Histone deacetylase activity is a novel target for epithelial barrier defects in patients with eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Studies have independently indicated that eosinophils and histone deacetylases (HDACs) may compromise the integrity of the epithelial barrier in nasal polyps; however, the underlying mechanisms are not clear. In this study, we aimed to investigate the role of eosinophilia and HDACs in regulation of tight junctions (TJs) and nasal epithelial barrier integrity in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. METHODS: Expression of mRNAs and proteins of TJs and HDACs of biopsy specimens and air-liquid interface (ALI) human nasal epithelial cell cultures (HNECs) from eosinophilic and noneosinophilic CRSwNP patients and healthy controls was assessed. The ALI HNECs were also assessed for changes in transepithelial electrical resistance (TER) and paracellular flux of fluorescein isothiocyanate (FITC)-labelled dextran. Meanwhile, the assessments for the effect of HDAC inhibitor in eosinophilic nasal polyps were also conducted. RESULTS: Decreased TER and increased paracellular flux of FITC-labelled dextran in the ALI cultures were found in both eosinophilic and noneosinophilic CRSwNP, along with irregular, patchy and reduced expression of claudin-1, 4, 7, occludin, zonula occludens (ZO)-1 and ZO-2 and increased expression of HDAC1, 9 and SIRT7 for both ALI culture cells and biopsy specimens, especially for the eosinophilic CRSwNP group. Treatment of eosinophilic CRSwNP ALI-HNECs with an HDAC inhibitor improved the TJs expression and epithelial barrier integrity. CONCLUSIONS: Our data suggest that eosinophilia and HDACs influence epithelial barrier function in CRSwNP patients by regulating TJ protein expression. Targeting HDACs with specific inhibitors may be a potential treatment option for patients with eosinophilic CRSwNP.

Intergenerational toxic effects of parental exposure to [Cn mim]NO3 (n = 2,4,6) on nervous and skeletal development in zebrafish offspring.

Ionic liquids (ILs) are thought to have negative effects on human health. Researchers have explored the effects of ILs on zebrafish development during the early stages, but the intergenerational toxicity of ILs on zebrafish development has rarely been reported. Herein, parental zebrafish were exposed to different concentrations (0, 12.5, 25, and 50 mg/L) of [Cn mim]NO3 (n = 2, 4, 6) for 1 week. Subsequently, the F1 offspring were cultured in clean water for 96 h. [Cn mim]NO3 (n = 2, 4, 6) exposure inhibited spermatogenesis and oogenesis in F0 adults, even causing obvious lacunae in the testis and atretic follicle oocytes in ovary. After parental exposure to [Cn mim]NO3 (n = 2, 4, 6), the body length and locomotor behavior were measured in F1 larvae at 96 hours post-fertilization (hpf). The results showed that the higher the concentration of [Cn mim]NO3 (n = 2, 4, 6), the shorter the body length and swimming distance, and the longer the immobility time. Besides, a longer alkyl chain length of [Cn mim]NO3 had a more negative effect on body length and locomotor behavior. RNA-seq analysis revealed several downregulated differentially expressed genes (DEGs)-grin1b, prss1, gria3a, and gria4a-enriched in neurodevelopment-related pathways, particularly the pathway for neuroactive ligand-receptor interaction. Moreover, several upregulated DEGs, namely col1a1a, col1a1b, and acta2, were mainly associated with skeletal development. Expression of DEGs was tested by RT-qPCR, and the outcomes were consistent with those obtained from RNA-Seq. We provide evidence showing the effects of parental exposure to ILs on the regulation of nervous and skeletal development in F1 offspring, demonstrating intergenerational effects.

[Pedigree Analysis and Diagnosis of Congenital Dysfibrinogenemia: A Case Report].

