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Journal of Immunology (Baltimore, Md. :... May 2020The adaptive immune system of all jawed vertebrates relies on the presence of B and T cell lymphocytes that aggregate in specific body sites to form primary and...
The adaptive immune system of all jawed vertebrates relies on the presence of B and T cell lymphocytes that aggregate in specific body sites to form primary and secondary lymphoid structures. Secondary lymphoid organs include organized MALT (-MALT) such as the tonsils and Peyer patches. -MALT became progressively organized during vertebrate evolution, and the TNF superfamily of genes has been identified as essential for the formation and maintenance of -MALT and other secondary and tertiary lymphoid structures in mammals. Yet, the molecular drivers of -MALT structures found in ectotherms and birds remain essentially unknown. In this study, we provide evidence that TNFSFs, such as lymphotoxins, are likely not a universal mechanism to maintain -MALT structures in adulthood of teleost fish, sarcopterygian fish, or birds. Although a role for TNFSF2 (TNF-α) cannot be ruled out, transcriptomics suggest that maintenance of -MALT in nonmammalian vertebrates relies on expression of diverse genes with shared biological functions in neuronal signaling. Importantly, we identify that expression of many genes with olfactory function is a unique feature of mammalian Peyer patches but not the -MALT of birds or ectotherms. These results provide a new view of -MALT evolution in vertebrates and indicate that different genes with shared biological functions may have driven the formation of these lymphoid structures by a process of convergent evolution.
Topics: Adaptive Immunity; Animals; B-Lymphocytes; Biological Evolution; Immunity, Mucosal; Lymphoid Tissue; Mucous Membrane; Neural Conduction; Palatine Tonsil; Peyer's Patches; T-Lymphocytes; Transcriptome; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Vertebrates
PubMed: 32238457
DOI: 10.4049/jimmunol.1901059 -
Cancer Radiotherapie : Journal de La... Apr 2020Postradiation nasopharyngeal necrosis (PRNN) is a notorious complication after radiotherapy that affects prognosis in patients with nasopharyngeal carcinoma (NPC). It is...
OBJECTIVE
Postradiation nasopharyngeal necrosis (PRNN) is a notorious complication after radiotherapy that affects prognosis in patients with nasopharyngeal carcinoma (NPC). It is important for clinical doctors to realize this problem in order to cope with this severe clinical situation. The aim of our study was to assess the bacteriology of PRNN and to demonstrate the antimicrobial susceptibility pattern that should guide the clinicians towards more appropriate antibiotic use.
METHODS
Sixty-nine NPC patients with PRNN in our department between March 2013 and December 2017 were retrospectively enrolled. Pathogenic culture and drug sensitivity test were performed in these 69 NPC patients with PRNN. The infection rate of Pathogens and the sensitivity of the drugs were analyzed based on these results.
RESULTS
Sixty-nine NPC patients with PRNN were enrolled in our study. Pathogens were identified in 58 (84%) patients. Of the 58 patients, Staphylococcus aureus was isolated in 34 (58.6%) patients. And the second most common group of bacterial isolates was Pseudomonas aeruginosa. Antibiotic sensitivity showed that Levofloxacin was the highest (88.5%), followed by Ciprofloxacin (85.2%) and Gentamicin (80.3%). The only pathologic fungus was Candidaalbicans, about 6.8%. The positive rates of bacterial and fungal culture in PRNN patients were not significantly different from the patients' gender, age, stage, number of radiotherapy courses (P>0.05), but the cure rate was statistically higher in culture-negative patients in comparison with culture-positive patients (63.6% vs 20.7%, P=0.011).
CONCLUSION
Our results provide an overall picture of the microbiology and drug susceptibility patterns for NPC patients with PRNN and could help implement guidelines for more rational treatment and improve therapeutic outcome.
Topics: Adult; Aged; Anti-Bacterial Agents; Candida albicans; Ciprofloxacin; Female; Gentamicins; Humans; Levofloxacin; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharynx; Necrosis; Pseudomonas aeruginosa; Radiation Injuries; Retrospective Studies; Staphylococcus aureus; Treatment Outcome
PubMed: 32057645
DOI: 10.1016/j.canrad.2019.09.008 -
Brain, Behavior, and Immunity Nov 2019Isorhynchophylline (IRN) has been demonstrated to have distinct anti-Alzheimer's disease (AD) activity in several animal models of AD. In this study, we aimed at...
