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Cell Communication and Signaling : CCS Jun 2024Mesenchymal stem cells (MSCs) are widely used in the development of therapeutic tools in regenerative medicine. However, their quality decreases during in vitro...
BACKGROUND
Mesenchymal stem cells (MSCs) are widely used in the development of therapeutic tools in regenerative medicine. However, their quality decreases during in vitro expansion because of heterogeneity and acquired cellular senescence. We investigated the potential role of podoplanin (PDPN) in minimizing cellular senescence and maintaining the stemness of tonsil-derived MSCs (TMSCs).
METHODS
TMSCs were isolated from human tonsil tissues using an enzymatic method, expanded, and divided into two groups: early-passaged TMSCs, which were cultured for 3-7 passages, and late-passaged TMSCs, which were passaged more than 15 times. The TMSCs were evaluated for cellular senescence and MSC characteristics, and PDPN-positive and -negative cells were identified by fluorescence-activated cell sorting. In addition, MSC features were assessed in siRNA-mediated PDPN-depleted TMSCs.
RESULTS
TMSCs, when passaged more than 15 times and becoming senescent, exhibited reduced proliferative rates, telomere length, pluripotency marker (NANOG, OCT4, and SOX2) expression, and tri-lineage differentiation potential (adipogenesis, chondrogenesis, or osteogenesis) compared to cells passaged less than five times. Furthermore, PDPN protein levels significantly decreased in a passage-dependent manner. PDPN-positive cells maintained their stemness characteristics, such as MSC-specific surface antigen (CD14, CD34, CD45, CD73, CD90, and CD105) and pluripotency marker expression, and exhibited higher tri-lineage differentiation potential than PDPN-negative cells. SiRNA-mediated silencing of PDPN led to decreased cell-cycle progression, proliferation, and migration, indicating the significance of PDPN as a preliminary senescence-related factor. These reductions directly contributed to the induction of cellular senescence via p16/Rb pathway activation.
CONCLUSION
PDPN may serve as a novel biomarker to mitigate cellular senescence in the clinical application of MSCs.
Topics: Mesenchymal Stem Cells; Humans; Cellular Senescence; Membrane Glycoproteins; Cyclin-Dependent Kinase Inhibitor p16; Palatine Tonsil; Cell Differentiation; Cell Proliferation; Signal Transduction; Cells, Cultured
PubMed: 38867259
DOI: 10.1186/s12964-024-01705-8 -
JMIR Research Protocols Jun 2024Testing for SARS-CoV-2 is essential to provide early COVID-19 treatment for people at high risk of severe illness and to limit the spread of infection in society. Proper... (Randomized Controlled Trial)
Randomized Controlled Trial
Molecular Detection of SARS-CoV-2 From Throat Swabs Performed With or Without Specimen Collection From the Tonsils: Protocol for a Multicenter Randomized Controlled Trial.
BACKGROUND
Testing for SARS-CoV-2 is essential to provide early COVID-19 treatment for people at high risk of severe illness and to limit the spread of infection in society. Proper upper respiratory specimen collection is the most critical step in the diagnosis of the SARS-CoV-2 virus in public settings, and throat swabs were the preferred specimens used for mass testing in many countries during the COVID-19 pandemic. However, there is still a discussion about whether throat swabs have a high enough sensitivity for SARS-CoV-2 diagnostic testing, as previous studies have reported a large variability in the sensitivity from 52% to 100%. Many previous studies exploring the diagnostic accuracy of throat swabs lack a detailed description of the sampling technique, which makes it difficult to compare the different diagnostic accuracy results. Some studies perform a throat swab by only collecting specimens from the posterior oropharyngeal wall, while others also include a swab of the palatine tonsils for SARS-CoV-2 testing. However, studies suggest that the palatine tonsils could have a tissue tropism for SARS-CoV-2 that may improve the SARS-CoV-2 detection during sampling. This may explain the variation of sensitivity reported, but no clinical studies have yet explored the differences in sensitivity and patient discomfort whether the palatine tonsils are included during the throat swab or not.
OBJECTIVE
The objective of this study is to examine the sensitivity and patient discomfort of a throat swab including the palatine tonsils compared to only swabbing the posterior oropharyngeal wall in molecular testing for SARS-CoV-2.
