Metabolic landscape of human alveolar type II epithelial cells undergoing epithelial-mesenchymal transition induced directly by silica exposure.

Epithelial-mesenchymal transition (EMT) plays an irreplaceable role in the development of silicosis. However, molecular mechanisms of EMT induced by silica exposure still remain to be addressed. Herein, metabolic profiles of human alveolar type II epithelial cells (A549 cells) exposed directly to silica were characterized using non-targeted metabolomic approaches. A total of 84 differential metabolites (DMs) were identified in silica-treated A549 cells undergoing EMT, which were mainly enriched in metabolisms of amino acids (e.g., glutamate, alanine, aspartate), purine metabolism, glycolysis, etc. The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica. Remarkably, glutamine catabolism was significantly promoted in the silica-treated A549 cells, and the levels of related metabolites (e.g., succinate) and enzymes (e.g., α-ketoglutarate (α-KG) dehydrogenase) were substantially up-regulated, with a preference to α-KG pathway. Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail (zinc finger transcription factor). Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.

Effects of Transverse Abdominis Plane (TAP) Block on the MACBAR of Sevoflurane in Gynecologic Patients with Laparoscopic Pneumoperitoneal Stimulation: An Up-Down Sequential Allocation Study.

Purpose: This study aimed to observe the effect of bilateral transverse abdominis plane (TAP) block on the MACBAR of sevoflurane in gynecological patients with laparoscopic pneumoperitoneal stimulation. Patients and Methods: Fifty patients who underwent laparoscopic surgery were randomly assigned to either the control group (n= 25) or the TAP block group (n= 25). Patients in the TAP block group were subjected to a bilateral transversal abdominal muscle plane block with 0.33% ropivacaine (20 mL on each side) guided by ultrasound. The control group received an equal volume of normal saline. The MACBAR of sevoflurane in each group was determined using a sequential allocation technique. Results: The MACBAR of sevoflurane in the TAP block group was significantly lower than that in the control group (4.20% [95% confidence interval {CI}, 4.02%-4.38%] vs 5.03% [95% CI, 4.89%-5.18%]). Conclusion: Bilateral TAP block can reduce the MACBAR of sevoflurane in gynecological patients with pneumoperitoneum stimulation. Trial Registration Number: ChiCTR2100046517. The trial is publicly available and registered at www.chictr.org.cn on May 18, 2021.

Alveolar bone loss is a significant contributor to tooth loss in dentate HIV+ patients: A retrospective study.

BACKGROUND: The study objectives were to determine tooth loss prevalence and to investigate the relationship between tooth loss and potential risk factors among adult dentate HIV+ patients on newer antiretroviral therapy (ART) regimens. METHODS: Health records of 450 human immunodeficiency virus (HIV)-infected individuals were surveyed. Eighty-eight records of dentate HIV+ individuals with full-mouth periodontal charting and intra-oral periapical radiographs were identified. We collected data on demographics, systemic risk factors, oral health, and HIV disease measures. Caries exposure and alveolar bone loss (ABL) were radiographically assessed. RESULTS: Eighty-eight percent of patients showed tooth loss. Patients with ABL ≥15% had a higher number of missing teeth (p < .01). Stepwise regression analyses indicated that tooth loss was positively associated with age (ß = 0.45, p < .01) and ABL (ß = 0.39, p < .01). By contrast number of years on ART was negatively associated with tooth loss (ß = -0.28, p < .05). CONCLUSIONS: Tooth loss remains prevalent among HIV+ patients, and periodontal disease is a significant contributor. The number of years on ART seem to improve oral health behavior and reduce tooth loss.

Evaluation and comparison of autologous particulate dentin with demineralized freeze dried bone allograft in ridge preservation procedures - a prospective clinical study.

