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Frontiers in Immunology 2024Protein kinases are indispensable reversible molecular switches that adapt and control protein functions during cellular processes requiring rapid responses to internal...
INTRODUCTION
Protein kinases are indispensable reversible molecular switches that adapt and control protein functions during cellular processes requiring rapid responses to internal and external events. Bacterial infections can affect kinase-mediated phosphorylation events, with consequences for both innate and adaptive immunity, through regulation of antigen presentation, pathogen recognition, cell invasiveness and phagocytosis. (), a human respiratory tract pathogen and a major cause of community-acquired pneumoniae, affects phosphorylation-based signalling of several kinases, but the pneumococcal mediator(s) involved in this process remain elusive. In this study, we investigated the influence of pneumococcal HO on the protein kinase activity of the human lung epithelial H441 cell line, a generally accepted model of alveolar epithelial cells.
METHODS
We performed kinome analysis using PamGene microarray chips and protein analysis in Western blotting in H441 lung cells infected with wild type () or with -a deletion mutant strongly attenuated in HO production- to assess the impact of pneumococcal hydrogen peroxide (HO) on global protein kinase activity profiles.
RESULTS
Our kinome analysis provides direct evidence that kinase activity profiles in infected H441 cells significantly vary according to the levels of pneumococcal HO. A large number of kinases in H441 cells infected with are significantly downregulated, whereas this no longer occurs in cells infected with the mutant strain, which lacks HO In particular, we describe for the first time HO-mediated downregulation of Protein kinase B (Akt1) and activation of lymphocyte-specific tyrosine protein kinase (Lck) via HO-mediated phosphorylation.
Topics: Streptococcus pneumoniae; Hydrogen Peroxide; Humans; Phosphorylation; Host-Pathogen Interactions; Cell Line; Protein Kinases; Pneumococcal Infections; Signal Transduction
PubMed: 38903521
DOI: 10.3389/fimmu.2024.1414195 -
BioRxiv : the Preprint Server For... May 2024During pregnancy, mammary tissue undergoes expansion and differentiation, leading to lactation, a process regulated by the hormone prolactin through the JAK2-STAT5...
During pregnancy, mammary tissue undergoes expansion and differentiation, leading to lactation, a process regulated by the hormone prolactin through the JAK2-STAT5 pathway. STAT5 activation is key to successful lactation making the mammary gland an ideal experimental system to investigate the impact of human missense mutations on mammary tissue homeostasis. Here, we investigated the effects of two human variants in the STAT5B SH2 domain, which convert tyrosine 665 to either phenylalanine (Y665F) or histidine (Y665H), both shown to activate STAT5B in cell culture. We ported these mutations into the mouse genome and found distinct and divergent functions. Homozygous mice failed to form functional mammary tissue, leading to lactation failure, with impaired alveolar development and greatly reduced expression of key differentiation genes. STAT5B failed to recognize mammary enhancers and impeded STAT5A binding. In contrast, mice carrying the mutation exhibited abnormal precocious development, accompanied by an early activation of the mammary transcription program and the induction of otherwise silent genetic programs. Physiological adaptation was observed in mice as continued exposure to pregnancy hormones led to lactation. In summary, our findings highlight that human STAT5B variants can modulate their response to cytokines and thereby impact mammary homeostasis and lactation.
PubMed: 38903072
DOI: 10.1101/2024.05.06.592736 -
Cureus May 2024Enhancing the availability of bone in the vertical dimension for implant insertion is thought to be possible through implant site preparation using direct or indirect...
Prevalence, Location, and Variations of the Posterior Superior Alveolar Canal With Age and Gender in the Indian Population: A Cone Beam Computed Tomography (CBCT)-Based Retrospective Study.
BACKGROUND
Enhancing the availability of bone in the vertical dimension for implant insertion is thought to be possible through implant site preparation using direct or indirect sinus lift. The posterior superior alveolar (PSA) canal is extremely vulnerable to trauma during this procedure. The anatomy of this region should be thoroughly evaluated to prevent traumatizing this artery and eventual perioperative bleeding. Due to a lack of relevant knowledge and the clinical importance of this problem, the position, diameter, detectability, and proximity of this canal to the alveolar ridge were assessed on cone beam computed tomography (CBCT) scans which were the main objectives of this study.
