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FEBS Open Bio May 2020Adenoidal hypertrophy (AH) is a common disorder in the pediatric population, with common symptoms including mouth breathing, nasal congestion, hyponasal speech, snoring...
Adenoidal hypertrophy (AH) is a common disorder in the pediatric population, with common symptoms including mouth breathing, nasal congestion, hyponasal speech, snoring and obstructive sleep apnea. Although the pathogenesis of AH has not been fully elucidated, recent studies have indicated that immune responses may play an important role in AH. Tumor necrosis factor-alpha (TNF-α)-induced protein-8 like-2 (TIPE2) is a newly identified protein that negatively regulates the activation of inflammatory pathways. Here, we investigated the effect of TIPE2 in AH in children. We observed that the levels of TNF-α and interleukin-6 were greater in the adenoid tissue of AH children than in healthy control subjects (P < 0.01), and this increase was positively correlated with the severity of AH. The level of TIPE2 expression was decreased compared with control and was negatively correlated with AH. TIPE2 overexpression in primary human monocytes (isolated from adenoid tissue of children with AH) inhibited the activation of nuclear factor-κB and the expression of TNF-α and interleukin-6. These results suggest that overexpression of TIPE2 may attenuate AH through inactivation of the nuclear factor-κB signaling pathway.
Topics: Adenoids; Child; Child, Preschool; China; Female; Humans; Hypertrophy; Inflammation; Interleukin-6; Intracellular Signaling Peptides and Proteins; Male; Monocytes; RNA, Messenger; Signal Transduction; Tumor Necrosis Factor-alpha
PubMed: 32100476
DOI: 10.1002/2211-5463.12821 -
The Pediatric Infectious Disease Journal May 2015The incidence of necrotizing pneumococcal pneumonia has increased during the past 2 decades. We hypothesized that increased pneumococcal load or augmented inflammatory...
BACKGROUND
The incidence of necrotizing pneumococcal pneumonia has increased during the past 2 decades. We hypothesized that increased pneumococcal load or augmented inflammatory cytokine production might lead to destructive pneumococcal lung disease.
METHODS
This study enrolled prospectively 0- to 18-year-old children with a diagnosis of community-acquired pneumonia with pleural effusion admitted to 6 medical centers from March 2010 to April 2012. Children were diagnosed with pneumococcal empyema if the pleural fluid tested positive for quantitative pneumococcal (lytA) detection by real-time polymerase chain reaction. Pneumococcal empyema cases were further divided into 4 groups according to necrosis severity: (0) nonnecrosis, (1) mild necrosis, (2) cavitation and (3) bronchopleural fistula. Nasopharyngeal and pleural pneumococcal load, as well as levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8), Th1-(IL-2, IFN-γ), Th2-(IL-4, IL-10) and Th17-cytokines (IL-17), in the pleural fluid was measured.
RESULTS
Serotypes 19A and 3 accounted for 69.4% and 12.5%, respectively, of 72 cases of pneumococcal empyema. Pleural pneumococcal load was significantly higher in serotypes 19A and 3 infection than in the other strains causing infection (P = 0.006). There was a correlation between nasopharyngeal and pleural pneumococcal load (ρ = 0.35; P = 0.05). In multivariate ordinal logistic regression analysis, pleural pneumococcal load (adjusted odds ratio: 1.79; 95% confidence interval: 1.03-3.06) and IL-8 (adjusted odds ratio: 2.64; 95% confidence interval: 1.21-5.75) were independent factors associated with the severity of lung necrosis.
CONCLUSIONS
Evolution of Streptococcus pneumoniae toward increased fitness in their interaction with host and exaggerated IL-8 expression may be responsible for the increase of necrotizing pneumococcal pneumonia.
Topics: Analysis of Variance; Bacterial Load; Cytokines; Empyema; Humans; Incidence; Lung; Nasopharynx; Necrosis; Pneumonia, Pneumococcal; Prospective Studies; Radiography; Streptococcus pneumoniae
PubMed: 25461475
DOI: 10.1097/INF.0000000000000631 -
The Laryngoscope Aug 2021The routine practices of examining submucosal lesions are not suitable for deep lesions. Therefore, we evaluated the efficacy of non-real-time image-guided transnasal...