METHODS
We will conduct a randomized controlled study to compare the molecular detection rate of SARS-CoV-2 by a throat swab performed from the posterior oropharyngeal wall and the palatine tonsils (intervention group) or the posterior oropharyngeal wall only (control group). Participants will be randomized in a 1:1 ratio. All participants fill out a baseline questionnaire upon enrollment in the trial, examining their reason for being tested, symptoms, and previous tonsillectomy. A follow-up questionnaire will be sent to participants to explore the development of symptoms after testing.
RESULTS
A total of 2315 participants were enrolled in this study between November 10, 2022, and December 22, 2022. The results from the follow-up questionnaire are expected to be completed at the beginning of 2024.
CONCLUSIONS
This randomized clinical trial will provide us with information about whether throat swabs including specimens from the palatine tonsils will improve the diagnostic sensitivity for SARS-CoV-2 molecular detection. These results can, therefore, be used to improve future testing recommendations and provide additional information about tissue tropism for SARS-CoV-2.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05611203; https://clinicaltrials.gov/study/NCT05611203.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/47446.
Topics: Humans; Specimen Handling; Pharynx; SARS-CoV-2; COVID-19; Palatine Tonsil; COVID-19 Nucleic Acid Testing; Adult; Male; Sensitivity and Specificity; Female; Randomized Controlled Trials as Topic; Middle Aged; COVID-19 Testing
PubMed: 38865190
DOI: 10.2196/47446 -
Primary Tuberculosis of Tonsils: Interesting Case Detected During the Histopathological Examination.Cureus May 2024Despite being a preventable and curable disease, tuberculosis, which mainly affects the lungs, is still a major cause of illness and death worldwide, with more than one...
Despite being a preventable and curable disease, tuberculosis, which mainly affects the lungs, is still a major cause of illness and death worldwide, with more than one million people dying from it each year. The affliction of the tonsils is uncommon, and isolated tonsillar tuberculosis in the absence of active pulmonary disease is an extremely rare condition that requires early and accurate diagnosis to provide proper management. Microscopic examination is one of the gold-standard tools for diagnosing tuberculosis. However, routine histopathological investigation for tonsillectomy specimens is not justified except in cases of unusual clinical or postoperative presentations. A 20-year-old female patient who experienced recurrent episodes of infections with enlarged tonsils and adenoids and showed a slightly unusual presentation was sent for a histopathology examination. Upon microscopic examination, a caseating granulomatous reaction was found, and staining for acid-fast bacilli tested positive. The patient was treated for tuberculosis of the tonsils, and their condition improved.
PubMed: 38832186
DOI: 10.7759/cureus.59616 -
Turkish Journal of Medical Sciences 2024Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder in children. Determination of risk factors for the development of OSA is essential for early...
BACKGROUND/AIM
Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder in children. Determination of risk factors for the development of OSA is essential for early diagnosis and treatment of the disease and decreases the risk of negative consequences. This study aimed to investigate the predictive values of Mallampati score, tonsillar size, and BMI z-score in the presence and severity of OSA in children.
MATERIALS AND METHODS
This prospective cross-sectional study included 114 children with OSA symptoms. All children were assessed by BMI z-score, Mallampati score, and tonsillar size and underwent overnight polysomnography. They were consecutively selected and assigned to 4 groups as follows: Group 1 included normal-weight with a low Mallampati score; Group 2 involved normal-weight with a high Mallampati score; Group 3 included obese with a low Mallampati score; and Group 4 involved obese with a high Mallampati score.
RESULTS
Of the 114 included children, 58 were female and 56 were male, with a mean age of 13.1 ± 2.9 years. OSA frequency and apnea-hypopnea index were significantly higher in group 4 compared with other groups (p = 0.003 and p < 0.0001, respectively), whereas average and minimum spO were significantly lower (for both, p = 0.001). Mallampati score and BMI z-score were found to be significant for predicting OSA (odds ratio = 4.147, 95% CI: 1.440-11.944; p = 0.008 and odds ratio = 1.760, 95% CI: 1.039-2.980; p = 0.035, respectively). Among OSA patients, the Mallampati score, tonsillar size, and BMI z-score were found to be significant for predicting OSA severity (odds ratio = 4.520, 95% CI: 1.332-15.335, p = 0.015, odds ratio = 9.177, 95% CI: 2.513-33.514, p = 0.001, and odds ratio = 2.820, 95% CI: 1.444-5.508; p = 0.002, respectively).
