha (ERα) and beta (ERß), two main estrogen receptors, have been reported to have an important role in the pathogenesis of thyroid cancer. When the ERα and ERß genes undergo the alternative RNA splicing, some ERα and ERß isoforms with incomplete functional domains may be formed. To date, several isoforms of ERα and ERß have been identified. However, their expression and roles in thyroid cancer are far from clear. In this review, we summarized the expressions and roles of ERα and ERß isoforms in thyroid cancer, aiming to provide the perspective of modulating the alternative RNA splicing of ERα and ERß against thyroid cancer.

The Effects of Sn Doping MnNiFeO4 NTC Ceramic: Preparation, Microstructure and Electrical Properties.

Sn-doped MnNiFeO4 ceramic with negative temperature coefficient (NTC) was prepared through the low-temperature solid-phase reaction route (LTSPR), aiming at improving the sintering behavior and modulating the electrical properties. The experimental results of the ceramic powder precursor indicate that the calcination of the ceramic precursors at above ~300 °C is an exothermic process, which contributes to the transition of the ceramic powder from the amorphous phase into the crystal spinel phase; the spinel phase of ceramic powders can be formed initially at ~450 °C and well-formed at ~750 °C. A high densification of ~98% relative densities and evenly distributed grains within an average size of 2~12 µm for the sintered Sn-doped specimen were obtained. The specific resistance and B-value were notably increased from 12.63 KΩ·cm to ~24.65 KΩ·cm, and from 3438 K to ~3779 K, respectively, with the Sn-doping amount. In contrast, the aging rates of the Sn-doped specimen have not changed markedly larger, waving around ~2.7%. The as-designed Sn-doped MnNiFeO4 can be presented as a candidate for some defined NTC requirements.

Serum Proteomic Analysis by Tandem Mass Tag-Based Quantitative Proteomics in Pediatric Obstructive Sleep Apnea.

Pediatric obstructive sleep apnea (OSA) is a frequent respiratory disorder with an estimated prevalence of 3-6% in the general population. However, the underlying pathophysiology of OSA remains unclear. Recently, proteomic analysis using high-resolution and high-throughput mass spectrometry has been widely used in the field of medical sciences. In the present study, tandem mass tag (TMT)-based proteomic analysis was performed in the serum of patients with OSA. The proteomic analysis revealed a set of differentially expressed proteins that may be associated with the pathophysiology of OSA. The differentially expressed proteins in patients with OSA were enriched in pathways including phagosome and glycan synthesis/degradation, immune response, and the hedgehog signaling pathway, indicating that such functions are key targets of OSA. Moreover, the experimental validation studies revealed that four proteins including ANTXR1, COLEC10, NCAM1, and VNN1 were reduced in the serum from patients with moderate and severe OSA, while MAN1A1 and CSPG4 protein levels were elevated in the serum from patients with severe OSA. The protein levels of ANTXR1, COLEC10, NCAM1, and VNN1 were inversely correlated with apnea-hypopnea index (AHI) in the recruited subjects, while the protein level of MAN1A1 was positively correlated with AHI, and no significant correlation was detected between CSPG4 protein and AHI. In summary, the present study for the first time identified differentially expressed proteins in the serum from OSA patients with different severities by using TMT-based proteomic analysis. The functional enrichment studies suggested that several signaling pathways may be associated with the pathophysiology of OSA. The experimental validation results indicated that six proteins including ANTXR1, COLEC10, NCAM1, VNN1, CGPG4, and MAN1A1 may play important roles in the pathophysiology of OSA, which requires further mechanistic investigation.

The emerging role of transcription factor FOXP3 in thyroid cancer.

Transcription factor FOXP3 is a crucial regulator in the development and function of regulatory T cells (Treg) that are essential for immunological tolerance and homeostasis. Numerous studies have indicated the correlation of tumor infiltrating FOXP3+ Treg upregulation with poor prognostic parameters in thyroid cancer, including lymph node metastases, extrathyroidal extension, and multifocality. Most immune-checkpoint molecules are expressed in Treg. The blockage of such signals with checkpoint inhibitors has been approved for several solid tumors, but not yet for thyroid cancer. Thyroid abnormalities may be induced by checkpoint inhibitors. For example, hypothyroidism, thyrotoxicosis, painless thyroiditis, or even thyroid storm are more frequently associated with anti-PD-1 antibodies (pembrolizumab and nivolumab). Therefore, Targeting FOXP3+ Treg may have impacts on checkpoint molecules and the growth of thyroid cancer. Several factors may impact the role and stability of FOXP3, such as alternative RNA splicing, mutations, and post-translational modification. In addition, the role of FOXP3+ Treg in the tumor microenvironment is also affected by the complex regulatory network formed by FOXP3 and its transcriptional partners. Here we discussed how the expression and function of FOXP3 were regulated and how FOXP3 interacted with its targets in Treg, aiming to help the development of FOXP3 as a potential therapeutic target for thyroid cancer.

