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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 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 -
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 -
EBioMedicine May 2021Coronavirus-2 (SARS-CoV-2) infection causes an acute respiratory syndrome accompanied by multi-organ damage that implicates a prothrombotic state leading to widespread...
BACKGROUND
Coronavirus-2 (SARS-CoV-2) infection causes an acute respiratory syndrome accompanied by multi-organ damage that implicates a prothrombotic state leading to widespread microvascular clots. The causes of such coagulation abnormalities are unknown. The receptor tissue factor, also known as CD142, is often associated with cell-released extracellular vesicles (EV). In this study, we aimed to characterize surface antigens profile of circulating EV in COVID-19 patients and their potential implication as procoagulant agents.
METHODS
We analyzed serum-derived EV from 67 participants who underwent nasopharyngeal swabs molecular test for suspected SARS-CoV-2 infection (34 positives and 33 negatives) and from 16 healthy controls (HC), as referral. A sub-analysis was performed on subjects who developed pneumonia (n = 28). Serum-derived EV were characterized for their surface antigen profile and tested for their procoagulant activity. A validation experiment was performed pre-treating EV with anti-CD142 antibody or with recombinant FVIIa. Serum TNF-α levels were measured by ELISA.
FINDINGS
Profiling of EV antigens revealed a surface marker signature that defines circulating EV in COVID-19. A combination of seven surface molecules (CD49e, CD209, CD86, CD133/1, CD69, CD142, and CD20) clustered COVID (+) versus COVID (-) patients and HC. CD142 showed the highest discriminating performance at both multivariate models and ROC curve analysis. Noteworthy, we found that CD142 exposed onto surface of EV was biologically active. CD142 activity was higher in COVID (+) patients and correlated with TNF-α serum levels.
INTERPRETATION
In SARS-CoV-2 infection the systemic inflammatory response results in cell-release of substantial amounts of procoagulant EV that may act as clotting initiation agents, contributing to disease severity.
FUNDING
Cardiocentro Ticino Institute, Ente ospedaliero Cantonale, Lugano-Switzerland.
Topics: Adult; Aged; Aged, 80 and over; Antigens, Surface; Biomarkers; COVID-19; Case-Control Studies; Diagnosis, Differential; Extracellular Vesicles; Female; Humans; Male; Middle Aged; Nasopharynx; SARS-CoV-2; Switzerland; Thromboplastin; Thrombosis; Tumor Necrosis Factor-alpha
PubMed: 33971404
DOI: 10.1016/j.ebiom.2021.103369 -
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 -
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 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Jun 2024To establish a staging system for guiding clinical treatment and prognostic risk assessment by retrospectively analyzing the cases with radionecrosis of the nasopharynx...
To establish a staging system for guiding clinical treatment and prognostic risk assessment by retrospectively analyzing the cases with radionecrosis of the nasopharynx and skull base (RNSB) after radiotherapy for nasopharyngeal carcinoma. A total of 86 cases of RNSB from January 2019 to December 2022 visited Department of Otorhinolaryngology Head and Neck, the People's Hospital of Guangxi Zhuang Autonomous Region. Seventeen patients gave up the treatment, and 69 patients who underwent treatment were included for analysis. By analyzing the results of electronic nasopharyngolaryngoscopy combined with magnetic resonance (MR), CT, and other imaging examinations, a staging system for RNSB was proposed. The relationship between the staging system and the surgical effectiveness and clinical prognosis was further analyzed. According to the severity and extent of destruction of soft tissue, bone, and the adjacent neurovascular structures, the RNSB was categorized into closed type (=5) and open type (=64), of which the open type was subdivided into five types: type Ⅰ(=4), type Ⅱ(=6), type Ⅲ(=39, of which 21 cases were type Ⅲa and 18 cases were type Ⅲb), type Ⅳ(=12), and type Ⅴ(=8). The clinical stage of RNSB were classified based on nasopharyngolaryngoscopy and imaging examinations, receiving the second course of radiotherapy or not, the involvement of the infection site, the extent of bone destruction, the degree of internal carotid artery involvement, and the degree of brain tissue necrosis: stageⅠ(1-2 scores), 11 cases at stageⅡ(3-4 scores), 24 cases at stage Ⅲ(5-6 scores), and 30 cases at stage Ⅳ( ≥ 7 scores or more). Twenty-two patients chose conservative treatment (2 patients at stage Ⅰ, 3 patients at stage Ⅱ, 7 patients at stage Ⅲ, and 10 patients at stage Ⅳ). Forty-seven patients chose nasal endoscopic surgical treatment (2 patients at stage Ⅰ, 8 patients at stage Ⅱ, 17 patients at stage Ⅲ, and 20 patients at stage Ⅳ), of which 16 cases had received free mucosal flap and/or stented septum mucosal flap repair. Patients at stages Ⅰ, Ⅱ, and Ⅲ achieved satisfactory efficacy after surgical treatment. In addition, higher clinical stage was found to correlate with the worse prognosis and higher incidence of perioperative complications, which included failure of healing because of surgical site infection, cerebrospinal fluid nasal leakage, progressive osteonecrosis, nasopharyngeal hemorrhage, and death. The staging system proposed in our study can be used for early detection of RNSB during regular follow-up, and is also valuable for clinical treatment guidance and prognosis assessment.