OBJECTIVES: To compare effectiveness of Autologous Particulate Dentin (APD) with Demineralized Freeze-Dried Bone Allograft (DFDBA) in ridge preservation, using radiographic and clinical parameters. MATERIALS AND METHODS: Thirty subjects with indication of mandibular posterior teeth extraction were randomly assigned to either test or control group. After atraumatic extraction, ridge preservation was performed using APD or DFDBA mixed with i-PRF in test and control groups respectively. Both groups had sockets sealed with A-PRF membrane. Clinical parameters (plaque, gingival and healing indices) and radiographic parameters (vertical ridge height, horizontal ridge width) were assessed at baseline and 6 months using CBCT. Statistical analysis was performed using an independent t-test to compare clinical and radiographic parameters between the groups. RESULTS: Both groups had significant decreases in ridge dimensions over 6 months (p < 0.001). The test group showed less reduction in ridge dimensions than control group at 6 months (p < 0.001). Mean change in vertical height was not significant (1.37 ± 1.32, 1.7311 ± 0.563), but in horizontal ridge width (1.3120 ± 1.13, 1.8093 ± 1.16) was significantly different between test and control groups respectively. There was no statistical difference in clinical parameters between the groups at 6 months (p > 0.001). CONCLUSIONS: APD grafts resulted in significant improvements in radiographic parameters, specifically in vertical ridge height and horizontal ridge width, compared to DFDBA group. CLINICAL RELEVANCE: Autologous particulate dentin is a promising, versatile substitute for regenerative procedures. While more research on its long-term efficacy and application is needed, current evidence suggests it could significantly improve patient care and outcomes.

The effects of chlorhexidine gel and tranexamic acid application after tooth extraction on the risk of alveolar osteitis formation: a double blind clinical study.

BACKGROUND: Alveolar osteitis(AO), one of the most common complications occurring in 1-10% of cases following tooth extraction, occurs due to the disruption of clot formation in the extraction socket. This study aims to evaluate the effect of using absorbable gelatin sponge, chlorhexidine gel, and tranexamic acid agents on the development of AO following extraction. METHODS: Between March and October 2023, the teeth of 98 healthy patients (average age: 38, range: 19-62) with extraction indications were extracted at Recep Tayyip Erdogan University, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery. 113 extraction sockets(85 molars and 28 premolars) were randomly treated with absorbable gelatin sponge(AGS), chlorhexidine gel with AGS, and tranexamic acid with AGS. Pain and edema levels were recorded using visual analog scale(VAS) ranging from 0 to 10 by the patients. Additionally, presence of halitosis, trismus and exposed bone was noted on forms on 3rd and 7th days (recorded as present or absent). The study prospectively aimed to prevent AO using 3 different dental agents in the extraction sockets. Statistical analyses of the study were conducted using the SPSS software package. RESULTS: Alveolitis was observed in 12 out of 113 tooth extractions(%10.6). Pain and edema scores significantly decreased in absorbable gelatin sponge group on the 7th day (p < 0.05). Pain score on the 7th day in chlorhexidine group and age, edema score on the 7th day in tranexamic acid group, were found to be significantly higher (p < 0.05). CONCLUSION: Incidence of AO, can be reduced by placing agents in the extraction socket, preventing post-extraction pain experienced by patients. CLINICAL TRIALS ID: NCT06435832.

Severe Granulomatosis With Polyangiitis Treated With Low-Dose Cyclophosphamide, Rituximab, Glucocorticoids, and Plasma Exchange: A Case Report.

Granulomatosis with polyangiitis (GPA) is a systemic vasculitis that affects blood vessels and presents with vague constitutional symptoms, but more serious manifestations can develop, including pulmonary complications and glomerulonephritis. Currently, there are no definitive treatment guidelines. We present a case of a 66-year-old male with no previous medical history who was admitted for generalized constitutional symptoms for the past month. Imaging of the patient's brain revealed dural enhancement. Bronchoalveolar lavage was done and revealed diffuse alveolar hemorrhage (DAH). A kidney biopsy revealed granulomatosis with polyangiitis. The patient's hospital course was complicated by acute renal failure and required hemodialysis. Due to the patient's multi-organ involvement, the patient was treated aggressively with cyclophosphamide, rituximab, plasma exchange (PE), and steroids. GPA is a systemic vasculitis that can present with multi-organ involvement. A prompt diagnosis is necessary to initiate treatment and preserve organ function. More research is needed to determine which combination therapies are the best treatment modalities in cases of severe multi-organ system involvement.

Outcome Difference between Short and Longer Dental Implants Placed Simultaneously with Alveolar Bone Augmentation: a Systematic Review and Meta-Analysis.

