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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 -
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 -
Fish & Shellfish Immunology Jun 2020Emerging evidence suggests that bitter and sweet Taste receptors (TRs) in the airway are important sentinels of innate immunity. TRs are G protein-coupled receptors that...
Emerging evidence suggests that bitter and sweet Taste receptors (TRs) in the airway are important sentinels of innate immunity. TRs are G protein-coupled receptors that trigger downstream signaling cascades in response to activation of specific ligands. Among them, the T1R family consists of three genes: T1R1, T1R2, and T1R3, which function as heterodimers for sweet tastants and umami tastants. While the other TRs family components T2Rs function as bitter tastants. To understand the relationship between TRs and mucosal immunity in teleost, here, we firstly identified and analyzed the molecular characteristics of three TRs (T1R1, T1R3, and T2R4) in rainbow trout (Oncorhynchus mykiss). Secondly, by quantitative real-time PCR (qPCR), we detected the mRNA expression levels of T1R1, T1R3 and T2R4 and found that the three genes could be tested in all detected tissues (pharynx, buccal cavity, tongue, nose, gill, eye, gut, fin, skin) and the expression levels of T1R3 and T2R4 were higher in buccal mucosa (BM) and pharyngeal mucosa (PM) compare to other tissues. It may suggest that T1R3 and T2R4 play important roles in BM and PM. Then, to analyses the changes of expression levels of the three genes in rainbow trout infected with pathogens, we established three infection models Flavobacterium columnare (F. cloumnare), infectious hematopoietic necrosis virus (IHNV) and Ichthyophthirius multifiliis (Ich). Subsequently, by qPCR, we detected the expression profiles of TRs in the gustatory tissues (BM, PM and skin) of rainbow trout after infection with F. cloumnare, IHNV, and Ich, respectively. We found that under three different infection models, the expression of the T1R1, T1R3 and T2R4 showed their own changes in mRNA levels. And the expression levels of the T1R1, T1R3 and T2R4 changed significantly at different time points in response to three infection models, respectively, suggesting that TRs may be associated with mucosal immunity.
Topics: Amino Acid Sequence; Animals; Ciliophora Infections; Fish Diseases; Fish Proteins; Flavobacteriaceae Infections; Flavobacterium; Gene Expression Profiling; Gene Expression Regulation; Hymenostomatida; Immunity, Innate; Immunity, Mucosal; Infectious hematopoietic necrosis virus; Oncorhynchus mykiss; Phylogeny; Receptors, G-Protein-Coupled; Rhabdoviridae Infections; Sequence Alignment
PubMed: 32244029
DOI: 10.1016/j.fsi.2020.03.055 -
Age and Ageing Aug 2020Statins are widely prescribed in the treatment of hypercholesterolemia. While their efficacy in the secondary prevention of vascular events is proven, their safety...
Statins are widely prescribed in the treatment of hypercholesterolemia. While their efficacy in the secondary prevention of vascular events is proven, their safety profile in older patients with multiple co-morbidities and polypharmacy remains questionable. Although rare, antihydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) myopathy is a severe adverse effect of statins, manifesting as myalgias, proximal muscle weakness, muscle cell necrosis and rhabdomyolysis. We report an uncommon case of an autopsy-proven anti-HMGCR necrotising myopathy predominately affecting pharyngeal muscles in an older patient, leading to dysphagia, pneumonia and death within 3 weeks from onset. Clinicians should screen for dysphagia in any patient with suspected anti-HMGCR myopathy, order an anti-HMGCR antibody titre and consider prompt immunosupressive therapy.
Topics: Aged; Autoantibodies; Autoimmune Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Myositis; Pharyngeal Muscles
PubMed: 32147707
DOI: 10.1093/ageing/afaa038 -
PloS One 2019Tonsil-derived mesenchymal stem cells (TMSC) have characteristics of MSC and have many advantages. In our previous studies, intraperitoneal (IP) injection of TMSC in...
