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Infection and Immunity Nov 2017We previously found CC chemokine ligand 3 (CCL3) to be a potent effector of inflammation during otitis media (OM): exogenous CCL3 rescues the OM phenotype of tumor...
We previously found CC chemokine ligand 3 (CCL3) to be a potent effector of inflammation during otitis media (OM): exogenous CCL3 rescues the OM phenotype of tumor necrosis factor-deficient mice and the function of macrophages deficient in several innate immune molecules. To further delineate the role of CCL3 in OM, we evaluated middle ear (ME) responses of mice to nontypeable (NTHi). CCL chemokine gene expression was evaluated in wild-type (WT) mice during the complete course of acute OM. OM was induced in and WT mice, and infection and inflammation were monitored for 21 days. Phagocytosis and killing of NTHi by macrophages were evaluated by an assay. The nasopharyngeal bacterial load was assessed in naive animals of both strains. Many CCL genes showed increased expression levels during acute OM, with CCL3 being the most upregulated, at levels 600-fold higher than the baseline. deletion compromised ME bacterial clearance and prolonged mucosal hyperplasia. ME recruitment of leukocytes was delayed but persisted far longer than in WT mice. These events were linked to a decrease in the macrophage capacity for NTHi phagocytosis and increased nasopharyngeal bacterial loads in mice. The generalized impairment in inflammatory cell recruitment was associated with compensatory changes in the expression profiles of CCL2, CCL7, and CCL12. CCL3 plays a significant role in the clearance of infection and resolution of inflammation and contributes to mucosal host defense of the nasopharyngeal niche, a reservoir for ME and upper respiratory infections. Therapies based on CCL3 could prove useful in treating or preventing persistent disease.
Topics: Animals; Bacterial Load; Cell Movement; Chemokine CCL2; Chemokine CCL3; Chemokine CCL7; Disease Models, Animal; Ear, Middle; Gene Expression Regulation; Haemophilus Infections; Haemophilus influenzae; Host-Pathogen Interactions; Leukocytes; Macrophages; Mice; Mice, Knockout; Monocyte Chemoattractant Proteins; Nasopharynx; Otitis Media; Phagocytosis; Signal Transduction
PubMed: 28847849
DOI: 10.1128/IAI.00148-17 -
Acta Otorrinolaringologica Espanola 2020to review the modifications and advances in reconstructive surgery of the soft tissues of the oral cavity exclusively based on flaps that depend on the facial artery... (Review)
Review
INTRODUCTION
to review the modifications and advances in reconstructive surgery of the soft tissues of the oral cavity exclusively based on flaps that depend on the facial artery system.
METHODS
review of the literature regarding oral cavity reconstructions based on main facial artery system flaps.
DISCUSSION
The reconstruction of the soft tissues of the oral cavity, based on facial artery system flaps, offers satisfactory results and allows limited reconstructions avoiding the use of pedicled regional flaps or free flaps.
CONCLUSIONS
Knowledge of reconstructive options using the facial artery system in oral cavity surgery allows expanding reconstructive options for head and neck surgeons, enabling safe, high quality and effective reconstructions, with limited resources consumption.
Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Humans; Male; Maxillary Artery; Middle Aged; Mouth Neoplasms; Nasopharynx; Necrosis; Oral Fistula; Palate; Prospective Studies; Plastic Surgery Procedures; Respiratory Tract Fistula; Surgical Flaps; Surgical Wound Dehiscence; Treatment Outcome
PubMed: 32143840
DOI: 10.1016/j.otorri.2019.10.002 -
Frontiers in Immunology 2021Tonsil hyperplasia is the most common cause of pediatric obstructive sleep apnea (OSA). Despite the growing knowledge in tissue immunology of tonsils, the...
Tonsil hyperplasia is the most common cause of pediatric obstructive sleep apnea (OSA). Despite the growing knowledge in tissue immunology of tonsils, the immunopathology driving tonsil hyperplasia and OSA remains unknown. Here we used multi-parametric flow cytometry to analyze the composition and phenotype of tonsillar innate lymphoid cells (ILCs), T cells, and B cells from pediatric patients with OSA, who had previous polysomnography. Unbiased clustering analysis was used to delineate and compare lymphocyte heterogeneity between two patient groups: children with small tonsils and moderate OSA (n = 6) or large tonsils and very severe OSA (n = 13). We detected disturbed ILC and B cell proportions in patients with large tonsils, characterized by an increase in the frequency of naïve CD27CD21 B cells and a relative reduction of ILCs. The enrichment of naïve B cells was not commensurate with elevated Ki67 expression, suggesting defective differentiation and/or migration rather than cellular proliferation to be the causative mechanism. Finally, yet importantly, we provide the flow cytometry data to be used as a resource for additional translational studies aimed at investigating the immunological mechanisms of pediatric tonsil hyperplasia and OSA.