OBJECTIVES/HYPOTHESIS
The routine practices of examining submucosal lesions are not suitable for deep lesions. Therefore, we evaluated the efficacy of non-real-time image-guided transnasal endoscopic fine-needle aspiration biopsy (FNAB) in diagnosing nasopharyngeal carcinoma (NPC) with submucosal lesions.
STUDY DESIGN
The effectiveness evaluation of diagnostic methods.
METHODS
Fifty suspected NPC patients who failed in conventional biopsies were enrolled in this study. The efficacy, maneuverability, and safety of FNAB in diagnosing these intractable cases were evaluated.
RESULTS
The definitive diagnostic results of these 50 patients were NPC (34/50, 68.0%), nasopharyngeal necrosis (1/50, 2.0%), nasopharyngeal mucositis (12/50, 24.0%), and other cancers (3/50, 6.0%), respectively. The results of the diagnostic efficacy of FNAB were sensitivity, 89.2%; specificity, 100.0%; positive predictive value, 100.0%; negative predictive value, 76.5%; and accuracy, 92.0%, respectively. The area under the receiver operating characteristic curves was 0.946 (95% confidence interval = 0.884-1.00, P < .001). No severe complications occurred after FNAB.
CONCLUSIONS
FNAB can improve the diagnostic efficiency of NPC occurring in the submucosal space. It can be an additional option for routine nasopharyngeal biopsy and is worthy of clinical application.
LEVEL OF EVIDENCE
4 Laryngoscope, 131:1798-1804, 2021.
Topics: Adult; Aged; Aged, 80 and over; Biopsy, Fine-Needle; Endoscopy; Female; Humans; Image-Guided Biopsy; Male; Middle Aged; Nasal Mucosa; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharynx; Predictive Value of Tests; ROC Curve; Young Adult
PubMed: 33616259
DOI: 10.1002/lary.29433 -
Clinical Laboratory Jan 2019We aimed to investigate the frequency of fibronectin binding protein (FBP), which is part of the first step of adhesion, and Panton-Valentine leukocidin (PVL) toxin,...
Investigation of Fibronectin Binding Protein (FBP) and Panton Valentine Leukocidin (PVL) Viulance Factors in Clinical Methicillin Sensitive and Resistant Staphylococcus Aureus Strains.
BACKGROUND
We aimed to investigate the frequency of fibronectin binding protein (FBP), which is part of the first step of adhesion, and Panton-Valentine leukocidin (PVL) toxin, which contributes to the destruction of host leukocytes and tissue necrosis, in clinical S. aureus strains.
METHODS
One hundred S. aureus strains were included in the study and distributed as follows; 33 from skinwound swabs and catheter tips (SWCT), 33 from body fluid and secretion specimens (BSFS) such as tracheal aspirate, sputum, and pleural effusion fluid, 18 from tissue biopsy specimens (TBS), 10 specimens from blood, and related specimens (BRS) such as bone marrow, and cerebral spinal fluid, and six specimens from mucosal membrane of pharynx, nose, and vagina (MMS). Methicillin resistance was tested by disk diffusion method. mecA (methicillin resistance coded gene), pvl and fnbA genes were investigated by using a PCR method.
RESULTS
Thirty-seven strains (37.0%) were identified as methicillin resistant S. aureus (MRSA) and 63 (63.0%) as methicillin susceptible S. aureus (MSSA) strains. fnbA was more frequent in S. aureus isolates of MMSs (100.0%); followed by BRSs (80.0%), SWCTs (78.8%), TBS (72.3%), and BSFs (66.7%), whereas pvl gene was more frequent in isolates of BRS (60.0%), followed by TBSs (50.0%), SWCTs (33.4%), BSFs (30.3%), and MMSs (16.7%). fnbA existed in 85.7% of MSSA and 56.8% of MRSA in contrast to pvl, which was more frequent in MRSA (70.3%) than those of MSSA strains (17.4%). These differences were statistically significant (p < 0.05).
CONCLUSIONS
Our different clinical specimens contained a high rate of fnbA (75.0%) and low-moderate frequency of pvl (37.0%). fnbA was most frequent in S. aureus of MMSs, followed by BRSs, and SWCTs, whereas pvl was ex-isted in high proportion in S. aureus of BRSs, followed by TBSs, and SWCTs. Presence of PVL in a high proportion in MRSA strains of superfical specimens such SWCT (24.4%) and deeper serious specimens such as BRS (16.3%) compared to MSSA strains from the same specimens, 3.2% and 0%, respectively, have shown that MRSA infections still threatens patients' lives and control of their spread is urgently needed.