Objectives: This systematic review and meta-analysis aim to provide detailed insights into the clinical performance of short and longer dental implants placed simultaneously with bone augmentation. Material and Methods: The search for literature was performed across MEDLINE (PubMed), ScienceDirect and the Cochrane Library databases, adhering to specific selection criteria and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only articles published in English between 2014 and 2024 were considered for data collection. Primary outcomes were survival rate (SR), marginal bone loss (MBL) and complications. Clinical outcomes were as follows: bleeding on probing (BOP), periodontal pocket depth (PPD), and implant stability quotient (ISQ). Quality and risk of bias assessment were evaluated by the Critical Appraisal Checklist tool for randomized controlled trials developed by the Joanna Briggs Institute. Results: A total of 14678 articles were screened, with 9 meeting the inclusion criteria and being utilized for this systematic review and meta-analysis. A total of 495 patients with 984 implants (491 short and 493 longer implants) showing a SR of 93.91% for the short implants and 91.83% for the longer implants. Meta-analysis revealed statistically significant difference between short implants and longer implants simultaneously placed with alveolar bone augmentation in relation to MBL (-0.513 mm, 95% CI = -0.93 to -0.096; P = 0.02), and in PPD (-0.247, 95% CI = -0.515 to 0.022; P = 0.07). Conclusions: When comparing the results of treatment with short and longer dental implants combined with alveolar bone augmentation, short implants showed better clinical results regarding the parameters of survival rate, marginal bone loss and complications.

Entinostat as a combinatorial therapeutic for rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common childhood soft tissue sarcoma. For the alveolar subtype (ARMS), the presence of the PAX3::FOXO1 fusion gene and/or metastases are strong predictors of poor outcome. Metastatic PAX3::FOXO1+ ARMS often responds to chemotherapies initially, only to subsequently relapse and become resistant with most patients failing to survive beyond 8 years post-diagnosis. No curative intent phase II or phase III clinical trial has been available for patients in the past 10 years (ARST0921). Thus, metastatic ARMS represents a significantly unmet clinical need. Chemotherapy resistance in ARMS has previously been attributed to PAX3::FOXO1-mediated cell cycle checkpoint adaptation, which is mediated by an HDAC3-SMARCA4-miR-27a-PAX3::FOXO1 circuit that can be disrupted by HDAC3 inhibition. In this study, we investigated the therapeutic efficacy of combining the epigenetic regulator entinostat, a Class I Histone Deacetylase (HDAC1-3) inhibitor, with RMS-specific chemotherapies in patient derived xenograft (PDX) models of RMS. We identified single agent, additive or synergistic relationships between relapse-specific chemotherapies and clinically relevant drug exposures of entinostat in three PAX3::FOXO1+ ARMS mouse models. This preclinical data provides further rationale for clinical investigation of entinostat, already known to be well tolerated in a pediatric phase I clinical trial (ADVL1513).

A five-in-one novel MOF-modified injectable hydrogel with thermo-sensitive and adhesive properties for promoting alveolar bone repair in periodontitis: Antibacterial, hemostasis, immune reprogramming, pro-osteo-/angiogenesis and recruitment.

Periodontitis is a chronic inflammatory disease caused by plaque that destroys the alveolar bone tissues, resulting in tooth loss. Poor eradication of pathogenic microorganisms, persistent malignant inflammation and impaired osteo-/angiogenesis are currently the primary challenges to control disease progression and rebuild damaged alveolar bone. However, existing treatments for periodontitis fail to comprehensively address these issues. Herein, an injectable composite hydrogel (SFD/CS/ZIF-8@QCT) encapsulating quercetin-modified zeolitic imidazolate framework-8 (ZIF-8@QCT) is developed. This hydrogel possesses thermo-sensitive and adhesive properties, which can provide excellent flowability and post-injection stability, resist oral fluid washout as well as achieve effective tissue adhesion. Inspirationally, it is observed that SFD/CS/ZIF-8@QCT exhibits a rapid localized hemostatic effect following implantation, and then by virtue of the sustained release of zinc ions and quercetin exerts excellent collective functions including antibacterial, immunomodulation, pro-osteo-/angiogenesis and pro-recruitment, ultimately facilitating excellent alveolar bone regeneration. Notably, our study also demonstrates that the inhibition of osteo-/angiogenesis of PDLSCs under the periodontitis is due to the strong inhibition of energy metabolism as well as the powerful activation of oxidative stress and autophagy, whereas the synergistic effects of quercetin and zinc ions released by SFD/CS/ZIF-8@QCT are effective in reversing these biological processes. Overall, our study presents innovative insights into the advancement of biomaterials to regenerate alveolar bone in periodontitis.