METHODOLOGY
A total of 240 CBCT scans were examined, and the position of the PSA canal, its diameter, the perpendicular distance from the inferior border of the PSA canal to the alveolar crest, and the perpendicular distance from the inferior border of the canal to the maxillary sinus floor was measured.
RESULTS
Intraosseous PSA canals were the most prevalent, followed by intrasinusal and extraosseous canals. Males had larger canal diameters and greater distances between the maxillary sinus floor and alveolar crest and the canal (< 0.05).
CONCLUSION
CBCT was proven to be a useful method for assessing and localizing the PSA artery to prevent intraoperative bleeding and further complications.
PubMed: 38899265
DOI: 10.7759/cureus.60658 -
Journal of Applied Oral Science :... 2024This study aimed to validate the integrated correlation between the buccal bone and gingival thickness of the anterior maxilla, and to gain insight into the reference...
OBJECTIVE
This study aimed to validate the integrated correlation between the buccal bone and gingival thickness of the anterior maxilla, and to gain insight into the reference plane selection when measuring these two tissues before treatment with implants.
METHODOLOGY
Cone beam computed tomography (CBCT) and model scans of 350 human subjects were registered in the coDiagnostiX software to obtain sagittal maxillary incisor sections. The buccal bone thickness was measured at the coronal (2, 4, and 6 mm apical to the cementoenamel junction [CEJ]) and apical (0, 2, and 4 mm coronal to the apex plane) regions. The buccal gingival thickness was measured at the supra-CEJ (0, 1mm coronal to the CEJ) and sub-CEJ regions (1, 2, 4, and 6 mm apical to the CEJ). Canonical correlation analysis was performed for intergroup correlation analysis and investigation of key parameters.
RESULTS
The mean thicknesses of the buccal bone and gingiva at different levels were 0.64~1.88 mm and 0.66~1.37 mm, respectively. There was a strong intergroup canonical correlation between the thickness of the buccal bone and that of the gingiva (r=0.837). The thickness of the buccal bone and gingiva at 2 mm apical to the CEJ are the most important indices with the highest canonical correlation coefficient and loadings. The most and least prevalent subgroups were the thin bone and thick gingiva group (accounting for 47.6%) and the thick bone and thick gingiva group (accounting for 8.6%).
CONCLUSION
Within the limitations of this retrospective study, the thickness of the buccal bone is significantly correlated with that of the buccal gingiva, and the 2 mm region apical to the CEJ is a vital plane for quantifying the thickness of these two tissues.
Topics: Humans; Gingiva; Cone-Beam Computed Tomography; Incisor; Maxilla; Female; Male; Adult; Young Adult; Reference Values; Reproducibility of Results; Alveolar Process; Middle Aged; Adolescent; Retrospective Studies
PubMed: 38896641
DOI: 10.1590/1678-7757-2024-0018 -
Journal of Clinical Medicine Jun 2024: A mucous retention cyst is a common, asymptomatic lesion that may cause complications during or after the sinus lift procedure. The goal of this study is to assess the...
: A mucous retention cyst is a common, asymptomatic lesion that may cause complications during or after the sinus lift procedure. The goal of this study is to assess the effectiveness of the Croco Eye Technique (CET), which allows simultaneous excision of the cyst and sinus floor elevation. : The technique was thoroughly described in two versions, and the group of 33 patients was analyzed. Patients who qualified for this procedure had insufficient alveolar ridge height, and their CBCT showed radiological images typical for retention cysts. Analyzed parameters included the version of CET, demographic data, anatomical parameters, intraoperative complications, recurrence of the cyst, success rate of the sinus lift and implants, and the follow-up period. : Out of the 33 cases, 9 were of the primary version (27.27%) and 24 of the final version (72.73%). The average height of a retention cyst was 24.05 mm, with the average alveolar ridge height of 1.86 mm. In three cases (9.09%), implants were placed immediately. The prevalence of uncontrolled Schneiderian membrane perforation was reduced from 55.56% to 4.17% between the primary and final versions. The cyst's recurrence rate was 3.13%. The implant survival rate was 100%. The mean follow-up period was 48.625 months (max 110 months). : The Croco Eye Technique, despite the perforation of the Schneiderian membrane, enables successful sinus lift and implantation with a success rate of 100%. Excision of the retention cyst, which is the cause of perforation, allows for limiting the risk of the cyst's recurrence.