Isorhynchophylline ameliorates cognitive impairment via modulating amyloid pathology, tau hyperphosphorylation and neuroinflammation: Studies in a transgenic mouse model of Alzheimer's disease.
Isorhynchophylline (IRN) has been demonstrated to have distinct anti-Alzheimer's disease (AD) activity in several animal models of AD. In this study, we aimed at evaluating the preventive effect of IRN on the cognitive deficits and amyloid pathology in TgCRND8 mice. Male TgCRND8 mice were administered with IRN (20 or 40 mg/kg) by oral gavage daily for 4 months, followed by assessing the spatial learning and memory functions with the Radial Arm Maze (RAM) test. Brain tissues were determined immunohistochemically or biochemically for changes in amyloid pathology, tau hyperphosphorylation and neuroinflammation. Our results revealed that IRN (40 mg/kg) significantly ameliorated cognitive deficits in TgCRND8 mice. In addition, IRN (40 mg/kg) markedly reduced the levels of Aβ, Aβ and tumor necrosis factor (TNF-α), interleukin 6 (IL-6) and IL-1β, and modulated the amyloid precursor protein (APP) processing and phosphorylation by altering the protein expressions of β-site APP cleaving enzyme-1 (BACE-1), phosphorylated APP (Thr668), presenilin-1 (PS-1) and anterior pharynx-defective-1 (APH-1), as well as insulin degrading enzyme (IDE), a major Aβ-degrading enzyme. IRN was also found to inhibit the phosphorylation of tau at the sites of Thr205 and Ser396. Immunofluorescence showed that IRN reduced the Aβ deposition, and suppressed the activation of microglia (Iba-1) and astrocytes (GFAP) in the cerebral cortex and hippocampus of TgCRND8 mice. Furthermore, IRN was able to attenuate the ratios of p-c-Jun/c-Jun and p-JNK/JNK in the brains of TgCRND8 mice. IRN also showed marked inhibitory effect on JNK signaling pathway in the Aβ-treated rat primary hippocampus neurons. We conclude that IRN improves cognitive impairment in TgCRND8 transgenic mice via reducing Aβ generation and deposition, tau hyperphosphorylation and neuroinflammation through inhibiting the activation of JNK signaling pathway, and has good potential for further development into pharmacological treatment for AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Brain; Cognition Disorders; Cognitive Dysfunction; Disease Models, Animal; Female; Hippocampus; MAP Kinase Signaling System; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neuroimmunomodulation; Oxindoles; Presenilin-1; tau Proteins
PubMed: 31476414
DOI: 10.1016/j.bbi.2019.08.194 -
Journal of Ethnopharmacology Jan 2024Hosta plantaginea (Lam.) Aschers flower is a famous Mongolian folk medicine in China and has a therapeutic effect on acute pharyngitis (AP). However, the effect and...
BACKGROUND
Hosta plantaginea (Lam.) Aschers flower is a famous Mongolian folk medicine in China and has a therapeutic effect on acute pharyngitis (AP). However, the effect and potential mechanism of H. plantaginea flower on AP have not been fully elucidated.
AIM OF THE STUDY
The present work aimed to evaluate the effects and mechanisms of the crude extract of H. plantaginea flowers (HP) and its four fractions of petroleum ether fraction (HPA), ethyl acetate fraction (HPB), n-butanol fraction (HPC), and water residue (HPD) against AP in rats.
MATERIALS AND METHODS
A 15% ammonia-induced AP rat model in rats was established. Therapeutic effects of HP and HPA∼D in model rats were evaluated based on body weight, histopathological analysis, and inflammatory parameters, including tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), interleukin 1β (IL-1β), and IL-6. The protein expression of nuclear factor kappa-B p65 (NF-κB p65), inhibitor of NF-κB alpha (IκBα), c-Jun N-terminal kinases (JNK), mitogen-activated protein kinase (MAPK) p38, extracellular signal-regulated kinase (Erk), just another kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) were detected by a Western blotting assay.
RESULTS
HP, HPB, and HPC treatments markedly alleviated AP in rats by increasing body weight and improving pathological damages in pharyngeal tissues. In addition, HP, HPB, and HPC treatments significantly inhibited inflammation, including decreasing the levels of TNF-α, PGE2, IL-1β, and IL-6, and suppressing phosphorylated protein expression of p65, IκBα, JNK, p38, Erk, JAK1, STAT3, PI3K, and Akt in pharyngeal tissues of rats.