OBJECTIVE: To improve the understanding and diagnosis and treatment of congenital dysfibrinogenemia (CD) through analyzing the clinical data of a pediatric patient and his pedigree. METHODS: The clinical manifestations, laboratory findings and treatment of a case of CD diagnosed at West China Second University Hospital, Sichuan University and those of its pedigree members were analyzed, and genetic tracing and follow-up were conducted on the patient and its pedigree. RESULTS: The child has no clinical manifestations at the time of admission. Coagulation function examination showed normal prothrombin time (PT), normal activated partial thrombin time (APTT), significantly prolonged thrombin time (TT), fibrinogen activity (Fg: C<0.5 g/L) measured with the Clauss method, and fibrinogen antigen (Fg: Ag) measured at 2.8 g/L with PT algorithm. Gene sequencing results showed that heterozygous missense mutation c.901C>T (p.Arg301Cys) in exon 8 of FGG gene. Combined with the family history, the child was diagnosed with CD. During the follow-up of 4 + months, the patient did not present bleeding, abnormal coagulation or thrombosis, and the coagulation function did not show significant changes compared with the findings obtained on admission. CONCLUSION: The diagnosis of CD is confirmed mainly based on genetic testing and the treatment is characterized by the principle of precise individualized treatment. No special treatment is needed for patients presenting no clinical manifestations. However, it is important to provide thorough prenatal diagnosis and follow-up services for female patients planning for pregnancy so as to prevent miscarriage and complications caused by postpartum coagulation dysfunction.

[Application Protocol of Standardized Neonatal Parenteral Nutrition Formulations].

With the improvements in medical technology, more premature infants and infants with congenital intestinal malformations or other conditions who need parenteral nutrition (PN) support can survive. PN technology has become an important therapeutic strategy in neonatal intensive care units. Due to differences in the qualifications of medical staffs, hospital pharmacy management, hospital level, etc, the composition and preparation methods of PN prescription vary greatly in different regions and hospitals in China. In addition, delays in the starting time of PN, unreasonable formula of nutrition components, poor prescription review, large workload involved in the preparation of PN for nurses, and waste of drugs are prone to happen. In view of these issues, our hospital independently developed standardized formulas of neonatal PN solution, which has been approved in Australia as a patented invention. Herein, we reported the composition and application protocol of this standardized PN solution for newborns.

Effect of lipophilicity on drug distribution and elimination: Influence of obesity.

AIMS: For a given passively-distributed lipophilic drug, the extent of in vivo distribution (pharmacokinetic volume of distribution, Vd ) in obese individuals increases in relation to the degree of obesity. The present study had the objective of evaluating drug distribution in relation to in vitro lipophilicity, and the relative increase in Vd associated with obesity across a series of drugs. METHODS: Cohorts of normal-weight control and obese subjects received single doses of drugs ranging from hydrophilic (acetaminophen, salicylate) to lipophilic (imipramine, verapamil). Lipid solubility was measured by the log-transformed values of the high-pressure liquid chromatographic (HPLC) retention index (Log10 (HPLC)), and the octanol-water partition coefficient (LogP). RESULTS: Among normal-weight controls, Vd normalized for protein binding was highly correlated with Log10 (HPLC) (R2 = .65) and with LogP (R2 = .78). Vd of all drugs was increased in the obese cohort, but the relative increase (compared to controls) for individual drugs was disproportionately greater as lipid solubility increased. Since clearance was unrelated to lipophilicity, the increased Vd produced a parallel disproportionate increase in elimination half-life in the obese cohort that was associated with Log10 (HPLC) (R2 = .62). CONCLUSION: Lipophilicity is a principal correlate of in vivo Vd , as well as the increased Vd of drugs in obese patients. The consequent prolongation of half-life in obesity has clinical safety implications in terms of delayed drug accumulation and washout during and after chronic dosage. The magnitude and importance of this effect for a given drug depends on the degree of obesity, as well as the lipid-solubility of the specific drug.

Tropomyosin in mugwort cross-reacts to house dust mite, eliciting non-Th2 response in allergic rhinitis patients sensitized to house dust mite.