Tonsil-derived mesenchymal stem cells (TMSC) have characteristics of MSC and have many advantages. In our previous studies, intraperitoneal (IP) injection of TMSC in acute and chronic colitis mouse models improved the disease activity index, colon length, and the expression levels of proinflammatory cytokines. However, TMSC were not observed to migrate to the inflammation site in the intestine. The aim of this study was to verify the therapeutic effect of conditioned medium (CM) released by TMSC (TMSC-CM) in a mouse model of dextran sulfate sodium (DSS)-induced chronic colitis. TMSC-CM was used after seeding 5×105 cells onto a 100 mm dish and culturing for 5-7 days. TMSC-CM was concentrated (TMSC-CM-conc) by three times using a 100 kDa cut-off centrifugal filter. Seven-week-old C57BL/6 mice were randomly assigned to the following 5 groups: 1) normal, 2) colitis, 3) TMSC, 4) TMSC-CM, and 5) TMSC-CM-conc. Chronic colitis was induced by continuous oral administration of 1.5% dextran sulfate sodium (DSS) for 5 days, followed by 5 additional days of tap water feeding. This cycle was repeated two more times (total 30 days). Phosphate buffered saline (in the colitis group), TMSC, TMSC-CM, and TMSC-CM-conc were injected via IP route 4, 4, 12, and 4 times, respectively. Reduction of disease activity index, weight gain, recovery of colon length, and decreased in the expression level of the proinflammatory cytokines, interleukin (IL)-1β, IL-6, and IL-17 were observed at day 30 in the treatment groups, compared to control. However, histological colitis scoring and the expression level of tumor necrosis factor α and IL-10 did not differ significantly between each group. TMSC-CM showed an equivalent effect to TMSC related to the improvement of inflammation in the chronic colitis mouse model. The data obtained support the use of TMSC-CM to treat inflammatory bowel disease without any cell transplantation.
Topics: Animals; Anti-Inflammatory Agents; Cell Proliferation; Chronic Disease; Colitis; Colon; Culture Media, Conditioned; Cytokines; Dextran Sulfate; Disease Models, Animal; Humans; Inflammation; Mesenchymal Stem Cells; Mice, Inbred C57BL; Palatine Tonsil; Protective Agents; Spleen
PubMed: 31790467
DOI: 10.1371/journal.pone.0225739 -
Annals of Palliative Medicine Jul 2021Necrotizing fasciitis (NF) is a rare, fulminant, lethal soft-tissue infection result in fascial necrosis, it is rarer in the head and neck area. Infection caused by...
Necrotizing fasciitis (NF) is a rare, fulminant, lethal soft-tissue infection result in fascial necrosis, it is rarer in the head and neck area. Infection caused by Klebsiella oxytoca is much less common. Therefore, we reported a case of NF in the maxillofacial region, neck and upper mediastinum caused by Klebsiella oxytoca as the main cause recently treated in our department. The patient is a middle-aged male with a 10-year history of diabetes with unstable insulin control. The main symptoms were pain on left side with dysphagia and fever and the situation was getting worse. The patient had limited ability to have mouth open and had hyperemia, swelling on the left pharynx, maxillofacial area, and upper left neck and skin tenderness, and all symptoms were getting worse quick. The CT mainly found out that left oropharyngeal wall, parotid gland area, bilateral submaxilla, left neck, and superior mediastinum are swelling with gas. The blood test result: leukocytes count 16.64×109/L, neutrophils percentage 85.8%; C-Pr 320 mg/L; urinary routine: urine glucose (+++++), ketone bodies (+++++); fasting glucose metabolism: glucose 21.33 mmol/L, glycosylated albumin 47.67%. Three incisions of facial and neck were performed to drain pus. Result of bacteria culture: Klebsiella oxytoca and Streptococcus constellatus During treatment of DKA and reduce patient glucose level, we also treated patient with neck and trachea incisions to drain pus and cleaned daily wound area and used different antibiotics according to the bacteria culture and CT results. And finally, the patient was cured and discharged from hospital. This case of NF was very rare not only the bacteria in this case but also the pathological changes related (involving the mediastinum). The report of his diagnosis and treatment can provide experience for future treatments.
