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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 -
Neurology India 2019
Topics: Brain; Cerebellum; Humans; Infarction; Male; Middle Aged; Palatine Tonsil
PubMed: 30860155
DOI: 10.4103/0028-3886.253573 -
Nutrients Jan 2022Pharyngitis is an inflammation of the pharynx caused by viral, bacterial, or non-infectious factors. In the present study, the anti-inflammatory efficacy of carvacrol...
Pharyngitis is an inflammation of the pharynx caused by viral, bacterial, or non-infectious factors. In the present study, the anti-inflammatory efficacy of carvacrol was assessed using an in vitro model of streptococcal pharyngitis using human tonsil epithelial cells (HTonEpiCs) induced with cell wall antigens. HTonEpiCs were stimulated by a mixture of lipoteichoic acid (LTA) and peptidoglycan (PGN) for 4 h followed by exposure to carvacrol for 20 h. Following exposure, interleukin (IL)-6, IL-8, human beta defensin-2 (HBD-2), epithelial-derived neutrophil-activating protein-78 (ENA-78), granulocyte chemotactic protein-2 (GCP-2), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and prostaglandin (PGE) were measured by enzyme-linked immunosorbent assays (ELISA). The levels of pro-inflammatory cytokines, IL-6, IL-8, ENA-78, and GCP-2 were decreased in a carvacrol dose-dependent manner. The production of HBD-2 was significantly suppressed over 24 h carvacrol treatments. PGE and COX-2 levels in the cell suspensions were affected by carvacrol treatment. TNF-α was not detected. The cell viability of all the tested carvacrol concentrations was greater than 80%, with no morphological changes. The results suggest that carvacrol has anti-inflammatory properties, and carvacrol needs to be further assessed for potential clinical or healthcare applications to manage the pain associated with streptococcal pharyngitis.
Topics: Biomarkers; Cell Wall; Cymenes; Epithelial Cells; Humans; Lipopolysaccharides; Palatine Tonsil; Peptidoglycan; Teichoic Acids
PubMed: 35276864
DOI: 10.3390/nu14030503 -
Cancer Apr 2010: Pharyngoesophageal defects traditionally have been reconstructed using a jejunal or radial forearm flap. In 2002, the authors began using the anterolateral thigh flap...
BACKGROUND
: Pharyngoesophageal defects traditionally have been reconstructed using a jejunal or radial forearm flap. In 2002, the authors began using the anterolateral thigh flap for pharyngoesophageal reconstruction, and it has become our preferred method. The purpose of this study was to analyze the clinical and functional outcomes achieved using this technique.
METHODS
: The medical records of 91 male and 23 female patients who underwent pharyngoesophageal reconstruction using an anterolateral thigh flap were retrospectively reviewed. Outcomes analyzed included length of hospital and intensive care unit stay, fistula and anastomotic stricture formation and other complications, swallowing and tracheoesophageal speech function, and survival. Most patients had primary (27%) or recurrent (42%) squamous cell carcinoma. Before reconstruction, 71% of patients had undergone surgery, radiotherapy, or both. There were 67 circumferential and 47 near-circumferential defects.
RESULTS
: Mean intensive care unit stay was 1.9 +/- 2.2 days, and mean hospital stay was 9.0 +/- 4.7 days. Two patients experienced total flap loss, and 1 patient had partial flap necrosis. Pharyngocutaneous fistulas and strictures occurred in 9% and 6% of patients, respectively. Ninety-one percent of patients tolerated an oral diet without the need for tube feeding. Tracheoesophageal puncture was performed for speech rehabilitation in 51 patients. Eight-one percent of patients with a secondary tracheoesophageal puncture achieved fluent speech versus 41% of patients with a primary tracheoesophageal puncture.
CONCLUSIONS
: This series demonstrates that excellent clinical and functional outcomes, with minimal donor site morbidity and quick recovery, are possible with pharyngoesophageal reconstruction using an anterolateral thigh flap. Cancer 2010. (c) 2010 American Cancer Society.