Severe Discoloration of the Alveolar Bone Secondary to Long-Term Minocycline Therapy: A Case Report.

Minocycline, the synthetic derivative of the antibiotic tetracycline, has been used for a variety of medical treatments. One such use for minocycline is for acne vulgaris. Although widely used, minocycline has a common side effect of discoloration of tissues, including bone, skin, and mucosa. This case report presents a 19-year-old female patient with a history of long-term minocycline therapy for acne vulgaris who presented for periodontal esthetic crown lengthening. The initial exam revealed a blue-gray discoloration of the mucosa. Upon surgical exploration, it was discovered that the discoloration originated from the underlying alveolar bone with minimal gingival involvement. Surgical removal and recontouring of the bony exostoses revealed that the bone remained deeply stained. Although the discolored bone was not fully removed, the patient was able to obtain an acceptable esthetic result.

Novel PAX3::MAML3 fusion identified in alveolar rhabdomyosarcoma, using DNA methylation profiling to expand the genetic spectrum of "fusion-positive" cases.

Alveolar rhabdomyosarcoma (ARMS) with FOXO1 gene rearrangements is an aggressive pediatric rhabdomyosarcoma subtype that is prognostically distinct from embryonal rhabdomyosarcoma and fusion-negative ARMS. Herein, we report two cases of ARMS with PAX3::MAML3 fusions. The tumors arose in an infant and an adolescent as stage IV metastatic disease (by Children's Oncology Group staging system). Histologically, both cases were small round blue cell tumors arranged in vague nests and solid sheets that were diffusely positive for desmin and myogenin. By methylation profiling and unsupervised clustering analysis, the tumors clustered with ARMS with classic FOXO1 rearrangements and ARMS with variant PAX3::NCOA1/INO80D fusions, but not with biphenotypic sinonasal sarcoma (BSNS) with PAX3::MAML3/NCOA2/FOXO1/YAP1 fusions, nor with other small round blue cell tumors, including embryonal rhabdomyosarcoma. The differentially methylated genes between ARMS and BSNS were highly enriched in genes involved in myogenesis, and 21% of these genes overlap with target genes of the PAX3::FOXO1 fusion transcription factor. On follow-up after initiation of vincristine/actinomycin/cyclophosphamide chemotherapy, the tumors showed partial and complete clinical response, consistent with typical upfront chemotherapy responsiveness of ARMS with the classic FOXO1 rearrangement. We conclude that PAX3::MAML3 is a novel variant fusion of ARMS, which displays a methylation signature distinct from BSNS despite sharing similar PAX3 fusions. These findings highlight the utility of methylation profiling in classifying ARMS with non-canonical fusions.

The Alveolar Variant of Lobular Carcinoma and Its Mimickers: A Case Series.

Invasive lobular carcinoma (ILC) is the most common special type of invasive breast cancer (IBC), accounting for 5-15% of IBCs. The distinct histomorphology of ILC reflects a special tumor biology, the hallmark of which is the lack of E-cadherin expression. However, the occasional presence of E-cadherin expression and the presence of IBC of no special type (IBC, NST)-like morphologies in ILC and vice versa make the diagnosis challenging.  We present two cases of the alveolar variant of ILC, a diagnostically challenging entity. The first case is an 81-year-old female with two discrete right breast masses at 1 o'clock and 9 o'clock positions.  The second case is a 61-year-old female with two discrete left breast masses located at 11 o'clock and 12 o'clock positions. Core needle biopsies and subsequent mastectomy were performed in both cases. On histology, three tumor foci were identified in the first case. The 1 o'clock focus showed IBC, NST, grade 3/3, ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). The 9 o'clock focus revealed ILC, classic and alveolar variants, grade 2/3, while a nearby third incidental focus was ILC, alveolar variant, both supported by lack of E-cadherin and ß-catenin immunostaining.  The second case showed ILC, alveolar variant, grade 1 with LCIS component in the 11 o'clock lesion on both biopsy and mastectomy specimens. The lesion at the 12 o'clock position was diagnosed as IBC, NST, grade 2 with high-grade DCIS and LCIS components.  It is challenging to distinguish the alveolar variant of ILC from IBC, NST, and in situ lesions because of the overlapping morphology and occasional E-cadherin expression. Altered adherence of lobular cells may also be due to loss of α-, ß-, and γ-catenins, and cytoplasmic re-localization of p120-catenin. Therefore, in ILC, the lack of ß-catenin can be used as an adjunct along with E-cadherin. Myoepithelial markers such as p63 and smooth muscle myosin heavy chain (SMMHC) can be used to distinguish the alveolar variant of ILC from LCIS.

