Sinus Microbiota in Patients With Eosinophilic and Non-Eosinophilic Chronic Rhinosinusitis With Nasal Polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by Th2-skewed inflammation and increased colonization by Staphylococcus aureus. CRSwNP can be distinguished as eosinophilic (ECRSwNP) and non-eosinophilic (NECRSwNP) by the infiltration of eosinophils. The local microbiota plays an important role in the persistent inflammation of CRSwNP. To evaluate the bacterial community composition on the distinct types of CRSwNP patients, we collected nasal swabs from 16 ECRSwNP patients, 18 NECRSwNP patients, and 39 healthy control subjects. The microbiome structure for all the samples were analyzed by high-throughput 16S rRNA gene sequencing. Concentration of S. aureus was determined using TaqMan quantitative polymerase chain reaction (qPCR) targeting the nuclease (nuc) gene. The result showed significant differences in the sinus microbiome among healthy control subjects and CRSwNP patients. Microbiota community diversity was significantly lower in NECRSwNP samples compared to that of healthy control subjects. Interestingly, the abundance of several pathogenic bacteria was diverse between ECRSwNP and NECRSwNP patients. Although Staphylococcus prevailed in all groups, the abundance of Staphylococcus was significantly higher in the healthy control group than the ECRSwNP group. More importantly, the abundance of S. aureus was much higher in NECRSwNP patients. This study highlights that microbiota composition may contribute to the different clinical types of CRSwNP, inspiring new therapeutic strategies to resolve this chronic inflammation process.

Download Full-text

Chronic Rhinosinusitis with Nasal Polyps: Age and Disease Severity Differences in the Levels of Inflammatory Markers

Medicina ◽

10.3390/medicina57030282 ◽

2021 ◽

Vol 57 (3) ◽

pp. 282

Author(s):

Justinas Vaitkus ◽

Astra Vitkauskienė ◽

Regimantas Simuntis ◽

Žygimantas Vaitkus ◽

Nora Šiupšinskienė ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Inflammatory Markers ◽

Nasal Polyps ◽

Clinical Symptoms ◽

Age Groups ◽

Magnetic Bead ◽

Control Group ◽

Control Subjects ◽

Nasal Tissue ◽

And Control

Background and objectives: The aim of our study was to analyze the concentrations of inflammatory markers in the nasal tissue of patients with chronic rhinosinusitis with nasal polyps (CRSwNPs) and controls of different age groups, as well as to find associations between age, inflammation development, and NPs. Materials and methods: Patients were divided into two groups—patients with CRSwNPs and control subjects who had nasal surgery for another reason beside CRS. Our analysis was performed across three different age groups (18–30 years, 31–50 years, and 51 years and more). Tissue biopsies from the sinus cavity for all study participants were taken and frozen at −80 °C, until use. The concentrations of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-13, IL-21, and IL-22, were quantified using a magnetic bead-based multiplex assay. Results: In the group aged 18–30 years, the levels of inflammatory markers IL-1, IL-2, IL-5, and IL-22 were significantly higher in patients with CRSwNPs than the control subjects. Among patients aged 31–50 years, significantly higher concentrations of IL-2, IL-4, IL-5, and IL-22 were recorded in patients with CRSwNPs, as compared to the control subjects. In the oldest group (aged 51 years and more), patients with CRSwNPs had significantly higher concentrations of IL-2, IL-4, and IL-22, as compared to the control group. In the CRSwNP group, only the concentration of IL-21 was significantly higher among patients aged 31–50 years, as compared with those aged 51 years and older (p = 0.013). Conclusions: IL-2 and IL-22 levels were significantly higher in patients with CRSwNP than the control, across all age groups. Only the concentration of IL-21 was higher among patients with CRSwNP in the middle age group, as compared to the oldest group. IL-2, IL-4, and IL-22 levels correlated with the severity of CRSwNPs. Elevated concentrations of IL-2, IL-4, and IL-22 were determined in patients’ groups with higher sinonasal outcome test (SNOT-22) scores, pointing to more severe clinical symptoms.