CONCLUSION
The coexistence of the Mallampati score and BMI z-score significantly increases the presence of OSA in children. Mallampati score, tonsillar size, and BMI z-score are promising parameters for predicting OSA severity.
Topics: Humans; Sleep Apnea, Obstructive; Male; Female; Palatine Tonsil; Cross-Sectional Studies; Body Mass Index; Prospective Studies; Child; Adolescent; Severity of Illness Index; Polysomnography; Predictive Value of Tests; Risk Factors
PubMed: 38812649
DOI: 10.55730/1300-0144.5791 -
Frontiers in Immunology 2024Sex-based differences in immune cell composition and function can contribute to distinct adaptive immune responses. Prior work has quantified these differences in...
Sex-based differences in immune cell composition and function can contribute to distinct adaptive immune responses. Prior work has quantified these differences in peripheral blood, but little is known about sex differences within human lymphoid tissues. Here, we characterized the composition and phenotypes of adaptive immune cells from male and female ex vivo tonsils and evaluated their responses to influenza antigens using an immune organoid approach. In a pediatric cohort, female tonsils had more memory B cells compared to male tonsils direct ex vivo and after stimulation with live-attenuated but not inactivated vaccine, produced higher influenza-specific antibody responses. Sex biases were also observed in adult tonsils but were different from those measured in children. Analysis of peripheral blood immune cells from vaccinated adults also showed higher frequencies of tissue homing CD4 T cells in female participants. Together, our data demonstrate that distinct memory B and T cell profiles are present in male vs. female lymphoid tissues and peripheral blood respectively and suggest that these differences may in part explain sex biases in response to vaccines and viruses.
Topics: Humans; Female; Male; Child; Palatine Tonsil; Adult; Influenza Vaccines; Influenza, Human; Sex Characteristics; Child, Preschool; Adolescent; Antibodies, Viral; Memory B Cells; Organ Specificity; Young Adult; Sex Factors; CD4-Positive T-Lymphocytes; B-Lymphocytes; Immunologic Memory
PubMed: 38812520
DOI: 10.3389/fimmu.2024.1373537 -
EJNMMI Research May 2024F-18-flurodeoxyglucose (FDG) PET/CT is routinely used for staging, evaluation of response to treatment and follow-up of most pediatric malignancies. Cervical lymph nodes...
BACKGROUND
F-18-flurodeoxyglucose (FDG) PET/CT is routinely used for staging, evaluation of response to treatment and follow-up of most pediatric malignancies. Cervical lymph nodes can be involved in some pediatric malignancies, but increased uptake in non-malignant cervical lymph nodes is not exceptional in this population. The aim of the present study is to identify predictors of the maximum uptake in non-malignant cervical lymph nodes in the pediatric population.
METHODS
191 FDG PET/CT studies of pediatric patients without malignant involvement of cervical lymph nodes were retrospectively reviewed. The maximal Standard Uptake Value in the hottest cervical lymph node (SUVmax), as well as demographic, technical and imaging variables were recorded. The predictive effect of those variables on SUVmax was estimated using linear regression models.
RESULTS
Increased FDG activity in cervical nodes was observed in 136/191 studies (71%). The mean SUVmax was 2.2 ± 1.3. Ipsilateral palatine tonsil SUVmax, mean liver uptake, and treatment status were all statistically significant predictors of SUVmax. However, in multivariate regression analysis, only ipsilateral palatine tonsil SUVmax was found to be significant. In addition, SUVmax was greater than the mean liver uptake in 50% of all studies. This proportion was higher in younger children, reaching 77% of studies of children younger than six years.
CONCLUSION
SUVmax in ipsilateral palatine tonsil is a strong predictor of the maximal uptake value of non-malignant cervical lymph nodes in children. The intensity of uptake in non-malignant cervical lymph nodes is frequently higher than liver uptake in children, and this tendency increases for younger patients.