The Coexistence of Microscopic Polyangiitis and Rheumatoid Arthritis: A Case Report.

Microscopic polyangiitis (MPA) is a rare autoimmune disease characterized by the inflammation and necrosis of small vessels, primarily affecting kidneys and lungs. It is classified as an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) due to the presence of ANCA. MPA can manifest as diffuse alveolar hemorrhage (DAH) and rapidly progressive glomerulonephritis. In contrast, rheumatoid arthritis (RA) is an inflammatory disease that mainly targets the synovial joints. The coexistence of these two conditions presents significant diagnostic challenges, highlighting the need for further research and understanding. We report a case of a 58-year-old male with a past medical history of RA, chronic bronchitis, tobacco use, and recent Legionella pneumonia who presented with acute dyspnea. The patient was intubated for acute hypoxemic respiratory failure. Laboratory workup revealed anemia, hyponatremia, and acute kidney injury. Urinalysis showed hematuria and proteinuria. A CT scan of the chest exhibited bilateral extensive patchy infiltrates. He was transfused with one packed red blood cell (PRBC) unit. Hemoglobin decreased below 6 g/dL after transfusion. A bronchoscopy revealed erythema throughout the tracheobronchial tree, and blood on bronchial alveolar lavage suggested DAH. High-dose steroids were started. Subsequent laboratory results were positive for rheumatoid factor (RF), perinuclear ANCA (p-ANCA), anti-myeloperoxidase (anti-MPO), and antinuclear antibody (ANA). The kidney biopsy demonstrated focal crescentic necrotizing glomerulonephritis pauci-immune type, confirming MPA. RA pathogenesis involves immune dysregulation and activation of various cells, leading to the release of cytokines. Antibodies such as RF and anti-cyclic citrullinated peptide (anti-CCP) can be detected up to 10 years before the clinical manifestation of RA. Recent studies have revealed a predominance of MPA in AAV while coexisting with RA. The underlying mechanism of its occurrence remains unclear. Our patient had recurrent respiratory symptoms and renal dysfunction before hospitalization. MPA-RA overlap syndrome is potentially treatable and clinicians should maintain a high index of suspicion when encountering patients with preexisting RA. Timely initiation of immunosuppressive therapy at early stages is essential to prevent renal and pulmonary complications. ANCA serology should be assessed in these cases.

Spatial and phenotypic heterogeneity of resident and monocyte-derived macrophages during inflammatory exacerbations leading to pulmonary fibrosis.