Topics: Child, Preschool; Female; Flow Cytometry; Humans; Hyperplasia; Immunity, Innate; Lymphocytes; Male; Memory B Cells; Palatine Tonsil; Receptors, CXCR5; Sleep Apnea, Obstructive; Tumor Necrosis Factor Receptor Superfamily, Member 7
PubMed: 34745084
DOI: 10.3389/fimmu.2021.674080 -
Immunobiology Jan 2022Head and neck squamous cell carcinoma (HNSCC) arises from the malignant mucosal epithelium of the oral cavity, pharynx, and larynx. Natural killer (NK) cells are...
Down-regulation of HLA-B-associated transcript 3 impairs the tumoricidal effect of natural killer cells through promoting the T cell immunoglobulin and mucin domain-containing-3 signaling in a mouse head and neck squamous cell carcinoma model.
Head and neck squamous cell carcinoma (HNSCC) arises from the malignant mucosal epithelium of the oral cavity, pharynx, and larynx. Natural killer (NK) cells are fundamental immune cells shaping the anti-HNSCC response. Elucidation of the regulatory mechanisms of NK cell activity is crucial for understanding anti-HNSCC immunity. In this study, we characterized the expression and function of HLA-B-associated transcript 3 (Bat3) in NK cells in a mouse HNSCC model. We found that Bat3 expression was down-regulated in HNSCC-infiltrating NK cells. SCC VII, the mouse HNSCC cell line used in this model, induced Bat3 downregulation through direct cell-to-cell contact. By applying lentivirus-mediated silencing of Bat3, we discovered that Bat3 knockdown impaired the tumoricidal effect of NK cells on SCC VII cells and Hepa1-6, a genetically modified liver cancer cell line. Furthermore, Bat3 knockdown resulted in a significant decrease in perforin, granzyme B, interferon-γ, and tumor necrosis factor-α in NK cells upon co-culture with SCC VII cells. Further investigations revealed that Bat3 knockdown promoted the binding of T cell immunoglobulin and mucin domain-containing-3 (Tim-3) to Fyn and thus activated the Tim-3 signaling. Blockade of Tim-3 with a neutralizing Tim-3 antibody counteracted the effect of Bat3 knockdown on NK cell cytotoxicity. Taken together, our data suggest that HNSCC might down-regulate Bat3 expression to augment Tim-3 signaling and ultimately suppress the tumoricidal activity of NK cells. This study unveils a novel mechanism by which HNSCC evades NK cell killing, and sheds light on designing novel anti-HNSCC immunotherapy targeting Bat3 and Tim-3 signaling.
Topics: Animals; Disease Models, Animal; Down-Regulation; HLA-B Antigens; Head and Neck Neoplasms; Hepatitis A Virus Cellular Receptor 2; Immunoglobulins; Killer Cells, Natural; Mice; Molecular Chaperones; Mucins; Nuclear Proteins; Squamous Cell Carcinoma of Head and Neck; T-Lymphocytes
PubMed: 34968777
DOI: 10.1016/j.imbio.2021.152127 -
Molecular Medicine Reports Jan 2018Recent studies have demonstrated that resveratrol can reduce blood sugar, improve insulin resistance, regulate abnormalities in lipid metabolism, and lower the secretion...
Recent studies have demonstrated that resveratrol can reduce blood sugar, improve insulin resistance, regulate abnormalities in lipid metabolism, and lower the secretion and expression of inflammatory factors. The present study investigated the anti‑inflammatory effects of resveratrol in animal models of acute pharyngitis, and its possible mechanisms. Commercial ELISA kits were used to measure tumor necrosis factor‑α, interleukin (IL)‑6, macrophage inflammatory protein‑2, cyclooxygenase‑2 levels and caspase‑3/9 activity. Toll‑like receptor (TLR)‑4, myeloid differentiation primary response protein MyD88, phosphorylated (p)‑nuclear factor (NF)‑κB and p‑IκB were analyzed using western blotting. In a rabbit model of acute pharyngitis, it was demonstrated that resveratrol inhibited tumor necrosis factor‑α and interleukin‑6 serum levels, macrophage inflammatory protein‑2 and cyclooxygenase‑2 activity levels, reactive oxygen species production and caspase‑3/9 activity. Resveratrol suppressed NACHT, LRR and PYD domains‑containing protein 3 and caspase‑1 protein expression, and reduced IL‑1β and IL‑18 protein expression in animal models of acute pharyngitis. Additionally, resveratrol suppressed TLR4 and myeloid differentiation primary response protein 88 protein expression, and reduced p‑NF‑κB and increased p‑IκB protein expression in animal models of acute pharyngitis. In conclusion, these findings indicated that the anti‑inflammatory activity of resveratrol prevents acute pharyngitis‑induced inflammation by inhibiting NF‑κB in animal models. Therefore, these data suggested an important clinical application of resveratrol in preventing acute pharyngitis.