Download Full-text

Comparative analysis of cutaneous bacterial communities of farmed Rana dybowskii after gentamycin bath

PeerJ ◽

10.7717/peerj.8430 ◽

2020 ◽

Vol 8 ◽

pp. e8430

Author(s):

Jia Bie ◽

Qing Tong ◽

Xiaoning Liu ◽

Xianhao Zhang ◽

Hongbin Wang

Keyword(s):

Bacterial Community ◽

Beta Diversity ◽

Pathogenic Bacteria ◽

High Throughput Sequencing ◽

Recovery Period ◽

Alpha Diversity ◽

Community Diversity ◽

Control Group ◽

Rrna Gene ◽

Rana Dybowskii

Introduction Pathogenic bacteria limit the success of Rana dybowskii breeding. Gentamicin is used to treat R. dybowskii disease. To understand the effects of gentamicin on the composition and structure of the cutaneous bacterial community of R. dybowskii, three groups (control, gentamicin and recovery) were established in this study. Materials & Methods The V3–V4 hypervariable region of the 16S rRNA gene was analyzed in samples by high-throughput sequencing. Alpha diversity and beta diversity were evaluated to compare the cutaneous bacterial community diversity. Results A total of 1,159,668 valid sequences and 3,132 operational taxonomic units (OTUs) were obtained from these three experimental groups. The number of OTUs obtained in the control group, gentamicin group and recovery group were 2,194, 2,288, and 2,047, respectively, and the number of shared OTUs was 1,313. The alpha diversity of the cutaneous bacterial community was not significantly affected by gentamicin, while beta diversity was significantly affected. Discussion & Conclusions The effect of a gentamicin bath on relative species abundance was greater than the effect on the species composition. The changes in Proteobacteria, Acinetobacter, and Chryseobacterium were significant, and reductions were observed after the recovery period. Six potentially pathogenic genera were detected, including Aeromonas, Citrobacter, Chryseobacterium, Pseudomonas, Staphylococcus, and Streptococcus. Among them, Aeromonas and Chryseobacterium were significantly inhibited by the gentamicin bath. The results of this study provide a theoretical basis for the application of gentamicin in R. dybowskii breeding.

Download Full-text

A case–control study on the association of intestinal flora with ulcerative colitis

AMB Express ◽

10.1186/s13568-021-01267-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yin-hua Tang ◽

Hong-cheng Liu ◽

Guang Song ◽

Tian-tian Wu ◽

Ying Zhao ◽

...

Keyword(s):

Ulcerative Colitis ◽

Pathogenic Bacteria ◽

Intestinal Flora ◽

16S Rrna Gene Sequencing ◽

Control Group ◽

Rrna Gene ◽

Healthy Controls ◽

Fecal Samples ◽

Healthy Control ◽

Rrna Gene Sequencing

AbstractThe association between intestinal flora and ulcerative colitis (UC) was studied in order to provide a basis and method for clinical treatment. Fresh fecal samples were collected from 30 active UC patients and 10 healthy controls. The intestinal flora DNA from each sample was extracted and 16S rRNA gene sequencing was carried out using HiSeq platform to identify the intestinal flora in fecal samples. The richness and diversity of intestinal flora in UC patients were significantly lower than those in healthy control group (P < 0.05). Significant differences were observed between the intestinal flora-species of UC patients and healthy controls. Synergistetes (P < 0.01) and Firmicutes (P < 0.05), along with probiotics Veillonella (P < 0.01), Ruminococcus and Coprococcus (P < 0.05) in the UC patients were lower than that in the healthy controls significantly. Furthermore, compared with the control group, Tenericutes (P < 0.01) and intestinal pathogenic bacteria, including Bacteroides (P < 0.01), Escherichia and Sutterella (P < 0.05) were significantly increased. The incidence of UC is significantly associated with the changes in intestinal flora. Changes in intestinal flora may lead to a decrease in the diversity of intestinal flora or to the enrichment of a particular intestinal flora.

Download Full-text

Circulating tumour DNA methylation in hepatocellular carcinoma diagnosis using digital droplet PCR

Journal of International Medical Research ◽

10.1177/0300060521992962 ◽

2021 ◽

Vol 49 (3) ◽

pp. 030006052199296

Author(s):

Juan Wang ◽

Liu Yang ◽

Yanjun Diao ◽

Jiayun Liu ◽

Jinjie Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Dna Methylation ◽

Likelihood Ratio ◽

Predictive Value ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Control Group ◽