Topics: Adult; Aged; Aged, 80 and over; Deglutition; Esophagus; Female; Humans; Laryngeal Neoplasms; Laryngectomy; Length of Stay; Male; Middle Aged; Pharyngectomy; Pharynx; Postoperative Complications; Plastic Surgery Procedures; Speech Intelligibility; Surgical Flaps; Thigh; Treatment Outcome
PubMed: 20120029
DOI: 10.1002/cncr.24947 -
Radiation Oncology (London, England) Jan 2022To define the clinical characteristics of irradiation-induced nasopharyngeal necrosis (INN) after intensity-modulated radiotherapy (IMRT) and identify the influence of...
Irradiation-induced nasopharyngeal necrosis (INN) in newly diagnosed nasopharyngeal carcinoma treated by intensity-modulated radiation therapy: clinical characteristics and the influence of treatment strategies.
PURPOSE
To define the clinical characteristics of irradiation-induced nasopharyngeal necrosis (INN) after intensity-modulated radiotherapy (IMRT) and identify the influence of treatment strategies on INN in primary nasopharyngeal carcinoma (NPC) patients.
PATIENTS AND METHODS
From 2008 to 2019, NPC patients pathologically diagnosed with INN after primary IMRT were reviewed. Those patients were matched with propensity scores for patients without INN in our center. The impact of treatment strategies on INN occurrence was assessed using univariate and multivariate logistic regression analysis.
RESULTS
The incidence rate of INN was 1.9% among the primary NPC population, and 53 patients with INN were enrolled. Headache and foul odor were the main symptoms, and 71.7% of cases had pseudomembrane during or at the end of radiotherapy. All patients were in early or middle stage INN, and no one presented with skull-based osteoradionecrosis. Then 212 non-INN patients were included based on propensity scores match. Overall survival (p = 0.248) and progression-free survival (p = 0.266) curves were similar between the INN and non-INN groups. Treatment strategies including combining chemotherapy or molecular targeted therapy with radiotherapy were not associated with INN occurrence, while boost dose (OR 7.360; 95% CI 2.301-23.547; p = 0.001) was a predictor factor for it. However, the optimal threshold for an accumulated dose to predict INN's occurrence was failed to determine.
CONCLUSION
In the IMRT era, the severity of INN in primary NPC patients is lessened. This study showed that treatment strategies contributed little to develop INN, while the accumulated dose of radiation may relate to its occurrence.
Topics: Adolescent; Adult; Aged; Female; Humans; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharynx; Necrosis; Radiation Injuries; Radiotherapy, Intensity-Modulated; Retrospective Studies; Young Adult
PubMed: 35062991
DOI: 10.1186/s13014-022-01980-0 -
Parasites & Vectors May 2021The liver fluke Fasciola gigantica secretes excretory-secretory proteins during infection to mediate its interaction with the host. In this study, we investigated the...
BACKGROUND
The liver fluke Fasciola gigantica secretes excretory-secretory proteins during infection to mediate its interaction with the host. In this study, we investigated the immunomodulatory effects of a recombinant tegumental calcium-binding EF-hand protein 4 of F. gigantica (rFg-CaBP4) on goat monocytes.
METHODS
The rFg-CaBP4 protein was induced and purified by affinity chromatography. The immunogenic reaction of rFg-CaBP4 against specific antibodies was detected through western blot analysis. The binding of rFg-CaBP4 on surface of goat monocytes was visualized by immunofluorescence assay. The localization of CaBP4 within adult fluke structure was detected by immunohistochemical analysis. The cytokine transcription levels in response to rFg-CaBP4 were examined using ABI 7500 real-time PCR system. The expression of the major histocompatibility complex (MHC) class-II molecule (MHC-II) in response to rFg-CaBP4 protein was analyzed using Flow cytometry.
RESULTS
The isopropyl-ß-D-thiogalactopyranoside-induced rFg-CaBP4 protein reacted with rat sera containing anti-rFg-CaBP4 polyclonal antibodies in a western blot analysis. The adhesion of rFg-CaBP4 to monocytes was visualized by immunofluorescence and laser scanning confocal microscopy. Immunohistochemical analysis localized native CaBP4 to the oral sucker, pharynx, genital pore, acetabulum and tegument of adult F. gigantica. Co-incubation of rFg-CaBP4 with concanavalin A-stimulated monocytes increased the transcription levels of interleukin (IL)-2, IL-4, interferon gamma and transforming growth factor-β. However, a reduction in the expression of IL-10 and no change in the expression of tumor necrosis factor-α were detected. Additionally, rFg-CaBP4-treated monocytes exhibited a marked increase in the expression of the major histocompatibility complex (MHC) class-II molecule (MHC-II) and a decrease in MHC-I expression, in a dose-dependent manner.