CONCLUSION
Collectively, HP, HPB, and HPC can attenuate pharynx injury in rats by suppressing inflammation via inhibition of NF-κB, MAPKs, JAK-STAT, and PI3K-Akt pathways, which supports the traditional use of H. plantaginea flowers.
Topics: Rats; Animals; Proto-Oncogene Proteins c-akt; NF-kappa B; Signal Transduction; NF-KappaB Inhibitor alpha; Phosphatidylinositol 3-Kinases; Hosta; Interleukin-6; Inflammation; Extracellular Signal-Regulated MAP Kinases; Tumor Necrosis Factor-alpha; Pharyngitis; Flowers
PubMed: 37499845
DOI: 10.1016/j.jep.2023.116966 -
Journal of Voice : Official Journal of... Jan 2022To assess the influence that several factors, such as the amount of obtained biopsies, difficult procedures, biopsy site and the experience of the attending physician,...
OBJECTIVES
To assess the influence that several factors, such as the amount of obtained biopsies, difficult procedures, biopsy site and the experience of the attending physician, have on accuracy of flexible endoscopic biopsy (FEB).
MATERIALS AND METHODS
203 FEB procedures for benign or malignant laryngopharyngeal lesions were prospectively included. During the procedure, three representative biopsies (macroscopically containing vital tumor tissue and not only necrosis or healthy tissue) were obtained. The accuracy of each biopsy was separately analyzed. Difficulties during the procedures leading to failure of acquiring three representative biopsies were recorded and classified into tumor, patient and procedural factors. Histological results of FEB were defined correct when consistent with clinical context, additional biopsies or Positron emission tomography-computed tomography (PET-CT) revealed equivalent pathology, or the lesion was stable or resolved in >6 months follow-up.
RESULTS
The first representative biopsy yielded a correct diagnosis in 65% of the cases. After the second representative biopsy, 78% was correctly diagnosed. The contribution of the third and fourth representative biopsies to accuracy was 3%. The overall accuracy of FEB was 85%. Difficult procedures were more likely to result in misdiagnosis, whereas biopsy site or experience of the attending physician did not influence results.
CONCLUSIONS
FEB was accurate in diagnosing laryngopharyngeal lesions when at least two representative biopsies were obtained. Accuracy of FEB could be further improved by limiting possible constraints during the procedures, for example by selecting, informing, and anesthetizing patients carefully.
Topics: Biopsy; Humans; Hypopharynx; Positron Emission Tomography Computed Tomography
PubMed: 32434679
DOI: 10.1016/j.jvoice.2020.04.015 -
Revista Medica Del Instituto Mexicano... Oct 2022Chemical substances are important causes of gastrointestinal tract injuries and usually affect two groups of patients: children under 5 years of age and adults who...
INTRODUCTION
Chemical substances are important causes of gastrointestinal tract injuries and usually affect two groups of patients: children under 5 years of age and adults who attempt suicide. Its effects can range from necrosis to perforation of the digestive tract, which can affect the mouth, pharynx, esophagus and stomach. The main complication of accidental caustic ingestion is esophageal stricture. The frequency with which esophageal strictures appear ranges from 15% to 35% and is related to the degree of injury induced by the ingested agent. They may become symptomatic by the second or third week after a latent repair phase or, in other cases, months or years after ingestion. Different forms of treatment have been applied to treat caustic esophageal strictures, and endoscopic dilation is the first line, with successful results in 60% to 80% of patients. If these are not effective, surgical treatment for esophageal replacement is indicated.
CLINICAL CASE
A clinical case of a 48-year-old male patient with no chronic degenerative history is presented, who began suffering after accidental ingestion of caustic substance 4 months ago with dysphagia to liquids and solids, for which he is protocolized in our unit for definitive surgical resolution by gastric pull-up.
CONCLUSIONS
Although associated with high rates of anastomotic stricture, transhiatal esophagectomy and gastric pull-up with cervical anastomosis are safe procedures for the treatment of caustic esophageal strictures.
Topics: Child; Male; Adult; Humans; Child, Preschool; Middle Aged; Caustics; Constriction, Pathologic; Burns, Chemical; Esophageal Stenosis; Retrospective Studies
PubMed: 36283060
DOI: No ID Found -
Medicine Oct 2019Cerebral aneurysm surgery has significant mortality and morbidity rate. Inflammation plays a key role in the pathogenesis of intracranial aneurysms, their rupture,...
Effect of local anesthesia with lidocaine on perioperative proinflammatory cytokine levels in plasma and cerebrospinal fluid in cerebral aneurysm patients: Study protocol for a randomized clinical trial.