BACKGROUND: Mugwort and house dust mite (HDM) are two of the most common inhalant allergens in Asia, however, whether mugwort affects polysensitized HDM+ allergic rhinitis (AR) patients has not been elucidated. METHODS: Overall, 15,884 AR outpatients were assessed for clinical status. Amino acid sequences of mugwort were determined by mass spectrometry. Afterward, cross-reactivity between mugwort tropomyosin and Dermatophagoides pteronyssinus 10 (Der p10) was analysed by ELISA inhibition and basophil activation experiments. To compare immunologic responses eliciting by two different tropomyosins, peripheral blood mononuclear cells (PBMCs) of HDM-monosensitized patients were stimulated by mugwort, HDM, Der p10 and synthetic peptides representing mugwort tropomyosin respectively. RESULTS: Polysensitized HDM+AR patients were mainly sensitized to cat and mugwort, and the positive rate of monosensitized HDM+AR out-clinic patients was increased during the mugwort pollen season. Tropomyosin protein was able to find in mugwort. Synthetic tropomyosin peptide of mugwort activated basophils which were primed by HDM-specific IgE; ELISA inhibition experiment showed synthetic tropomyosin peptide of mugwort inhibited IgE binding to HDM tropomyosin, Der p10. Unlike HDM and Derp 10, mugwort and mugwort tropomyosin mainly induced IFN-γ and IL-17 release in PBMCs of monosensitized HDM+AR patients, but not IL-5. CONCLUSIONS: Pan-allergen tropomyosin accounts for the cross-reactivity between mugwort and HDM, which reminds HDM+ patients to reduce mugwort exposure in mugwort pollen season in virtue of the tropomyosin induced mild inflammation.

Synthesis and biological evaluation of novel 3-benzylcoumarin-imidazolium salts.

A series of novel 3-benzylcoumarin-imidazolium salts were prepared and evaluated in vitro against a panel of human tumor cell lines. The results showed that the existence of 5,6-dimethyl-benzimidazole ring and substitution of the imidazolyl-3-position with a naphthylacyl group were vital for modulating cytotoxic activity. Notably, compound 38 was found to be the most potent derivative with IC50 values of 2.04-4.51 µM against five human tumor cell lines, while compound 34 were more selective to SW-480 cell lines with IC50 value 40.0-fold lower than DDP. Mechanism of action studies indicated that compound 38 can cause the G0/G1 phase cell cycle arrest and apoptosis in SMMC-7721 cell lines.

Synthesis and biological activity of new bisbenzofuran-imidazolium salts.

A series of novel bisbenzofuran-imidazolium salts were designed and prepared. The in vitro antitumor activity of these derivatives was evaluated against a panel of human tumor cell lines (A549, HL-60, MCF-7, SMMC-7721 and SW480). Results demonstrated that 2-methyl-benzimidazole ring and substitution of the imidazolyl-3-position with a 4-methoxyphenacyl or 2-naphthylacyl substituent were important for promoting cytotoxic activity. Notably, compound 23 was found to be the most potent compound with IC50 values of 0.64-1.47 µM against five human tumor cell lines, and exhibited higher selectivity to MCF-7 and SW-480 cell lines with IC50 values 15.3-fold and 9.1-fold lower than DDP.

A multiplex one-tube nested real time RT-PCR assay for simultaneous detection of respiratory syncytial virus, human rhinovirus and human metapneumovirus.