The Knockdown of Nrf2 Suppressed Tumor Growth and Increased the Sensitivity to Lenvatinib in Anaplastic Thyroid Cancer.

Papillary thyroid cancer can dedifferentiate into a much more aggressive form of thyroid cancer, namely into anaplastic thyroid cancer. Nrf2 is commonly activated in papillary thyroid cancer, whereas its role in anaplastic thyroid cancer has not been fully explored. In this study, we used two cell lines and an animal model to examine the function of Nrf2 in anaplastic thyroid cancer. The role of Nrf2 in anaplastic thyroid cancer was investigated by a series of functional studies in two anaplastic thyroid cancer cell lines, FRO and KAT-18, and further confirmed with an in vivo study. The impact of Nrf2 on the sensitivity of anaplastic thyroid cancer cells to lenvatinib was also investigated to evaluate its potential clinical implication. We found that the expression of Nrf2 was significantly higher in anaplastic thyroid cancer cell line cells than in papillary thyroid cancer cells or normal control cells. Knockdown of Nrf2 in anaplastic thyroid cancer cells inhibited their viability and clonogenicity, reduced their migration and invasion ability in vitro, and suppressed their tumorigenicity in vivo. Mechanistically, knockdown of Nrf2 decreased the expression of Notch1. Lastly, knockdown of Nrf2 increased the sensitivity of anaplastic thyroid cancer cells to lenvatinib. As knockdown of Nrf2 reduced the metastatic and invasive ability of anaplastic thyroid cancer cells by inhibiting the Notch 1 signaling pathway and increased the cancer cell sensitivity to lenvatinib, Nrf2 could be a promising therapeutic target for patients with anaplastic thyroid cancer.

Investigation into the association between obstructive sleep apnea and incidence of all-type cancers: a systematic review and meta-analysis.

Obstructive sleep apnea (OSA) is one of the most common sleep-related breathing disorders and is featured by complete or partial obstruction of the upper airway using sleep. Conflicting reports regarding the association between obstructive sleep apnea (OSA) and cancer incidence are existing in different studies. The aim of this study is to determine whether OSA is independently associated with incidence of all-type cancers by using the meta-analysis. Medline, Embase, PubMed, Ovid, the Cochrane Library database, Web of Science, and Google Scholar were searched by two independent reviewers until 31 January 2021. Studies that evaluated OSA and the cancer incidence were included. Pooled risk ratios (RR) and corresponding 95% confidence intervals (CI) were calculated. Twelve studies, involved 184,915 participants, were pooled in this meta-analysis. Fixed-effects model analysis showed that patients with OSA had an increased risk of cancer incidence (RR: 1.52, 95% CI: 1.39-1.66, P < 0.001). The subgroup analysis showed that the pooled RRs of cancer incidence were 1.14 (95% CI: 1.04-1.25, P = 0.006) for mild OSA, 1.36 (95% CI: 1.32-1.92; P < 0.001) for moderate OSA and 1.59 (95% CI: 1.45-1.74; P < 0.001) for severe OSA, respectively. Patients with moderate and severe OSA were identified to have an increased risk of cancer incidence when compared to patients with mild OSA. In addition, patients with severe OSA also showed an increased risk of incident cancer (RR: 1.18, 95% CI: 1.08-1.28, P < 0.001) when compared to patients with moderate OSA. In conclusion, from most updated literatures, our meta-analysis results indicated that OSA was independently associated with incidence of all-type cancers when stratified the severity of OSA. However, further detailed analysis and clinical studies are warranted to decipher the association between OSA and cancer prevalence.

Knockdown of miR-203a-3p alleviates the development of bronchopulmonary dysplasia partly via the up-regulation of vascular endothelial growth factor A.