BACKGROUND
Cerebral aneurysm surgery has significant mortality and morbidity rate. Inflammation plays a key role in the pathogenesis of intracranial aneurysms, their rupture, subarachnoid hemorrhage and neurologic complications. Proinflammatory cytokine level in blood and cerebrospinal fluid (CSF) is an indicator of inflammatory response. Cytokines contribute to secondary brain injury and can worsen the outcome of the treatment. Lidocaine is local anesthetic that can be applied in neurosurgery as regional anesthesia of the scalp and as topical anesthesia of the throat before direct laryngoscopy and endotracheal intubation. Besides analgesic, lidocaine has systemic anti-inflammatory and neuroprotective effect.Primary aim of this trial is to determine the influence of local anesthesia with lidocaine on the perioperative levels of pro-inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in plasma and CSF in cerebral aneurysm patients.
METHODS
We will conduct prospective randomized clinical trial among patients undergoing craniotomy and cerebral aneurysm clipping surgery in general anesthesia. Patients included in the trial will be randomly assigned to the lidocaine group (Group L) or to the control group (Group C). Patients in Group L, following general anesthesia induction, will receive topical anesthesia of the throat before endotracheal intubation and also regional anesthesia of the scalp before Mayfield frame placement, both done with lidocaine. Patients in Group C will have general anesthesia only without any lidocaine administration. The primary outcomes are concentrations of cytokines interleukin-1β, interleukin-6 and tumor necrosis factor-α in plasma and CSF, measured at specific timepoints perioperatively. Secondary outcome is incidence of major neurological and infectious complications, as well as treatment outcome in both groups.
DISCUSSION
Results of the trial could provide insight into influence of lidocaine on local and systemic inflammatory response in cerebrovascular surgery, and might improve future anesthesia practice and treatment outcome. TRIAL IS REGISTERED AT CLINICALTRIALS.GOV:: NCT03823482.
Topics: Adolescent; Adult; Aged; Anesthesia, Conduction; Anesthesia, General; Anesthesia, Local; Anesthetics, Local; Craniotomy; Cytokines; Female; Humans; Intracranial Aneurysm; Intubation, Intratracheal; Laryngoscopy; Lidocaine; Male; Middle Aged; Pharynx; Postoperative Complications; Prospective Studies; Randomized Controlled Trials as Topic; Scalp; Treatment Outcome; Young Adult
PubMed: 31626100
DOI: 10.1097/MD.0000000000017450 -
Food & Function Jan 2020Lactobacillus salivarius AR809 is a newly discovered probiotic strain from a healthy human pharynx and has potential ability to adhere to the pharyngeal epithelium and...
Lactobacillus salivarius AR809 is a newly discovered probiotic strain from a healthy human pharynx and has potential ability to adhere to the pharyngeal epithelium and inhibit Staphylococcus aureus (S. aureus)-induced inflammatory response. Pharyngeal spray administration of AR809 exhibited protective effects in a S. aureus-induced mouse model of pharyngitis. The inhibitory effect and underlying molecular mechanism of AR809 on S. aureus-stimulated pharyngitis were further investigated. AR809 significantly increased phagocytosis and bactericidal activity, reduced the production of inflammatory mediators (intracellular reactive oxygen species (ROS), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), nitric oxide (NO), inducible NOS (iNOS)) and the expression of inflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)), and induced macrophages to adopt the M2 phenotype. AR809 also attenuated S. aureus-induced phosphorylations of protein kinase B (Akt) and rapamycin (mTOR), and elevated the autophagic protein (light chain 3 from II (LC3-II) and Beclin-1) level. Furthermore, AR809 inhibited nuclear transcription factor kappa-B (NF-κB) activation by suppressing the nuclear translocation of NF-κB p65. Likewise, 740Y-P (a PI3K activator) decreased the anti-inflammatory effect of AR809 against S. aureus-induced inflammatory response, while AR809 treatments with wortmannin (a PI3K inhibitor) markedly reversed this inflammatory response. AR809 prevents S. aureus-induced pharyngeal inflammatory response, possibly by regulating TLR/PI3K/Akt/mTOR signalling pathway-related autophagy and TLR/PI3K/Akt/IκB/NF-κB pathway activity, and therefore has potential for use in preventing pharyngitis and other inflammatory diseases.