Control Subjects ◽

Droplet Pcr ◽

Healthy Control

Objective To evaluate the performance of a DNA methylation-based digital droplet polymerase chain reaction (ddPCR) assay to detect aberrant DNA methylation in cell-free DNA (cfDNA) and to determine its application in the detection of hepatocellular carcinoma (HCC). Methods The present study recruited patients with liver-related diseases and healthy control subjects. Blood samples were used for the extraction of cfDNA, which was then bisulfite converted and the extent of DNA methylation quantified using a ddPCR platform. Results A total of 97 patients with HCC, 80 healthy control subjects and 46 patients with chronic hepatitis B/C virus infection were enrolled in the study. The level of cfDNA in the HCC group was significantly higher than that in the healthy control group. For the detection of HCC, based on a cut-off value of 15.7% for the cfDNA methylation ratio, the sensitivity and specificity were 78.57% and 89.38%, respectively. The diagnostic accuracy was 85.27%, the positive predictive value was 81.91% and the negative predictive value was 87.20%. The positive likelihood ratio of 15.7% in HCC diagnosis was 7.40, while the negative likelihood ratio was 0.24. Conclusions A sensitive methylation-based assay might serve as a liquid biopsy test for diagnosing HCC.

Download Full-text

Expression of Transcript Variants of PTGS1 and PTGS2 Genes among Patients with Chronic Rhinosinusitis with Nasal Polyps

Diagnostics ◽

10.3390/diagnostics11010135 ◽

2021 ◽

Vol 11 (1) ◽

pp. 135

Author(s):

Wioletta Pietruszewska ◽

Wojciech Fendler ◽

Marta Podwysocka ◽

Adam J. Białas ◽

Piotr Kuna ◽

...

Keyword(s):

Healthy Volunteers ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Direct Sequencing ◽

Adult Patients ◽

Control Group ◽

Reliable Test ◽

Aggressive Disease ◽

Transcript Variants

To date, there has been no reliable test to identify unfavorable course of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), especially in aspirin intolerant patients. The research aimed to analyze the expression of transcript variants of PTGS1 and PTGS2 genes in the pathobiology of the disease. The study was performed on 409 adult patients: 206 CRSwNP patients including 44 (21.36%) aspirin intolerant patients and 203 healthy volunteers in the control group. Transcript variants of the PTGS1 and PTGS2 genes named as follows: COX1.1 for NM_000962, COX1.2 for NM_080591, COX1.3 for NM_001271165.1, COX1.4 for NM_001271368.1, COX1.5 for NM_001271166.1, COX2.1 for NM_000963.3, COX2.2 for AY_151286 and COX2.3 for BQ_722004 were confirmed using direct sequencing and quantified using targeted qPCR. The coexistence of all examined transcript variants in the study and the control group and significant differences between both were found. In aspirin sensitive patients, the levels of COX1.2, COX1.3, COX1.4 and COX1.5 isoforms were higher compared to aspirin-tolerant patients. The severity of symptoms was bigger in patients with higher expressions of variants: COX1.1 (R with dCt = −0.134; p = 0.0490), COX1.3 (R = −0.1429; p = 0.0400) and COX1.5 (Rs = −0.1499; p = 0.032). The expression of COX1.1 (Rs = −0.098; p = 0.049) and COX1.5 (Rs = −0.141; p = 0.043) isoforms increased with polyposis advancement in endoscopy. With the CT extent of sinuses opacification, COX1.1 isoform also significantly increased (Rs = −0.163; p = 0.020). The isoforms COX1.3, COX1.4, COX1.5 and COX2.1 may promote milder CRSwNP course. On the contrary, the variants COX1.1, COX1.2 and COX2.2 may be involved in a more aggressive disease.

Download Full-text

Characterization of Cytokines and Proliferation Marker Ki67 in Chronic Rhinosinusitis with Nasal Polyps: A Pilot Study

Medicina ◽

10.3390/medicina57060607 ◽

2021 ◽

Vol 57 (6) ◽

pp. 607

Author(s):

Rudolfs Janis Viksne ◽

Gunta Sumeraga ◽

Mara Pilmane

Keyword(s):

Connective Tissue ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Cellular Proliferation ◽