BACKGROUND: Respiratory syncytial virus (RSV), human Rhinovirus (HRV) and human Metapneumo Virus (HMPV) are important viral pathogens causing acute respiratory tract infections in the hospitalized patients. Sensitive and accurate detection of RSV, HRV and HMPV is necessary for clinical diagnosis and treatment. RESULTS: A locked nucleic acid (LNA)-based multiplex closed one-tube nested real-time RT-PCR (mOTNRT-PCR) assay was developed for simultaneous detection of RSV, HRV and HMPV. The sensitivity, specificity, reproducibility and clinical performance of mOTNRT-PCR were evaluated and compared with individual real time PCR (RT-qPCR) assay using clinical samples. The analytical sensitivity of mOTNRT-PCR assay was 5 copies/reaction for RSV, HRV and HMPV, respectively, and no cross-reaction with other common respiratory viruses was observed. The coefficients of variation (CV) of intra-assay and inter-assay were between 0.51 to 3.67%. Of 398 nasopharyngeal aspirates samples tested, 109 (27.39%), 150 (37.69%) and 44 (11.06%) were positive for RSV, HRV and HMPV, respectively, whereas 95 (23.87%), 137 (34.42%) and 38 (9.55%) were positive for RSV, HRV and HMPV, respectively, by individual RT-qPCR assay. Thirty three samples that were positive by mOTNRT-PCR but negative by RT-qPCR were confirmed as true positives by sequencing using reported traditional two-step nested PCR assay. CONCLUSION: mOTNRT-PCR assay reveals extremely higher sensitivity than that of RT-qPCR assay for detecting RSV, HRV and HMPV in clinical settings.

A triplex quantitative real-time PCR assay for differential detection of human adenovirus serotypes 2, 3 and 7.

BACKGROUND: Human adenovirus (HAdV) serotypes 2, 3 and 7 are more prevalent than other serotypes and have been associated with severe pneumonia in pediatric children. Molecular typing of HAdV is not routinely performed in clinical diagnostic laboratories as it is time-consuming and labor-intensive. METHODS: In the present study, we developed a triplex quantitative real-time PCR assay (tq-PCR) in a single closed tube for differential detection and quantitative analysis of HAdV serotypes 2, 3 and 7. The sensitivity, specificity, reproducibility and clinical performance of tq-PCR were evaluated. RESULTS: The analytical sensitivity of the tq-PCR was 100 copies/reaction for each of HAdV serotypes 2, 3 and 7, and no cross-reaction with other common respiratory viruses or HAdV serotypes 1,4,5,6,31,55 and 57 was observed. The coefficients of variation (CV) of intra-assay and inter-assay were between 0.6% to 3.6%. Of 138 previously-defined HAdV-positive nasopharyngeal aspirates samples tested, the detection agreement between tq-PCR and nested PCR was 96.38% (133/138). CONCLUSION: The proposed tq-PCR assay is a sensitive, specific and reproducible method and has the potential for clinical use in the rapid and differential detection and quantitation of HAdV serotypes 2, 3 and 7.

Development of a reverse transcription recombinase-aided amplification assay for the detection of coxsackievirus A10 and coxsackievirus A6 RNA.

Hand, foot and mouth disease (HFMD) is a serious public health problem, and coxsackievirus A6 (CVA6) and coxsackievirus A10 (CVA10) are two of the major causative pathogens, in addition to enterovirus 71 (EV71) and coxsackievirus A16 (CVA16). A simple and rapid reverse transcription recombinase-aided amplification assay (RT-RAA) was developed for the detection of CVA10 and CVA6 in this study. The analytical sensitivity for detection of CVA10 and CVA6 at 95% probability by probit regression analysis was 35 copies per reaction and 38 copies per reaction, respectively, with 100% specificity. Compared with commercial RT-qPCR assays, when testing 455 fecal specimens, the kappa value of the RT-RAA assay for CVA10 and CVA6 was 0.920 (p < 0.001) and 0.952 (p < 0.001), respectively. Moreover, four samples that were positive for CVA10 and five that were positive for CVA6 by RT-RAA but negative by RT-qPCR were further determined to be true positives. These results demonstrate that the proposed RT-RAA assays are very valuable tools for the detection of CVA10 and CVA6 and have potential for use in resource-limited settings.

Adenovirus associated with acute diarrhea: a case-control study.