Topics: Adhesins, Bacterial; Bacterial Proteins; Bacterial Toxins; Drug Resistance, Microbial; Exotoxins; Humans; Leukocidins; Methicillin; Methicillin-Resistant Staphylococcus aureus; Penicillin-Binding Proteins; Staphylococcal Infections; Virulence Factors
PubMed: 30775902
DOI: 10.7754/Clin.Lab.2018.180625 -
Brazilian Journal of Otorhinolaryngology 2020Obstrutive sleep apnea syndrome is characterized by repeated episodes of upper airway obstruction, associated with intermittent hypoxia and hypercapnia, and the main...
INTRODUCTION
Obstrutive sleep apnea syndrome is characterized by repeated episodes of upper airway obstruction, associated with intermittent hypoxia and hypercapnia, and the main risk factor in childhood is adenotonsillar hypertrophy. The lymphocytes in these structures are responsible for local and systemic immune responses.
OBJECTIVE
Verify the levels of the inflammatory markers, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, CRP and α1-GP, in the tonsils of children with and without obstructive sleep apnea syndrome.
METHODS
This cross-sectional prospective study included 34 children with complains of snoring, difficulty breathing during sleep or recurrent tonsillitis. Patients underwent to a complete otorhinolaryngological examination, nasal endoscopy and polysomnography and were divided into two groups with 17 children each: obstructive sleep apnea syndrome group and control group. All underwent an adenotonsillectomy. Cytokines were measured in the collected tonsils (ELISA and Multiplex methods).
RESULTS
Statistically significant increasing were observed between IL-8 and IL-10 cytokines of patients with obstructive sleep apnea when compared to the control group; also between c-reactive protein and α1-GP of the tonsils cortical region in children with obstructive sleep apnea syndrome when compared with the medullary region. There were no statistically significant differences for the remaining inflammatory mediators.
CONCLUSION
After the analysis of the levels of pro and anti-inflammatory markers (IL-1β, IL-4, IL-6, IL-8, IL-10, Il-15, TNF-α, CRP, α1-GP) in the tonsils, we observed higher levels of markers IL-8 and IL-10 in pediatric patients with obstructive sleep apnea syndrome.
Topics: Biomarkers; C-Reactive Protein; Child; Child, Preschool; Cross-Sectional Studies; Cytokines; Female; Humans; Inflammation; Interleukins; Male; Orosomucoid; Palatine Tonsil; Prospective Studies; Sleep Apnea, Obstructive; Tonsillectomy; Tumor Necrosis Factor-alpha
PubMed: 30213594
DOI: 10.1016/j.bjorl.2018.08.001 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Dec 2023To explore the mechanism of in treatment of Alzheimer's Disease (AD).
OBJECTIVES
To explore the mechanism of in treatment of Alzheimer's Disease (AD).
METHODS
The active ingredients and targets of for treatment of AD were screened with network pharmacology methods, the protein-protein interaction (PPI) network was constructed and the core targets were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriching analysis was performed. The peripheral blood lymphocytes were extracted and lymphoblastoid cell lines (LCL) were constructed and an cell model of LCL-SKNMC was established. MTT and CCK-8 methods were used to quantify SKNMC/LCL cells, 2 ´, 7 ´-dichlorodihydrofluorescein diacetate (DCFH-DA) probe was used to detect reactive oxygen species (ROS), and immunofluorescence staining was used to detect the generation of Aβ in a co-cultured model. Western blotting was used to detect protein expression in the co-culture model. The lifespan of N2 nematodes was observed under oxidative stress, normal state, and heat stress; ROS generated by N2 nematodes was detected by DCFH-DA probes. The paralysis time of CL4176 N2 nematodes was evaluated by paralysis assay, and Aβ deposition in the pharynx was detected by Thioflavin S staining.