Topics: Animals; Anti-Inflammatory Agents; Chemokine CXCL2; Cyclooxygenase 2; Drug Evaluation, Preclinical; Interleukin-6; Male; NF-kappa B; Pharyngitis; Pharynx; Rabbits; Reactive Oxygen Species; Resveratrol; Signal Transduction; Stilbenes; Tumor Necrosis Factor-alpha
PubMed: 29115472
DOI: 10.3892/mmr.2017.7933 -
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 -
Georgian Medical News Oct 2022The aim of the study was to analyze the effectiveness of the repair of post-laryngectomy pharyngostomas using supraclavicular flap. In a group of 4 patients treated in...
The aim of the study was to analyze the effectiveness of the repair of post-laryngectomy pharyngostomas using supraclavicular flap. In a group of 4 patients treated in 2018-2021. in 2 (50.0%) patients, the healing process was successful. One patient had a minor fistula due to rupture of wound sutures, which closed spontaneously. Another patient had partial necrosis of the flap, leading to formation of small-sized fistula that required another surgery. This type of flap, which has a low risk of local complications at the donor site and satisfactory functional and aesthetic results in the defect area, can be an alternative to other flaps used in the reconstruction of postoperative defects in the pharynx after laryngectomy.
Topics: Humans; Plastic Surgery Procedures; Laryngectomy; Treatment Outcome; Surgical Flaps; Fistula; Retrospective Studies; Postoperative Complications
PubMed: 36539137
DOI: No ID Found -
Journal of Virology Jul 2017Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we...
Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 10 to 10 50% tissue culture infective doses (TCID) consistently infected all the animals, and many monkeys receiving 10 or 10 TCID developed paralysis. There was no apparent difference in the susceptibilities of the three macaque species (rhesus, cynomolgus, and bonnet) used. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia, and virus was isolated from tonsils, gut mucosa, and draining lymph nodes. Viral replication proteins were detected in both epithelial and lymphoid cell populations expressing CD155 in the tonsil and intestine, as well as in spinal cord neurons. Necrosis was observed in these three cell types, and viral replication in the tonsil/gut was associated with histopathologic destruction and inflammation. The sustained response of neutralizing antibody correlated temporally with resolution of viremia and termination of virus shedding in oropharynges and feces. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), extending previous studies of poliovirus pathogenesis in humans. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis and to assess the efficacy of candidate antiviral drugs and new vaccines. Early pathogenic events of poliovirus infection remain largely undefined, and there is a lack of animal models mimicking natural oral human infection leading to paralytic poliomyelitis. All 39 macaques fed with single high doses ranging from 10 to 10 TCID Mahoney type 1 virus were infected, and many of the monkeys developed paralysis. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia; tonsil, mesentery lymph nodes, and intestinal mucosa served as major target sites of viral replication. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), thereby supplementing historical reconstructions of poliovirus pathogenesis. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis, candidate antiviral drugs, and the efficacy of new vaccines.
Topics: Animal Structures; Animals; Disease Models, Animal; Epithelial Cells; Feces; Leukocytes; Macaca; Nasopharynx; Poliomyelitis; Poliovirus; Virus Shedding
PubMed: 28356537
DOI: 10.1128/JVI.02310-16 -
JAMA Dermatology Mar 2015Ear, nose, and throat (ENT) lesions are frequently involved in Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), although a detailed description is...
IMPORTANCE
Ear, nose, and throat (ENT) lesions are frequently involved in Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), although a detailed description is lacking in the literature.
OBJECTIVES
To describe ENT lesions at the acute stage and follow-up in a large series of patients with SJS/TEN and identify factors associated with the severe ENT form.
DESIGN, SETTING, AND PARTICIPANTS
Retrospective study of 49 patients with SJS/TEN hospitalized in a referral care center from 2005 to 2010. Patients who underwent a full ENT workup including examination and a nasal fiberoptic endoscopy by an otorhinolaryngologist in the acute phase and during follow-up at 2 and 12 months were included in the study.
MAIN OUTCOMES AND MEASURES
Recorded variables included maximal body surface area (BSA) detachment, SCORTEN (Score of Toxic Epidermal Necrosis [a severity of illness score]), sites and type of ENT mucosal lesions, intensive care unit transfer, pulmonary infection, and mortality. "Severe ENT form" was defined by the occurrence of laryngeal lesions with the risk of airways obstruction. Clinical characteristics associated with severe ENT form were analyzed in univariate and multivariable analysis.