BACKGROUND: Diarrhea is a major source of morbidity and mortality among young children in low-income and middle-income countries. Human adenoviruses (HAdV), particular HAdV species F (40, 41) has been recognized as important causal pathogens, however limited data exist on molecular epidemiology of other HAdV associated with acute gastroenteritis. METHODS: In the present preliminary study, we performed a case-control study involving 273 children who presented diarrheal disease and 361 healthy children matched control in Children's hospital of Hebei Province (China) to investigate the relationship between non-enteric HAdV and diarrhea. HAdV were detected and quantified using quantitative real-time PCR (qPCR) and serotyped by sequencing and phylogenetic analysis. Odds ratio (OR) was used to assess the risk factor of HAdV. RESULTS: HAdV were detected in 79 (28.94%) of 273 children with diarrhea including 7 different serotypes (HAdV 40, 41, 3, 2,1,5 and 57) with serotypes 40, 41 and 3 being the most dominant and in 26 (7.20%) of 361 healthy children containing 9 serotypes (HAdV 40, 41, 3, 2,1,5,57,6 and 31). A majority (91.14%) of HAdV positives occurred in diarrhea children and 65.38% in controls< 3 years of age. No significant difference in the viral load was found between case and control groups or between Ad41-positive patients and healthy controls. In addition to HAdV 40 and 41, HAdV 3 was also associated with diarrhea (OR = 17.301, adjusted OR = 9.205, p < 0.001). CONCLUSIONS: Our results demonstrate a high diversity of HAdV present among diarrhea and healthy children and implicate that non-enteric HAdV3 may lead to diarrhea.

VSITA, an Improved Approach of Target Amplification in the Identification of Viral Pathogens.

OBJECTIVE: Unbiased next generation sequencing (NGS) is susceptible to interference from host or environmental sequences. Consequently, background depletion and virome enrichment techniques are usually needed for clinical samples where viral load is much lower than background sequences. METHODS: A viral Sequence Independent Targeted Amplification (VSITA) approach using a set of non-ribosomal and virus-enriched octamers (V8) was developed and compared with traditionally used random hexamers (N6). Forty-five archived clinical samples of different types were used in parallel to compare the V8 and N6 enrichment performance of viral sequences and removal performance of ribosomal sequences in the step of reverse transcription followed by quantitative PCR (qPCR). Ten sera samples from patients with fever of unknown origin and 10 feces samples from patients with diarrhea of unknown origin were used in comparison of V8 and N6 enrichment performance following NGS analysis. RESULTS: A minimum 30 hexamers matching to viral reference sequences (sense and antisense) were selected from a dataset of random 4,096 (46) hexamers (N6). Two random nucleotides were added to the 5' end of the selected hexamers, and 480 (30 × 42) octamers (V8) were obtained. In general, VSITA approach showed higher enrichment of virus-targeted cDNA and enhanced ability to remove unwanted ribosomal sequences in the majorities of 45 predefined clinical samples. Moreover, VSITA combined with NGS enabled to detect not only more viruses but also achieve more viral reads hit and higher viral genome coverage in 20 clinical samples with diarrhea or fever of unknown origin. CONCLUSION: The VSITA approach designed in this study is demonstrated to possess higher sensitivity and broader genome coverage than traditionally used random hexamers in the NGS-based identification of viral pathogens directly from clinical samples.

Race, Gender, and Genetic Polymorphism Contribute to Variability in Acetaminophen Pharmacokinetics, Metabolism, and Protein-Adduct Concentrations in Healthy African-American and European-American Volunteers.