Bronchopulmonary dysplasia (BPD) is characterized by impaired vascular and alveolar development, and the underlying molecular mechanisms have remained elusive. MicroRNAs are important players in various biological functions including the pathogenesis of BPD. The present study aimed to examine the expression of miR-203a-3p in the peripheral blood of BPD patients and elucidate the mechanisms underlying miR-203a-3p-mediated progression of BPD. We examined the expression of miR-203a-3p in the peripheral blood of BPD patients and found that miR-203a-3p was up-regulated in the patients. Additionally, the mRNA expression levels of vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor-1alpha were down-regulated in the BPD patients. Further in vitro studies showed that miR-203a-3p suppressed the expression of VEGFA in RLE-6TN cells by targeting the VEGFA 3' untranslated region. Overexpression of miR-203a-3p inhibited the viability of RLE-6TN cells and induced cell apoptosis, whereas the knockdown of miR-203a-3p exerted opposite effects. VEGFA treatment significantly attenuated the increase in the RLE-6TN cell apoptotic rates induced by miR-203a-3p overexpression; while VEGFA knockdown significantly increased the cell apoptotic rates of RLE-6TN cells, which was partially reversed by the treatment with miR-203a-3p inhibitor. Furthermore, miR-203a-3p was up-regulated, whereas VEGFA was down-regulated in the lung tissues of BPD rats, and sequestration of the expression of miR-203a-3p prevented hyperoxia-induced lung damage, increased VEGFA mRNA and protein expression levels, and promoted the protein expression of ERK, PI3K, and p38 in the lung tissues of BDP rats. In summary, the findings of our study indicate that miR-203a-3p knockdown alleviates hyperoxia-induced lung tissue damage in the BPD rat model, and its effect may be associated with the up-regulation of VEGF.

Yan-Hou-Qing formula attenuates ammonia-induced acute pharyngitis in rats via inhibition of NF-κB and COX-2.

BACKGROUND: Yan Hou Qing (YHQ) is a Chinese medicinal formula designed to alleviate sore throat symptoms, but underlying mechanism of YHQ treatment for pharyngitis is poorly defined up to now. METHODS: In this study, the modulation of YHQ on pharyngitis is investigated in ammonia-induced acute pharyngitis rat models. After treatment with YHQ or dexamethasone respectively for five consecutive days, all rats were sacrificed for biomolecular and histopathologic study. Protein expressions of MAPKs, NF-κB, COX-2 and 5-LOX in pharyngitis tissue were evaluated by western blot analysis and the levels of TNF-α, IL-6, prostaglandin (PG) E2, leukotrienes (LT)-B4 and LT-D4 in pharyngeal tissue were measured via ELISA assay. Evans blue (EB) dye exudation test was performed parallelly to assess the integrity of pharyngeal tissue. RESULTS: Compared with normal control group, EB dye exudation, and inflammatory cytokines in the model group were significantly increased, and the pharynx tissue was obviously infiltrated by inflammatory cells. YHQ treatment improved the inflammatory infiltrate in pharyngeal tissue, and reduced EB dye exudation in AP rat models. The up-regulated TNF-α and IL-6 in pharyngeal tissue of AP were significantly reduced by YHQ through inhibition of phosphorylation of p38, Erk and NF-κB. YHQ treatment also reversed the increased level of PGE2 through down-regulation of COX-2. CONCLUSIONS: YHQ formula attenuated the pharyngitis related symptoms via suppression of COX-2 and phosphorylation of p38, Erk and NF-κB (p65).

Association of Changes in Metabolic Syndrome Status With the Incidence of Thyroid Nodules: A Prospective Study in Chinese Adults.

Although several cross-sectional studies have shown an association of metabolic syndrome (MetS) with nodular thyroid disease, related prospective studies are scarce. This study investigated the association of MetS with thyroid nodule (TN) incidence in Chinese adults, and explored whether the development of or recovery from MetS is associated with changes in the risk of developing TNs. A total of 4,749 Chinese aged 18-65 years were involved in this 6-year prospective study. The association of MetS with TN prevalence was examined. TN-free individuals at baseline (n = 3,133) were further examined. TN incidence rates in groups with different MetS statuses (MetS-free, MetS-developed, MetS-recovery and MetS-chronic) were analyzed. Of all participants, 18.21 and 31.65% had MetS and TNs, respectively. MetS patients had a higher TN prevalence than the non-MetS group (31.08 vs. 19.81% in males, p < 0.01; 59.52 vs. 39.59% in females, p < 0.01). Sex, age and MetS were independent risk factors for TNs. At a median follow up of 5.94 years, the MetS-chronic group (4.37/100 person-years) had a higher risk of TNs (adjusted incidence rate ratio [IRR] = 1.288 [95% CI 1.014-1.636]) compared with the MetS-free group (2.72/100 person-years) in the whole cohort. In males, the MetS-chronic group (3.76/100 person-years) had a higher risk of TNs (adjusted IRR = 1.367 [95% CI 1.017-1.835]) compared with the MetS-free group (2.31/100 person-years). In females, the risk of TNs was significantly higher in the MetS-chronic (6.44/100 person-years) and MetS-developed (6.31/100 person-years) groups compared with the MetS-free group (3.23/100 person-years).