PubMed: 38893004
DOI: 10.3390/jcm13113293 -
Journal of Clinical Medicine May 2024: Dental rehabilitation after extended tumour resection and jaw reconstruction is challenging. The present study aimed to report the prosthetic outcome and quality of...
: Dental rehabilitation after extended tumour resection and jaw reconstruction is challenging. The present study aimed to report the prosthetic outcome and quality of life (QoL) in patients with head and neck cancer (HNC) after microvascular alveolar ridge reconstruction. : The prosthetic outcomes of all consecutive patients with HNC who underwent microvascular alveolar ridge reconstruction at the University Hospital Salzburg between 2011 and 2018 were investigated. Oral health-related QoL (OHrQoL) and overall QoL were assessed using the validated Oral Health Impact Profile-49 (OHIP-49) and Short Form-36 questionnaires. : During the study period, 115 consecutive patients with head and neck cancer underwent microvascular jaw reconstruction. Among them, 23.3% and 27.4% received conventional tissue-borne prostheses and implant-supported prostheses, respectively, while 48.7% did not undergo dental rehabilitation. The prosthetic outcome was not associated with tumour stage ( = 0.32). Oral health-related quality of life (OHrQoL) was best in patients with implant-supported dental rehabilitation (OHIP-49 median score = 7) and worst in those with conventional removable dentures (OHIP-49 median score = 54). The corresponding OHIP-49 median score for patients who could not undergo dental rehabilitation was 30.5. All Short Form-36 subscale scores were equal to or higher than the malignancy norm scores. : After microvascular jaw reconstruction, approximately one-third of the HNC patients received adequate implant-supported dental rehabilitation. However, the risk of dental rehabilitation failure was 50%. The different prosthetic outcomes affected OHrQoL, but not overall QoL.
PubMed: 38892821
DOI: 10.3390/jcm13113110 -
Journal of Clinical Medicine May 2024Accidents involving the maxillofacial area are sudden and unforeseen, such as traffic accidents and physical altercations. The COVID-19 pandemic was a critical threat...
Accidents involving the maxillofacial area are sudden and unforeseen, such as traffic accidents and physical altercations. The COVID-19 pandemic was a critical threat to the public in aspects not only involving physical health but also those affecting psychological health due to isolation, leading to a higher incidence of stress and depression among the general population and specifically in patients with OMF trauma. This study assessed the relationship between the impact of the COVID-19 pandemic and the quantity and severity of maxillofacial injuries. : Data were retrieved from the Department of Maxillofacial Surgery of the University Clinical Centre in Gdansk from March 2019 to August 2023. There was an increased risk of injury occurrence to the condylar process of the mandible, especially the left side, Le Fort type II/III fractures, injuries of the maxillary alveolar process, and displacement of the upper facial mass. Simultaneously, a decreased occurrence of certain injuries i.e., Le Fort type III fractures and Le Fort type I/II fractures, was recorded. : The COVID-19 pandemic led to an increased occurrence of high-energy injuries, including displacement of the upper facial mass ( = 0.010).
PubMed: 38892806
DOI: 10.3390/jcm13113095 -
Anti-Inflammatory Activity of No-Ozone Cold Plasma in Lipopolysaccharide-Induced Periodontitis Rats.International Journal of Molecular... Jun 2024Periodontitis is an inflammatory disease caused by () in the oral cavity. This periodontal disease causes damage to the periodontal ligament and alveolar bone and can...