Introduction: Genetic mutations in critical nodes of pulmonary epithelial function are linked to the pathogenesis of pulmonary fibrosis (PF) and other interstitial lung diseases. The slow progression of these pathologies is often intermitted and accelerated by acute exacerbations, complex non-resolving cycles of inflammation and parenchymal damage, resulting in lung function decline and death. Excess monocyte mobilization during the initial phase of an acute exacerbation, and their long-term persistence in the lung, is linked to poor disease outcome. Methods: The present work leverages a clinical idiopathic PF dataset and a murine model of acute inflammatory exacerbations triggered by mutation in the alveolar type-2 cell-restricted Surfactant Protein-C [SP-C] gene to spatially and phenotypically define monocyte/macrophage changes in the fibrosing lung. Results: SP-C mutation triggered heterogeneous CD68+ macrophage activation, with highly active peri-injured cells relative to those sampled from fully remodeled and healthy regions. Ingenuity pathway analysis of sorted CD11b-SigF+CD11c+ alveolar macrophages defined asynchronous activation of extracellular matrix re-organization, cellular mobilization, and Apolipoprotein E (Apoe) signaling in the fibrosing lung. Cell-cell communication analysis of single cell sequencing datasets predicted pro-fibrogenic signaling (fibronectin/Fn1, osteopontin/Spp1, and Tgfb1) emanating from Trem2/TREM2 + interstitial macrophages. These cells also produced a distinct lipid signature from alveolar macrophages and monocytes, characterized by Apoe expression. Mono- and di-allelic genetic deletion of ApoE in SP-C mutant mice had limited impact on inflammation and mortality up to 42 day after injury. Discussion: Together, these results provide a detailed spatio-temporal picture of resident, interstitial, and monocyte-derived macrophages during SP-C induced inflammatory exacerbations and end-stage clinical PF, and propose ApoE as a biomarker to identify activated macrophages involved in tissue remodeling.

DMP-1 expression in alveolar bone socket following Anredera cordifolia (Ten.) Steenis treatment: A histological study.

Objective: The study aimed to ascertain how Anredera cordifolia (Ten.) Steenis Gel affects the expression of protein dentin matrix protein-1 (DMP-1) in alveolar Wistar rats after tooth extraction. Materials and Methods: Rats were given A. cordifolia (Ten.) Steenis gel was in the socket after tooth extraction, and then the wound was sutured. The rats were sacrificed for 8 and 15 days following tooth extraction. The results on the 8th and 15th days demonstrate that the expression of DMP-1 in the treatment group is significantly higher than in the control group. Results: Expression of DMP-1 in the socket after tooth extraction on days 8 and 15 with a 400x magnification light microscope in both of the A. cordifolia (Ten.) Steenis gel treatment groups showed significant differences compared to the control group. Conclusion: The use of A. cordifolia (Ten.) Steenis gel can stimulate DMP-1 expression in alveolar bone after tooth extraction.

Healing patterns of alveolar bone following ridge preservation procedures.

OBJECTIVES: Examine the histomorphometric bone composition, following alveolar ridge preservation techniques and unassisted socket healing. MATERIALS AND METHODS: Forty-two patients (42) requiring a single rooted tooth extraction were randomly allocated into three groups (n = 14 per group): Group 1: Guided Bone Regeneration (GBR) using deproteinised bovine bone mineral (DBBM) and a porcine collagen membrane; Group 2: Socket Seal (SS) technique using DBBM and a porcine collagen matrix; Group 3: Unassisted socket healing (Control). Trephined bone biopsies were harvested following a 4-month healing period. Forty-two samples underwent Back-Scattered Electrons -Scanning Electron Microscopy (BSE-SEM) imaging, with 15 samples examined using Xray Micro-Tomography (XMT) (n = 6 for each GBR/SS and n = 3 Control). Images were analysed to determine the percentage (%) of connective tissue, new bone formation, residual DBBM particles and direct bone to DBBM particle contact (osseointegration). RESULTS: BSE-SEM analysis demonstrated that new bone formation was higher in the Control (45.89% ± 11.48) compared to both GBR (22.12% ± 12.7/p < .004) and SS (27.62% ± 17.76/p < .005) groups. The connective tissue percentage in GBR (49.72% ± 9), SS (47.81% ± 12.57) and Control (47.81% ± 12.57) groups was similar. GBR (28.17% ± 16.64) and SS (24.37% ± 18.61) groups had similar levels of residual DBBM particles. XMT volumetric analysis indicated a lower level of bone and DBBM particles in all test groups, when matched to the BSE-SEM area measurements. Osseointegration levels (DBBM graft and bone) were recorded at 35.66% (± 9.8) for GBR and 31.18% (± 19.38) for SS. CONCLUSION: GBR and SS ARP techniques presented with less bone formation when compared to unassisted healing. GBR had more direct contact/osseointegration between the DBBM particles and newly formed bone.

Role of Sticky Bone in the Management of Various Alveolar Bone Defects: A Systematic Review.