Over 30 years ago, black Africans from Kenya and Ghana were shown to metabolize acetaminophen faster by glucuronidation and slower by oxidation compared with white Scottish Europeans. The objectives of this study were to determine whether similar differences exist between African-Americans and European-Americans, and to identify genetic polymorphisms that could explain these potential differences. Acetaminophen plasma pharmacokinetics and partial urinary metabolite clearances via glucuronidation, sulfation, and oxidation were determined in healthy African-Americans (18 men, 23 women) and European-Americans (34 men, 20 women) following a 1-g oral dose. There were no differences in acetaminophen total plasma, glucuronidation, or sulfation clearance values between African-Americans and European-Americans. However, median oxidation clearance was 37% lower in African-Americans versus European-Americans (0.57 versus 0.90 ml/min per kilogram; P = 0.0001). Although acetaminophen total or metabolite clearance values were not different between genders, shorter plasma half-life values (by 11-14%; P < 0.01) were observed for acetaminophen, acetaminophen glucuronide, and acetaminophen sulfate in women versus men. The UGT2B15*2 polymorphism was associated with variant-allele-number proportional reductions in acetaminophen total clearance (by 15-27%; P < 0.001) and glucuronidation partial clearance (by 23-48%; P < 0.001). UGT2B15 *2/*2 genotype subjects also showed higher acetaminophen protein-adduct concentrations than *1/*2 (by 42%; P = 0.003) and *1/*1 (by 41%; P = 0.003) individuals. Finally, CYP2E1 *1D/*1D genotype African-Americans had lower oxidation clearance than *1C/*1D (by 42%; P = 0.041) and *1C/*1C (by 44%; P = 0.048) African-Americans. Consequently, African-Americans oxidize acetaminophen more slowly than European-Americans, which may be partially explained by the CYP2E1*1D polymorphism. UGT2B15*2 influences acetaminophen pharmacokinetics in both African-Americans and European-Americans.

Interleukins (from IL-1 to IL-38), interferons, transforming growth factor ß, and TNF-α: Receptors, functions, and roles in diseases.

There have been extensive developments on cellular and molecular mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic infections during the last few years. Better understanding the functions, reciprocal regulation, and counterbalance of subsets of immune and inflammatory cells that interact through interleukins, interferons, TNF-α, and TGF-ß offer opportunities for immune interventions and novel treatment modalities in the era of development of biological immune response modifiers particularly targeting these molecules or their receptors. More than 60 cytokines have been designated as interleukins since the initial discoveries of monocyte and lymphocyte interleukins (called IL-1 and IL-2, respectively). Studies of transgenic or gene-deficient mice with altered expression of these cytokines or their receptors and analyses of mutations and polymorphisms in human genes that encode these products have provided essential information about their functions. Here we review recent developments on IL-1 to IL-38, TNF-α, TGF-ß, and interferons. We highlight recent advances during the last few years in this area and extensively discuss their cellular sources, targets, receptors, signaling pathways, and roles in immune regulation in patients with allergy and asthma and other inflammatory diseases.

[Sulfur-containing derivatives as characteristic chemical markers in control of sulfur-fumigated Moutan Cortex].

The amount of sulfur dioxide residue is currently employed by Chinese Pharmacopoeia (CP) as an index to screen sulfur-fumigated herbs, but it is unclear if this index can objectively reflect the quality of sulfur-fumigated herbs. In the present study, sulfur-containing derivatives were confirmed in sulfur-fumigated Moutan Cortex (MC) by UPLC-QTOF-MS/MS analysis, and the contents of sulfur-containing derivatives and sulfur dioxide residues were statistically analyzed both in self-made and commercially available sulfur-fumigated and non-fumigated MC as well as the samples thereof before and after eight-month storage. The amount of sulfur dioxide was significantly decreased, but that of the newly-generated sulfur-containing markers was not, after eight-month storage of the sulfur-fumigated MC samples, indicating that the amount of sulfur dioxide residue may not be positively correlated with the quality of sulfur-fumigated MC. Therefore, sulfur dioxide residue index alone may not objectively reflect the sulfur-fumigation extent (quality change extent) of MC, more specific method using characteristic sulfur-containing derivatives as chemical markers should be developed to supplement the sulfur dioxide residue determination in the quality control of sulfur-fumigated MC.

Staging of development in Terrien's degeneration based on corneal curvatures detected by optical coherence tomography.