RESULTS
Through network pharmacology, 15 potential active ingredients and 103 drug-disease targets were identified. PPI analysis showed that the might play anti-AD roles through albumin, Akt1, tumor necrosis factor, epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), mammalian target of rapamycin (mTOR), amyloid precursor protein (APP) and other related targets. KEGG analysis showed that the pharmacological effects of might involve the biological processes of Alzheimer's disease, endocrine resistance, insulin resistance; and neuroactive ligand-receptor interaction, phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, calcium signaling pathway, AGE-RAGE signaling pathway in diabetes complications, neurotrophic factor signaling pathway and others. The cell experiments showed that was able to reduce the production of ROS and Aβ (both <0.01), inhibit the expression of β-secretase 1 (BACE1), APP and Aβ proteins (all <0.05), up-regulate the expression of p-PI3K/PI3K, p-AKT/AKT, p-GSK3β/GSK3β in SKNMC cells (all <0.05). The studies further confirmed that prolonged the lifespan of under stress and normal conditions, reduced the accumulation of ROS and the toxicity of Aβ deposition.
CONCLUSIONS
may reduce the production of Aβ in AD and inhibit its induced oxidative stress, which may be achieved by regulating the PI3K/Akt/GSK-3β pathway.
Topics: Animals; Alzheimer Disease; Amyloid Precursor Protein Secretases; Drugs, Chinese Herbal; Glycogen Synthase Kinase 3 beta; Proto-Oncogene Proteins c-akt; Vascular Endothelial Growth Factor A; Caenorhabditis elegans; Network Pharmacology; Phosphatidylinositol 3-Kinases; Reactive Oxygen Species; Aspartic Acid Endopeptidases; Amyloid beta-Protein Precursor; Paralysis; Mammals; Fluoresceins
PubMed: 38105702
DOI: 10.3724/zdxbyxb-2023-0362 -
Ear, Nose, & Throat Journal 2019
Review
Topics: Acetaminophen; Administration, Intranasal; Cicatrix; Debridement; Dysphonia; Female; Humans; Larynx; Middle Aged; Nasal Cartilages; Nasopharynx; Necrosis; Substance-Related Disorders; Trachea; Vocal Cords
PubMed: 30939912
DOI: 10.1177/0145561319836807 -
The Annals of Otology, Rhinology, and... Jul 2020Surgical procedure is considered in patients with severe dysphagia when conservative treatment fails. This study aimed to evaluate laryngeal suspension (LS) and upper...
OBJECTIVES
Surgical procedure is considered in patients with severe dysphagia when conservative treatment fails. This study aimed to evaluate laryngeal suspension (LS) and upper esophageal sphincter (UES) myotomy for treating severe dysphagia due to brain disease.
METHODS
Fourteen patients underwent LS and UES myotomy, with a median follow-up of 5 years and 6 months when conservative treatment failed. The penetration-aspiration scale (PAS), the Dysphagia Severity Scale (DSS), the Eating Status Scale (ESS), and diet contents were evaluated just before surgery, at discharge, and at the last follow-up.
RESULTS
Preoperative intake was tube feeding in all patients. The patients learned the extended head and flexed neck posture to open the esophageal inlet. PAS, DSS and ESS scores, and diet contents were significantly improved at discharge compared with before surgery, and were maintained until the last follow-up. Eight patients had pneumonia during their hospital stay, and five had pneumonia between discharge and at the last follow-up. Age was significantly, negatively correlated with DSS and ESS at the last follow-up.
CONCLUSION
Although LS and UES myotomy require a long inpatient rehabilitation and the risk of pneumonia after surgery is high, the outcome is favorable and the effects last for a long time.
Topics: Aged; Cerebellar Neoplasms; Cerebral Hemorrhage; Cerebral Infarction; Deglutition Disorders; Enteral Nutrition; Esophageal Sphincter, Upper; Female; Hemangioblastoma; Humans; Laryngoplasty; Larynx; Lateral Medullary Syndrome; Male; Middle Aged; Myotomy; Severity of Illness Index; Subarachnoid Hemorrhage; Treatment Outcome
PubMed: 32037848
DOI: 10.1177/0003489420904741 -
Experimental Cell Research Aug 2014Acute liver failure, the fatal deterioration of liver function, is the most common indication for emergency liver transplantation, and drug-induced liver injury and...