Periodontitis is an inflammatory disease caused by () in the oral cavity. This periodontal disease causes damage to the periodontal ligament and alveolar bone and can cause tooth loss, but there is no definite treatment yet. In this study, we investigated the possibility of using no-ozone cold plasma to safely treat periodontitis in the oral cavity. First, human gingival fibroblasts (HGFs) were treated with -derived lipopolysaccharide (PG-LPS) to induce an inflammatory response, and then the anti-inflammatory effect of NCP was examined, and a study was conducted to identify the mechanism of action. Additionally, the anti-inflammatory effect of NCP was verified in rats that developed an inflammatory response similar to periodontitis. When NCP was applied to PG-LPS-treated HGFs, the activities of inflammatory proteins and cytokines were effectively inhibited. It was confirmed that the process of denaturing the medium by charged particles of NCP is essential for the anti-inflammatory effect of NCP. Also, it was confirmed that repeated treatment of periodontitis rats with NCP effectively reduced the inflammatory cells and osteoclast activity. As a result, this study suggests that NCP can be directly helpful in the treatment of periodontitis in the future.
Topics: Animals; Porphyromonas gingivalis; Periodontitis; Lipopolysaccharides; Rats; Anti-Inflammatory Agents; Humans; Gingiva; Fibroblasts; Ozone; Plasma Gases; Male; Cytokines; Disease Models, Animal; Nitric Oxide; Cells, Cultured
PubMed: 38892350
DOI: 10.3390/ijms25116161 -
Cells May 2024Pulmonary surfactants play a crucial role in managing lung lipid metabolism, and dysregulation of this process is evident in various lung diseases. Alternations in lipid... (Review)
Review
Pulmonary surfactants play a crucial role in managing lung lipid metabolism, and dysregulation of this process is evident in various lung diseases. Alternations in lipid metabolism lead to pulmonary surfactant damage, resulting in hyperlipidemia in response to lung injury. Lung macrophages are responsible for recycling damaged lipid droplets to maintain lipid homeostasis. The inflammatory response triggered by external stimuli such as cigarette smoke, bleomycin, and bacteria can interfere with this process, resulting in the formation of lipid-laden macrophages (LLMs), also known as foamy macrophages. Recent studies have highlighted the potential significance of LLM formation in a range of pulmonary diseases. Furthermore, growing evidence suggests that LLMs are present in patients suffering from various pulmonary conditions. In this review, we summarize the essential metabolic and signaling pathways driving the LLM formation in chronic obstructive pulmonary disease, pulmonary fibrosis, tuberculosis, and acute lung injury.
Topics: Humans; Lung Diseases; Lipid Metabolism; Animals; Macrophages; Macrophages, Alveolar; Signal Transduction
PubMed: 38891022
DOI: 10.3390/cells13110889 -
Frontiers in Immunology 2024Varicella zoster virus (VZV) causes varicella and can reactivate as herpes zoster, and both diseases present a significant burden worldwide. However, the mechanisms by...
INTRODUCTION
Varicella zoster virus (VZV) causes varicella and can reactivate as herpes zoster, and both diseases present a significant burden worldwide. However, the mechanisms by which VZV establishes latency in the sensory ganglia and disseminates to these sites remain unclear.
METHODS
We combined a single-cell sequencing approach and a well-established rhesus macaque experimental model using Simian varicella virus (SVV), which recapitulates the VZV infection in humans, to define the acute immune response to SVV in the lung as well as compare the transcriptome of infected and bystander lung-resident T cells and macrophages.
RESULTS AND DISCUSSION
Our analysis showed a decrease in the frequency of alveolar macrophages concomitant with an increase in that of infiltrating macrophages expressing antiviral genes as well as proliferating T cells, effector CD8 T cells, and T cells expressing granzyme A (GZMA) shortly after infection. Moreover, infected T cells harbored higher numbers of viral transcripts compared to infected macrophages. Furthermore, genes associated with cellular metabolism (glycolysis and oxidative phosphorylation) showed differential expression in infected cells, suggesting adaptations to support viral replication. Overall, these data suggest that SVV infection remodels the transcriptome of bystander and infected lung-resident T cells and macrophages.
Topics: Animals; Macaca mulatta; Lung; Macrophages, Alveolar; Transcriptome; T-Lymphocytes; Varicellovirus; Macrophages; Herpesviridae Infections; Herpesvirus 3, Human; Disease Models, Animal; Single-Cell Analysis
PubMed: 38887303
DOI: 10.3389/fimmu.2024.1408212