TRIAL WAS REGISTERED
In the internal hospital registry under TRN 0209-22-HMO on date 23.04.2022.
PubMed: 38809472
DOI: 10.1186/s13550-024-01110-9 -
International Journal of Molecular... May 2024Tonsillectomy with steroid pulse therapy (SPT) has been established as an effective treatment for immunoglobulin A nephropathy (IgAN) in Japan. However, the underlying...
Tonsillectomy with steroid pulse therapy (SPT) has been established as an effective treatment for immunoglobulin A nephropathy (IgAN) in Japan. However, the underlying mechanisms supporting tonsillectomy remain unclear. This study assessed palatine tonsils from 77 patients with IgAN, including 14 and 63 who received SPT before and after tonsillectomy, respectively. Tonsils from 21 patients with chronic tonsillitis were analyzed as controls. Specific tonsillar lesions were confirmed in patients with IgAN, correlating with active or chronic renal glomerular lesions and SPT. T-nodule and involution of lymphoepithelial symbiosis scores in tonsils correlated with the incidence of active crescents and segmental sclerosis in the glomeruli, respectively. The study revealed an essential role of the tonsil-glomerular axis in early active and late chronic phases. Moreover, the SPT-preceding group demonstrated no changes in the T-nodule score, which correlated with active crescent formation, but exhibited a considerable shrinkage of lymphatic follicles that produced aberrant IgA1. The study underscores the involvement of innate and cellular immunity in IgAN and advocates for tonsillectomy as a necessary treatment alongside SPT for IgAN, based on a stepwise process.
Topics: Humans; Glomerulonephritis, IGA; Tonsillectomy; Palatine Tonsil; Female; Male; Adult; Kidney Glomerulus; Retrospective Studies; Middle Aged; Tonsillitis; Young Adult; Immunoglobulin A
PubMed: 38791337
DOI: 10.3390/ijms25105298 -
PloS One 2024Altered immunological responses in the palatine tonsils may be involved in the pathogenesis of IgA nephropathy (IgAN). The germinal center serves as the site for...
BACKGROUND
Altered immunological responses in the palatine tonsils may be involved in the pathogenesis of IgA nephropathy (IgAN). The germinal center serves as the site for antigen-specific humoral immune responses in the palatine tonsils. Germinal center involution is frequently observed in the palatine tonsils of IgAN (IgAN tonsils). However, the pathogenic significance of these characteristic changes remains unclear. This study aimed to investigate the morphological changes in secondary lymphoid follicles in IgAN tonsils and to evaluate the correlation between the morphometric results and the clinicopathological severity of IgAN.
METHODS
The tonsils of age-matched patients with recurrent tonsillitis (RT tonsils) were used as controls. The correlation between the degree of lymphoid follicular involution and histopathological severities in clinical or kidney biopsy was evaluated.
RESULTS
In total, 87 patients with IgAN were included (48% male, median age 35 years, median estimated glomerular filtration rate: 74 mL/min/1.73 m2). Compared to RT tonsils, IgAN tonsils showed smaller median sizes of lymphoid follicles and germinal centers (P < 0.001). The relative areas of lymphoid follicles (%LFA) and germinal centers (%GCA) in the total tonsillar tissue were smaller in the IgAN tonsils than in the RT tonsils (P < 0.001). In contrast, the median proportion of mantle zones in the total tonsillar tissue was comparable between the groups. A lower %LFA was associated with a longer period from the onset of urinary abnormalities to biopsy diagnosis and higher urinary protein excretion (P = 0.01). %LFA showed significant negative correlations with frequencies of glomeruli with both global and segmental sclerosis.
CONCLUSIONS
The present study confirmed accelerated germinal center involution in the tonsils of patients with IgAN. This characteristic change in the IgAN tonsil correlates with heavy proteinuria and advanced chronic histopathological changes in the kidneys, thereby suggesting the involvement of repeated tonsillar immunoreactions during IgAN progression.