Acute liver failure, the fatal deterioration of liver function, is the most common indication for emergency liver transplantation, and drug-induced liver injury and viral hepatitis are frequent in young adults. Stem cell therapy has come into the limelight as a potential therapeutic approach for various diseases, including liver failure and cirrhosis. In this study, we investigated therapeutic effects of tonsil-derived mesenchymal stem cells (T-MSCs) in concanavalin A (ConA)- and acetaminophen-induced acute liver injury. ConA-induced hepatitis resembles viral and immune-mediated hepatic injury, and acetaminophen overdose is the most frequent cause of acute liver failure in the United States and Europe. Intravenous administration of T-MSCs significantly reduced ConA-induced hepatic toxicity, but not acetaminophen-induced liver injury, affirming the immunoregulatory capacity of T-MSCs. T-MSCs were successfully recruited to damaged liver and suppressed inflammatory cytokine secretion. T-MSCs expressed high levels of galectin-1 and -3, and galectin-1 knockdown which partially diminished interleukin-2 and tumor necrosis factor α secretion from cultured T-cells. Galectin-1 knockdown in T-MSCs also reversed the protective effect of T-MSCs on ConA-induced hepatitis. These results suggest that galectin-1 plays an important role in immunoregulation of T-MSCs, which contributes to their protective effect in immune-mediated hepatitis. Further, suppression of T-cell activation by frozen and thawed T-MSCs implies great potential of T-MSC banking for clinical utilization in immune-mediated disease.
Topics: Adult; Animals; Blotting, Western; Cell Proliferation; Cell- and Tissue-Based Therapy; Cells, Cultured; Chemical and Drug Induced Liver Injury; Concanavalin A; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Galectin 1; Hepatocytes; Humans; Immunoenzyme Techniques; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Mitogens; Palatine Tonsil; RNA, Messenger; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes
PubMed: 24954408
DOI: 10.1016/j.yexcr.2014.06.007 -
Journal of Advanced Research Jan 2022Honokiol (HO) exerts neuroprotective effects in several animal models of Alzheimer's disease (AD), but the poor dissolution hampers its bioavailability and therapeutic...
INTRODUCTION
Honokiol (HO) exerts neuroprotective effects in several animal models of Alzheimer's disease (AD), but the poor dissolution hampers its bioavailability and therapeutic efficacy.
OBJECTIVES
A novel honokiol nanoscale drug delivery system (Nano-HO) with smaller size and excellent stability was developed in this study to improve the solubility and bioavailability of HO. The anti-AD effects of Nano-HO was determined.
METHODS
Male TgCRND8 mice were daily orally administered Nano-HO or HO at the same dosage (20 mg/kg) for 17 consecutive weeks, followed by assessment of the spatial learning and memory functions using the Morris Water Maze test (MWMT).
RESULTS
Our pharmacokinetic study indicated that the oral bioavailability was greatly improved by Nano-HO. In addition, Nano-HO significantly improved cognitive deficits and inhibited neuroinflammation via suppressing the levels of TNF-α, IL-6 and IL-1β in the brain, preventing the activation of microglia (IBA-1) and astrocyte (GFAP), and reducing β-amyloid (Aβ) deposition in the cortex and hippocampus of TgCRND8 mice. Moreover, Nano-HO was more effective than HO in modulating amyloid precursor protein (APP) processing via suppressing β-secretase, as well as enhancing Aβ-degrading enzymes like neprilysin (NEP). Furthermore, Nano-HO more markedly inhibited tau hyperphosphorylation via decreasing the ratio of p-Tau (Thr 205)/tau and regulating tau-related apoptosis proteins (caspase-3 and Bcl-2). In addition, Nano-HO more markedly attenuated the ratios of p-JNK/JNK and p-35/CDK5, while enhancing the ratio of p-GSK-3β (Ser9)/GSK-3β. Finally, Nano-HO prevented the gut microflora dysbiosis in TgCRND8 mice in a more potent manner than free HO.
CONCLUSION
Nano-HO was more potent than free HO in improving cognitive impairments in TgCRND8 mice via inhibiting Aβ deposition, tau hyperphosphorylation and neuroinflammation through suppressing the activation of JNK/CDK5/GSK-3β signaling pathway. Nano-HO also more potently modulated the gut microbiota community to protect its stability than free HO. These results suggest that Nano-HO has good potential for further development into therapeutic agent for AD treatment.
Topics: Alzheimer Disease; Animals; Biphenyl Compounds; Cognition; Cognitive Dysfunction; Gastrointestinal Microbiome; Glycogen Synthase Kinase 3 beta; Lignans; Male; Mice; Neuroinflammatory Diseases
PubMed: 35024199
DOI: 10.1016/j.jare.2021.03.012