CONCLUSIONS
These findings provide additional evidence that calcium-binding EF-hand proteins play roles in host-parasite interaction. Further characterization of the immunomodulatory role of rFg-CaBP4 should expand our understanding of the strategies used by F. gigantica to evade the host immune responses.
Topics: Animals; Calcium-Binding Proteins; Cytokines; Fasciola; Fascioliasis; Goats; Immunomodulation; Monocytes; Recombinant Proteins
PubMed: 34022913
DOI: 10.1186/s13071-021-04784-5 -
Environmental Toxicology and... Sep 2013To study the effect of air pollution on the microecology of the respiratory tracts and the relationship of the biotopes with respiratory diseases, Wistar rats exposed to...
To study the effect of air pollution on the microecology of the respiratory tracts and the relationship of the biotopes with respiratory diseases, Wistar rats exposed to mixed air pollutants were used as poisoning models. The bacterial floras of respiratory tract were analyzed as well as expression of pro-inflammatory mediators of the respiratory epithelium. The mRNA and protein expression levels of pro-inflammatory factor and cytokines measured showed that there were significant changes in the microbiocenosis of the respiratory tract. The microorganisms underwent quantitative and qualitative changes following exposure to mixed air pollutants including a decline of indigenous microflora and increase of the content of conditionally pathogenic microorganisms. These changes depended on the degree of air pollution severity. Measurement of pro-inflammatory factors CC16, TNF-α and IL-6 revealed a similar time-dependent relationship between the content of conditionally pathogenic microorganisms and the interference of CC16 secretion, as well as up-expression of TNF-α and IL-6.
Topics: Air Pollutants; Animals; Bronchoalveolar Lavage Fluid; Dose-Response Relationship, Drug; Female; Gene Expression Regulation; Inflammation Mediators; Inhalation Exposure; Interleukin-6; Male; Pharynx; RNA, Messenger; Rats; Rats, Wistar; Time Factors; Tumor Necrosis Factor-alpha; Uteroglobin
PubMed: 23834961
DOI: 10.1016/j.etap.2013.04.012 -
Clinical Infectious Diseases : An... Apr 2019Viral upper respiratory infections (URIs) are common and often precipitate acute otitis media (AOM), caused by bacterial otopathogens, in young children. Acute...
BACKGROUND
Viral upper respiratory infections (URIs) are common and often precipitate acute otitis media (AOM), caused by bacterial otopathogens, in young children. Acute inflammatory responses initiated in the early phase of viral URI contribute to preventing the development of AOM. Stringently-defined otitis-prone (sOP) children are susceptible to recurrent AOM.
METHODS
We assessed proinflammatory cytokine and chemokine levels in the nasopharynxes during viral URIs, and examined the different nasopharyngeal responses between viral URI events and the following AOM episodes in both sOP and non-otitis-prone (NOP) children.
RESULTS
The sOP children exhibited significantly more AOM episodes per child (8.86-fold higher), viral URIs (P < .0001), and viral URIs followed by AOMs (P < .0001) than the NOP children. The sOP children had lower nasal proinflammatory levels of interleukin (IL)-6 (P = .05), IL-10 (P = .001), tumor necrosis factor (TNF)-α (P = .004), and regulated on activation, normal T-cell-expressed and -secreted (RANTES; P = .002) than NOP children during viral URIs. NOP children had higher levels of IL-6 (P = .02), IL-10 (P = .02), interferon-γ (P = .003), TNF-α (P = .006), IL-1β (P = .022), monocyte chemoattractant protein 1 (P = .028), RANTES (P = .005), IL-2 (P = .002), and IL-17 (P = .007) during viral URIs versus AOMs following the URIs, when compared to sOP children.
CONCLUSIONS
We conclude that sOP children have more frequent viral URIs than NOP children, due to deficient antiviral nasopharyngeal proinflammatory cytokine and chemokine responses.