Topics: Humans; Male; Female; Skull Base; Nasopharyngeal Neoplasms; Retrospective Studies; Middle Aged; Necrosis; Radiation Injuries; Nasopharynx; Adult; Aged; Magnetic Resonance Imaging; Prognosis; Tomography, X-Ray Computed
PubMed: 38858113
DOI: 10.13201/j.issn.2096-7993.2024.06.007 -
Frontiers in Immunology 2021In coronavirus disease 2019 (COVID-19), ulcerative lesions have been episodically reported in various segments of the gastrointestinal (GI) tract, including the oral...
In coronavirus disease 2019 (COVID-19), ulcerative lesions have been episodically reported in various segments of the gastrointestinal (GI) tract, including the oral cavity, oropharynx, esophagus, stomach and bowel. In this report, we describe an autopsy case of a COVID-19 patient who showed two undiagnosed ulcers at the level of the anterior and posterior walls of the hypopharynx. Molecular testing of viruses involved in pharyngeal ulcers demonstrated the presence of severe acute respiratory syndrome - coronavirus type 2 (SARS-CoV-2) RNA, together with herpes simplex virus 1 DNA. Histopathologic analysis demonstrated full-thickness lympho-monocytic infiltration (mainly composed of CD68-positive cells), with hemorrhagic foci and necrosis of both the mucosal layer and deep skeletal muscle fibers. Fibrin and platelet microthrombi were also found. Cytological signs of HSV-1 induced damage were not found. Cells expressing SARS-CoV-2 spike subunit 1 were immunohistochemically identified in the inflammatory infiltrations. Immunohistochemistry for HSV1 showed general negativity for inflammatory infiltration, although in the presence of some positive cells. Thus, histopathological, immunohistochemical and molecular findings supported a direct role by SARS-CoV-2 in producing local ulcerative damage, although a possible contributory role by HSV-1 reactivation cannot be excluded. From a clinical perspective, this autopsy report of two undiagnosed lesions put the question if ulcers along the GI tract could be more common (but frequently neglected) in COVID-19 patients.
Topics: Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Autopsy; Blood Platelets; COVID-19; Gastrointestinal Tract; Herpesvirus 1, Human; Humans; Hypopharynx; Immunohistochemistry; Inflammation; Lymphocytes; Monocytes; Mucous Membrane; Muscle, Skeletal; Necrosis; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Thrombosis; Ulcer
PubMed: 34290701
DOI: 10.3389/fimmu.2021.676828 -
Journal of Immunology (Baltimore, Md. :... Dec 2022Nasal immunity is an ancient and conserved arm of the mucosal immune system in vertebrates. In teleost fish, we previously reported the presence of a...
Nasal immunity is an ancient and conserved arm of the mucosal immune system in vertebrates. In teleost fish, we previously reported the presence of a nasopharynx-associated lymphoid tissue (NALT) characterized by scattered immune cells located in the trout olfactory lamellae. This diffuse NALT mounts innate and adaptive immune responses to nasal infection or vaccination. In mammals, lymphoid structures such as adenoids and tonsils support affinity maturation of the adaptive immune response in the nasopharyngeal cavity. These structures, known as organized NALT (O-NALT), have not been identified in teleost fish to date, but their evolutionary forerunners exist in sarcopterygian fish. In this study, we report that the rainbow trout nasal cavity is lined with a lymphoepithelium that extends from the most dorsal opening of the nares to the ventral nasal cavity. Within the nasal lymphoepithelium we found lymphocyte aggregates called O-NALT in this study that are composed of ∼ 56% CD4+, 24% IgM+, 16% CD8α+, and 4% IgT+ lymphocytes and that have high constitutive aicda mRNA expression. Intranasal (i.n.) vaccination with live attenuated infectious hematopoietic necrosis virus triggers expansions of B and T cells and aicda expression in response to primary i.n. vaccination. IgM+ B cells undergo proliferation and apoptosis within O-NALT upon prime but not boost i.n. vaccination. Our results suggest that novel mucosal microenvironments such as O-NALT may be involved in the affinity maturation of the adaptive immune response in early vertebrates.
Topics: Animals; Gastric Mucosa; Germinal Center; Mammals; Biomarkers; Adenoids; Immunoglobulin M
PubMed: 36426979
DOI: 10.4049/jimmunol.2200396