Insights into the expression profiles and functions of circRNAs in a newborn hyperoxia-induced rat bronchopulmonary dysplasia model.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a severe chronic lung disease in preterm infants. Circular RNAs (circRNAs) are key regulators of various biological processes. The present study aimed to explore the biological roles of circRNAs in BPD pathogenesis. METHODS: A newborn BPD rat model was developed to construct a circRNA library; Illumina deep sequencing (Illumina, San Diego, CA, USA) was used to reveal differential expression of circRNAs in the hyperoxia-induced BPD rat models. Sanger sequencing and a reverse transcription-polymerase chain reaction were performed to confirm circRNAs that may be related to BPD. After miRNA binding-site prediction, we constructed a network diagram of circRNA-competing endogenous RNAs (ceRNAs) related to transforming growth factor (TGF)-ß and p53 pathways using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: In total, 256 differentially expressed circRNAs were detected between the hyperoxia group and the normoxia group. Of these circRNAs, 195 were up-regulated and 61 were down-regulated. The differences of circRNA distribution between the two groups were analyzed and six circRNAs were validated in the tissue samples. GO analysis indicated that 6519 target genes were enriched in cell location and biological processes. KEGG pathway enrichment analysis showed that circRNAs involved in 242 KEGG pathways. A network diagram of circRNA-ceRNA related to TGF-ß and p53 pathways was constructed. CONCLUSIONS: CircRNAs are differentially expressed between the BPD model and control group. Many target genes of circRNAs are involved in the developmental process, which suggests that BPD may be associated with pathways including extracellular matrix-receptor interaction, vascular endothelial growth factor signaling and vascular smooth muscle contraction.

Vasoactive intestinal peptide alleviates food allergy via restoring regulatory B cell functions.

The immune regulatory cell dysfunction is associated with many immune diseases including food allergy (FA). This study aims to investigate the role of vasoactive intestinal peptide (VIP) in the maintenance of regulatory B cell (Br cell)'s immune suppressive functions by stabilizing thrombospondin (TSP1) expression. In this study, blood samples were collected from patients with food allergy (FA) and healthy control (HC) subjects. Br cells were isolated from the samples through flow cytometry cell sorting and analyzed by immunological approaches to determine the immune regulatory capacity. We found that the immune suppressive functions of Br cells were impaired in FA patients. The serum VIP levels were associated with the production of immune suppressive function-related mediators (interleukin-10, IL-10) of Br cells in FA patients. VIP counteracted IL-10 mRNA decay in Br cells by up regulating the TSP1 expression. TSP1 inhibited tristetraprolin (TTP) to prevent IL-10 mRNA decay in Br cells. Administration of VIP inhibited FA response through restoration of immune suppressive functions in Br cells. In conclusion, administration of VIP can alleviate FA response through up regulating expression of TSP1 to stabilize IL-10 expression in FA Br cells and recover the immune regulatory functions. The results have translational potential for the treatment of FA and other disorders associated with immune regulatory dysfunction of Br cells.

Mal-deficiency impairs the tolerogenicity of dendritic cell of patients with allergic rhinitis.

The tolerogenic dendritic cell dysfunction is associated with the pathogenesis of immune diseases. Microbial stimulus is required in the maintenance of immune functions. This study aims to elucidate the role of Mal signal in the maintenance of DEC205+ DC (decDC) immune tolerogenic function. In this study, peripheral DCs were collected from allergic rhinitis (AR) patients and healthy control (HC) subjects to assess the functional status of decDCs. An AR murine model was developed to test the role of Mal signals in the maintenance of decDCs' functions. We observed that AR decDCs (decDCs obtained from AR patients) were incompetent in the induction of type 1 regulatory T cells (Tr1 cells). AR decDCs expressed less IL-10 than that in HC decDCs. IL-10 mRNA decayed spontaneously in AR decDCs. Tat-activating regulatory DNA-binding protein-43 (TDP43) protected IL-10 mRNA from decay. AR decDCs expressed lower levels of Mal than that in HC decDCs. Mal depletion resulted in IL-10 mRNA decay in HC decDCs. Reconstitution of Mal in AR decDCs restored the capacity of inducing Tr1 cells and attenuated experimental AR in mice. In conclusion, Mal plays a critical role in the maintenance of decDC's immune tolerogenic function. The absence or insufficient Mal signal impairs decDC's tolerogenic property. Reconstitution of Mal in AR decDCs can restore the immune tolerogenic capacity, which may have translational potential in the treatment of AR and other allergic diseases.

Deep Illumina sequencing reveals differential expression of long non-coding RNAs in hyperoxia induced bronchopulmonary dysplasia in a rat model.