PURPOSE: We aimed to explore a new classification system based on the change of focal corneal curvatures and corneal thickness in Terrien's corneal degeneration with optical coherence tomography. METHODS: This was a cross-sectional study. Ninety eyes of 59 patients with Terrien's degeneration were examined with slit lamp biomicroscopy, Orbscan II corneal tomography and the Visante OCT system, and were staged according to Süveges's classification. RESULTS: The ratio of female to male patients was 1.57:1. The ratio of bilateral to unilateral lesions was 1.27:1. The occurrence of bilateral lesion was higher in males than in females (x(2) = 7.791, p = 0.005). There was no difference in the mean age between female and male patients (t = 1.859, p = 0.068), or between patients with bilateral and unilateral lesions (t = 1.797, p = 0.078).The minimum corneal thickness at the thinnest point (MinCT) and anterior curvature of the peripheral cornea were almost normal in the initial stages of disease. The anterior curvature was flattened when MinCT became less than 0.56 mm, returned to normal when MinCT was no more than 0.24 mm, and bowed forward when MinCT was no more than 0.13 mm. The posterior corneal curvatures were bowed forward from their normal curvatures in 42 of 90 eyes when MinCT was no more than 0.41 mm. These eyes' MinCT ranged from 0 to 0.41 mm. There was a strong correlation between change of corneal curvatures and MinCT (r = -0.943, p < 0.01). A new classification of six stages based on corneal curvatures is proposed for evaluating the development of Terrien's degeneration. Statistically, there was a moderate correlation between either the Süveges staging or the new staging and the width and circumference of corneal lesions, visual acuity, and simulated keratometric value (all r < 0.6). The correlation of MinCT with the new classification based on corneal curvatures was higher than that with Süveges's classification (r 1 vs. r 2 , -0.943 vs. -0.801). CONCLUSION: The proposed new classification based on focal corneal curvatures is closely associated with corneal thinning, is valuable for evaluating the development of Terrien's degeneration and may enhance surgical planning.

The expression of epithelial intercellular junctional proteins in the sinonasal tissue of subjects with chronic rhinosinusitis: a histopathologic study.

OBJECTIVE: To evaluate the expression of five epithelial intercellular junctional proteins in the sinonasal tissue of subjects with chronic rhinosinusitis (CRS). METHODS: Forty-one samples of nasal polyp tissue of CRS patients with nasal polyps (wNP), 20 ethmoid sinus mucosa of CRS patients without nasal polyps (sNP) and 19 nasal mucosa of controls were collected and assessed for the expression of zonulae occludens (ZO-1), claudin-1, E-cadherin and desmoglein-1 and -2 (DSG1, DSG2) using immunohistochemical staining. Interleukin (IL)-5, IL-6 and IL-8 concentrations in the tissues were also measured using ELISA. RESULTS: The expression of ZO-1, claudin-1, DSG1 and DSG2 in the CRSwNP patient group and the expression of claudin-1, DSG1 and DSG2 of the CRSsNP patient group was significantly lower compared to that of the control group. Furthermore, the expression of DSG1 in the CRSwNP patient group was also significantly lower than in the CRSsNP patient group. In contrast, the expression of E-cadherin in the CRSwNP and the CRSsNP patient groups was significantly greater compared to the controls. The assessment of associations between the expression of the intercellular junctional proteins and cytokines demonstrated negative correlations between IL-5 and claudin-1, IL-6 and claudin-1, IL-6 and DSG2, IL-8 and DSG1, and IL-8 and DSG2. In contrast, a positive correlation was found between IL-8 and E-cadherin. CONCLUSIONS: Differences in the expression of epithelial intercellular junctional proteins may play an important role in the pathogenesis of CRS.

The HPE1 RNA-binding protein modulates chloroplast RNA editing to promote photosynthesis under cold stress in Arabidopsis.

Cold stress has severe negative consequences for plant growth and crop yield. Here, we report that an Arabidopsis thaliana mutant that lacks the HPE1 gene, which encodes an RNA-binding protein, maintains higher photosynthetic activity under cold stress, together with higher accumulation of thylakoid proteins. We showed that HPE1 interacts with MORF2 and MORF9 and thereby mediates RNA editing in chloroplasts. Loss of HPE1 function increased the editing efficiency at four RNA editing sites, rpoC-488, ndhB-149, ndhB-746 and matK-706, under cold stress and altered the expression of nuclear photosynthesis-related genes and cold-responsive genes. We propose that HPE1-mediated RNA editing acts as a trigger for retrograde signaling that affects photosynthesis under cold stress.