Topics: Child, Preschool; Cytokines; Female; Humans; Infant; Inflammation; Male; Nasopharynx; Otitis Media; Prospective Studies; Respiratory Tract Infections
PubMed: 30188973
DOI: 10.1093/cid/ciy750 -
Stereotactic body radiation therapy for head and neck tumor: disease control and morbidity outcomes.Journal of Radiation Research 2011We evaluated the efficacy and safety of stereotactic body radiation therapy (SBRT) for patients with head and neck tumors. From April 2005 through April 2008, 34...
We evaluated the efficacy and safety of stereotactic body radiation therapy (SBRT) for patients with head and neck tumors. From April 2005 through April 2008, 34 patients with head and neck tumors were treated with CyberKnife SBRT. Twenty-one of them had prior radiotherapy. Treatment sites were orbit (n = 7), cervical lymph nodes (n = 6), nasopharynx (n = 5), oropharynx (n = 4) and others (n = 12). The prescribed dose ranged from 19.5 to 42 Gy (median, 30 Gy) in 3-8 fractions for consecutive days. The target volume ranged from 0.7 to 78.1 cm(3) (median, 11.6 cm(3)). The median follow-up was 16 months. Treatment was well tolerated without significant acute complications in any cases. Complete response rate and partial response rate were 32.4% and 38.6%, respectively. The overall survival rates were 70.6% and 58.3% at 12 and 24 months, respectively. The overall survival was better in patients without prior radiotherapy within the previous 24 months or in case of smaller target volume. Six patients suffered severe late complications. All these patients had prior radiotherapy, and 2 of them developed massive hemorrhage in the pharynx and both died of this complication 5 and 28 months, respectively, after SBRT. Our preliminary results suggest that SBRT is an effective treatment modality for head and neck tumors. However, re-irradiation has significant risk of severe and even fatal late complications in the form of necrosis and hemorrhage in re-irradiated areas.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Head and Neck Neoplasms; Humans; Middle Aged; Prevalence; Radiosurgery; Risk Assessment; Risk Factors; Survival Analysis; Survival Rate; Treatment Outcome; Whole-Body Irradiation; Young Adult
PubMed: 21127390
DOI: 10.1269/jrr.10086 -
BMC Genomics Dec 2018The epithelium is the first line of defense against pathogens. Notably the epithelial cells lining the respiratory track are crucial in sensing airborne microbes and...
BACKGROUND
The epithelium is the first line of defense against pathogens. Notably the epithelial cells lining the respiratory track are crucial in sensing airborne microbes and mounting an effective immune response via the expression of target genes such as cytokines and chemokines. Gene expression regulation following microbial recognition is partly regulated by chromatin re-organization and has been described in immune cells but data from epithelial cells is not as detailed. Here, we report genome-wide changes of the H3K27ac mark, characteristic of activated enhancers and promoters, after stimulation of nasopharyngeal epithelial cells with the bacterial endotoxin Lipopolysaccharide (LPS).
RESULTS
In this study, we have identified 626 regions where the H3K27ac mark showed reproducible increase following LPS induction in epithelial cells. This indicated that sensing of LPS led to opening of the chromatin in our system. Moreover, this phenomenon seemed to happen extensively at enhancers regions and we could observe instances of Super-enhancer formation. As expected, LPS-increased H3K27ac regions were found in the vicinity of genes relevant for LPS response and these changes correlated with up-regulation of their expression. In addition, we found the induction of H3K27ac mark to overlap with the binding of one of the NF-kB members and key regulator of the innate immune response, RELA, following LPS sensing. Indeed, inhibiting the NF-kB pathway abolished the deposition of H3K27ac at the TNF locus, a target of RELA, suggesting that these two phenomena are associated.
CONCLUSIONS
Enhancers' selection and activation following microbial or inflammatory stimuli has been described previously and shown to be mediated via the NF-kB pathway. Here, we demonstrate that this is also likely to occur in the case of LPS-sensing by nasopharyngeal epithelial cells as well. In addition to validating previous findings, we generated a valuable data set relevant to the host immune response to epithelial cell colonizing or infecting pathogens.
Topics: Cell Line, Tumor; Epithelial Cells; Gene Expression Regulation; Histones; Humans; Immunity, Innate; Lipopolysaccharides; Nasopharynx; Transcription Factor RelA; Tumor Necrosis Factor-alpha
PubMed: 30587130
DOI: 10.1186/s12864-018-5295-4