Topics: Animals; Autophagy; Cyclooxygenase 2; Cytokines; Dinoprostone; Inflammation; Ligilactobacillus salivarius; Macrophages; Male; Mice; Mice, Inbred ICR; Nitric Oxide; Pharyngitis; Phosphatidylinositol 3-Kinases; Probiotics; Proto-Oncogene Proteins c-akt; Signal Transduction; Staphylococcus aureus; Transcription Factor RelA; Tumor Necrosis Factor-alpha
PubMed: 31957758
DOI: 10.1039/c9fo02476j -
PloS One 2020Memory B cell (mBC) induction and maintenance is one of the keys to long-term protective humoral immunity. MBCs are fundamental to successful medical interventions such...
Human CD27+ memory B cells colonize a superficial follicular zone in the palatine tonsils with similarities to the spleen. A multicolor immunofluorescence study of lymphoid tissue.
BACKGROUND
Memory B cell (mBC) induction and maintenance is one of the keys to long-term protective humoral immunity. MBCs are fundamental to successful medical interventions such as vaccinations and therapy in autoimmunity. However, their lifestyle and anatomic residence remain enigmatic in humans. Extrapolation from animal studies serves as a conceptual basis but might be misleading due to major anatomical distinctions between species.
METHODS AND FINDINGS
Multicolor immunofluorescence stainings on fixed and unfixed frozen tissue sections were established using primary antibodies coupled to haptens and secondary signal amplification. The simultaneous detection of five different fluorescence signals enabled the localization and characterization of human CD27+CD20+Ki67- mBCs for the first time within one section using laser scanning microscopy. As a result, human tonsillar mBCs were initially identified within their complex microenvironment and their relative location to naïve B cells, plasma cells and T cells could be directly studied and compared to the human splenic mBC niche. In all investigated tonsils (n = 15), mBCs appeared to be not only located in a so far subepithelial defined area but were also follicle associated with a previous undescribed gradual decline towards the follicular mantle comparable to human spleen. However, mBC areas around secondary follicles with large germinal centers (GCs) in tonsils showed interruptions and a general widening towards the epithelium while in spleen the mBC-containing marginal zones (MZ) around smaller GCs were relatively broad and symmetrical. Considerably fewer IgM+IgD+/- pre-switch compared to IgA+ or IgG+ post-switch mBCs were detected in tonsils in contrast to spleen.
CONCLUSIONS
This study extends existing insights into the anatomic residence of human mBCs showing structural similarities of the superficial follicular area in human spleen and tonsil. Our data support the debate of renaming the human splenic MZ to 'superficial zone' in order to be aware of the differences in rodents and, moreover, to consider this term equally for the human palatine tonsil.
Topics: Adolescent; Adult; Aged; B-Lymphocytes; Cellular Microenvironment; Child; Germinal Center; Humans; Middle Aged; Palatine Tonsil; Spleen; Tumor Necrosis Factor Receptor Superfamily, Member 7
PubMed: 32187186
DOI: 10.1371/journal.pone.0229778 -
Dysphagia Jun 2020The purpose of this study was to identify factors associated with the severity of dysphagia after lateral medullary infarction (LMI). Patients with dysphagia after... (Comparative Study)
Comparative Study
The purpose of this study was to identify factors associated with the severity of dysphagia after lateral medullary infarction (LMI). Patients with dysphagia after lateral medullary infarction who were admitted to a rehabilitation unit were included and divided into two groups (non-severe vs. severe). Severe dysphagia was defined as the condition showing decreased bilateral pharyngeal constriction without esophageal passage in a videofluoroscopic swallowing study that initially required enteral tube feeding. Their clinical data (age, sex, lesion side, duration of the illness, penetration-aspiration scale, functional oral intake scale, Modified Barthel index, National Institutes of Health Stroke Scale, and anatomical lesion on diffusion-weighted MRI) were compared to find differences between the two groups. Twelve patients had absence of esophageal passage among a total of 30 patients with dysphagia after LMI. Only anatomical lesion location and extent were significantly different between the two groups. The severe group showed posterolateral involvement in the upper and lower parts of the medulla. Otherwise, there were no significant differences between the two groups. The location and extent of involvement in the medulla were the most important factors associated with the severity of dysphagia after LMI.
Topics: Aged; Brain Stem Infarctions; Deglutition; Deglutition Disorders; Diffusion Magnetic Resonance Imaging; Female; Humans; Male; Medulla Oblongata; Middle Aged; Oropharynx; Severity of Illness Index
PubMed: 31375916
DOI: 10.1007/s00455-019-10043-8