Topics: Fasciitis, Necrotizing; Humans; Klebsiella oxytoca; Male; Mediastinum; Middle Aged; Neck; Streptococcus constellatus
PubMed: 33977729
DOI: 10.21037/apm-20-2427 -
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 -
Frontiers in Immunology 2021The intercellular adhesion molecule-1 (ICAM-1), known as CD54, is a transmembrane cell surface glycoprotein that interacts with two integrins (i.e., LFA-1 and Mac-l)...
Molecular Characterization and Expression Analysis of Intercellular Adhesion Molecule-1 (ICAM-1) Genes in Rainbow Trout () in Response to Viral, Bacterial and Parasitic Challenge.
The intercellular adhesion molecule-1 (ICAM-1), known as CD54, is a transmembrane cell surface glycoprotein that interacts with two integrins (i.e., LFA-1 and Mac-l) important for trans-endothelial migration of leukocytes. The level of ICAM-1 expression is upregulated in response to some inflammatory stimulations, including pathogen infection and proinflammatory cytokines. Yet, to date, our knowledge regarding the functional role of ICAM-1 in teleost fish remains largely unknown. In this study, we cloned and characterized the sequence of ICAM-1 in rainbow trout () for the first time, which exhibited that the molecular features of ICAM-1 in fishes were relatively conserved compared with human ICAM-1. The transcriptional level of ICAM-1 was detected in 12 different tissues, and we found high expression of this gene in the head kidney, spleen, gills, skin, nose, and pharynx. Moreover, upon stimulation with infectious hematopoietic necrosis virus (IHNV), G (), and (Ich) in rainbow trout, the morphological changes were observed in the skin and gills, and enhanced expression of ICAM-1 mRNA was detected both in the systemic and mucosal tissues. These results indicate that ICAM-1 may be implicated in the mucosal immune responses to viral, bacterial, and parasitic infections in teleost fish, meaning that ICAM-1 emerges as a master regulator of mucosal immune responses against pathogen infections in teleost fish.
Topics: Animals; Ciliophora Infections; Fish Diseases; Fish Proteins; Flavobacteriaceae Infections; Flavobacterium; Gene Expression Regulation; Hymenostomatida; Infectious hematopoietic necrosis virus; Intercellular Adhesion Molecule-1; Oncorhynchus mykiss; Rhabdoviridae Infections
PubMed: 34489953
DOI: 10.3389/fimmu.2021.704224 -
EBioMedicine Mar 2020Human immunology research is often limited to peripheral blood. However, there are important differences between blood immune cells and their counterparts residing in...
BACKGROUND
Human immunology research is often limited to peripheral blood. However, there are important differences between blood immune cells and their counterparts residing in secondary lymphoid organs, such as in the case of germinal center (GC) T follicular helper (Tfh) cells and GC B cells.
METHODS
We developed a versatile ex vivo lymphoid organ culture platform that is based on human pharyngeal tonsils (adenoids) and allows for drug testing. We systematically phenotyped Tfh and GC B cell subsets in explant- and suspension cultures using multicolor flow cytometry and cytokine multiplex analysis.
FINDINGS
Phenotypic changes of certain ex vivo cultured immune cell subsets could be modulated by cytokine addition. Furthermore, we optimized an activation-induced marker assay to evaluate the response to T cell stimulation. We provide proof-of-concept that Tfh and GC B cells could be modulated in these cultures by different anti-inflammatory drugs in unstimulated states and upon activation with vaccine-derived antigens. For example, GC B cells were lost upon CD40L blockade, and clinically approved JAK inhibitors impacted Tfh and GC B cells, including down-regulation of their key transcription factor BCL6. BCL6 regulation was affected by IL-6 signaling in T cells and IL-4 in B cells, respectively. Furthermore, we demonstrated that JAK signaling and TNF signaling contributed to the stimulation-induced activation of tonsil-derived T cells.
INTERPRETATION
Our optimized methods, assays, and mechanistic findings can contribute to a better understanding of human GC responses. These insights may be relevant for improving autoimmune disease therapy and vaccination efficacy.
FUNDING
This work was supported by a project grant under the joint research cooperation agreement of LMU Munich, LMU University Hospital, and Sanofi-Aventis Deutschland GmbH, as well as by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - Emmy Noether Programme BA 5132/1-1 and BA 5132/1-2 (252623821), SFB 1054 Project B12 (210592381), and SFB 914 Project B03 (165054336).