BACKGROUND: Bronchopulmonary dysplasia (BPD) in premature infants is a predominantly secondary occurrence to intrauterine inflammation/infection and postpartum mechanical ventilation; The purpose of this study is to explore the biological roles of lincRNA in the pathogenesis of BPD. METHODS: Newborn rats were randomly assigned to hyperoxia (85% O2) or the control group: the normoxia group (21% O2). Lung tissues were collected on days 1-14. The BPD animal model was validated using HE staining, Masson staining, and real-time RT-PCR. Deep Illumina sequencing was used to reveal the differential expression of long non-coding RNAs in hyperoxia bronchopulmonary dysplasia rat models. KEGG and GO functions were predicted. Nine possible BPD-related target lincRNAs were verified by RTq-PCR. RESULTS: The histopathologic changes in lung tissues manifested as hyperaemia, edema, hemorrhage, and inflammation cell infiltration after continuous exposure to hyperoxia for 3 days, and became aggravated after 7 days of hyperoxic exposure. The above lung tissue inflammatory manifestations were alleviated and taken over by pulmonary interstitia hyperplasia and fibrocyte proliferation after 14 days of hyperoxic exposure. The expressions of lincRNA differed between the hyperoxia bronchopulmonary dysplasia model group and the normoxia group. 1175 different lincRNAs were detected in the hyperoxia group and the normoxia group, of which 544 were up-regulated and 631 were down-regulated. 673 moleculars related to GO functions were enriched, including cell location and biological process. Pathway enrichment analysis showed that lincRNA was involved in 257 KEGG pathways. 9 lincRNA were validated in the sample, and the difference was statistically significant. CONCLUSION: LincRNAs were identified differently between the BPD model and the normoxia group. Many target genes were involved in the developmental process, including cell component biogenesis, biological regulation, transcription regulator, and translation regulator. The BPD might be caused by the activation of the pathways of the EMC-receptor interaction, cytokine-cytokine receptor interaction, cell cycle, and cell adhesion molecules. The present study provides new insight into the pathogenesis mechanism of BPD.

Tonsillectomy for adult obstructive sleep apnea: A systematic review and meta-analysis.

OBJECTIVES/HYPOTHESIS: To determine if sleepiness and sleep study variables (e.g., Apnea-Hypopnea Index [AHI] and lowest oxygen saturation) improve following isolated tonsillectomy for adult obstructive sleep apnea (OSA). STUDY DESIGN: Systematic review and meta-analysis. METHODS: Nine databases (PubMed/MEDLINE included) were searched through November 24, 2015. RESULTS: Seventeen studies (n = 216 patients, 34.4 ± 10.0 years and body mass index: 29.0 ± 6.1 kg/m(2) ) met criteria. Tonsils sizes were hypertrophied, large, enlarged, extremely enlarged, or grades 2 to 4. Apnea-Hypopnea Index decreased by 65.2% (from 40.5 ± 28.9/hour to 14.1 ± 17.1/hour) (n = 203). The AHI mean difference (MD) was -30.2 per hour (95% confidence interval [CI] -39.3, -21.1) (P value < 0.00001). The AHI SMD was -1.37 (-1.65, -1.09) (large effect). Lowest oxygen saturation improved from 77.7 ± 11.9% to 85.5 ± 8.2% (n = 186). Lowest oxygen saturation MD was 8.5% (95% CI 5.2, 11.8) (P value < 0.00001). The Epworth Sleepiness Scale decreased from 11.6 ± 3.7 to 6.1 ± 3.9 (P value < 0.00001) (n = 125). Individual patient outcomes (n = 54) demonstrated an 85.2% success rate (AHI < 20/hour and ≥ 50% reduction) and a 57.4% cure rate. Individual patient data meta-analysis showed preoperative AHI < 30 per hour to be a significant predictor of surgical success (P value < 0.001) and cure (P value = 0.043); among patients with preoperative AHI < 30 per hour, tonsillectomy success rate was 100% (25 of 25) and cure rate was 84% (21 of 25) with a mean postoperative AHI of 2.4 ± 2.1 per hour; this compares to tonsillectomy success rate of 72.4% (21 of 29), cure rate of 10 of 29 (34.4%), and mean postoperative AHI of 14.3 ± 13.9 per hour for patients with preoperative AHI ≥ 30 per hour. CONCLUSION: Isolated tonsillectomy can be successful as treatment for adult OSA, especially among patients with large tonsils and mild to moderate OSA (AHI < 30/hour). Laryngoscope, 2016 Laryngoscope, 126:2176-2186, 2016.