Rank Correlation ◽

Control Group ◽

Relative Distribution ◽

Proliferation Marker ◽

Ki 67 ◽

Stimulation Of

Background and Objectives: Chronic rhinosinusitis (CRS) is a condition that affects as much as 10.9% of the population and, along with presence of nasal polyps, is associated with significant morbidity and decreased quality of life. Studies on molecular pathways that have been activated in nasal polyp tissue are mainly based on cytokine concentration detection. Therefore, our aim is to investigate the complex appearance, relative distribution and interlinks of IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 and Ki 67 in chronic rhinosinusitis with nasal polyps (CRSwNP) affected human nasal mucosa. Materials and Methods: Samples of nasal polyps were obtained from 12 patients with previously diagnosed CRSwNP and no prior surgery. Control group consisted of samples from 17 otherwise healthy individuals with isolated nasal septum deviation. Tissues were stained for IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 and Ki67 immunohistochemically. Non-parametric statistic, Mann–Whitney U test and Spearman’s rank correlation coefficient were used. Results: All factors, except connective tissue cytokine IL-10 and proliferation marker Ki-67, had increased presence in connective tissue and decreased presence in epithelium of nasal polyps when compared to controls. Very strong and strong positive correlations between factors were observed. Conclusions: Decreased appearance of IL-1α, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 positive structures in the nasal epithelium with selective increase of IL-1α and IL-12 in nasal subepithelial connective tissue characterize the cytokine endotype with dysfunctional epithelial barrier and local stimulation of immune response in the connective tissue in case of chronic rhinosinusitis with polyps. Decrease of IL-6 in both—epithelium and connective tissue with strong correlation between it and IL-7 and IL-10 in connective tissue suggests significant stimulation of this regulatory cytokine and, possibly, the important role in pathogenesis of the development in nasal polyps. Correlations between Ki67 and cytokines indicate possible involvement of IL-4, IL-7 and IL-12 in regulation of cellular proliferation.

Download Full-text

Association between obesity and chronic rhinosinusitis with nasal polyps: a national population-based study

BMJ Open ◽

10.1136/bmjopen-2020-047230 ◽

2021 ◽

Vol 11 (5) ◽

pp. e047230

Author(s):

Jae-Sung Nam ◽

Yun Ho Roh ◽

Wasan Almazouq Fahad ◽

Hae-Eun Noh ◽

Jong-Gyun Ha ◽

...

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Chronic Rhinosinusitis ◽

Logistic Regression Analysis ◽

Central Obesity ◽

Nasal Polyps ◽

Control Group ◽

Cross Sectional ◽

Cross Sectional Analysis ◽

Sectional Analysis

ObjectivesWe performed a cross-sectional analysis of data from the nationwide Korea National Health and Nutrition Examination Survey to evaluate the association between obesity and chronic rhinosinusitis with nasal polyps (CRSwNP) or without nasal polyp (CRSsNP).DesignRetrospective cross-sectional analysis of health survey data.SettingVoluntary survey of representative South Korean populations.ParticipantsIn total, 32 384 individuals aged 19 years or older with available data on CRS and obesity were included.Primary and secondary outcome measuresDiagnosis of CRSwNP or CRSsNP was performed by trained otolaryngologists through sinus endoscopy and surveys of medical history. General and central obesity was diagnosed using body mass index (BMI) and waist circumference (WC), respectively.MethodsA multivariate logistic regression analysis was used to clarify the association between CRSwNP or CRSsNP and obesity according to BMI and WC. Non-obese individuals were recruited as controls.ResultsThe prevalence of CRSwNP was higher in the general (OR, 1.438; 95% CI, 1.170 to 1.768; p<0.001) and central (OR, 1.251; 95% CI, 1.031 to 1.520; p=0.033) obesity groups than in the control group. Prevalence of CRSsNP was not correlated with obesity. In a logistic regression analysis, olfactory dysfunction (OR, 1.329; 95% CI, 1.137 to 1.553; p<0.001) and purulent discharge (OR, 1.383; 95% CI, 1.193 to 1.603; p<0.001) showed a higher incidence in the central obesity group than in the control group.ConclusionsWe demonstrated an association between CRSwNP and general and central obesity. Further investigations on the mechanism underlying this correlation are necessary for an improved understanding of the pathogenesis of CRSwNP.

Download Full-text

CD133, a Progenitor Cell Marker, is Reduced in Nasal Polyposis and Showed Significant Correlations with TGF-β1 and IL-8

International Archives of Otorhinolaryngology ◽

10.1055/s-0041-1726043 ◽

2021 ◽

Author(s):

Wagner Vargas Souza Lino ◽

André Luis Lacerda Bachi ◽

José Arruda Mendes Neto ◽

Gabriel Caetani ◽

Jônatas Bussador do Amaral ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Nasal Polyposis ◽

Transforming Growth Factor ◽

Middle Turbinate ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Histologic Analysis ◽

Aspirin Intolerance ◽

Tgf Β1

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.