Topics: Adenoids; Anti-Inflammatory Agents; B-Lymphocytes; Cells, Cultured; Child; Child, Preschool; Germinal Center; Humans; Immunophenotyping; Interleukins; Janus Kinases; Proto-Oncogene Proteins c-bcl-6; T Follicular Helper Cells; Tissue Culture Techniques; Tumor Necrosis Factor-alpha
PubMed: 32114393
DOI: 10.1016/j.ebiom.2020.102684 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Jul 2022Because of its peculiar anatomical location, most patients with hypopharyngeal and cervical esophageal cancer are at advanced stage when they visit the hospital. At...
OBJECTIVES
Because of its peculiar anatomical location, most patients with hypopharyngeal and cervical esophageal cancer are at advanced stage when they visit the hospital. At present, the treatment for hypopharyngeal and cervical esophageal cancer is primarily surgical resection and radiotherapy. However, due to the wide range of surgical resection, it can often lead to a large range of annular defects. Therefore, the upper digestive tract reconstruction after tumor resection is very important. We use the free anterolateral thigh flap (ALT) and free jejunum (FJ) transfer to reconstruct the hypopharyngeal and cervical esophagus, and to investigate the effect of both reconstruction methods on upper gastrointestinal tract defects.
METHODS
A retrospective analysis was conducted to investigate the clinical data of 42 patients with hypopharyngeal and cervical esophageal cancer (Clinical Stage IV) from Jan. 2004 to Jan. 2016 in the Second Xiangya Hospital of Central South University. All patients underwent total laryngopharyngectomy and cervical esophageal resection. The hypopharyngeal circumferential and cervical esophageal defects were reconstructed with free ALT (=22) or FJ (=20). Four patients who underwent radiotherapy and chemotherapy before surgery did not receive radiotherapy or chemotherapy after surgery. The remaining 38 patients underwent postoperative radiotherapy and chemotherapy. All patients were followed up by telephone or outpatient review, with a follow-up deadline in Jan. 2021. We compared the differences between the 2 groups in postoperative complications, radiotherapy complications, and survival rate. The differences in individual characteristics between 2 groups were analyzed using Fisher test. The differences in postoperative and radiotherapy complications between two groups were analyzed using χ² test. The 3- and 5-year overall survival rates were calculated using Kaplan-Meier survival curve method.
RESULTS
In the ALT group, the postoperative complications mainly included anastomotic fistula, chylous fistula and subcutaneous hematoma of the donor site. The radiotherapy complication was anastomotic stenosis. However, in the FJ group, the postoperative complications mainly included chylous fistula, intestinal obstruction, and intestinal fistula. The radiotherapy complications mainly contained anastomotic fistula and tissue flap necrosis. The cases of postoperative complications in the ALT group and the FJ group were 7 and 5, respectively (=0.625), and the cases of radiotherapy complications were 3 and 4, respectively (=0.563). The 3-year overall survival rates in the ALT group and the FJ group were 52.9% and 46.7%, respectively, and the 5-year total survival rates were 35.1% and 31.9%, respectively (=0.53). The cases of anastomotic stenosis after radiotherapy in the ALT group were more than those in the FJ group (=0.097). However, the cases of jejunal necrosis and anastomotic fistula after radiotherapy in the FJ group were more than those in the ALT group (=0.066).
CONCLUSIONS
There are no significant differences in postoperative and radiotherapy complications and 3-and 5-year survival rates between the ALT group and the FJ group. The reconstruction with ALT is prone to develop anastomotic stricture. The reconstruction with FJ cannot withstand high-dose radiotherapy. The ALT and FJ are effective methods in the reconstruction of hypopharynx and cervical esophagus. The treatment protocol should be carefully chosen based on its advantages and disadvantages of these 2 methods.
Topics: Constriction, Pathologic; Esophageal Neoplasms; Fistula; Free Tissue Flaps; Humans; Hypopharynx; Jejunum; Necrosis; Postoperative Complications; Plastic Surgery Procedures; Retrospective Studies; Thigh
PubMed: 36039585
DOI: 10.11817/j.issn.1672-7347.2022.210763