Topics: Humans; Glomerulonephritis, IGA; Palatine Tonsil; Germinal Center; Male; Female; Adult; Tonsillitis; Middle Aged; Young Adult; Kidney
PubMed: 38709804
DOI: 10.1371/journal.pone.0301853 -
Fujita Medical Journal May 2024To determine whether the combination of the pharyngeal tonsil grade and palatine tonsil grade results in differences in the apnea-hypopnea index (AHI) and to determine...
OBJECTIVE
To determine whether the combination of the pharyngeal tonsil grade and palatine tonsil grade results in differences in the apnea-hypopnea index (AHI) and to determine whether each parameter separately (pharyngeal tonsil grade and palatine tonsil grade) results in differences in severe obstructive sleep apnea (OSA).
METHODS
This cross-sectional study involved 107 children (mean age, 7.2 years; range, 4-12 years) suspected of having OSA because of snoring or sleep-related complaints. The patients underwent polysomnography, and their palatine and pharyngeal tonsils were graded.
RESULTS
In examining whether the palatine tonsils and pharyngeal tonsils could be risk factors for severe OSA, the adjusted odds ratios were 4.42 for palatine tonsil grade 4 versus 1-3 and 10.40 for pharyngeal tonsil grade 4 versus 1-3; both were highly statistically significant. We also found that the AHI when both the pharyngeal and palatine tonsils were grade 4 was higher than the AHI expected for the pharyngeal and palatine tonsils alone.
CONCLUSIONS
The combination of grade 4 pharyngeal tonsils and grade 4 palatine tonsils resulted in an AHI much higher than the AHI of other combinations (pharyngeal tonsils grades 1-3 and 4, palatine tonsils grades 1-3 and 4). We believe that grade 4 pharyngeal tonsils and grade 4 palatine tonsils have a great influence on severe OSA and that grade 4 pharyngeal tonsils increase the AHI.
PubMed: 38708074
DOI: 10.20407/fmj.2023-011 -
Sleep Medicine Jul 2024Most children treated for obstructive sleep disordered breathing (oSDB) are not systematically assessed by polysomnography (PSG) nor by structuredsymptom quantification...
OBJECTIVE/BACKGROUND
Most children treated for obstructive sleep disordered breathing (oSDB) are not systematically assessed by polysomnography (PSG) nor by structuredsymptom quantification before surgical treatment. The main objective of this study wasto investigate the effect of adeno-tonsillotomy (ATO) on symptom burden and PSGparameters.
METHODS
Children aged 2-10 years with oSDB were selected for ATO based uponclinical findings according to current standards of care in Denmark. Each childunderwent standardized assessment before and 3 months after surgery, including aPSG, tonsil size assessment, and the Pediatric Sleep Questionnaire -Sleep RelatedBreathing Disorder (PSQ) to quantify symptom burden. Obstructive sleep apnea (OSA)was defined as an obstructive apnea-hypopnea index (oAHI) ≥2/h. Successfultreatment was defined as post-surgery oAHI ≤5/h, and complete cure as oAHI ≤2/h.
RESULTS
Fifty-two children were included. Mean age was 5.0 years (SD ± 1.76). Thirteen children were identified with baseline oAHI <2/h. Significant improvement inOSA severity was observed in children with moderate-to-severe OSA, in whom oAHI decreased from 15.7/h to 2.6/h (p < 0.001). Treatment success was obtained in 85% and cure was obtained in 42% of children. PSQ-score significantly improved from 0.52 (CI 0.47-0.56) to 0.26 (CI 0.21-0.32) (p < 0.001). Baseline OSA severity was notcorrelated to baseline symptom burden nor to symptom relief after ATO. There were noserious adverse events.
CONCLUSIONS
Adeno-tonsillotomy significantly reduced symptom burden in otherwise healthy children with oSDB symptoms. Significant improvement in oAHI was observedonly in children with moderate-to-severe OSA. We recommend combining clinicalevaluation with PSQ and oAHI.
Topics: Humans; Male; Female; Sleep Apnea, Obstructive; Child, Preschool; Tonsillectomy; Child; Polysomnography; Treatment Outcome; Surveys and Questionnaires; Denmark; Adenoidectomy; Palatine Tonsil; Severity of Illness Index
PubMed: 38652931
DOI: 10.1016/j.sleep.2024.04.014