RESULTS
Of the 49 patients who underwent a full ENT workup (female to male ratio, 1.1:1), ENT symptoms (eg, odynophagia, dysphagia, dysphonia, dyspnea, earache, nasal obstruction) occurred in 48 (98%). Dyspnea or dysphonia were significantly associated with severe ENT form (21% [P = .03] and 50% [P < .001], respectively). Topographic frequencies of lesions were as followed: lips and oral cavity (n = 46 [93%]) and pharynx and vestibule of the nose (n = 26 [53%]). Fourteen patients (29%) had severe ENT form. Findings for other recorded variables for those with vs without ENT examination are as follows: maximal BSA detachment (20% [0%-95%] vs 5.5% [0%-95%]; P = .004), SCORTEN (1 [0-5] vs 1 [0-5]; P = .54), intensive care unit transfer (10 [20%] vs 9 [19%]; P = .80), pulmonary infection (9 [18%] vs 6 [13%]; P = .10), and mortality (3 [6%] vs 5 [10%]; P = .70). In multivariable analysis, pulmonary infection was significantly associated with severe ENT form (odds ratio, 5.9 [95% CI, 1.1-32.8] [P = .04]). After remission of SJS/TEN, a complete ENT mucosal healing occurred in 36 patients (74%) at 2 months and in nearly all patients (n = 48 [98%]) at 1 year of follow-up.
CONCLUSIONS AND RELEVANCE
Severe ENT form is associated with pulmonary infection and is easily detected by nasal fiberoptic endoscopy. ENT evaluation should be suggested when dysphonia or dyspnea is observed at the acute stage of SJS/TEN.
Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Eye Diseases; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Nose Diseases; Pharyngeal Diseases; Retrospective Studies; Severity of Illness Index; Stevens-Johnson Syndrome; Young Adult
PubMed: 25671761
DOI: 10.1001/jamadermatol.2014.4844 -
Cellular and Molecular Biology... Feb 2022The purpose of this study was to investigate the effects of propofol anesthesia combined with remifentanil on inflammation, stress response, and immune function in... (Randomized Controlled Trial)
Randomized Controlled Trial
The purpose of this study was to investigate the effects of propofol anesthesia combined with remifentanil on inflammation, stress response, and immune function in children undergoing tonsil and adenoid surgery. For this aim, 126 children admitted to our hospital for elective temperature-controlled radio-frequency of tonsils and adenoids from October 2020 to September 2021 were randomly divided into an observation group (n=63) and a control group (n=63). The observation group was anesthetized with propofol in combination with remifentanil, while the control group underwent propofol combined with ketamine. The mean arterial pressure (MAP), heart rate, serum C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), epinephrine, cortisol (Cor), CD3+ T lymphocytes, CD4+ helper T lymphocytes, CD8+ suppressor T lymphocytes and CD4+/CD8+ ratio were compared between the two groups before induction of anaesthesia (T1), upon intubation (T2), at the beginning of surgery (T3), at the end of surgery (T4) and 5 min after extubation (T5). -(TNF-α). The recovery time from anaesthesia and adverse reactions after extubation were observed in the two groups. Results showed that the MAP and heart rate in both groups increased significantly at T2 compared to T1, but the observation group had lower values than the control group after the maintenance of anaesthesia (P<0.05). Serum CRP, IL-6 and TNF-α levels increased with time in both groups, and the increase was considered significant (P<0.05). In addition, serum epinephrine and Cor levels gradually rose from T1 to T4 in both groups, and then decreased at T5. The difference was statistically significant (P<0.05) between any two-time points. CRP, IL-6, TNF-α, epinephrine and Cor in the observation group were significantly lower than those in the control group from T3 to T5 (P<0.05). CD3+, CD4+ and CD4+/CD8+ ratio decreased whereas CD8+ went up in both groups at T4 and T5, and which were considered statistically significant when compared with data from T1 to T3 (P<0.05). However, CD3+, CD4+, CD8+ and CD4+/CD8+ ratios did not differ statistically significantly between the two groups at each time point (P>0.05). In the observation group, the time to recovery of spontaneous respiration, the time to resumption of limb movements and the span from discontinuation of anaesthetic to extubation were all significantly shorter than those in the control group, and the incidence of agitation during the awakening period was lower than that in the control group (P<0.05). Then propofol combined with remifentanil is more effective in inflammation, stress response and immune function in anesthetizing children undergoing tonsil and adenoid surgery. The observation group presented more stable hemodynamics, lower levels of inflammation and stress reactions, rapid awakening and fewer adverse effects, so the combination therapy was worthy of clinical promotion in pediatric surgery requiring general anesthesia.
Topics: Adenoids; Anesthesia, General; C-Reactive Protein; Child; Epinephrine; Humans; Immunity; Inflammation; Interleukin-6; Palatine Tonsil; Propofol; Remifentanil; Tumor Necrosis Factor-alpha
PubMed: 35869719
DOI: 10.14715/cmb/2022.68.2.13