Download Full-text

JAK2 Phosphorylation Signals and Their Associated Cytokines Involved in Chronic Rhinosinusitis with Nasal Polyps and Correlated with Disease Severity

Biomolecules ◽

10.3390/biom11071059 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1059

Author(s):

Yu-Tsai Lin ◽

Wei-Chih Chen ◽

Ming-Hsien Tsai ◽

Jing-Ying Chen ◽

Chih-Yen Chien ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Disease Severity ◽

Nasal Polyps ◽

Inflammatory Diseases ◽

Janus Kinase ◽

Sinus Surgery ◽

Control Group ◽

Jak2 Inhibitor ◽

Ifn Γ ◽

Snot 22

Janus kinase 2 (JAK2) is a member of the JAK family that transduces cytokine-mediated signals via the JAKs/STATs (signal transducer and activator of transcription proteins) pathway, which plays an important role in many inflammatory diseases. This study investigates the association of p-JAK2 and JAK2-associated cytokines from nasal polyp (NP) tissue with disease severity, and evaluates the p-JAK2-mediated STATs in chronic rhinosinusitis (CRS) with NP. Sixty-one CRSwNP patients with nasal polyps undergoing endoscopic sinus surgery were enrolled, while the turbinate tissues from 26 nasal obstruction patients were examined as the control group. Elevated levels of p-JAK2 were detected in CRSwNP, and significantly correlated with scores of disease severity (LMK-CT, TPS, and SNOT-22). Expressions of the JAK2-associated cytokines, such as IL-5, IL-6, IL-13, G-CSF, and IFN-γ were significantly higher in CRSwNP than in the controls, while the levels of IL-5, IL-6, IL-13, or G-CSF had positive correlation with scores of disease severity. Moreover, markedly increased expression of p-STAT3 in CRSwNP was observed relative to the control. Taken together, these data showed that the JAK2-associated cytokines including IL-6 and G-CSF may stimulate JAK2 phosphorylation to activate p-STAT3, indicating an association with disease severity and supporting its development of JAK2 inhibitor as a potential therapeutic agent for CRS.

Download Full-text

Nrf2 Dysregulation in Major Depressive and Bipolar Disorders

Galen Medical Journal ◽

10.31661/gmj.v10i0.2074 ◽

2021 ◽

Vol 10 ◽

pp. e2074

Author(s):

Maryam Ghanbarirad ◽

Mehrdad Hashemi ◽

Seyed Mehdi Saberi ◽

Ahmad Majd

Keyword(s):

Mental Disorders ◽

Defense Mechanisms ◽

Bipolar Disorders ◽

Expression Level ◽

Control Group ◽

Roc Curve Analysis ◽

Major Depressive ◽

Control Subjects ◽

Healthy Control ◽

Nrf2 Expression

Background: Major depressive disorder (MDD) and bipolar disorder (BPD) are two of the most important mental disorders that greatly impact different aspects of life. These conditions imply heavy health and economic burden and are heterogeneous in nature. Inflammation is reported as the etiology of mental disorders. Nrf2 transcription factor plays a key role in the defense mechanisms against inflammation and oxidative stress. So, this study aimed to evaluate the expression level of Nrf2 in MDD and BPD patients and compared it with healthy control subjects. Materials and Methods: In this study, real-time PCR was conducted to evaluate the expression level of Nrf2 in 100 MDD and 100 BPD patients compared to 100 healthy control subjects. Statistical analysis conducted on GraphPad Prism 8 and SPSS21 included ANOVA, Tukey’s test, receiver operating characteristic (ROC), and odds ratio. Results: Results suggest a significant downregulation of Nrf2 in these conditions compared to the control group. ROC curve analysis demonstrates Nrf2 as a biomarker of these psychiatric disorders. Conclusion: The elevated levels of reactive oxygen species and downregulation of detoxifying enzymes were observed in MDD and BPD, which can be associated with the downregulation of Nrf2. Concerning its role in inflammatory response pathways, alternation of Nrf2 expression can be associated with the pathology of these conditions.

Download Full-text