AIM: This systematic review aimed to evaluate the effectiveness of sticky bone in managing various alveolar bone defects, examining both its benefits and drawbacks. MATERIALS AND METHODS: The review adhered to PRISMA guidelines and employed a thorough search strategy using major databases, medical subject headings (MeSH) keywords, and Boolean operators. As a result, the systematic review identified 12 studies focusing on the efficacy of sticky bone in treating alveolar bone defects. Inclusion criteria consisted of randomized controlled trials and case series reporting on the outcomes of sticky bone use for bone defect treatment. Two examiners meticulously performed screening, data extraction, and bias assessment, with the risk of bias evaluated using the Cochrane tool. RESULT: The findings indicated significant improvements in bone quality, width, height, and volume, with enhanced predictability in socket preservation and implant placement. Sticky bone was particularly effective in ridge augmentation, guided bone regeneration, and filling periodontal defects, often outperforming alternatives like concentrated growth factors (CGFs) and autologous fibrin glue (AFG). It simplified procedures and reduced resorption during healing, underscoring its value as a versatile adjunct in bone reconstruction surgery. CONCLUSION: Sticky bone demonstrated exceptional results in various oral surgeries, effectively addressing issues such as furcation defects, bone loss, and ridge augmentation, with significant clinical and radiographic improvements. Further research is needed to explore its full potential and refine protocols for broader oral surgery and periodontics applications.

IL-4-induced SOX9 confers lineage plasticity to aged adult lung stem cells.

Wound healing in response to acute injury is mediated by the coordinated and transient activation of parenchymal, stromal, and immune cells that resolves to homeostasis. Environmental, genetic, and epigenetic factors associated with inflammation and aging can lead to persistent activation of the microenvironment and fibrosis. Here, we identify opposing roles of interleukin-4 (IL-4) cytokine signaling in interstitial macrophages and type II alveolar epithelial cells (ATIIs). We show that IL4Ra signaling in macrophages promotes regeneration of the alveolar epithelium after bleomycin-induced lung injury. Using organoids and mouse models, we show that IL-4 directly acts on a subset of ATIIs to induce the expression of the transcription factor SOX9 and reprograms them toward a progenitor-like state with both airway and alveolar lineage potential. In the contexts of aging and bleomycin-induced lung injury, this leads to aberrant epithelial cell differentiation and bronchiolization, consistent with cellular and histological changes observed in interstitial lung disease.

Senescence in Alveolar Epithelial Type II Cells Promotes Acute Lung Injury and Impairs Regeneration.

Mortality of acute lung injury (ALI) increases with age. Alveolar epithelial type 2 cells (AEII) are the progenitor cells of the alveolar epithelium and crucial for repair after injury. We hypothesize that telomere dysfunction-mediated AEII senescence impairs regeneration and promotes the development of ALI. To discriminate between the impact of old age and AEII senescence in ALI, young (3 months) and old (18 months) Sftpc-Ai9 mice and young Sftpc-Ai9-Trf1 mice with inducible Trf1 knockout-mediated senescence in AEII were treated with 1 µg lipopolysaccharide (LPS)/g BW (n=9-11). Control mice received saline (n=7). Mice were sacrificed 4 or 7 days later. Lung mechanics, pulmonary inflammation and proteomes were analyzed and parenchymal injury, AEII proliferation and AEI differentiation rate were quantified using stereology. Old mice showed 55% mortality by day 4, whereas all young mice survived. Pulmonary inflammation was most severe in old mice, followed by Sftpc-Ai9-Trf1 mice. Young Sftpc-Ai9 mice recovered almost completely by day 7, while Sftpc-Ai9-Trf1 mice still showed mild signs of injury. An expansion of AEII was only measured in young Sftpc-Ai9 mice at day 7. Aging and telomere dysfunction-mediated senescence had no impact on AEI differentiation rate in controls, but the reduced number of AEII in Sftpc-Ai9-Trf1 mice also affected de-novo differentiation after injury. In conclusion, telomere dysfunction-mediated AEII senescence promoted parenchymal inflammation in ALI, but did not enhance mortality like old age. While Differentiation rate remained functional with old age and AEII senescence, AEII proliferative capacity was impaired in ALI, affecting the regenerative ability.